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.

I want to acknowledge the expert error checking of Dr Yangming Cao (UCSF – Fresno) in the section ‘Why are Potassium Citrate Pills an Alkali Load?’ He corrected a significant error in the original article. 

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?

In the citric acid cycle citrate is metabolized as citric acid, meaning that 3 protons are taken up from blood with each molecule. Removing protons is identical to adding alkali. Typical dosing is about 20 – 40 mEq of potassium salt daily, but the amount can vary widely.

Commercial potassium citrate contains 1080 mg of the compound in a 10 mEq pill. Typically the potassium citrate salts have a potassium on each of the three anion sites on the citrate molecule. The MW of citrate anion is 189.1. Urocit K, a common commercial version, is a crystalline monohydrate salt so it has a MW of 3×39 (for 3 potassium ions) + 189.1 (for citrate) + 18 for the one water molecule, or 324.1 in all. Given 324.1 for 3 mEq of base, the 10 mEq tablet contains 10/3 x 324.1 or 1080 mg.

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.


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 3 protons per molecule metabolized, which is the same as saying it provides 3 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.


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?


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.


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.


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.



  1. Roger Coggan

    Dr. Coe,
    I clicked on Jill Harris’ diet program site and received a letter stating, “Currently, the only type of stones that can be effectively treated with pills are uric acid stones. Potassium citrate pills can, in fact, dissolve this particular type of stone. However, uric acid stones account for only 5-10% of all kidney stones as the vast majority of stones are calcium oxalate. Calcium oxalate stones require a more holistic approach to treatment.” Based upon what I understand from your articles, would you agree with this, and add that potassium citrate may have an important role in inhibiting calcium oxalate kidney stones in that the citrate binds with calcium, thereby inhibiting calcium oxalate kidney stones; but that said, the best course is to first lower sodium and increase calcium, and then focus on the total amount of food oxalates consumed, and then, if necessary fit potassium citrate into the mix?
    Really enjoy your articles!
    Informative and fun!
    Roger Coggan

    • jharris

      Hi Roger,
      I am terribly sorry that perhaps my wording was taken out of context in my email. To be clear, I was simply stating that uric acid stones were the only stone that could be dissolved with the use of a pill, that being potassium citrate. But it is not its only use. Of course, it can be used as an effective treatment in regard to calcium oxalate stones as well. Many patients will ask if calcium oxalate stones can be dissolved and that was my point. They cannot, but uric acid stones can. I am sorry for any confusion.
      Very best,

    • Fredric L Coe, MD

      Hi Roger, Potassium citrate has been used in multiple trials against calcium stones with reasonable success, How it works is probably in part calcium binding, partly inhibition of crystallization. But in the linked article I do make clear that I try to take diet to the best point possible and then add citrate or thiazide as needed. Regards, Fred Coe

  2. Pamela

    Thank you Dr. Coe, both for this informative article and your willingness to interact directly with readers.

    I first had a (calcium oxalate) kidney stone at age 62. I did not (knowingly) pass another stone until I was 67 (also calcium oxalate). At that time, a scan showed that my kidneys harbored perhaps a hundred stones of various sizes.

    After my first scan, I was advised to follow a low-oxalate diet, take calcium citrate supplements and drink lots (!) of water. I did that, from age 62 on, but doing so did not stop the formation of many new stones. (I continued on a high protein diet during those years, which I had begun around age 59.)

    My research led me to ask for a Potassium Citrate prescription; I now take 20 mEq daily. I am also on a low dose diuretic, to reduce the amount of calcium my body dumps into my urine.

    I understand this regimen may help prevent FUTURE stones. However, is there anything more I can do to get rid of the stones I already have?

    Thank you for your guidance and generosity.

  3. Holly

    Hi Dr. Coe, I have had kidney stones since 2002 and have taken potassium citrate pills daily to prevent them. I’ve increased drinking water daily, cut back on eating meat and fish, cut back on coffee, etc. In the past, my Urologist had me take Potassium Citrate 10 MEQ once a day, which helped. Then they had me see a Nephrologist who switched me to only 5 MEQ pill once a day, and in the past year alone, I had more kidney stones than ever. He won’t switch my dose back until my 24- UA collection, which I’m doing this weekend. My concern is, I’m trying to order “extra” pills incase we ever have an earthquake again (Anchorage had a big one Nov 2018), and I’m worried incase I get separated from home and can’t get access to my pills. I’d like to have extra Potassium Citrate supplements on hand with me. But when I tried to order on Amazon, there are SO many brands and variety of doses, so I was wondering what is the reliable place to get supplements at or a certain brand, if you had any in mind? I also bought Chanca Piedra, liquid form, from our whole food store and I only take it when I feel I have a bigger stone and need to pass it. It tastes awful after I dilute it with water, but it worked for me. Now, I’m just trying to make sure I have extra Potassium Citrate pills on hand, incase of emergencies. Thank you! Holly

