HOW POTASSIUM CITRATE PILLS WORK

MeIf the lives of the Tudor nobility were luxurious, they were dangerous in equal proportions, for the King who bestowed their riches could in a moment wipe them, and those who possessed them, out. So intimacy with the person of the King and with the whole Royal Family was prized and feared. They lived, these powerful and dangerous people, in their Royal Palaces, to which you must go or have no influence. Even worse, King and Consorts made Royal Progresses, staying here and there as guests of the high nobility. Imagine that, the King as your houseguest. A person, like any other, and yet not at all like any other: glamorous, dangerous, and involved with high concerns.

You could say this is a silly preface to my common discourse on citrate, but not so. I have written before about its powers in our little domain: It binds calcium, it inhibits crystals, giving it reduces stones. But I have not said how it gets into the urine.

It comes as a royal visitor to some Duke or Marquess, Earl, Viscount, or Baron.

For this molecule has high purposes. It is noble and powerful. What it does in urine is but a tiny fraction of its many actions and probably not one of the more important ones. But what we do when we take citrate calls into play a vast biology. For all our lives we eat a diet that imposes an acid load on our kidneys, our bones, and elsewhere. Our kidneys, especially, adapt to that acid load, so what we call our ‘normal’ state is actually at one extreme. The pills, being alkali, reverse this lifelong adaptation and thereby profoundly alter the physiology of the kidneys and bone. In general one might say the alterations are for the better.

This is a long article but one worth reading for those who prescribe or take potassium citrate pills.

A Picture of the Kidney

Many of you are physicians or scientists who know about the kidney, but a few reminders are always worthwhile. Others are neither and we need to have names in common. Human pic_nephronkidneys are made of about one million individual nephron units. The renal process begins with filtration of small molecules like citrate, or atoms like sodium and calcium, through the glomerulus, which is a complex of capillaries whose filtration pressure arises from the heart not a foot away.

A majority of the filtered water, salts, and molecules is reabsorbed in the proximal tubule. The distal tubule (highly simplified here) performs tightly regulated absorption or secretion, so as to produce a final urine and maintain blood concentrations in their normal ranges.

These loops will come up again and again on this site so I should comment on the thin and thick portions. The long thin loops of Henle (Henle was the scientist who is credited with describing this part of the kidney) extract water specially well.The thick portions just below the ‘Distal tubule’ notation are called, appropriately enough, the Thick Ascending Limbs of the Loop of Henle. The thick limbs reabsorb NaCl, but not water, and in doing that entrain a marvelous system for – of all things – retaining water! In an article so long as this one, and concerned with citrate, I cannot pause longer here. But we will be back, someday.

Citrate is in the Blood

Kidneys Filter and Reabsorb Citrate

In one published study, concentration of citrate in blood is about 80 – 170 micromolar. A recent review places it at 120 micromoles/liter. If we use 120 micromoles/liter as a reasonable average, and a common value for glomerular filtration of 120 milliliters/minute, the filtration of citrate is about 21 millimoles a day. Of this about 1 – 4 millimoles appear in the urine, the rest being reabsorbed by the kidney cells. So the fraction of filtered citrate excreted is about 5 to 20%, and regulation of this fraction controls the amount of citrate in the urine.

Citrate in Blood Binds Calcium

The concentration in blood of calcium not bound with proteins is about 1 millimole/liter. Citrate concentration is about 0.12 mmol/liter, so in principle about 10% of non -protein bound – calcium can be bound by citrate. Because in calcium citrate crystals 2 citrate molecules can bind 3 calcium atoms, the the figure would seem to rise to to 15%. But in solutions like blood, other materials compete with calcium for a place on citrate – magnesium is one example. So the actual fraction is difficult to estimate. Normally blood citrate level is stable, so although significant, citrate binding of calcium is not likely to influence calcium metabolism by, for example, altering regulation of parathyroid hormone secretion.

Citrate has Signalling Roles

My purposes here are humble purposes, so all I wish to do is put here a tiny list of known effects of citrate on systems throughout the body without pursuing the details. Citrate concentration regulates lipid metabolism via malonyl-CoA. Citrate is sensed by the hypothalamus and thereby affects glucose intake and glucose metabolism by liver. To do these things citrate must enter the relevant cells, and it can do this only via a transporter that takes it across cell membranes.

The Citrate Transporters

NaDC1 and NaDC3

picture of renal cell with citrate transporters reference in text
From Pfleugers Arch 466:119, 2014

NaDC1 is on the apical membranes of the proximal tubule cells of the kidney – the surface facing into the tubule fluid – and regulates the rate of reabsorption of the citrate that has been filtered. Its gene is named SLC13A2. This same transporter is on the food side of the small intestine cells and permits absorption of citrate from foods. The featured image for this article shows the structure of the transporter.

The citrate that enters the renal cells can be used for metabolism, or transported out the other side – called the basolateral side, facing the blood – via another transporter called the Organic Acid Transporter (OAT). Yet another transporter, NaDC3, permits citrate to enter kidney cells from blood. Because it appears to regulate urine citrate, my focus is on NaDC1.

The citrate transporter DC1 couples sodium and citrate movement. Since not everyone who reads this will know, let me mention an almost universal property of living cells: they pump sodium out of themselves and pump potassium in. Because they do this, sodium will tend to move into cells if given an opportunity – a hole. DC1 and DC3 can be thought of as sophisticated holes, or channels, through which sodium atoms can move if they have a citrate molecules with them. The actual proportions are 3 sodium atoms move with one citrate molecule, and the form of citrate which moves is one we have encountered before. Recall how citrate binds calcium because each molecule can have 2 or three negative charges on it. The doubly negative (divalent anionic) form of citrate is the one that traverse the channel.

They Transport More than Citrate

NaDC1 permits not only citrate to cross cell membranes but also succinate, alpha ketoglutarate, fumarate, malate, and a variety of less biologically relevant molecules. One might ask why, and I presume it is because the named molecules are all part of the citric acid cycle, which is the main engine of cell energy production. NaDC3 transports all of the same molecules as NaDC1, along with glutarate and a very long list of other molecules not in the citric acid cycle.

This cycle is at the center of that metabolism which uses oxygen to produce energy from food. The reference is to an excellent textbook review that is free online. Another chapter in that book finishes the story of how the cycle produces energy. The antiquity and centrality of the citric acid cycle will become apparent to you if you even browse these chapters. If you read them, you will encounter some of the most important aspects of living cells.

Why are Potassium Citrate Pills an Alkali Load?

Commercial potassium citrate contains 1080 mg of the compound in a 10 mEq pill. Since potassium atomic weight is 39, and citrate molecular weight is 197, there are only 2 potassium atoms (1080 – 78)/197 = 5 mmol which gives 10 mEq. This means it is titrated so that the third negative site (there are 3) is bound to a proton. In the citric acid cycle citrate is metabolized as citric acid, meaning that 2 protons are taken up from blood with each molecule. Removing protons is identical to adding alkali.

The Flow of Citrate

In an earlier era organ physiology was popular and scientists often gathered together Simpson - picture of citrate renal metabolismmeasurements to paint a picture of how things work overall. Here is such a picture from a wonderful review of renal citrate handling by Simpson. Values in small circles are micromoles (umol) per minute.

Citrate is presented to the glomerular filter at 44 umol/min, and 36 umol/min leaves the glomerulus (8.8 umol/min filtered) in blood what will pass by the blood side of the proximal tubules. From that 36 umol/min, 1.5 umol.min are taken up by renal proximal tubule cells and metabolized in the citric acid cycle. Of the 8.8 umol/min filtered, 6.6 umol/min are taken up on the urine side of the same cells making 8.1 umol/minute for metabolism. The remaining 2 umol/minute (3.17 mmol/day) are lost in the urine. NaDC1 and NaDC3 had not been cloned and sequenced at this early time, but physiologists knew the transporters were there and toted up what they did.

Urine Citrate Varies With Acid Base Status

Acid loads, such as high protein diets, will increase citrate uptake into the renal cells and thereby reduce urine citrate. Alkali loads such as diets high in fruits and vegetables or potassium alkali supplements reduce uptake and increase urine citrate.

Alkali

Clinical Response

In a trial, calcium stone formers with low urine citrate excretion eating a constant diet were given sodium bicarbonate or table from kcit nacho3 trialpotassium citrate, 20 mEq three times a day. Urine citrate rose with both treatments, as did the urine pH. Not relevant here, but in later articles, the sodium alkali did not change urine calcium, but the potassium alkali lowered urine calcium. Alkali itself lowers urine calcium, sodium raises it, and their antagonism is the reason for the differences.

Mechanism May be Increase of pH

If the citrate transporter is placed into test cells, the movement of citrate can be studied, and such a study shows how powerful is the effect of pH.

ph dependence of citrate transport from pajor first jbc paperSuccinate is a citric acid cycle intermediate like citrate, but its uptake by the citrate transporter is not affected by the acidity or alkalinity of the medium (pH). Citrate uptake is powerfully affected.

We have encountered pH before and remind ourselves here that urine values vary from about 4.5 to just below 8. Likewise, citrate has three sites that can accept protons, the acid component of water systems. As I mentioned in the paragraphs just above this point, the charge on the citrate molecule rises with pH as protons are progressively removed, and the sequence of pH values (the pKa values for the dissociating sites for those of you who know about such matters) are 3.13, 4.76, and 6.40. Obviously, in urine, the divalent (2 open negative sites) form will predominate until urine pH rises above 6 and will fall to about 1/2 of the total at 6.4. At about 6.4 transport of citrate was indeed just about half of that at the lowest pH. 

pH in the Proximal Tubule

But it is not urine pH which affects citrate transport, it is the pH of filtrate in the proximal tubule of the kidneys, and that pH is not the same as that of the urine. At the end of the proximal tubule, the pH is about 6.7 to 6.8, and at that pH more than half of citrate is in the trivalent form and not available for transport. With alkali loads, as in the experiment in the table, the pH will rise, and citrate transport fall below normal, so citrate appears in the urine.

Problems with the pH Idea

Strangely, modern sources do not mention an older literature which raises questions about this mechanism. Simpson, in an important review from late antiquity (1983), mentions that the drug acetazolamide, which raises pH inside the proximal tubule and lowers pH inside the renal cells raises urine citrate only slightly and at first, but shortly after administration urine citrate falls despite a continuously alkaline urine and presumably tubule fluid. This suggests that even a high tubule fluid pH is not enough to counter the effects of changes in pH within cells or perhaps the blood. So it is not only tubule fluid pH that matters, but perhaps the pH inside the renal proximal tubule cell.

Acid Loads

Those unfamiliar with the matter may not realize that the diet we eat in the US and most of the other first world countries  imposes an acid load that must be excreted daily in the urine. So the urine citrate excretion we find in our clinics and in experiments on ‘normal’ diets are those consistent with an acid load. When we give potassium citrate or other alkali we often do little more than neutralize this acid load, yet urine citrate usually rises. Experiments about acid loads add to the diet acid an extra amount of acid.

Tubule Fluid pH

As for alkali loads, a lower proximal tubule fluid pH will increase the fraction of filtered citrate in the divalent form which is transported by NaDC1. The pH of the tubule fluid will fall with acid loads for several reasons. Acid loads – for example a high protein meal – are buffered on blood bicarbonate which lowers the concentration of bicarbonate, and therefore the pH of the filtrate. LIkewise, the tubule cells are stimulated to increase their reabsorption of filtered bicarbonate which further lowers pH. All of this implies that kidneys sense the acidity or alkalinity of the blood, which they surely do.

Transport Adaptation

Over time – many hours to days – the NaDC1 transporter and its gene (SLC13A2) increase presig figure from 2007 about endothelintheir abundances. This increase is mediated by endothelin – 1 (ET-1) through the endothelin B receptor (ETb).

This figure from the above reference shows thinking about acid and endothelin as it was in 2007 and seems to be still. A fall in pH in proximal tubule cells can be sensed by a protein named Pyk2, which activates by adding a phosphate to one of its amino acids (tyrosine) and, interacting with another protein (c-Src) increases the abundance of the mRNA of ET – 1 which then signals through its ETb receptor to increase renal acid excretion – bicarbonate reabsorption – via NHE3, a transporter that reabsorbs sodium and secretes acid into the proximal tubule fluid.

This same ET -1 and its ETb receptor also signal increase of NaDC1 transport. Here, mice engineered to have (ETb+/+)or have not (ETb-/-) the receptor were challenged with an acid load. mice with or without ETb receptor and citrate signallingCitrate uptake by isolated NaDC1 transporters in the deficient mice do not respond to acid.

So one and the same effect, acid sensing and endothelin – 1 signalling increases acid excretion and citrate conservation.

But, you may ask, why am I grouping these two together?

It is because both concern acid base balance.

Citrate is metabolized as citric acid, taking up 2 protons per molecule metabolized, which is the same as saying it provides 2 molecules of alkali – like bicarbonate. Loss of citrate is therefore loss of potential alkali. NHE3 is a main driver of acid – protons – out of blood into proximal tubule fluid which reclaims filtered bicarbonate – conserving alkali.

So urine citrate, which we are interested in because it binds calcium and inhibits crystals, has a much larger role to play – part of the grand system which maintains a constant blood pH against the acid or base loads of diet.

Which pH?

I have spoken about pH of the proximal tubule fluid, of the blood, of the urine, but the one that is central to regulation of NaDC1 is the pH inside the proximal tubule cells. That pH appears to respond to acid or alkali loads, but the manner of its response is not simple. The signalling is through the Pyk-2 sensor already discussed and a parallel pathway via ERK (same diagram, above) which I did not discuss. But how sensing works, what is sensed, this remains very much an open research issues, and I will leave off here as this article was about urine citrate and the conversation has already taken us through many byways, beautiful if exhausting to follow.

Potassium

But – that awful word – one important fact remains to be uttered. Depletion of potassium lowers the pH inside kidney cells and lowers urine citrate. I will not pursue the details of this well worn story, except to point out its extreme clinical relevance. Diuretics that are used in stone prevention, or for hypertension, deplete cell potassium stores. It is the potassium citrate we give to patients.

Ammonium, and the Rest of the Story

How can I leave off without filling out the details of how kidney cells respond to acid challenge with production of ammonia that balances acid load with acid excretion?

Bicarbonate

A Better Buffer than Most

A buffer keeps pH relatively constant by taking up protons when they enter a solution and giving them up when alkali enters. It is a kind of shock absorber.

At the beginning, evolution favored bicarbonate. It is a buffer of considerable virtue in that it can take up protons or release them, like common buffers do, but has a special trait.

Bicarbonate is forever in equilibrium with carbon dioxide gas (CO2). When bicarbonate takes on a proton to become carbonic acid, much of that acid becomes carbon dioxide gas. When protons are taken out of blood, CO2 gas forms new carbonic acid which donates a new proton to the solution, and essentially bicarbonate appears in solution ‘out of thin air’. That it flows from solution into thin air and back makes bicarbonate a more stable buffer than those which live only in solution so it was an excellent choice.

What Kidneys do with Bicarbonate

Moe drawing of PT bicarbonateIt is this very molecule, bicarbonate, which the kidneys traffic in when they respond to alkali or acid loads, and it is, of course, CO2 the lungs regulate in blood under the control of the brain.

The figure is from the ‘A’ panel of a lovely drawing in a lively and engaging review. Being small, bicarbonate is filtered, and being the main buffer of the blood almost all of what is filtered must be reclaimed. So the proximal tubule cells, which do most of that reclamation, busy themselves forever with that task.

The way they do it is the simplest way. They add protons (H+) to bicarbonate in the tubule fluid, which becomes, as I have said, carbonic acid that transforms into carbon dioxide (CO2), which gas passes through the cell walls into the interior. Note, ‘CA’ is carbonic anhydrase an enzyme which speeds up the process of the transformation. In the cell, the CO2 becomes carbonic acid. Because protons are being pumped into the tubule fluid, protons are stripped off the carbonic acid so it becomes bicarbonate. The bicarbonate enters the blood with Na via the NBCe1A transporter.

There are two proton pumps. One uses ATP for energy to move the protons. The other (NHE3) uses the low Na in the cell as a gradient; sodium moves in through a channel like a revolving door, which makes one proton go out for every Na that moves in. At the blood side of the cell, the ancient ‘Great’ ATPase pumps Na out and potassium in, as it does in most cells that live on Earth. NHE3, the exchanger, is the molecule we met a few paragraphs above. It is increased by Endothelin 1 via the ET1b receptor.

At the top of the left side of the picture is citrate, our little slice of this massive structure. A few scraps of proton add to citrate so it has 2, not 3 negative sites, and can be reabsorbed. Its gene is regulated by endothelin 1 so when NHE3 is increased so is NaDC1.

Phosphate

Reclaiming bicarbonate is Sisyphean work. Nothing happens to get rid of acid loads from meals. But more protons are secreted than are needed to reclaim bicarbonate. Some are buffered on phosphate. But all the protons buffered on phosphate produce bicarbonate from carbonic acid inside the cell, and that bicarbonate enters the blood via NBCe1A.

Ammonium Ion

Ammonia is produced in the proximal tubule by removal of nitrogen from glutamine, pictured at left. As always, 266px-L-Glutamin_-_L-Glutamine.svgkinks are carbon atoms in this kind of drawing. The first one on the left has an oxygen and NH2 group, and a bond to the next carbon. Carbons typically form 4 bonds each. The next 2 carbons are merely linked to one another. The fourth has another NH2 and the final one at the right 2 oxygens. The left hand one is removed by an enzyme to produce NHand glutamic acid. The second one is removed to produce α-Ketogluteric acid which lacks any NH3. The 5 carbon skeleton remains unchanged.

Ammonia (NH3) can tale up a proton to form NH4+, ammonium ion, which has a pKa of 9.3 meaning that at the pH of proximal tubules and cells, it is fully protonated. Loss of this ammonium ion in urine represents net acid excretion because the protons that were taken up came from carbonic acid which is converted to bicarbonate and transported into blood. Unlike titration of phosphate, excretion of ammonium ion does not increase urine pH because the pK is far above the pH of urine.

Under normal meal conditions, about 40 – 60 mmol/day of acid are excreted, of which about 2/3 is ammonium. Large acid loads, as for example, a ketogenic diet for weight loss, would induce a large increase in ammonia production so acid excretion can keep pace with acid production.

α-Ketogluterate

One might think this byproduct of glutamine metabolism, the 5 carbon skeleton, might be metabolized and done with, but no. A significant amount is metabolized. But some is not.

What is not metabolized traverses the kidney to cells in the later nephron, the intercalated cells in the collecting ducts, which usually pump protons into the tubule fluid to create the final urine palpha ketogluterate pt dt loopH which is critical to supersaturation and stone formation. But these same cells can reverse themselves and pump bicarbonate into the tubule fluid and protons into the blood, and they do this when confronted by an alkali load.

It turns out that α-Ketogluterate is itself filtered and reabsorbed in proximal tubule, and its reabsorption is profoundly reduced under alkali conditions so that more is delivered distally to a receptor (Oxgr1). When occupied by α-Ketogluterate this receptor signals the reversed intercalated cells (B and non-A cells) to increase their secretion of bicarbonate. The transporter for α-Ketogluterate is NaDC1. The net effect is to enhance bicarbonate – alkali – loss which offsets alkali loads.

The same receptor signalling stimulates pendrin, a complex exchanger which moves bicarbonate and Na together with chloride to effect NaCl and NaHCO3 reabsorption. Because acute acid challenge increases and acute base loading reduces proximal tubule NaCl reabsorption, this action would tend to maintain salt balance in that the intercalated cells would increase salt reabsorption as proximal tubule reduces salt reabsorption. Of note, although chronic acid challenge increases NHE3 abundance and activity, it reduces NaCl reabsorption via effects on other transporters. For these reasons the α-Ketogluterate – pendrin link is probably more important in minute to minute or hour to hour regulation than in adaptation to acid or base loading diets or treatments.

Citrate and Oxalate

You would think I had exhausted the topic by now, but no. NaDC1 and slc26a6, the citrate transporter and the anion nadc1 slc26a6 interactionstransporter (oxalate is an anion it can transport) which disengages NaCl transport from NHE3, themselves interact in relation to kidney stone formation.

At least in animals and in cell experiments, the two transporters – which are present in a complex within the renal cell membrane – interact as in the figure. Slc26a6 inhibits NaDC1, so that when actively transporting oxalate into tubule fluid citrate reabsorption is reduced, urine citrate rises, and binds urine calcium to reduce risk of calcium oxalate stones. When oxalate secretion is minimal, NaDC1 increases to salvage citrate.

These animal and cell experiments imply that in human urine citrate and oxalate excretions should show parallel changes; this has not been tested.

Putting it All Together

Just Diet

Our urine citrate is an outcome of our biologies, which are variable, and our diets. Most of us eat a diet that imposes a net acid load, so our kidneys tend to conserve citrate and α-Ketogluterate, our intercalated cells pump protons not bicarbonate in to the final urine, our proximal tubules produce considerable ammonia and our urine pH is about 5 – 6.

Some of us, vegetarians whose diets do not have a proper balance of protein, very massive fruit eaters, as examples, have low citrate reabsorptions and high distal deliveries of α-Ketogluterate; our intercalated cells are reversed and stimulated to put bicarbonate into the final urine, our proximal tubules do not make much ammonia.

But the words ‘most’ and ‘some’ are misleading. In the US, certainly, chronic acid loading is the overwhelming rule, and the same throughout Europe and considerable parts of urban Asia. So our ‘normal’ poise centers on adaptations to acid load. It is not that we live in a neutral acid base condition, demanding from our kidneys little excretion of acid or of alkali. Life long we demand acid excretion. That is where we start. It is to that task our kidneys – and our bones, as I shall someday speak about – apply themselves all the days of our lives. However it is, for good or for evil, that lifelong adaptation to acid load affects us, that is our state, our permanent condition.

What Does Normal Mean?

When we give potassium citrate or any other alkali in doses of 40 to 60 mmol/day we neutralize a large fraction of diet acid. This is best considered not so much as an ‘alkali load’ as it is the removal of that acid load to which we have long been adapted.

Of course, urine citrate rises. Because we give alkali over months or even years, renal cells will adapt fully to the changes. But by ‘adapt’ I mean they give up the adaptations to acid loading. In the case where the dose of alkali just matches acid production one might best say the kidneys are relieved of their burdens in either direction, and reveal the way they would function if not driven to either extreme.

Like the small sailor plying the simple waters of a bay fills its sails sometimes southerly, sometimes northerly, making little way, dancing before a playful breeze, the cells shift their powerful machinery a bit here or there as one meal gives way to another. What shall I call this state of freedom? Why is this not the ‘normal’ from which point we register the responses to extra alkali or acid?

I have read where it was in Eden a condition of fruit, as the animals were not for them to eat. Perhaps I am wrong, and if Eden was as it says in our books the ‘normal’ state was alkali load. Perhaps Milton is wrong. After all he was not there, merely a poet making into life what he read in a holy book.

Potassium Citrate Pills

Raise Urine Citrate and pH

The expected changes are a decrease of proximal tubule reabsorption through reversal of the effects of chronic acid load. ET-1 signalling must fall, citrate reabsorption must fall because NaDC1 is no longer stimulated by ET-1 and because proximal tubule fluid pH will rise and with it the fraction of trivalent negative citrate.

Urine bicarbonate and urine pH will also rise. Partly, blood bicarbonate will rise and with it filtrate bicarbonate concentration and pH. NHE3 transport will be decreased vs. chronic diet acid loading, the baseline in the first world countries, and much of the proton secretion will be used in reclamation of bicarbonate. Naturally, NH3 production will be greatly reduced because the Pyk-2 sensing system will be signalling a higher pH.

Increases in Citrate and pH Vary Among People

But the biology is complex enough that in some people the main response will be citrate, and in other bicarbonate. Given all of the regulatory steps and signalling pathways involved a variety of responses is inevitable. Clinically this means one must measure and determine if the main effect is mainly increase of citrate excretion or of pH and therefore of CaP SS.

What is the Ideal Dose?

A nimble answer is enough to match net acid production – urine sulfate excretion is a decent index. I suspect that answer because of the problem of high urine pH in some people, and because as a clinician I never find it perfectly suits most patients. Yet it is a good starting dose because it aims at neutral acid base balance.

A Simple Pill with Powerful Effects

Physicians who treat kidney stones may well be the main ones who prescribe alkali loads to people with normal kidney function over months or even years or decades of life. This is indeed a remarkable physiological and clinical experiment, and that we do it makes the physiology and cell biology of acid base balance a central topic in clinical practice of stone prevention.

Likewise patients who take this humble medicine undergo what amounts to a reversal of cultural norm, which is a condition of chronic acid loading.

Thence, and for this reason, I have written a very long article about the topic, for physicians and their patients, and especially for scientists who know more about this topic than I do but may not see things from exactly the same view point.

 

194 Responses to “HOW POTASSIUM CITRATE PILLS WORK”

  1. Joyce

    Hello, Dr. Coe!

    I’ve stopped in to re-read this article several times, and I appreciate it so much! It’s been very informative for me.

    I had kidney stones during a couple of my pregnancies, but no problems with obstruction, and no determination of composition at those times. Last year, I did a high protein diet (150 g a day) for about 6 months. I’m an ultrasound tech, and noticed after about 6 months of doing this, I was developing diffuse nephrocalcinosis. I was also taking no vitamin D during that time – I’m a hypothyroid (Hashimoto’s) patient and had previously been low in vitamin D. I started urinating brown flakes.

    After cystoscope w/ retrograde pyelogram, CT scan, and lithotripsy, they determined I have medullary nephrocalcinosis and the stone I passed was 100% calcium phosphate. My urine pH was 6.8, and citrate was 334. I saw urology and nephrology. They said I likely have some sort of acidifying problem, but not a full RTA, and I’m being treated with 15 mEq of Potassium Citrate twice a day.

    My questions are this: 1) I am pregnant now and am told to continue the Potassium Citrate, but it’s a Category C. Do you agree? 2) My endocrinologist started me on Vitamin D again (my level was 23), and said this could have contributed to the calcium deposition. I’m on 4,400 IU a day 3) Because I had no nephrocalcinosis at all before, and my kidney function is now a bit less (GFR 83), I am worried this will cause permanent damage if it worsens. Is there anything else I should be doing for treatment? They recommended lots of water and low sodium.

    Thanks so much for your time. I can give more information on 24 h urine results if helpful at all!

    Reply
    • Joyce

      Another question I had: my PH rose to 7.33 after treatment with Potassium Citrate. My urine calcium, and supersaturations were all pretty normal to begin with. With the second 24 hour urine (showing pH of 7.33), my SSCaP was only 0.47, when prior to it had been 1.66 (still normal, however). Do you still agree this is necessary treatment given that the SS weren’t high to begin with? I’m worried the rise in pH will hurt more than help.

      Reply
      • Fredric Coe, MD

        Hi Joyce, as I mentioned potassium citrate for CaP stones is moot and a bit fraught. Keep the CaP SS below 1 and after your pregnancy test again and see what is wrong. Regards, Fred Coe

        Reply
    • Fredric Coe, MD

      Hi Joyce, WHen you say ‘developing’ nephrocalcinosis so you mean you had a normal scan and then began to see calcifications? If so, things went very fast indeed. High protein intake raises urine calcium, sometimes a lot, and that can cause considerable calcium deposition. The high protein should have lowered urine pH and causes calcium oxalate not calcium phosphate stones so something kept your urine pH up. A search for Hashimoto’s and renal tubular acidosis in PubMed yielded five papers but all patients had Sjogren syndrome, a known cause of RTA. I suspect your urine calcium is too high and CaP SS above 1. As for potassium citrate, no trials support its use as yet. I have written about this problem and begged people to do this trial. Perhaps you might best benefit from low sodium diet and thiazide – I prefer chlorthalidone, perhaps 12.5 mg/day after your pregnancy. Do not make 24 hour urine measurements while pregnant as hypercalciuria is placental driven and of no long term interest. Regards, Fred Coe

      Reply
      • Joyce

        Thank you for your reply! Yes, I have read that there have been no trials for CaPhos formers and Potassium Citrate. I am taking the Potassium Citrate, however, as my Nephrologist and OB/GYN both said the 15 mEq/ twice a day, is safe and hopefully of benefit. It did raise my Citrate from 334 to 436, so it makes sense that it would be beneficial.

        Yes- the nephrocalcinosis was VERY fast. I have been scanning my kidneys for years (as like I said- I am an ultrasound tech). Within 6 months – they went from completely normal (minus a couple small stones, which I had developed during pregnancies over the last 6 years, and had been stable) to macroscopic nephrocalcinosis. Like I said, my protein intake was VERY high, and I have no idea what my urine would have looked like at this time- I didn’t have a 24 h urine test until several months after I had stopped this diet.

        I have reason to believe that the CaPhos stone that they broke up with Litho, and that I passed, was an old stone developed during a previous pregnancy. I believe it was one I had seen for years. So, then I guess the nephrocalcinosis could likely have been caused by my high protein and calcium intake and lack of vitamin D during those several months (and could have indeed been CAox deposition from high protein).

        Do you believe a low Vit D could indeed cause rapid nephrocalcinosis? Like I said, I had previously been taking Vit D and stopped for several months when this developed. My endo seems to think this may have contributed.

        I just want to make sure I am doing everything I can to protect my kidneys from further deposition, and potential loss of function. I am only 30, and otherwise healthy. My BMI is normal and I exercise daily.

        Thank you!

        Reply
  2. Marian

    Hi,
    I had Cushing’s and have had a trapped kidney stone in my right kidney for years. Though we don’t know the composition of the stone, it does not appear on xrays and Cushing’s patients often have a higher instance of uric acid stone.

    I’m on blood thinners and experience recurrent hematuria while exercising (running, long walks). The urologist thinks the stone has changed position and has given me Potassium Citrate to dissolve it.

    My urine pH has been < 6 for years and is now in the 6.5 – 7.0 range. How long does a 1 cm stone take to dissolve? Do they generally just dissolve or do they dissolve and pass? How much water should I drink?

    Reply
    • Marian

      I probably should have said the cystography, CT, and cytology were all negative, except for the stone.

      Reply
    • Fredric Coe, MD

      Hi Marion, uric acid stones will dissolve in urine of pH >6, but it may take a long time. Your physicians can determine the density of the stone on your CT; uric acid has a very low density. Be sure you have been fully evaluated – medical practice is better without too many assumptions. Regards, Fred Coe

      Reply
  3. Rachel Penney

    Hi Dr. Coe,
    I was the one in Jill’s last class on Monday, May 1st, 2017, that has a permanent ileostomy, fat malabsorption, short gut syndrome, secretory/chronic diarrhea. My urine citrate in the 3/6/17 24 hour urine collection was <18; urine oxalate 32, urine pH 5.697; SS uric Acid 1.34, urine calcium 58, Na24 <12, Mg24 was 21. I have since increased my fluids/daily to 4.2 liters; calcium via food to 1200 mg., since doing this collection/test. I know you said Citrate Potassium supplements/meds will not increase my urine citrate; but to take 10 gr. sodium bicarbonate 2-3 times daily. I just want to make sure this is correct and I didn't misunderstand. Also, I am very concerned the extremely low urine citrate level will cause more kidney stones. I started the sodium bicarbonate on 5/1/17 and bought pedialyte to increase my glucose. Can I take the next 24 hr urine test on May 21 or 29th or is that too soon to see if the sodium bicarbonate is helping? (I have a fast exit system where food/meds are out in my appliance in 8-10 minutes and sometimes need more meds to be effective than other patients). Lastly, since purchased pedialyte has potassium citrate, but home made does not, can I start making mine at home to save money and hopefully calories? Lastly, how will the sodium bicarbonate raise my urine citrate enough? (I thought taking 5 ml-3 x daily of potassium citrate would do the trick, but evidently not!). Many, many thanks for all of your guidance and expertise. Rachel Penney

    Reply
    • Fredric Coe, MD

      Hi Rachel, Ileostomy is a special problem of potassium and sodium and alkali depletion. SOdium bicarbonate is absorbed in the upper intestine and will work. The tablet and dose are as you wrote them. You need followup in a few weeks because it should work right away. You can indeed make your own high glucose high sodium drinks at home. But I want to emphasize that your treatment needs immediate monitoring by your physicians as ileostomy management is complex. Be sure. Regards, Fred Coe

      Reply
      • Rachel Penney

        Thank you so much for your fast response, Dr. Coe. Two more questions. (1). I am on Potassium Citrate liquid 5 ml three times daily, basically at my request, since I was and still am concerned re. my very low urine citrate level. Now that I am on sodium bicarbonate, should I still stay on Potassium Citrate or get off of it? My new understanding is that I don’t need any potassium citrate supplement since I am on sodium bicarbonate? Is this correct or am I wrong? My doctors are more than willing to go by your opinion. (2). I am closely monitored by my doctors re. blood tests, etc. Are you referring to blood tests (CBC/Basic Metabolic Profile) when you say about monitoring? I did have a blood test done a month ago but of course b/f the sodium bicarbonate was added. That is what I had to get years ago every so often when on sodium bicarbonate. Fortunately, the doctors finally have most of my dehydration under control, even with a very high output, unless I get sick with kidney stones, intestinal obstruction, acute pancreatitis, stomach virus, etc. I ordered my 24 hr. urine collection kit from Litholink and it should arrive next week. Again, many thanks for all of your help and expertise! Rachel

        Reply
        • Fredric Coe, MD

          Hi Rachel, Sodium bicarbonate and potassium citrate are alike in action both producing alkali. I suggested the former because your urine sodium is remarkably low and you are safer with sodium. You can take both and the net alkali load will be the sum of the two. As for blood testing it is about potassium, and bicarbonate – total CO2 – as your physicians well know. The goal is to maintain urine pH, prevent dangerous sodium depletion, and raise citrate if possible. So use both if you can tolerate the potassium. Regards, Fred Coe

          Reply
          • Rachel Penney

            Hi Dr. Coe, Thank you for getting back to me. I saw my GI doctor today and he will monitor my blood levels closely re. potassium, bicarbonate, calcium levels etc. He is very pleased you put me on Sodium Bicarbonate. I have no issues yet with Potassium Citrate Liquid. He has agreed if I get any signs of dehydration/stomach virus, etc., that he will arrange for me to go to the hospital immediately for IV’s to protect my kidney function. He is very pleased you are helping with my kidneys as he said you are the expert and no one can come near you. He will gladly make sure I have whatever I need to take care of my kidneys/prevent stones. Thank you for being so patient with me and answering all of my questions! You rock, Dr. Coe! Take care of yourself. With appreciation and respect, Rachel

            Reply
  4. Cory Nutter

    Dr. Coe,

    I’m working with your friends at the Cleveland Clinic (Dr. Manoj Monga) – and wanted your input on my test results. I was a bit confused during our conference call with Jill Harris yesterday (05/01/2017).

    I have been forming calcium phosphate stones – last stone analysis was 90% calcium phosphate / 10% calcium oxalate (stone measured 27mm). Stone removed on 03/15/2017.

    Litholink Results (04/02/2017):
    24 hr calcium = 338H
    24hr citrate = 357L
    24hr oxalate = 29
    Supersaturation CaOx = 2.83L
    Supersaturation CaP = 1.37
    Urine pH = 6.644H
    Urine Volume = 4.33H

    24hr Magnesium = 125H
    24hr Phosphorus = 1.163
    24hr Urea Nitrogen = 13.04
    24hr Potassium = 88
    24hr Sodium = 116
    24hr Sulfate = 50
    24hr Ammonium = 42
    24hr Chloride = 129
    Protein Catabolic Rate = 1.1

    24hr Creatinine Per Kilogram Body Weight = 26.7H
    24hr Calcium Per 24hr Creatinine = 146H

    Based upon the course work and my findings – it seems like I have a case for hypercalciuria. I don’t believe that I will be able to make future dietary restrictions to bring the levels down further. I’ve read your articles about thiazide diuretics and also potassium citrate.

    I’d like your input here… It would appear that I’m a candidate for a thiazide diuretic (perhaps 12.5mg of chlorthalidone?). What is your take on staggering this with potassium citrate? My urine pH is already elevated quite high… won’t potassium citrate push those numbers even higher?

    If you think potassium citrate would be of benefit to my situation – what dosage would be appropriate?

    Best Regards,
    Cory Nutter

    Reply
    • Fredric Coe, MD

      Hi Cory, You do indeed have hypercalciuria with calcium phosphate stones. Thiazide might well be ideal. But your urine sodium is too high – I would lower it to 1500 mg/day, or 65 mEq/day before using the drug. Given calcium phosphate stones potassium citrate is untested – it will raise urine pH with is bad but also may raise urine citrate which is good. No trial exists for this kind of stone. So, lower sodium intake more and then consider the drug you mentioned. But – Dr Monga is quite expert, and does not need my advice; perhaps he has a different view and if so I would go with it and ignore me as an outsider. Please send him my regards. Fred

      Reply
      • Cory Nutter

        Dr. Coe,

        Thank you for your valuable input, much appreciated. It seems fairly odd that sodium came back elevated. I tracked my diet the day of the urine study and calculated a daily intake of 1170mg. Anyhow I’ve been tracking daily values and have been averaging somewhere around 1200mg/day. I’m currently seeking reopinion from Heidi Digennaro – I’d like to avoid calcium phosphate stones. I’ve taken your suggestion not to wait 6 months for follow up and am trying to be proactive with my prevention measures. I truly appreciate your expertise.

        All the best to you,
        Cory Nutter

        Reply
        • Fredric Coe, MD

          Hi Cory, The urine sodium tracks well with intake if intake is reasonably constant. So if the urine is higher than your diet tracker says and this occurs regularly your tracker is not correct. Regards, Fred Coe

          Reply
  5. Ayman

    I have been taking urocit 10meq three times a day for 3 years to dissolve uric acid stones. A recent CT scan showed the stones have dissolved but incidentally I have bilateral adrenal adenomas.
    Any connection between potassium citrate tabs and the occurrence of adrenal adenomas ?

    Reply
  6. Bill

    Dr. Coe:

    I have endeavored to read most of your site, but I haven’t come across this issue: 2 years ago I had 2 stones removed uteroscopically. My urologist put me on potassium citrate ER 10 MEQ TB X 3 times per day. I have assiduously taken them. I get debilitating ocular migraines since then. I only recently questioned the connection and came across this: https://www.ncbi.nlm.nih.gov/pubmed/1555928

    I have researched/tried many many other things, but the ocular migraines are increasing in frequency, to at least 1 per day and up to 3 per day. I am at desperation level. Just wondering if you have any comments or recommendations. Daily ocular migraine or occasional kidney stone? It’s getting to be a toss-up.

    Reply
    • Fredric Coe, MD

      Hi Bill, I read the abstract. They refer to local potassium concentrations of 15 to 20 mmol/l, blood is 4 mmol/liter. If blood values rose to even 6 – 7 mmol/l the heart would stop. Given the massive cellular potassium pool and the relatively tiny amounts of potassium involved I doubt any relationships between the pills and migraines based on the abstract. Especially because the potassium pills are slow release, I doubt blood levels of potassium even rise. I might point out that US diet recommendations call for 4500 mg of potassium from fruits and veggies, which would be about 4 of the pills; you might try diet. Likewise beverages like Crystal light provide 20 mEq/liter of potassium citrate. Finally, do you really need this medication. Check this out and be sure you have been fully evaluated and that this medication is right. Regards, Fred Coe

      Reply
      • Bill

        Dr. Coe:
        Thank you for your response. I have tried in the past 2 weeks to work up to drinking 2.5 liters of water/day. It is almost impossible and I usually don’t take in that much. I have now developed reflux all day. My urologist suggested reducing my water intake to about 1.5 liters/day. He also recommends I keep taking the potassium citrate, but I stopped taking it and have had no migraines since doing so. Now my dilemma is kidney stones or migraines or reflux – pick one. This is all so difficult.

        Reply
        • Fredric Coe, MD

          Hi Bill, My rewsponse suggested you get a full evaluation to determine if you need potassium citrate at all. As for water, perhaps you might work your way up to 2.5 liters slowly. Low volumes such as 1500 ml/d will not prevent stones. Regards, Fred Coe

          Reply
        • Eben

          Hi There
          Have you tried Sodium bicarbonate as a substitute?

          Reply
        • Michelle Mason

          Hi Bill. I have studied migraines quite extensively, due to many years of crippling migraines. My research has shown that *most* migraines are caused by low magnesium. Further, mangesium and potassium need to be in balance, or an increase in one will decrease the other- kind of like a teeter-totter. My theory then, is that your potassium pills are increasing your potassium enough to lower your magnesium, and this low magnesium is causing your migraines. A generic magnesium supplement taken daily can help prevent future migraines.

          For any ladies reading this, your cycle causes hormonal changes, which make your magnesium dip, especially 2-3 days before you start. Taking extra mag that day can help prevent cycle-based migraines. Also, know that Milk chocolate lowers your magnesium, while dark chocolate brings it up- the darker the better. So if you just *have* to have some milk chocolate, take some magnesium with it to offset it. 20 years of cycle migraines here before I learned this, love the idea of helping someone else overcome migraines.

          Reply
  7. Michael

    Hi Dr. Coe,

    After initiating dietary changes, a recent metabolic follow-up for a history of calcium oxalate stones reveals blood potassium & sodium and urine sodium & citrate levels within normal range, but continued high levels of urine oxalate & calcium. With urine pH continuing to measuring between 5-5.5, my specialist has proposed taking 60mEq/day of potassium citrate.

    Can this medication be of benefit where there is no indication of hypocitraturia?
    Can efficacy be achieved at a lower dose or is there a minimum effective dose required?
    Can pure lemon juice (eg. 85ml/day) impart equivalent benefits with less risk?

    Kindly direct to your website should I have missed the answers therein. Thank you for your follow-up.

    Reply
  8. Nihal

    Dear Dr. Coe,

    Since it seems like urine pH is very important (for forming and dissolving) uric acid stones, what is the best way to measure urine pH at home? You have mentioned pH strips but my experience has not been very good. I got HealthyWiser pH strips from amazon (it has probably the highest reviews) and since I had some doubts, bought a HealthyWiser digital pH meter as well. With some difficulty I was able to calibrate the digital pH meter to get close to the calibration solution. But when I used the pH strips to measure the same calibration solution (supposedly 6.86pH in one case), it showed me about 8 pH. Then there is the fact that the strips don’t have that high of a resolution. It shows it in increments of 0.25.

    Can you recommend a brand/model of pH strips or digital meter that is quite accurate and repeatable that can be used at home? If not is there some certification that I should look for when buying a pH meter/strips?

    I am sorry if I am asking too many questions. I sincerely appreciate everything that you do.

    Thanks

    Nihal

    Reply
    • Fredric Coe, MD

      Hi Nihal, No; you really do need to have some structured care by people who know this trade. I would not try ‘do it yourself’ anylonger because more stones may come. Regards, Fred Coe

      Reply
      • Nihal

        Dear Dr. Coe,

        Now you have me worried. When you say “more stones may come”, are you referring to Calcium phosphate stones forming due to pH being above 6.3, or is there some other mechanism that you are referring to?

        I have responded to another thread asking for more information about getting some structured care from you.

        Thanks

        Nihal.

        Reply
        • Fredric Coe, MD

          Hi Nihal, Merely this: You do not have an organized prevention program and while without one new stones are more likely than with one. Regards, Fred Coe

          Reply
  9. Al R.

    Hi Dr. Coe,
    This has got me puzzled. Small doses seem OK, but when we increased K supplements to 40 mEq, CA 24 increased a lot – like 75 or more. It seems like more than coincidence because it happened twice, a year apart. Once with K citrate, and then with K gluconate.
    Grateful for any thoughts on what might possibly be the cause of this. Best regards, Al

    Reply
    • Fredric Coe, MD

      Hi Al, K Cit lowers urine calcium for the prevailing urine – diet – sodium. Here is a link to the right article. It cannot raise urine calcium. Either your urine sodium rose, or your diet calcium rose. Regards, Fred Coe

      Reply
      • Al R.

        Hi Dr. Coe,
        My doctor noticed something odd that I had missed. Maybe coincidental, but maybe the answer to this mystery: A big jump in both Ca 24 and pH appeared at the same time I increased output from a bit over 3 to around 4 liters to try to lower SSs. Diet and Ca intake were quite constant.
        Wondering if you may have any thoughts on a mechanism that might explain how increasing volume could potentially spike Ca 24 and pH?
        And whether a rise in total Ca 24 (as opposed to Ca/liter) may actually be expected as a result of the volume increase? (Of course, I’m interested due to the implications for bone health too.)
        Sorry for so many questions. Thanks again and best regards, Al

        Reply
        • Fredric Coe, MD

          Hi Al, urine volume has no effect on urine calcium; but look at urine sodium, which has a huge effect. It may have gone up. As for pH, higher volumes have a small effect to raise pH because of buffer dilution. Regards, Fred Coe

          Reply
          • Al R.

            Thank you very much! Just to close…
            Despite your unimaginably generous and patient help, my nephrologist, her consultation with Dr. Bushinski, and my own research, this remains a bona-fide mystery.
            Na 24 differed by only by one, and PCR was identical, yet Ca 24 surged by almost 100 and pH by 0.7. Not a hint of any systemic disease again this year.
            I’ll keep working on this! Best, Al

            Reply
            • Fredric Coe, MD

              Hi Al, so much can influence urine calcium: diet intake that day, protein intake that day, acid load that day, variation in the rate of absorption of diet calcium in the meals that day. In our clinical research center we see variability of the kind you mention when everyone is eating a fixed and standard diet. So I do not see the issue as directly suited to either clinical or research analysis, and doubt it has real clinical significance. My regards to Dr Bushinsky and your excellent nephrologist. Fred Coe

              Reply
  10. Jennifer

    Dr. Coe…

    I’ve been using Crystal Light for about a year, with mixed results. Mostly because I’m not 100% “compliant.” I find the stuff so very sweet, it’s hard to drink as much as I should. And so, I am still getting stones. Some rather big ones if I’ve let myself get dehydrated.

    But that’s not why I’m back. My MD has suggested that I drink alkaline water. I know that there are a lot of crazy claims about alkaline diets and water etc… but I’m wondering 2 things.

    1. Can it help raise the ph of my urine, and it turn help with my uric stones?

    2. If I use it to make my Crystal Light, will it actually LOWER the citric acid of the lemonade and make it not work? Or will it add to the efficacy?

    3. Okay, three questions. I am not investing in a $2k ionizer, but rather bought supplement drops to add to my water that contain: Potassium Lactate, Tripotassium phosphate, Potassium bicarbonate, Potassium citrate, Magnesium chloride, Zinc Lactate, Sodium selenite, and Calcium chloride.

    Thank you for your time!

    Reply
    • Fredric Coe, MD

      Hi Jennifer, Given you have uric acid stones all treatment hinges on raising urine pH. If Crystal light is just too sweet and you do not use it consistently how about potassium citrate to provide some fraction of the needed alkali and crystal light or possibly other of the beverages you mention for the rest. I do not know how much alkali there is in alkaline water and therefore if it can raise urine pH; THe additives you mention are also hard for me to know about because it is all about how much alkali you get in each day. That usually needs to be a lot – 40 mEq is usual – and uric acid stones can form and grow quickly while you experiment. So, I favor a simpler approach as noted, for safety. Regards, Fred Coe

      Reply
      • Jennifer

        Thank you for your reply!

        When you say “How about potassium citrate” do you mean a pill like Uricit-K?
        I cannot take that, I’ve tried 3x, and it has a very very bad effect on a heart arrhythmia I have (PVCs.) That’s why I’m trying to go with the Crystal Light.

        The drops I have claim to raise water ph to 8. Test papers seem to show only 7ish. Is that enough to make a difference?

        Also, if I make my Crystal Light with the alkaline water, will they “cancel each other out?” Meaning, will the acid lowering properties of the Alkaline drops take away the citric acid of the Crystal Light? (Wow, that even confused me!)

        Reply
        • Fredric Coe, MD

          Hi Jennifer, The pH does not tell us much about the effects of the water. The buffer capacity is what matters and you cannot tell – the manufacturer has to say how many mEq of buffer are in a liter. You can use alkaline water with the Crystal Light and it will not affect the citrate. Regards, Fred Coe

          Reply
          • Jennifer

            Thank Dr. Coe. I truly appreciate the personal time you take to answer all questions. You are a good man.

            Reply
  11. Jaya

    Dr.Coe,
    Thank you for a most informative site/articles. My question pertains to a little understood condition called Citric Acid intolerance. There is very little medical information on the web and most sufferers are left to resources from Good Samaritan websites like this one – http://milind.com/2013/10/12/citric-acid-intolerance-acetic-acid-digestion-and-metabolism-disorder/.

    My intolerance started with a (large) exposure to mercury through 13 mercury amalgams. A very interesting journey has ensued . The question is this – if one is intolerant of citric acid (in any form) but certainly when ingested as an additive, does it predispose one to the formation of stones – as you understand the underlying bio-chemistry, does this point to other metabolism issues that would place a burden on the kidneys and hence the bladder? Your input would be greatly valued.

    Reply
    • Fredric Coe, MD

      Hi Jaya, A brief search of PubMed for (“citric acid”[MeSH Terms] OR (“citric”[All Fields] AND “acid”[All Fields]) OR “citric acid”[All Fields]) AND intolerance[All Fields] came up with nothing. One paper in rats found that giving extra citrate to mice when added to extra table sugar reduced glucose tolerance. But there are no papers at all on citric acid intolerance. The citric acid cycle in mitochondria is an ancient pathway for energy production and storage via fat. Abnormalities exist, so your question is apt but alas none so far fit your specific one. The web page you linked to has no reliable science, so I cannot evaluate it one way or another. Regards, Fred Coe

      Reply
      • Jaya

        Thanks Dr.Coe! Yes citric acid intolerance turns up nothing but there are so many of us that suffer terribly from this particular intolerance. The symptoms range from acute gastric distress to headaches, malaise, and fatigue. The thing that seems to help many is a supplement of cofactors for boosting liver metabolism pathways.

        If i came to you with citric acid intolerance and a case of urinary calculi in the bladder would you connect the dots as probable cause and effect? Or are there too many unknowns about the implications (not it’s cause) of this particular intolerance.

        Reply
        • Fredric Coe, MD

          Hi Jaya, You are very astute and perhaps there is more than we know. If you did indeed present as you say I would analyse the stones and find out what they were made of and then try to figure out why they formed. But intolerance to citric acid would not occur to me as I know nothing about it and do not have a satisfactory source to turn to. Science is imperfect because what we cannot properly imagine is beyond science. What we can imagine may be beyond any present ways of testing in real life. I think citric acid intolerance is in the second group. Regards, Fred Coe

          Reply
  12. Al R.

    Hi Dr. Coe,
    From what I have read, dietary NaCl, and also KCl supplements, impose a significant acid load and, in normal people, are expected to lower urine pH. However, you indicated that reducing dietary sodium may actually reduce high urine pH.
    Can you please explain? E.g. are there other factors your are thinking of that may counteract the reduced acid load from lowering sodium intake and actually reduce urine pH?
    Thanks & best regards, Al

    Reply
    • Fredric Coe, MD

      Hi Al, THere is no acid load from sodium chloride or potassium chloride. Being salts of strong acids they do not donate or take up protons. I do not recall where I wrote that low sodium diet will lower urine pH; can you point me to it so I can understand the context? Regards, Fred

      Reply
      • Al R.

        Hi Dr. Coe,
        For context, please see my initial question and your first reply to my comment from October 13, 2016 in “Does Too Much Protein Increase Stones or Damage Bones?” (No need to go further since the discussion diverges.)

        I’m really trying to understand the mechanisms and effects of diet & supplements on unwanted acid load and urine pH because these are so important for bone health and stone prevention.
        Thanks again for your time and help. -Al

        Reply
  13. Nihal

    Dear Dr. Coe.

    I have kidney stone (7mm) in my right kidney which is clearly visible in the CT scan. I had an xray done as well, and for some reason the stone is not clearly visible. My local urologist said that it might be blocked by stool or gas or it could be a pure or partial uric acid stone. He has given me potassium citrate (1080 mg tablets 2 times a day), in case it is a uric acid stone.

    I have scheduled a ureteroscopy with an out of town urologist (because he comes recommended by a friend) in about 9 weeks. My plan is to get a CT scan done in about 8 weeks to see if the stone has reduced in size before going ahead with the surgery. My initial questions are

    1. Is 8 weeks of the above potassium citrate dosage enough to observe a noticeable reduction in the size of the stone?

    2. is it really possible for stool or gas to block the stone in an xray? I would think since stool normally appears dark in an xray (meaning that it allows the xrays to pass through) , any calcium oxalate stone would appear light since it would block the xrays, even if the stool was in front of the stone blocking it.

    Thanks

    Nihal

    Reply
    • Fredric Coe, MD

      Hi Nihil, A CT scan will show a stone that cannot be seen on a routine x ray. The difference in visibility does not establish it is a uric acid stone. More helpful would be the Hounsfield number – density – measured on the CT. Removal of the stone would be because of pain, obstruction, bleeding or infection, not just because it is there. The citrate is not likely to change even a uric acid stone is only a few weeks, but why is the surgery being done?? Whatever happens, if removed be sure the stone is analysed and you are evaluated to find the cause and get prevention. Here is a good plan. Regards, Fred Coe

      Reply
      • Nihal

        Dear Dr. Coe,

        Thank you for your quick response.

        Fortunately there is no pain , non obstruction and no infection. I had blood in the urine after running, and that is what prompted the CT scan. After some time, I saw blood in the urine even without exercise, but it seems like after starting to take the potassium citrate, there is no visible blood (I see faint yellow streaks maybe). Maybe there are two stones very close to each other, located somewhat in between the renal pelvis and lowest calyx. The location is such that I feel if the stone gets dislodged, it would fall into the lower calyx, since it would have to jump over a hump to get to the ureter. The reason for contemplating surgery, is I would like to start running again and I am afraid if I do that it might for one cause bleeding, but more importantly the impact might cause it to get dislodged and jump over the hump and get to the ureter and block it.

        I got the CT scan on a disk and after right clicking and doing a point analysis and moving the cursor over the smaller stone the HU numbers are between 300-354 HU. For the bigger stone (7mm) the highest point is 613 HU (everything else is below 600, few 500’s, mostly 400’s and 300s). I am doing this on the image WITH Contrast. I have to admit, I am somewhat clueless about what I am doing, but do those numbers tell anything?

        If in fact this is a uric acid stone, how long do I need to take the potassium citrate to observe a noticeable reduction in stone size?

        Do you think I am rushing to surgery?

        Thanks

        Nihal

        Reply
        • Fredric Coe, MD

          Hi, The low values for the larger stone do suggest it contains uric acid. Potassium citrate might dissolve the uric acid, but I would think months would be needed. ALso, as it dissolves portions might separate off and pass. Regards, Fred Coe

          Reply
          • Nihal

            Hi Dr. Coe,

            When you say months would be needed to dissolve a uric acid stone, how many months is that? I have been given potassium citrate (1080 mg, 2 times a day). Is that the right dosage or should I ask for an increase? What is a reasonable time frame that I should take another CT scan to see if the medication has had any effect ?

            Also I would like to know how potassium citrate would affect my kidneys since I am a type 2 diabetic. I ask this because my father was a diabetic and he eventually died of kidney failure, and at one point the doctors told him not to take any food that contains potassium. My microalbumin/creatinine ratio is 22 prior to starting the potassium citrate. It was only 10 slightly over a year ago.

            Thanks for all your wisdom.

            Nihal

            Reply
            • Fredric Coe, MD

              Hi Nihal, You ask all the right questions but I am not your physician and one hesitates from this distance to go beyond the proper general statements. I do not know the real details of your medical situation. In general diabetics form uric acid stones because of a low urine pH, and the amount of potassium citrate needed is determined by sequential follow up 24 hour urine measurements. Months is a kind of order of magnitude estimate, so no one could become more precise. Potassium citrate will not itself damage kidneys. Diabetics can have disordered renal potassium handling and that is something your physicians need to determine as you use the potassium. The increase of microalbuminuria may reflect blood – be sure about whether the urine sample had any blood by dipstick. Sorry I cannot do more but I am sure you understand. Regards, Fred Coe

              Reply
  14. Al R.

    Hi Dr. Coe,
    Would you please help me understand the effect of potassium gluconate on urine pH compared to potassium citrate when taken to balance Chlorthalidone?
    I realize that K gluconate does not have the alkalinizing effect of citrate, but it still increases K excretion. So it seems like it would increase pH to some extent as eating K-rich foods does.
    Best regards, Al

    Reply
    • Fredric Coe, MD

      Hi Al, Potassium rich foods have their potassium as the salts of metabolizable anions like citrate, malate, etc. But potassium gluconate will provide potassium and that is important in itself. Low potassium stores lower urine citrate, so any potassium supplement will help restore urine citrate which is an important defense against stones. Regards, Fred

      Reply
      • Al R.

        Hi Dr. Coe, OK, that part makes sense now. I’m still trying to get my head around the effect of KCl and NaCl though.
        First, I’ve read that KCl supplements acidify urine. Do they somehow impose an acid load on the body?
        Second, you mentioned last October (protein/bone article comments), “The best course for you is to lower sodium intake as far as possible – I believe urine pH will fall.” Can you please help me understand how the mechanism?
        (My 24hr tests don’t tell me whether this worked because I lowered meat and sodium at the same time, but the good news is that citrate is rising.)
        Thank you again for your help and patience! –Al

        Reply
  15. Dom

    Dr. Coe –
    I have been on Klor Con (Potassium Chloride for a while due to Crohn’s and low blood potassium). Thanks to Crohn’s disease for over 30 years, I have developed more than 50 kidney stones. My urine citrate was extremely low (less than 31) and I am now on Potassium Citrate. However, in order for approval, I had to stop the Klor Con. Will the potassium citrate still supply the needed potassium to keep my blood levels in normal range??? Thanks!

    Reply
    • Fredric Coe, MD

      Hi Dom, Klorcon is potassium chloride; Klorcon/EF is potassium bicarbonate. The low blood potassium can be raised with either but the chloride may be more efficient. Do plain KCl tablets not work?? I doubt your stones are due only to low blood potassium with low urine citrate – oxalate is usually a problem and low urine volume. I have not yet written the articles on the diseases, but I will soon. Regards, Fred Coe

      Reply
  16. Jerry

    Dr, Coe,

    Have been diagnosed with a 5-6mm calcium kidney stone, and have it lodged in my ureter for the past month, making slow headway to the bladder. No blood in urine per visits to doctor and ER.
    The pain was strong in December, nothing for weeks and flared up again on January 8th, lasting three days. Pain free now and drinking lots of water.
    The proposed next course is surgical removal. Would taking Potassium Citrate Pills act to dissolve the stone?
    My brother was a chronic kidney stone producer and now, free of stones for a few years, swears by lemon juice to prevent, but will it dissolve and assist in flushing it out?

    Reply
    • Fredric Coe, MD

      Hi Jerry, Potassium will not dissolve the stone unless it is uric acid. Even then if the stone does not pass it needs to be removed because of the danger of obstruction and kidney damage. Dissolving even a uric acid stone takes quite a while. When it is gone, get a proper evaluation to find out why you formed it, and seek rational prevention. Regards, Fred Coe

      Reply
      • Jerry

        Thank you Dr. Coe.
        Right after I posted my comment, I read further into you other responses and realized it was a false hope to dissolve my stone.
        At this point I am still hoping to pass it, lots of water and .4 mg Tamsulosin at bedtime.
        Not in any pain, but pretty sure it is still there. Nothing in the filter to prove otherwise.
        Dreading having it surgically removed. wondering if anything, reasonable of course, else I can do to get it through the final few inches of my uterer.
        Walking, jumping up and down, massaging the area, hanging inverted perhaps?

        Reply
        • Fredric Coe, MD

          Hi Jerry, I cannot blame you for disliking surgery; who would not? Prevention is critical and I already pointed out some articles for you. Nothing you mention or I know of specially works. Sorry, Fred Coe

          Reply
    • Lee

      Dr, Coe,
      After a 24 hr urine test, I had both very low urine citrate and urine pH. I drank lemon juice with water 3x a day and it brought the urine citrate level way up, but the urine pH is still very low. I don’t want to take a supplement, so I drank baking soda by itself and it raised my pH level. I’ve read that you can mix the two, baking soda and lemon juice, but when I did that, it seems like the juice was neutralized because there wasn’t that sour lemon taste. If those 2 things are combined, will the lemon juice still be effective in raising urine citrate, or does baking soda cancel that out? I can check the urine pH level with testing strips, but can’t test the urine citrate on my own. Thank you

      Reply
      • Fredric Coe, MD

        Hi Lee, Low citrate and pH is not a common pattern and usually found in people with gastrointestinal problems. Mixing sodium bicarbonate with lemon juice is not necessarily a good idea because the sodium load may increase urine calcium. Before trying experiments, take a look at this approach to interpreting your lab report; note that the type of stone is critical, and may be uric acid in your case – thence the version in the link. Here is for calcium stones. The mixing approach you describe will not be either fully rational or effective in any event and should be discussed with your physicians. Regards, Fred Coe

        Reply
  17. Elen

    Hi doc…
    I was diagnosed having a 2-3mm calyceal nephrolithiasis and my doctor prescribed a potassium citrate with a brand name urecit is there a brandnamelike this urecit isearch on the internetand i always find potassium citrate urocit is thereany difference between the two brands?…if i may ask is it really effective treating a calyceal nephrolithiasis? And is it safe to consume 1080mg 3x a day…i have stomach upset and slight muscle cramp..and i experienceda little discomfort on my lower to witch i did not experience before taking this medicine…is ok with that…iam confusedand afraid pls give me an enlightenment about this..thanks
    Elen

    Reply
    • Fredric Coe, MD

      Hi Elen, Potassium citrate is just that; be sure of the dose which is usually 10 mEq (1080 mg) per tablet. Three daily is a common dose. But be sure you need it. Stones often gather in calyces, so the words mean stones in the kidneys. If your doctor said calyceal diverticulum then one does not treat those medically, but only with removal if necessary. It it means stones, the you need evaluation to know the actual cause – here is a good approach. Regards, Fred Coe

      Reply
  18. Jose

    Hello Dr. Coe – First, I want to thank you for such an informative blog. I really appreciate your time and effort in providing such authoritative information from a true expert in the field of kidney stones. I was researching kidney stones on the internet and there is so much junk and pseudoscience; it is re-assuring to have an authoritative medical source. I suffered my first kidney stone this past weekend(Male, age 41) and my left lower back hurt like the dickens for about 3 hours! I was in a lot of pain and I commiserated, albeit briefly, with my wife on child birth. That crazy woman, how could she do that twice! The ER doctor said it was probably a small stone passing from the kidney through the ureter into the bladder. He recommend lots of water, gave me filters so I could possibly catch the stone, and a followup with my primary car physician.

    In researching kidney stones on the internet, citrate intake is recommend to reduce the formation of stones; but some websites actually seem to suggest that this will somehow “dissolve” the stones. Is this true? Does anything “dissolve” a stone? My lay understating is that citrate inhibits formation of new stones by binding with oxalates. Does citrate help with all types of kidney stones and does it matter if I’m using potassium citrate or if I’m ingesting citrate via fresh lemon juice. Thanks Doc! – Joe

    Reply
  19. Karlo V.

    Hello Dr. Coe,

    What a fascinating, informative read. Truly one of the most insightful things I’ve read so far in my never ending search for relief. I’m a 34 year old male of Asian decent. For the past 13 months now, I’ve had to be rushed to the ER 3 times (give or take 4 months apart) for a kidney stone. Every single time it’s been anywhere from 4-6 mm calcium oxalate stones that are so jagged and sharp. The pain has been extreme each time, and it’s always the same routine. Morphine in ER, IV drips, cat scans, then I’m sent home with a prescription of flomax, Percocet and anti-nausea pills. I drink up to one gallon of water daily. I avoid salty and fatty foods. I only take a multivitamin. I don’t know what to do. Last week was the third time I was rushed to the ER. Please help. I feel like I’m out of options.

    Reply
    • Fredric Coe, MD

      Hi Karlo, It sounds like recurrent calcium oxalate stones and no prevention. You need a program approach, and here is my choice. This article pulls together the other articles about how to be evaluated and how to use your physicians in the most efficient manner. It is truly time to do this. Stones are crystals, at heart, crystals obey physical laws, we know the laws, so it is just getting things done. Regards, Fred Coe

      Reply
      • Karlo V.

        Thank you so much for taking the time to respond doctor. I just have to say that I’m very grateful for your continued work in trying to help people out there. You really are a hero and you’re making the world a better place just by being the compassionate you. I’ll read everything I can from your site and share what I can with fellow sufferers. My deepest gratitude kind sir.

        Reply
  20. Bill Schramm

    I have a very large existing stone that has firmly lodged in my kidney. it is KUB monitored every 6 months and hasn’t moved for years. If it should move I would have limited options, as I have had surgical removal of a stone before and lithotripsy stone-breaking would simply create an unmanageable number of smaller chunks.
    I have been prescribed, and taking, 1080 mg tabs 2/x day Potassium citrate the past two years as a way to help prevent new stone formation.
    I am now experiencing consistent lower back pack pain and regular spasms for the past two months. Chiropractic attempts seem to rule out standard muscle strain.
    My question: Do P-C pills “eat away” at existing stones enough to dislodge them?

    Reply
  21. Bernadette Popp

    My husband had stage three kidney disease (40). Dr prescribed potassium citrate 1080, 2 pills twice a day. Two months, now had blood test now stage four (25) My pharmacist says it’s the pot cit. Dr says no, we’re afraid?

    Reply
    • Fredric Coe, MD

      Hi Bernadette, I presume your physician prescribed potassium citrate for stone prevention and that your husband has kidney disease whose cause is known. The potassium citrate should not of itself altered kidney function. I would speak with your physician about whether a nephrologist might be useful here as a consultant. Use of potassium supplements in someone with reduced kidney function is best reviewed by such a specialist. Regards, Fred Coe

      Reply
  22. Leon

    I have one more question Dr. Coe:

    I myself am taking potassium citrate not to prevent kidney stones but for potassium loss by hydrochlorothiazid and because I (like most people) get too little dietary potassium (at least not the recommended 4700 mg).
    I would like to ask: Did you ever examine possible negative consequences of getting so much citrate? Is anything known? For example, could it raise the risk for some types of cancer?

    Reply
    • Fredric Coe, MD

      Hi Leon, citrate is metabolized as citric acid which is why it is an alkali, and urine citrate rises because of the alkali so the production of alkali from the oral citrate is balanced by a loss of urine citrate – more or less null outcome after a few days. Citrate itself being metabilized does not rise in blood. It is a central metabolite in the Krebs cycle = citric acid cycle. SO, no. Regards, Fred Coe

      Reply
      • Leon

        Again, thank you very much for your reassuring reply!

        I was considering supplements for hypertension and came across citrulline and arginine but then found out that they might stimulate some types of cancer, so I was wondering about the citrate – I didn’t know it doesn’t rise in blood – contrary to amino acids of course.

        Reply
        • Fredric Coe, MD

          Hi, Let me be clear; blood citrate may rise, slightly, with citrate dosing, but there are no links to cancer. As for the other two molecules you mention, I would be sceptical of real links as well – but they are not my focus. Regards, Fred Coe

          Reply
          • Leon

            Hi, I think there is still a lot of research to be done, but there is some reason to suppose citrulline and arginine in (excessive) dosis might stimulate (not cause) the growth of some cancers:

            Citrulline and arginine increase the growth of the Ward colon tumor in parenterally fed rats.

            https://www.ncbi.nlm.nih.gov/pubmed/8844725

            Arginine dependence of tumor cells: targeting a chink in cancer’s armor

            https://www.ncbi.nlm.nih.gov/pubmed/27109103

            I worry much less about citrate and I think the benefits of additional amounts of potassium by far outweigh the minute (if any) and unproven/undiscovered risk of citrate. Judging from the research I saw, additional potassium for most people might prevent many CVD, strokes and MI and might be far superior to, for example, statins. But of course, potassium cannot be patented and there is nothing to gain for the pharmaceuticval industry…

            Thank you again for your help – I’m sure your patients must be very happy with you.

            Kind regards, Leon

            Reply
  23. Leon

    Dear Dr. Coe,

    Potassium citrate is given to prevent or even dissolve some type sof stones that grow in an acid environment.
    Now, I would like to ask you: When you make the urine neutral or alkali by taking a potassiam citrate supplement – could that cause other types of stone to form (those that grow in an alkali environment)? And if so, could that already happen when one takes 20-30 mEq long term?

    Reply
    • Fredric Coe, MD

      Hi Leon, Calcium phosphate stones are favored by high pH but if urine citrate rises it inhibits such crystals. The question of potassium citrate and calcium phosphate stones is an open research issue and needs a trial. Regards, Fred Coe

      Reply
  24. Dale Hensel

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    Reply
  25. Al R.

    Hi Dr. Coe,
    Hope all is well with you. I started the traditional chlorthalidone and potassium citrate last year for Ca stones. I developed symptoms that looked like heartburn, apparently because of stomach irritation related to the potassium. So my doctor prescribed omeprazole.
    To make a long story short, we found that I’m one of a handful of people for whom PPIs, especially rabeprazole in my case, cause hypokalemia – much more than the chlorthalidone alone. Weaning off the PPI is taking months. Taking more K citrate tablets only feeds the vicious cycle. Amiloride didn’t help significantly.
    Enteric coated K citrate tablets would seem to make sense, but apparently are considered dangerous to the intestine.
    So I have a very practical question…Do you have any thoughts on a way to get, say, 10 mEq of potassium citrate, or an equivalent, with the least risk of stomach irritation?
    For example any idea whether dissolving the contents of ten or eleven OTC 99 mg (0.92 mEq) K citrate capsules in, say, 8 oz of water taken with a meal might be more or less irritating to the stomach than the usual 10 mEq extended release tablet?
    Grateful for any help you might offer! Take care,
    Al

    Reply
    • Fredric Coe, MD

      Hi, Marked potassium loss with chlorthalidone usually means urine sodium is too high. Try to lower it to below 65 mEq (1500 mg) daily before using the CTD and add amiloride at the same time as the drug. That may lessen the need for potassium. You could use plain potassium chloride to replace potassium losses and these are slow release and also in liquid form. Regards, Fred Coe

      Reply
      • Al R.

        Hi Dr. Coe,
        Thank you for several options. Yes, I’m on a low salt diet.
        I’ve found potassium chloride much more irritating. But potassium citrate remains an interesting option because it also provides beneficial citrate. You’ve mentioned Cytra-K, which is available as a liquid. They claim it is well tolerated.
        Do you have any experience or ideas about whether drinking that in a glass of water or juice would tend to be more or less irritating than the same dose as an extended release tablet? Best regards,
        Al

        Reply
        • Fredric Coe, MD

          Hi Al, The best way to negotiate these details of medication use is to work with your pharmacist and physician to find what works for you. I am too far from the action to be a safe or useful guide. Regards, Fred Coe

          Reply
          • Al R.

            Hi Dr. Coe,
            Thank you for your kind help! Just to close the loop for anyone interested:
            We have not been able to find any research. However, they all agreed that, in their opinion, the ER tablet seemed to be as good as it is going to get. That would slowly release the potassium over long as 8 hours. One could try sipping liquid all day, but it would be hard to spread it out more than the ER tablet would. Factors beyond that would involve pure speculation. Best regards,
            Al

            Reply
    • Leon

      Here in Europe one can get potassium citrate capsules (no extended/slow release).
      I myself take them for potassium loss by hydrochlorothiazid (diuretic). I take 200 mg capsules, 5 times a day, after food and with a full glass of water – no stomach problems. And I use ranitidine, which is much better than PPI’s in general (eg safer for the heart).
      For uric acid stones prevention (together with diet): potassium citrate 500 mg, 3 times a day (combined with sodium bicarbonate 500 mg 4 times a day) is given here in the Netherlands.

      Reply
  26. Crystal

    My dr recently prescribed potassium citrate er 15 meq tb taken twice daily. After a couple years of frequency, urgency, burning, bladder spasms, visible pus in urine with elevated white cell count but no bladder infection found via culturing, I was finally diagnosed with cystitis cystica. I am 64 yoa. I had been two months on Doxycyclne, phenazopyridine, gabapentin, AZO, with no help to frequency or urgency until the potassium citrate was added. I came here trying to understand why after all this time of hourly urinating day and night, I am beginning to go less often. Slept 5 hours last night before needing to go. Although not a vegetarian, I have eaten mostly salads with some chicken at times for years because it is easier on my colon. I notice that most of your posters have stones and worse problems. I don’t pretend to understand much of your article but I read the whole thing and did pick out that vegetarians get their PH out of balance. Sounds like maybe I fall into that category?

    Reply
    • Fredric Coe, MD

      Hi Crystal, Potassium citrate inhibits crystal formation, and crystals are often part of the bladder condition you refer to. I suspect that is why it is of some help. If it continues to work I see no reason to not use it. Be sure your physicians keep track of your blood potassium – I am sure they would. Regards, Fred Coe

      Reply
  27. Anthony Krall

    I am 81 years old & have passes kidney stones & have had urinary tract infections about every 5 months for the past 2 years. I have had no pain through all of this. I have a large prostate. My urologist in trying to figure this out has blasted my kidney stones a year ago &
    just last Wednesday prescribed Potassium Chloride 20 meq (2 times per day. Since last Thursday I have been urinating on the hour each day and during my sleep at night and thus, not getting any sleep.
    I took the pills for the past 4 days and at noon today, Aug., 8, 2016,
    I have dizzy spells when I get up to walk; urinating once every 20 minutes (sometimes just a dribble); vomited once; I feel weak; drink water; heavy breathing. Tomorrow I go in for a CT scan of my bladder. Could the potassium pills have given me these complications? I’d appreciate your answers to this. Thank you.

    Reply
    • Fredric Coe, MD

      Hi Anthony, It sounds like the prostate is a major issue in that retained bladder urine can lead to infections and bladder stones. But the kidney stones would be from some other cause; it is important to know what they are made of, and presumably that was determined by stone analysis on the fragments a year ago. I would have thought the pills were potassium citrate, not potassium chloride, but in any case vomiting weakness, and heavy breathing sound like serious symptoms which your physician should evaluate right away. I would not delay this. Regards, Fred Coe

      Reply
  28. Joe T

    It is now 1:30 pm. About 20 minutes ago I was pissing razor blades with bloody discharge at the end– the pain was horrible– but I could not pass the stone (if there is a stone in there). My surgeon called me back right away after I left a message. He told me to increase my Potassium Citrate to 6 (1080mg) pills a day divided into 3 doses. He also told me to take AZO to soothe the irritation in the urethra. He said he was very sure he got everything out. He suggested he can do a cystoscopy in the office to check if there is a particle there but he said most of his patients think there is a particle there but it is just irritation from the procedure.

    I just sent my son to the drugstore to get the AZO.

    I’ll add to this If I don’t pass out from the pain the next time I pee.

    Reply
  29. Joe T

    I happened upon this website and I am both impressed and befuddled at the complexity of the topic. I have a bachelor’s degree in aerospace engineering, but this is way over my head.

    On June 13, 2016 I submitted a 24 hour urine collection to Quest Labs in order to determine the StoneRisk Diag Profile:

    STONERISK(r) DIAG PROFILE
    Result Date: 06/17/16

    Analyte Result Value Ref. Range Units Out of Range

    TOTAL URINE VOLUME 1.43 >2 L/day L
    PH URINE 6.2 5.5-7.0
    CALCIUM URINE 300 <250 mg/day H
    OXALATE URINE 49 <45 mg/day H
    URIC ACID URINE 789 320 mg/day
    SODIUM URINE 151 <200 mEq/day
    SULFATE URINE 28 <30 mmol/day
    PHOSPHORUS URINE 1115 60 mg/day
    AMMONIUM URINE 23 14-62 mEq/day
    POTASSIUM URlNE 74 19-135 mEq/day
    CREATININE URINE 1799 800-2000 mg/day
    CALCIUM OXALATE 3.75 < 2.00 H
    BRUSHITE 3.94 < 2.00 H
    SODIUM URATE 4.19 < 2.00 H
    STRUVITE 1.70 < 75.00
    URIC ACID 1.52 < 2.00

    THE PATIENT HAS: See Below
    Hypercalciuria
    Hyperoxaluria
    Hyperuricosuria
    Low urine volume

    SUPERSATURATION INDEX: See Below
    Calcium oxalate
    Brushite (Ca phosphate)
    Monosodium urate

    SUSPECTED PROBLEM IS: See Below
    Hypercalciuric Nephroithiasis
    Hyperoxaluric Nephrolithiasis
    Hyperuricosuric Nephrolithiasis

    It confuses me that I have both high Uric Acid (an acid) and high Oxylate (an alkaline base) at the same time. Does this mean I could have had both Uric Acid Stones and Calcium Oxylate stones at the same time???

    On July 7, 2016 I had my bladder stones (infected with enterococcus faecalis) removed with a laser procedure. My surgeon and a different surgeon I saw six months before told me the same story. They promised that after the stones were pulverized, all debris will be removed and theta there would be no pain before or after surgery. THEY BOTH LIED BIGTIME. OUCH. Over the course of 48 hours from the time of the surgery, I passed small crystals with considerable pain. Now, I want to know how to prevent the formation of future stones.

    What kind of stones were removed? The lab has not yet come back with the results. I will will return here to let you know. In the meanwhile, the surgeon has put me on Amoxicillin 2x/day, Potassium Citrate 1080mg 2x/day, Uroxatral 10mg 1x/day, Doc-Q-Lace 100mg 3x/day as needed. I'm also taking two 480mg capsules of Marshmallow Root 2x/day to soothe my urethra.

    I've taken the Potassium Citrate from the evening of July 7 until today and my urine is still acidic Ph 5.0. I will now begin to try to give up meat, dairy and eggs and sugar as best I can. I think this will help.

    I will keep you updated on my experience and the lab tests.

    I will set up a new email account in order to answer anybody who has questions about the procedure and/or my experience. I will post the email address as soon as I get it set up.

    Reply
    • Fredric Coe, MD

      Hi Joe, Your results suggest you have idiopathic hypercalciuri causing the high urine calcium and also a high urine oxalate excretion which could be from high oxalate diet or low calcium diet or both. That the stones were bladder stones is a bit unusual and suggests perhaps bladder outflow obstruction (prostate??); you did not say if there are kidney stones. The approach to treatment is to reduce your urine supersaturation with respect to the crystals in your stones and we do not know those crystals as yet, so let us know. The infection is an additional issue and I presume your urologist is treating it. It points to bladder outflow obstruction, as do the bladder stones. Regards, Fred coe

      Reply
  30. Katherine

    I’m trying hard to understand all of this but, just learning and much of this is still over my head. I’m trying to find a combination of therapies rather than megadoses of potassium citrate (45-60MEq/day). If sodium bicarb is effective in the same manner, I wonder whether magnesium bicarbonate (as in magnesium water) or potassium bicarbonate (or more likely a combination of all three) would be as effective as potassium citrate in raising citric acid levels in urine output.

    Reply
  31. Monica Driscoll

    My urologist wants me to build up to 4 Potassium Citrate pills qd. The only thing I (with help from pharmacist) can find are time-released formulations that are not to be crushed or split. I CANNOT TAKE THESE LARGE PILLS. If I am to take up to 4 qd, can I crush them afterall and take them throughout the day? What alternative can you suggest? I am a 70-year-old white female and have been forming stones for 47 years. Thank you.

    Reply
    • Fredric Coe, MD

      Hi Monica, There are 1/2 size 5 mEq pills, and they are smaller. Try the – need two to do the work of one large one. Regards, Fred Coe

      Reply
  32. LDOWNA

    I did 2 24 hr tests and the end result was my citrate levels were 220 and my production was well under at 980 and 1200. My doc suggested I take citrate medications and increase fluid intake but has not confirmed what I should do about the stones I have. I had 17 total last count after passing some and gaining others. I started out with around 14. Passing them is real painful and I was told the ones I have now is around 6 – 7 mm. The doc hasn’t said what I should do about the current stones since they will not dissolve. They just keep asking well do the bother you. YES!! Thus an emergency room visit, taking off from work, and coming to see you. Any thoughts?

    Reply
    • Fredric Coe, MD

      Hi Ldowna, It is a dilemma. If you can stop new stones, perhaps the most conservative approach is to let those left pass as opposed to having a procedure. There is no point in surgery if new stones are actively forming. So, I would suggest you use the medication and be sure new ones are not forming, take some time to be sure. Then decide if surgery is worthwhile for you. In the absence of obstruction, infection, or important bleeding, surgery for pain is a personal not a medical choice. Regards, Fred Coe

      Reply
  33. charles howe

    my urine cit rate number is 360 and my ph 5.674 ss uric acid is 1.44 should i be taking potassium cit rate i have had 20 + stones in my life 3 surgery finally did a urine 24 hour test what will prevent the stones

    Reply
  34. Mark

    I forget to mention, they are calcium….

    Reply
  35. Mark

    I forget to mention,, my stones are _”calcium”…..

    Reply
  36. Mark

    I might have missed something in this article…
    My question is..
    I was put on 5000mg of Vitamin D and within 2 months developed 3 kidney stones, I never was bothered with this before, (I am 62)
    My urologist told me D is the worst.
    I still have one in the kidney but he feels it will not come up and through the utterers because of its location. He is waiting for it to grow in size so he can blast it.
    He put me in touch with a kidney doctor who has me on 12.5 mg water pill..
    He said this will be my life from now on.
    I have read your article and I am hoping that this potassium citrate will keep stones at bay.
    I have also read an article from Dr. Peterson, who claims magnesium and the citrate will dissolve or flatten the stones?
    Can you please explain, in laymen’s terms?
    Thank you,,,

    Reply
    • Fredric Coe, MD

      Hi Mark, Although the vitamin D could have worsened things, it is likely that there was always something lurking and the vitamin simply exaggerated it. My guess is you have genetic hypercalciuria. The proper approach is 24 hour urine testing with appropriate fasting bloods which perhaps your physician has already obtained. If so, take a look. Be sure your evaluation has been orderly and complete. The diuretic at 12.5 mg daily is usually chlorthalidone or hydrochlorothiazide, and it is in treatment of hypercalciuria. Magnesium has never had a successful trial, I do not know why anyone touts it, and I do not know the article by Dr Patterson unless you mean this one:. It is a review of Canadian guidelines and I see no mention of magnesium as a prefered treatment. I do see the need for proper evaluation and I hope you have had such. Potassium citrate is a valuable treatment for prevention, as noted, if stones are calcium oxalate; for calcium phosphate trial data are limited. Citrate nor magnesium will flatten or dissolve calcium stones. Regards, Fred Coe

      Reply
      • Mark

        Thank you for your response .
        The article was Dr. Dale Peterson, Wellness Clubs Of America.
        Yes, I have had all the urine testing and blood work done.
        I just don’t want to hear in a year or two that I have kidney failure from the diuretics, which has happened to a few people that I know. So I guess what you are saying is, the only thing for me, is the diuretics. Very sorry to hear this.. Again, I thank you for your time.

        Reply
        • Fredric Coe, MD

          Hi Mark, If you have idiopathic hypercalciuria as a proposed cause of stones, low sodium diet with high diet calcium – for your bones, and high fluids may well be enough. Chlorthalidone in the dose mentioned has millions of patient uses as it is a first line antihypertensive. Allergic reactions are very rare and reverse on drug cessation. The drug has no known danger to produce kidney failure. Think about prevention in a larger context than just one drug – it is a low more flexible than that, and also do not be alarmed by a drug so old and so much used as this one. Regards, Fred Coe

          Reply
        • CS

          Mark, …I’m a 68 year old male. After six surgeries in the ’90s, I had constant, continual, calcium kidney stones. I tried the Coke/asparagus technique – it worked, but…… Then, by chance I started drinking coconut water – WOW!….a year now – no stones. I am drinking ‘only’ 4 oz every-other-day. Do not “over-do” this… Good Luck

          Reply
  37. Lutz

    Dear Dr. Coe, I have been suffering from Ca oxalate stones until age 50, where I was diagnosed with renal carcinoma (clear cell type). Subsequently I had partial nephrectomy surgery. After surgery I continued to grow kidney stones, no longer oxalate stones but predominantly uric acid stones. My doctor prescribed a combination of potassium citrate and Allopurinol in an effort to “dissolve” remaining kidney stones and to keep uric acid low (especially after I had my first gout attack). My question to you would be, is it really possible to completely dissolve existing urate stones inside the kidneys, based on a dose of 2x 10MEq and 100mg Allopurinol daily? I had passed horribly big yellow urate stones (around 12mm) and they are growing into this size in about one year. During passage they may have damaged some of the kidney function, and if so would that have to do with the sudden production of these kind of stones? I just wonder, if that K-Citra is going to work as intended. Keeping up my hopes…
    Thanks
    Lutz

    Reply
    • Fredric Coe, MD

      Hi Lutz, Uric acid stones are caused by low urine pH in a mechanical – chemical actually – manner and prevented by raising the pH to about 6. You are taking a marginal dose of potassium citrate and perhaps new stones are forming because the pH is still too low. Allopurinol will stave off gout but has almost no benefit for uric acid stones. Here is what to do. Check out your 24 hour lab reports for uric acid stone risk. If your urine pH is indeed 6 on a 24 hour urine average, perhaps there are troughs – get some urine pH paper and check voidings during the day and overnight. After doing your own work, see your physician, show your results and get input about the best next step. I have written and stand behind this: Recurrent uric acid stones are virtually always preventable. As for dissolving stones, the odds are poor. They grow from small to large so the surface to volume ratio falls a lot. They shrink from outside in. You can try. I will wager you need more alkali but check first, as I have said. Regards, Fred Coe

      Reply
  38. Dave

    I notice the Potasium Citrate pills in my stool several times a month from normal observation.
    I suspect that is a small fraction of what gets passed. Is there something I can eat or drink when I take them to get them to start dissolving? What’s the time-release glue? I know it’s not recommended, but what will happen if I break it in half? thirds? quarters? before swallowing?

    Reply
  39. Kay

    I’m trying to understand all of this in better detail. 1st what is it that causes your body not to produce Potassium Citrate? And Magnesium? Other than producing additional kidney stones, what are the other real risk of not talking ir? Are there any further concerns with using the crystals through a feeding tube ? Any help and answers you are able to provide I would really appreciate.

    Reply
    • Fredric Coe, MD

      Hi Kay, Low urine citrate has more than a few causes, and I am sorry I have not written an article on this matter as yet. The common reason may be heredity. Other reasons are bowel diseases and potassium depletion. Low urine magnesium is due to bowel disease, or other diseases and is not a part of common stone disease. Feeding tubes are never used for anything except when there is severe bowel disease or in hospitalized patients. In people with calcium oxalate stones citrate can reduce new stones. The reasons are a in the article. Regards, Fred Coe

      Reply
  40. Jason

    An alkaline pH favors the crystallization of calcium- and phosphate-containing stones, whereas and acidic urine pH promotes uric acid or cystine stones
    http://www.ncbi.nlm.nih.gov/pubmed/21170875

    So don’t take citrate for calcium oxalate stones?

    Reply
  41. Afeena

    Hello, Dr. I’ve been taking Potassium Citrate for a week and a half now. My nephro advised me to drink 6 tablets per day, 2tabs each meal. Do you think the potassium citrate is already taking effect? I’m not feeling anything at all while taking this medicine.

    Reply
  42. Michele Lewris

    Hi, I’m going to be having my 5th ESWL done within the last 20 years. Fragments that are left continue to grow, so I’m not producing new stones. Calcium oxalate. I’ve had various work ups during the years and I have high urinary oxalate and low ph. I take Theralith xr but I also take Lisinopril and Hydrochlorothiazide. One depletes and the other stores potassium. So, the Theralith daily supplies 198 mg of potassium citrate along with magnesium and b6. I have recently started drinking lemon water, adapted a low sodium diet, cut down on protein and cut down on high oxalate foods. Should I consider taking prescription potassium citrate? Also, I read that IP6 is a good supplement to take for kidney stones. Do you do phone consults? I live right outside NYC.

    Reply
    • Fredric Coe, MD

      Dear Michelle, If I may be forgiven for commenting from a distance, you may have had enough SWL procedures and benefit from ureteroscopy as an alternative. You might want to discuss this with your personal physicians. Growth of retained fragments is commonplace and fostered by the templating effects of crystals in fragments to support growth of more crystal mass. I wonder how high the urine oxalate is; commonly values for ‘high’ are 45 – 60. The potassium citrate dose is too low to influence potassium stores or affect stone formation. Inositol hexaphosphate is proposed for cancer and dementia and for all I know as a means for promoting world peace. The scientific foundations are not known to me and I am sceptical. For stones, no evidence. I can speak with you by phone but to make it worthwhile I would need to see your medical records. My secretary Kathleen is at 773 702 1475. Regards, Fred Coe

      Reply
  43. Dwight kett

    Thank you
    Do you still have an office in burr ridge
    I would like a consult
    What number should I call

    Reply
    • Fredric Coe, MD

      Hi Dwight, I was never in Burr Ridge, the University of Chicago is my home and it is in Hyde Park, Chicago. I am not sure how the Burr Ridge address got on the web, perhaps it is that the University billing group is situated there. My secretary Kathleen is at 773 702 1475. Regards, Fred Coe

      Reply
  44. Ron

    My doctor prescribed this:
    http://medlibrary.org/lib/rx/meds/cytra-k-crystals/

    It is a little cheaper than the pills. I have low urine citrate and low pH. Will it work as good as the pills? I noticed the cytra has alot of citric acid. Is that bad?

    Reply
    • Fredric Coe, MD

      Hi Ron, It is the same as other K Citrat4, the citric acid is not a problem. Just watch the dose and be sure it conforms to what was prescribed. Potassium is safe so long as the dose is right. Fred Coe

      Reply
  45. Dwight kett

    After a 1 hour spin class I take 30 meq kcitrate and a alkaline smoothie and my urine oh still stays 5.5 ph
    If I don’t workout it goes to 6.5
    Is recovery that long?

    Reply
    • Fredric Coe, MD

      Hi Dwight, I imagine you are seeing the well known effect of low urine flow to lower urine pH. If you are a stone former, consider that during your workout you might need additional fluids. Regards, Fred Coe

      Reply
  46. Fredric Coe, MD

    This is an email dialogue between Drs Ronald Kallen, me, and Orson Moe that occurred at the end of December 2015. It alludes to some very interesting matters concerning citrate handling and both renal and intestinal cells. With their permission I have placed it here for general interest. Fred Coe

    Hi Fred,
    I am revising a book chapter on RTA and wanted to say something about how ingested preformed citrate alkalinizes the urine, since it seemed that citrate would be absorbed and metabolized to CO2 and H2O by enterocyte mitochondria. Anyway, your digression into the wiles of the Tudors was an unexpected intro to my exploration of citrate.

    In reply to RON KALLEN.
    Hi Ron, A rather elegant thesis, and perhaps true. Is it original with you? Any mitochondria will do, I suppose, and why not there? If asked I would always point to the liver because it is so big and always doing things. The Tudors have a bad rep because so vicious, but there was Gloriana, and for all her ways, she kept England out of war, made the people a wealthy nation, and founded one of the great ages of English letters and music – Shakespeare, Dowland, Donne. All the best, Fred

    Fred,
    Your commentary above is illuminating about the wiles of citrate and its salubrious effects on human health, if not kidney health.
    Assuming that ingested citrate is absorbed in an intestinal segment by an apical transporter (NaDC1 ?) of an enterocyte, and that the citrate is metabolized therein (mitochondria) completely such that no citrate exits the enterocyte and flows northward in the portal stream, how then is the ingested citrate transduced into an increase in urinary citrate?
    Best, Ron

    Hi Ron, Here is what must always be the case so far as I can tell. Citrates are used in the Krebs cycle as citric acid, and at the end of the cycle we have CO2 and water. So whether in the liver or enterocyte, protons have to be taken out of the blood as citrate is taken up into the cycle as citric acid. The removal of a proton from blood produces a bicarbonate molecule because of the CO2 buffer system being predominant and that new bicarbonate signals kidney cells as I reviewed in the article. Your point is really interesting – that intestinal cells could be the locale of citrate use. I would say it is testable in animals and a nice insight. As for cluttering the site, no you are not. A large number of physicians and scientists lurk on this site – I know that – and this kind of commentary may get a few to come out of the shadows and say something. Warmest regards, Fred

    I did not want to burden your blog and elegant review of the salubrious effect of K Citrate. Of course, I don’t mean ‘climate change’ as in the recent Paris meeting but the climate change of the internal environment that makes stones or breaks stones. I have been puzzled for a long time as to how orally administered citrate ‘transduces’ to increased urinary citrate. I have sketched a schematic that attempts to integrate some of this (which I can send separately). But one paradox that crops up is: if increased urinary citrate as a consequence of acidity sensing (Pyk-2 sensor, ET-1, etc cascade ?) after citrate administration dials down proximal tubule NaDC1 citrate transport, then it should do the same for the intestinal NaDC1, assuming that the enterocyte also senses a pH change somewhere (extracellular or intracellular). The paradox is that this would also dial down intestinal absorption of citrate via NaDC1 and thus vitiating the intended effect of the administered citrate (if I have this right or else I am totally bonkers), thus recapitulating the usual scenario of the Chicago Bears: third down, no gain, forced to punt.
    All these considerations have come up as I revise a book chapter on RTA. Moreover, I have a stone-forming patient with presumed RTA, who I have followed for about 10 years. Despite K Citrate, the urinary citrate remains phenomenally low. He has had many measurements at Litholink and I have had an email exchange with John Asplin about this conundrum.

    Dear Ron, these ideas are really interesting. I do not know if enterocytes are known to metabolize citrate taken up from the bowel lumen, nor if their transporter is regulated by blood pH or bicarbonate. I am copying Orson Moe who probably does know, as one expert can save us a lot of work.

    From Orson Moe:

    Fred, Ronald:
    You raised some very important points. I will try to answer as bullets.
    • The study of citrate transport in the gut is very sparse and somewhat due to technical hurdles. As a result, we know very little about the route and even less the regulation of intestinal citrate absorption. The presence of NaDC-1 transcript per se does not prove they mediate transport. No one has put the intestine on Ussing chambers or make intestinal BBM vesicles from the NaDC-1 null mouse to measure flux. We always assumed complete absorption because in normal individuals in steady state zero balance, the ingestion mEq is the same as the mEq in urine but mechanisms of transport is unknown.
    • Whole animal studies of intestinal citrate are hard. Isotope flux is impossible to interpret because all 6 carbons on citrate will become CO2 and get exhaled as labeled CO2. Chemically, any unabsorbed citrate will get consumed by colonic bacteria so stool measurements are always very low and does not reflect absorption. The definite assays are Ussing chamber ex vivo and portal and hepatic vein sampling in vivo after small bowel luminal bolus. Even in these conditions, interpretation of flux is confounded by cellular metabolism.
    • The mechanism of citraturia from oral citrate ingestion in my view is purely *at least mostly) due to sensing of a base load in the liver, which then signals the kidney to release base in the urine. Since one cannot afford bicarbonaturia on a regular basis due to risk of calcium phosphate precipitation, citraturia is the best way to excrete base in urine. Some have suggested years ago that some absorbed citrate “escapes” into the urine using citrate acid (acid-base neutral molecule) as a test molecule. I personally do not think that is true; or at least very low in magnitude. If ingested citrate does not undergo complete (or at least near complete) hepatic metabolism, it will be fatal. A nice bolus of breakfast orange juice in the morning will beget fatal hypocaclemia for the heart as the blood traverse the hepatic vein to the SVC and right heart. Only a massive oral dose (accidental poisoning) of citrate can overwhelm the liver and create systemic low ionized calcium. When we give it in a central vein in CRRT, we bypass the liver and we can often see low ionized calcium.
    • I think there are generic pH sensing mechanisms that all cells use for cell pH defense. The renal epithelia is special as it defends systemic acid-base and not just the cell itself. The Preisig-Alpern cascades may not be operational in the intestine. i.e. I doubt acidosis will suppress NaDC in the gut. A good example is the Na/H exchange NHE3 which is present in the proximal tubule vs. the small and large intestine. This apical membrane transporter is identical but very few of the regulatory mechanisms are shared. Intestinal NHE3 has been studied in acidosis and there is no regulation. It will be easy to measure NaDC transport in BBMV, protein, and transcript in the gut with acid loading. I think it will be negative but has not been done to my knowledge.
    • The existence of non-response to K Citrate in RTA patients is very real. We have collected quite a few of these patients in Dallas. Typically, their UKV will increase by 60 mEq/day (as prescribed) but the Ucitrate V increases by perhaps 10 mEq/Day. The increase in urinary anion appears to be a plethora of other anions including loss of chloride. We cannot measure stool citrate to interrogate lack of absorption. None of the rodent genetic models of RTA has this phenomenon. In the acquired “pan RTA” model induced by Topiramate, there is a discrepancy of delta UKV vs. delta UcitrateV but nowhere close to the non-responding patients we see; so I have not jumped on this model to investigate citrate non response. This can stem from a base deficit in the bone from chronic acidosis (absorbed from the gut but not end up in the urine; a form of “pay-back”) but quantitatively, we cannot account for the >60 mEq base gain/day by the bone for months or even years (not enough bone). We may push the topiramate rat model harder and do some portal and hepatic vein sampling (easy in a Sprague-Dawley) but I need some motivated individual. In short, our docs (many) have seen this over and over and it represents a physiologic conundrum and a real problem in clinical practice.

    ORSON – WHY DOES CHLORIDE RISE WHEN THESE ODD PATIENTS GET K CITRATE?

    Good point, Fred. Electrical neutrality mandates some form of anion. Chloride happens to be most abundant. If there an intestinal citrate absorption defect, perhaps the K is absorbed with Cl (e.g. K/H exchange in parallel with Cl/HCO3 exchange). I am just taking liberty to speculate. If the 60-90 mEq of prescribed citrate enters, the same quantity of base has to go the the bone or the urine.
    • The existence of K Citrate non-responders is very real. We have collected quite a few of these patients in Dallas between the mineral clinic and urology. Typically, their UKV will increase by 90 mEq/day (as prescribed) but the Ucitrate V increases by perhaps 10 mEq/Day. The increase in urinary anion appears to be mostly Cl plus a plethora of other anions. As mentioned above, we cannot measure stool citrate to interrogate lack of absorption. None of the rodent genetic models of RTA has this phenomenon. In the acquired pan RTA model induced by Topiramate, there is a discrepancy of UKV vs. UcitrateV but nowhere close to the non-responding patients we see, so I have not jumped on this model to investigate citrate non response. We looked at whether this can stem from a base deficit in the bone (absorbed from the gut but not end up in the urine) from chronic acidosis but quantitatively, we cannot account for the 60-80 mEq base gain/day by the bone for months or even years (not enough bone). I ran this by the ultimate master of acid-base (in my opinion), Mitch Halperin, and Mitch has not been able to help me solve this problem. We may push the topiramate rat model harder and do some portal and hepatic vein sampling (easy in a Sprague-Dawley) but I need some motivated individual. In short, our docs (many) have seen this over and over and it represents a physiologic conundrum and a real problem in clinical practice.

    Reply
  47. Kirt

    Hello,
    I have a case of encrusted cystitis following mitomycin instillation to treat urothelial carcinoma, crystals composed of calcium phosphate. Did urine and bloodwork with a Nephrologist (largely unremarkable), urine PH normal, but the Nephrologist has prescribed a rather high dose of potassium citrate. Isn’t this backwards? Is it time to seek a second opinion?

    Reply
    • Fredric Coe, MD

      Hi Kirt, The crystals are forming because the bladder lining cells have lost their normal coating and protections against them, so the problem is like kidney stones but not the same. Urine is generally supersaturated, so crystallization is prone to occur whenever surface defenses give way. The high dose of citrate will raise pH and therefore calcium phosphate stone forming propensity. If it raises urine citrate appreciably the citrate is a potent crystal poison, and can reduce crystallization. So the effects will offset each other. The best strategy is very high fluid volumes to dilute everything and the potassium citrate in hopes of an increase excretion and therefore concentration for the given volume. Since the amount of calcium excreted should be as low as possible, low sodium diet or even thiazide is ideal with a goal of a CaP supersaturation below 1 despite the high pH. Followup urines should be scrutinized for the final concentration of citrate vs. supersaturation with calcium phosphate, the higher that ratio the better. SOmetimes only the pH goes up, and the citrate is futile. Sometimes higher doses raise pH but not citrate so the increases above conventional dosages do no good. IN other words you need some trial and error to find your best balance. Regards, Fred Coe

      Reply
  48. Jennifer

    Dr. Coe I am so happy to have found your site. And here I am, another stone sufferer seeking advice.
    I make recurring Uric stones… They are generally small, but constant every few weeks. If I do allow myself to dehydrate, they tend to be bigger. I have drastically cut down on my protein, but it doesn’t seem to help much. I cannot take Urocit-K or any potassium pills because I also have PVC arrhythmias (controlled with Atenolol) and any time I’ve tried the pills, my arrhythmia goes wild. To add to the mix, I also take Byetta which has a desired affect of delayed stomach emptying, but that also affects other meds I take, they’re delayed too.
    Do you think the Crystal Light “therapy” will help? Do you have any other advice you can offer?
    Thank you so much in advance!

    Reply
    • Fredric Coe, MD

      Hi Jennifer; as it happens I just finished my article on uric acid stones, not yet even fully cited in the pages. Any alkali at all will do more or less the same things, and you can read about the whole matter. The article on price of potassium citrate offers a lot of alternatives. You are forming more stones because your alkali intake is too low and your urine pH is also low. Check out the articles and come back if you are not cured. Uric acid stones never have to occur at all. Regards, Fred Coe

      Reply
      • Jennifer

        Dr. Coe, for the first time in years, I actually feel hope! Thank you.
        I read your article on uric stones (sad that such a pretty crystal causes such havoc!) and much of all the others cited here.
        I’m going to give Crystal Light a try. I’ve decided on 17 oz / 4x a day, with each meal and before bed. I’m hoping that will spread things out, and help keep an even level.
        I have one more challenge ahead, I’m leaving for Tanzania on a 12 day Safari next week, where water is scarce and bathrooms are scarcer ; ) I will bring the travel sticks of powered Crystal Light and hopefully keep to my plan!

        I would like to add for anyone trying Crystal Light as their main source, to use a straw when drinking and rinse your mouth out with water after you finish. All the citric acid can damage your tooth enamel.

        Reply
        • Fredric Coe, MD

          Dear Jennifer, I am glad you read the article. Be sure your urine pH is high enough. I believe you can purchase urine pH paper at drug stores and check it from time to time yourself. I did not include that in the article but should have. Water will be scarce on your trip so pH is everything. Be careful. Crystal light has a high content of citrate meaning that the citric acid is not in its acid but in its salt form so it has a higher pH and should not disturb teeth. Best, Fred Coe

          Reply
  49. Lisa Landon

    Dear Dr. Coe, I’ve enjoyed reading your article and responses to the comments made.
    The paternal side of my family has a genetic condition called M.E.N.1. I’ve recently undergone my third parathyroid surgery in a final attempt to stop my production of kidney stones. My first surgery was in my early 20s, and my second surgery was 14 years ago during my second trimester with my second daughter to prevent her from developing rickets in utero. I experienced many years of lithotripsy, ‘scooping’, suffering the passings, and once, percutaneous nephrolithotomy removal of one stone nearly 2 cms. in size. The most recent renal calculus analysis reported major component Calcium Phosphate and minor component Calcium oxalate. Currently my blood calcium is within normal range, but my urine calcium 24h (8.4 memol/d) and PTH (13.5 pom/L) are both still high.
    My endocrinologist advises against a fourth surgery of the known remaining small piece of the parathyroid gland that was relocated to my inside forearm in the last surgery. Instead, in conjunction with advice from my urologist, he’s prescribed a combination of 25mEq potassium citrate dissolving tablets x2/day, and 25mg Teva-Hydrochlorothiazide x1/day.
    My question is, given your advice that although potassium citrate is as yet an unproven treatment against calcium phosphate stones, do you agree this is still the best course of treatment?

    Reply
    • Fredric Coe, MD

      We have found, not rarely, persistent hypercalciuria after successful parathyroid surgery. So the treatment with a thiazide seems a good idea. I do not like hydrochlorothiazide once a day as that has never been tested in a trial only twice a day. A long acting thiazide type drug as mentioned in the linked article is better. Thiazide will not work well without careful diet sodium reduction to 65 – 80 mEq/day, which you should do. As for calcium phosphate stones you are right, there are no trials and I would shun it in favor of low sodium + thiazide. Of course, very high fluids are critical for you, over 2.5 liters daily and consistent. Regards, Fred Coe

      Reply
  50. Ron Kallen

    Fred,
    Your commentary above is illuminating about the wiles of citrate and its salubrious effects on human health, if not kidney health.

    Assuming that ingested citrate is absorbed in an intestinal segment by an apical transporter (NDC1 ?) of an enterocyte, and that the citrate is metabolized therein (mitochondria) completely such that no citrate exits the enterocyte and flows northward in the portal stream, how then is the ingested citrate transduced into an increase in urinary citrate? Rather than clutter this blog with my musings, if you reply to my email, I can add to my thought process.
    Best,
    Ron

    Reply
    • Fredric Coe, MD

      Hi Ron, Here is what must always be the case so far as I can tell. Citrates are used in the Krebs cycle as citric acid, and at the end of the cycle we have CO2 and water. So whether in the liver or enterocyte, protons have to be taken out of the blood as citrate is taken up into the cycle as citric acid. The removal of a proton from blood produces a bicarbonate molecule because of the CO2 buffer system being predominant and that new bicarbonate signals kidney cells as I reviewed in the article. Your point is really interesting – that intestinal cells could be the locale of citrate use. I would say it is testable in animals and a nice insight. As for cluttering the site, no you are not. A large number of physicians and scientists lurk on this site – I know that – and this kind of commentary may get a few to come out of the shadows and say something. Warmest regards, Fred

      Reply
  51. RON KALLEN

    Hi Fred,
    I am revising a book chapter on RTA and wanted to say something about how ingested preformed citrate alkalinizes the urine, since it seemed that citrate would be absorbed and metabolized to CO2 and H2O by enterocyte mitochondria. Anyway, your digression into the wiles of the Tudors was an unexpected intro to my exploration of citrate.

    Best,
    Ron

    Reply
    • Fredric Coe, MD

      Hi Ron, A rather elegant thesis, and perhaps true. Is it original with you? Any mitochondria will do, I suppose, and why not there? If asked I would always point to the liver because it is so big and always doing things. The Tudors have a bad rep because so vicious, but there was Gloriana, and for all her ways, she kept England out of war, made the people a wealthy nation, and founded one of the great ages of English letters and music – Shakespeare, Dowland, Donne. All the best, Fred

      Reply
  52. LINDA B

    Can potasium citrate cause dizzyness, vertigo, or stomach aches and nausea? Or, could it be my minicycline causing these things? Please e-mail my answers. It’s very important. Sometimes I am dizzy for a week at a time and can’t find out why. Thank you for your reply.

    Reply
    • Fredric Coe, MD

      Hi Linda, potassium citrate can certainly cause intestinal symptoms of all kinds. Minicycline is very likely to do this. Perhaps you might want to try one at a time – perhaps a week each – and see which it is that causes your symptoms. True vertigo – the room going around you – is not caused by either drug so far as I know. Dizziness is common with nausea, so I cannot be sure whether it is a primary symptom or not. Fred Coe

      Reply
  53. Renee F

    Hi Dr Coe,
    Can potassium citrate still break up a big stone (between 4-7mm) in my Ureter? I think it is up by the Pelvic Junction? I was given these some time ago by my doctor but I read alot of people get very sick with this pill and my stomach can just look at a pill and get sick !! Is there a way to counter act the sickness that would come from taking this pill?
    Thanks much,
    Renee

    Reply
    • Fredric Coe, MD

      Hi Renee, Unless your stone is made of uric acid, it cannot be dissolved with medication. If you indeed have a stone lodged in your ureter, it is very important for your physician to be following its progress. Such stones can obstruct the kidney and damage it. So, it is not a pill matter once the stone is in the ureter. Pills are to prevent more stones. IN order to use them wisely your physicians will need to study your 24 hour urine and blood to determine the causes of your stones, and then take the proper steps to prevent them. Regards, Fred Coe

      Reply
      • Richard Thomas

        Dr Coe
        What medications tend to dissolve uric acid stones/

        Reply
        • Fredric Coe, MD

          Hi Richard, Only one medication can dissolve uric acid stones and that is potassium citrate – or another alkali – sufficient to raise the pH of the urine above 6. These stones form because of an acid urine and stop forming when the urine becomes alkaline. Treatment with alkali is near perfect. Now, dissolving uric acid stones is a bit tricky because such stones are not usually one thing but a cluster of smaller stones. So when you take alkali you make begin to pass the smaller fragments. Obviously you should not undertake treatment without your personal physician supervising. Potassium salts are not without risks, and assessing urine pH and the progress of stones requires medical supervision. But given that supervision the treatment should be excellent. Regards, Fred Coe

          Reply
  54. Emmett Garlock

    On September 30 I had surgery to remove a stone analyzed as a uric acid stone. At that time the urologist prescribed 15 mEq (1620mg) of potassium citrate twice daily. On October 19,2015, having been on the potassium citrate for 19 days a 24 hour urine collection test was performed . The results were oxalate urine 67 ( high), uric acid 851 (high) , sodium urate 4.77 (high) sodium urine 301 (high ) The urologist referred me to a nephrologist, and I’m awaiting the appointment date. I was not instructed to not eat or drink any food or beverages containing vitamin C 24 hours before the 24 hour urine collection test, which I have read as a direction for the test. My research seems to tell me that Vitamin C and potassium citrate are related (derivatives) My question is , would taking the 1650mg of potassium citrate twice a day, contributed to the high 67 metabolic level of oxalate, and if potassium citrate is supposed to help dissolve uric acid stones, would taking the potassium citrate helping to dissolve the stones have increased the uric acid urine resulting in the high 851 test result and the super saturation high reading of 4.77 ? Simply, could taking the potassium citrate for 19 days before the 24 hour urine collection test have contributed to the high level test results? I appreciate your response as I await my visit to the nephrologist.

    Reply
    • Fredric Coe, MD

      Hi Emmett, Great questions! Let me presume the stone is pure uric acid. The potassium citrate is the ideal treatment. Although you do not give it, the urine pH controls uric acid crystallization to such an extent nothing else really matters. When you raise the pH, urine uric acid often rises, because it had been crystallizing before – when you were making stones – because the urine pH was too low. The sodium acid urate supersaturation can be ignored in your case as it has to do with other settings. The high urine sodium reflects your very high sodium intake – over three times the recommended upper limit for the US. Urine sodium is what we have eaten, no other sources. As for the oxalate, there is some in vitro conversion of vitamin C to oxalate especially when urine pH is high, so I suppose that could have happened. YOu may have a low calcium diet – a very bad idea – which will raise urine oxalate, or just eat a lot of oxalate. It is not mainly the potassium citrate. As I said, the supersaturation with respect to sodium acid urate is irrelevant to you. So, if the pH is above 6, the main supersaturation you care about, for uric acid, will be below 1; if not, higher urine volume and a bit more potassium citrate will do. It is a cure for uric acid stones. Regards, Fred Coe

      Reply
  55. karen motlow

    Dear Dr. Coe – thank you for your informative article. you mention re: potassium citrate – “The pills can be costly, and there are alternatives to the expensive forms of this supplement. Some alternatives are simple beverages.” what might those beverages be? thank you for your time.

    Reply
    • karen motlow

      dr Coe –
      i read about drinking Crystal Lite! ugh. i drink no sodas. i do have a meyer lemon tree though. i drink coffee, tea (all varieties), some grapefruit and carrot juices and the occasional glass of champagne. drinking hard liquors seems to exacerbate my gout.

      Reply
      • Fredric Coe, MD

        Hi Karen, I guess you read the article and found Crystal Lite. There are other beverages in the table as well. Lemons are too irregular to use as a medication. The juices are filled with sugar and add calories. In the article ‘A thirst for Variety’ Jill Harris goes through a lot more beverage classes. Between that article and the one on the cost of potassium citrate you know all I do. Regards, Fred Coe

        Reply
    • Fredric Coe, MD

      Hi Karen, In the article on the price of potassium citrate we put in all we knew about alternatives. Subsequently many commentators have added valuable alternatives. Of the beverages, they are listed in the article and Crystal Lyte does win the prize. Regards, Fred Coe

      Reply
  56. Rudy Watz

    Hi Dr. Coe,
    I’ve had KSs for over forty years and they have been analyzed as oxalate. Four months ago my doctor at NYU put me on Four 1080 mg Potasium Citrate regimen. I currently don’t have any stone pain that i’m aware of. I take two pills at night after dinner with my other pills and two in the morning on rising, again with my regular pills. Later in the morning, approximately thfree hours after the pils wer taken, I had a bowel movement, and lo and ehold floating on top wer two of the pills. Yes, I picked them up and they seemed basically intact.
    Any thought before I go back to my doctor, who meantime has moved on to Columbia Hosp.
    Thank you in advance for any information you may be able to provide.
    RW

    Reply
    • Fredric Coe, MD

      Hi Rudy, Many people have observed this, and I understand that what you are seeing is simply the wax matrix that once held the potassium citrate and that the potassium citrate itself has been leached out and absorbed. Ask your physician to look at the changes in your urine chemistry with treatment, and be sure you are actually absorbing the Drug. Expected changes between before and during treatment: With treatment urine potassium and pH will rise, the difference between urine sulfate and ammonium ions will fall. Urine citrate may rise, but that is not so predictable. Regards, Fred Coe

      Reply
      • Rudy Watz

        Thank you very much for being so responsive Dr. Coe.

        Reply
        • Fredric Coe, MD

          Hi Chris, I do not know; John Asplin analyzed the pure lemonade, and not the sugar free. From your note I would doubt they are the same. One liter of the pure lemonade is 20 mEq of potassium citrate, so it will be more than your tablets. Fred Coe

          Reply
  57. Scot Standke

    My wife has been battling recurring stones for the better part of 15 years, this time they are so large, her Dr told me that he has never seen a case so bad. I started researching natural help and stumbled upon calcium citrate. Why has her Dr not brought up this option before? Why did we have to find this out on our own? I’m rather upset about this. She has endured at least a dozen surgeries and/or lithotripsy procedures so far.

    Her latest bought is with calcium phosphate stones, but I believe earlier stones were calcium phosphate but I’m not 100% sure about that.

    We had to bring up the 24 hour urine collection to her Dr as well. Again, why didn’t he tell us about this say, 5-10 occurrences ago? Hopefully this will give us a starting point.

    What would be your recommendations in the 2-3 week interim here?

    Thank you.

    Reply
    • Scot Standke

      her earlier stones were oxalate, sorry about that and again I’m not 100% sure on that.

      Reply
    • Fredric Coe, MD

      Hi Scot, Calcium phosphate stones are harder to prevent than calcium oxalate, more numerous, too. Calcium citrate is not a treatment for stone prevention; potassium citrate is the medication in the articles. For calcium phosphate stones, potassium citrate is as yet an unproven treatment. As the article points out this agent makes the urine more alkaline which would raise supersaturation for calcium phosphates. Given her 24 hour urine studies, you need to look for the cause of her stones. Stones are made of crystals, crystals follow the laws of physics, so there is always a cause in the urine chemistries. Usually the urine pH will be too high and the urine calcium high as well from idiopathic hypercalciuria or perhaps another cause of hypercalciuria. Prevention is always possible and usually a lot more simple than surgery. Take a look at the articles I linked for you. Fred Coe

      Reply
  58. Dr. Ken Goldstein

    A most interesting article, Dr. Coe. I researched why I was getting huge oxalate stones, several times a year, & seven years ago, began taking 10 MEQ KCit three times a day, & have not had an oxalate stone since. However, I had an emergency cholecystectomy in 2013, & have started having gout episodes, including tophi. My bloodwork indicates borderline hyperuricemia (8.0-8.4 mg/dL), & I have been taking 0.6 mg Colcrys QAD, which leaves me symptom-free, except for tophi. I have no signs of RA (I’m a martial arts instructor), & I am wondering why my KCit has not mitigated the gout. Of course my loss of one kidney to a papilloma 6 years ago does confuse the issue a bit. My PCP & Rheumatologist are scratching their heads. Any ideas or suggestions?

    Reply
    • Fredric Coe, MD

      Hi Ken, I am not surprized that K Cit has prevented CaOx stones. The two reasonable trials were pretty convincing. Your gout is from NaHUrate crystals, and I would not have expected K Cit to be of much help there. I have had several patients tell me K Cit was associated with worse gout attacks and I cannot imagine a reason for that, either. Loss of the one kidney will surely worsen risk of gout because of a reduction of urate clearance. Is everyone sure it is gout – not calcium pyrophosphate crystals – pseudogout? Regards, Fred

      Reply
  59. Laurie

    I was wondering about the citrate affecting glucose intake and metabolism. Does it in any way lead to problems with diabetes? I am hesitant to take it on a regular basis … possibly the rest of my life, however your article gives me some hope that it is not all bad for my body. I have MSK and we are trying to decrease my stone formation.

    Reply
    • Fredric Coe, MD

      Hi Laurie, I know of no reason why potassium citrate should worsen glucose tolerance or risk of diabetes. Potassium itself is somewhat low in our present diets compared with what we appear to have eaten during evolutionary time. Citrate is metabolized to bicarbonate in the liver and kidney and seems to simply neutralize the daily acid load from foods. Although no one ever knows for sure in medicine, this particular agent should be pretty safe. Regards, Fred Coe

      Reply
  60. Lisa

    9 month’s ago had a kidney stone as big a nichel they litho broke up the stone having stones every day for 9 month’s taking potassium citrate pills stop my right kidney. Please make them stop

    Reply
    • Fredric Coe, MD

      Hi Lisa, I am not clear about all that has happened. Certainly your physicians have analysed that stone, and I imagine they are trying to prevent more. If the potassium citrate is not working, let them know so they can find an alternative for you. Above all drink a lot, at least three liters a day of fluids. Regards, Fred Coe

      Reply
  61. Celia Mac Donald

    Hi Fredric, it’s me again! Obviously all the chemistry involved in kidney function, absorption, excretion and reabsorption is diffucult for me to understand. although I do understand the importance of the effects potassium citrate has on increasing alkaline urine, preventing cystalization thus stone formations, but I have just one question. One of our members today posted about just recently starting potassium citrate treatment, and is now noticing white shards, gravel in the urine. In your opinion, besides increasing urine pH, binding with calcium, decreasing crystalization thus preventing stones, could it possibly help to dissolve calcifications? In nephrocalinosis and MSK for example? Thank you!

    Reply
    • Fredric Coe, MD

      Hi Celia. I believe the urine pH has risen, urine supersaturation with respect to calcium phosphate has risen with the pH, and she is forming de novo crystals of calcium phosphate. Potassium citrate is a fraught treatment for calcium phosphate stone formers, especially those with hypercalciuria. It is a race between two opposing forces: High pH and high CaP SS against the effects of the supplement to lower urine calcium, bind calcium, and inhibit crystal formation. I think this person lost: Crystals mean the balance is not right. Higher fluids, perhaps a lower dose, perhaps attention to her urine calcium. I would not rest content with the soothing but unlikely idea that stones are dissolving. The key response is to let the prescribing physician know, who will be in the best position to decide what is the best course of action here. I may have some expertise, but only the responsible physician can really be sure to take the right action. Warmest regards, Fred Coe

      Reply
  62. Jake Gracz

    Dr. Coe, Thanks a lot for this very interesting article. I’ve calcium oxalate stones since 7 years, gout, hypertension and higher level of blood uric acid. From my research I’ve realized that all these issues are caused by my diet/blood acidity. I don’t really eat too much of meat and purines, however I’m not a vegetarian either and getting gout attack a few times a year. I’m very interested in starting with potassium citrate (already did) in proper quantities: 1 gram 3 x day, so perhaps I will be able to neutralize my diet’s acidity. However I’m not sure if I understand that correctly: is using potassium citrate going to lower my blood uric acid levels? or perhaps potassium citrate affects only urine PH, and citrate levels. Do you think that potassium citrate can be effective in decreasing my blood uric acid levels? Thanks again, J.G.

    Reply
    • Fredric Coe, MD

      Hi Jake, I guess your stones are calcium oxalate, and do not contain uric acid. Potassium citrate will increase your urine pH and in that way prevent uric acid stones. It will increase urine citrate and citrate can help prevent calcium oxalate stones by binding calcium and by inhibiting calcium crystal formation. The drug will not alter serum uric acid. That you have gout and high blood pressure gets me to ask if your blood glucose is always normal or a bit high, and likewise in your 24 hour urines is your citrate really low or high; likewise, what is your 24 hour urine calcium? All these factors make a difference to answering your question. Regards, Fred Coe

      Reply
      • Jake G.

        Dr. Coe, Thank you very much for your explanation. My recent 24 hour urine (with acid) and with no acid tests came out in range (around 2.5 L in volume). The only result that is above is serum uric acid. In the recent past I’ve had a little of triglyceride increase above normal range, that’s all. MRI of abdomen is all good except kidney simple cists, one larger 5cm (Bosniak II).
        I’ve observed that my hypertension fluctuates seemingly without any reason, sometimes normal other times high. Perhaps it is relevant to fluctuation of my serum uric acid that can affect that. I was told that changes in my diet (fairly difficult to achieve since I already eat (almost) only “good stuff”) and increased water intake would help with serum uric acid. Hence my question, rather then having “mostly greens” diet, how can I affect my serum uric acid (without allopurinol), by way of supplements? Is there anything else that can be added to a diet for that very reason or genetics and diet only can regulate that? Cheers, J.G.

        Reply
        • Fredric Coe, MD

          Hi Jake, You are really speaking about the management of gout as the serum uric acid level itself is not the problem but that high levels can result in crystallization of urate salts in joint fluid with acute arthritis. How your gout is managed is separate from stones, and really needs to be overseen by your personal physician. Likewise, high blood pressure is a serious issue and is treated with weight loss, aerobic exercise, reduced sodium intake and medications as needed. That, too, is the work of your personal physicians. No amount of water will itself lower serum uric acid that I know about, although reducing purine intake – purines come from the breakdown of DNA and RNA so foods with cell nuclei provide the substrate for uric acid (meats, some bean products) – is of modest help. Regards Fred Coe

          Reply
  63. Jane Richard

    Dr. Coe, I thoroughly enjoyed your exemplary article. I too have DRTA. Potassium citrate was not helpful. After my trial with it, we did another 24 hours urine collection and just as my team suspected, my citrate levels were “in the toilet.” My nephrologist has moved on and no one else seems to know what to do. I continue to deteriorate…well…only in a physical sense…doing just great otherwise. What next? Be well. Peace, Jane R.

    Reply
    • Fredric Coe, MD

      Dear Jane, I presume you are making more stones, and I guess they must be calcium phosphate stones. While you may have low urine citrate and benefit from potassium citrate to raise the urine citrate, basic principles of treatment are the same for you as for everyone else. Your urine volume should be as high as possible, certainly 3 liters a day – if you are indeed making new stones on a regular basis. Your urine calcium excretion should be below 200 mg daily. I suspect what you meant by the potassium citrate being not helpful is that stones continued; with enough water and attention to urine calcium stones should stop forming at a high rate; whether potassium citrate is ideal or not depends on other issues like the pH of your urine and exactly what your stones have been made of. Regards, Fred Coe

      Reply
  64. Fredric Coe, MD

    Dear Dr Unikowski, thank you for these excellent comments and questions.

    You are correct that each 10 mEq tablet contains 10 mEq of potassium and therefore there are 10 mEq of base equivalents.

    It works this way.

    Citrate is a trivalent anion molecule. When taken, the citrate enters the enteric venous circulation and is metabolized in the liver as citric acid. In order to take up the citrate as citric acid, protons must come from the hepatic blood thereby producing bicarbonate: For each proton removed from the bicarbonate buffer system of the blood, a new bicarbonate is produced via simple shifts of equilibrium, from carbonic acid and ultimately from dissolved carbon dioxide gas. The citric acid is metabolized so that none of its acidic metabolites re-enters the blood, with the result that one obtains 3 bicarbonate molecules from a single molecule of trivalent citrate. The pills give the mole equivalents, and one bicarbonate is produced for each equivalent.

    You are perceptive about the citric acid cycle. Protons are produced and used to create a proton gradient which transfers energy to produce ATP. The protons do not get out of mitochondria to affect blood pH.

    Warm regards, Fred Coe

    Reply
  65. Trish McClain

    Dr. Coe,
    Thank you so much for this. I have had dRTA for 50 years in March or April. I have had these pills prescribed and have trouble being compliant… I have to force myself . I have a better understanding of the nephrons and how the kidney works. Since my stones are not primarily calcium oxalate, I wonder how much good the pills do. I know I have to have a 24 urine test and other lab work to determine this. I know that these pills are the best science has to offer for my disease. I trust my doctors and will have to become compliant.

    I probably will have some stones removed as a preventative treatment to improve kidney function later this year. A doctor called this debulking my kidneys. I know not all urologists believe in this. I also found out the hard way that my stones are called “difficult stones” and urologists who have the skill and experience to treat me are few and far between. I had help from some other medical professionals who taught me things I never needed to know until 2007.

    I enjoy this web site and look foreword to reading everything I can. I wish I had taken more science classes in college so this is easier to figure out. I know you are writing this for lay people, and not other doctors, residents and medical professionals. Thanks

    Trish

    Reply
    • Fredric Coe, MD

      Dear Trish, Since you have distal renal tubular acidosis, your stones are most likely calcium phosphate. This disease reduces the ability of the kidneys to remove acid loads from diet, so potassium citrate is ideal. It neutralizes the diet acid load and corrects the acidic condition of the blood. I would hope it has reduced stone formation, as well. If it has not done so, perhaps your physicians might want to consider additional measures. Best, Fred Coe

      Reply
  66. Fredric Coe, MD

    IF you do not have any reason for magnesium deficiency – for example some drugs cause it – there is no special proven value to magnesium supplements. Brief trials have given ambiguous results so far. The generic pill should do as well as the name brand as best we know.

    Reply
  67. Sharon Jusick

    My husband passed your article on to me to decipher what it could mean to him because he has kidney stones. I’m sorry to say this article is far too technical for me so I have no answer for him. I may try looking up potassium citrate on line and see if I can find a simpler explanation because citrate may have some indications for my husband.

    Reply
    • Fredric Coe, MD

      Dear Mrs Jusick,

      Thank you so much for your thoughtful comment. In it you sum up the dilemma of medicine on the web and point to where a possible solution might be found. The dilemma is the unavoidable tension between between the story and the details. Without a ruling story the details become unusable; without its details the story becomes untrue. It is precisely here we find the reason why physicians need so much education as they do, and why the problem of time haunts the practice of medicine right now.

      One way I can help you is to point out the other articles on the site. The only evidence potassium citrate works is from the trials. Take a look: This is really all anyone has to go on. The pills work exactly for those they were tried on. The pills can be costly, and there are alternatives to the expensive forms of this supplement. Some alternatives are simple beverages.

      Other articles fill in around what citrate does. It binds calcium in the urine, which helps prevent calcium stones. It inhibits stone crystals from forming and growing. Throughout is the problem of what kind of stones we want to prevent. Uric acid stones are completely prevented by citrate, calcium oxalate stones are main ones in the trials, and are reduced. Calcium phosphate stones are an open issue, as the drug may be good or bad. The need for stone analysis is therefore paramount.

      The big article that has rightly set you wondering where to find useful information takes us into the reality of the drug, and is meant as the end of the story, not where one would start. So you have shown me a need to add something on this site – a guide to wayfarers, an overview, and there is now so much about citrate already here I should have written one before.

      Take a look at the links I have put out for you, and see if your husband seems a proper candidate. But – awful word – physicians do have a key role. Wise patients educate themselves; the wisest of all then seek counsel. Regards, Fred Coe

      Reply

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