    • Fredric L Coe, MD

      Hi Holly, 5 mEq of potassium citrate is very low, and not a common dose. Even 10 mEq once a day likewise. I would speak with my physician about why so little. As for Amazon, all pills that contain potassium citrate OTC are low dose, about 3 mEq each. That is because of the potential dangers from potassium. The brands do not matter so much as the content of potassium citrate. But if your physician has limited your intake perhaps you have some medical condition that affects your tolerance for potassium. Since I know nothing about you, I can only suggest that you discuss the matter – of dose and Amazon – with your physician and understand what reasoning governs your present treatment. Regards, Fred Coe

  4. Andre

    Hello Dr. Coe, Thank you for your article and education. I am diagnosed with early-stage ADPKD. I have been reading that potassium citrate and citric acid may slow the progression of cysts. I understand a trial is underway for the use of oxypurinol. If approved it still may prove unaffordable as a preventative treatment, and I’m not sure about the safety of using allopurinol long-term. All considered – my understanding is that tolvaptan may not have a major impact on renal preservation with ADPKD, so I am thinking to seek natural dietary intervention of alkalizers as my long-term treatment plan. Will discuss this further with my nephrologist but tolvaptan aside, a low-plant-based-protein and high water intake have been the advice so far.

    • Fredric L Coe, MD

      Hi Andre, I went over your questions with Dr Arlene Chapman, who is my colleague at the University of Chicago and an expert clinician and scientist in the field of ADPKD. She offers her email address and a willingness to speak with you directly: I would take up her offer as she knows what you want to learn. If you choose rather otherwise, she is willing to tell me some answers to your questions that I can forward, but that seems to me a less ideal course of action. Regards, Fred Coe

      • Andre

        Dr. Coe, That you took the time to make this connection is meaningful to me. Thank you for your kindness. I will contact Dr. Chapman, who is likewise so generous in her offer. My best wishes to you and yours.

  5. Mica

    Thank you for this excellent article. I wish that this info was widely available to healthcare practitioners, as none of my doctors have suggested anything with regards to this intervention. As usual, I have had to rely on my own research to find the solution. I am diabetic (well controlled). I have gout and occasional kidney stones (usually small and easy to pass without much pain) and I have cut back significantly on meat and fructose. Cutting back on fructose is what made the biggest difference for me (the only fructose I was eating was in occasional honey, coconut sugar, and fresh/dried fruit).

    But it’s not enough, because I just got a bout of kidney stones, the worst ever (I’ve peed out 6 in the last 48 hours and more are on the way). So it seems the next step for me is to hydrate WAY more, try to alkalize my urine as much as possible with diet, and also take potassium citrate. I also bought pH strips and will be monitoring my urine at home. I am also not getting a CT due to coronavirus unless the kidneys are shown to be irreversibly stressed.

    1) should I also be concerned about restricting foods high in oxalic acid? I know oxalic acid can also cause kidney stones in combination with calcium. Given that I also have gout, it’s likely that uric acid is the problem, but should I restrict oxalic acid rich foods just in case? I’ve avoided chard, spinach, and rhubarb for years ever since the first stone. I’ve also read that some stones are a combination of uric and oxalic acid?
    2) I am concerned that so many stones have developed all at once. Is this explainable simply by chronic dehydration, high urine pH, and high uric acid level? I did eat more meat and homemade ketchup (high in fructose) than normal last week. Maybe it was a huge load of uric acid that totally overwhelmed the system. This episode has resulted in higher BP and kidney stress, but these are slowly resolving.
    3) How long does it typically take for a uric acid stone of significant size to form? Days, weeks, months?

    Thank you!

    • Fredric L Coe, MD

      Hi Mica, Of highest importance is the nature of the stones. As a diabetic uric acid would be expected. Likewise urine pH would be low – below 5.5 in general. The fact of many stones all at once makes me think uric acid is the true cause. If it is uric acid stones, diet is insufficient and you require supplemental alkali. If the stones are calcium oxalate, perhaps oxalate may matter. If they are calcium phosphate oxalate is a minor thing. Get the stone analysed. A clue, often UA stones are red or red brown. Regards, Fred Coe

  6. Jon Turner

    Out of the blue, I had severe pain in my back on the left side. I’m a 53-year-old male that has never had kidney stones before, but, both my mother and father suffered from uric acid kidney stones. I have been on allopurinol for years for gout. I went to my general practitioner who took Xrays and a urine sample. While difficult to see, they identified two 3mm stones. My urine analysis found a PH of 6. Because of the coronavirus issues, my doctor did not recommend going in for a CT scan and recommended trying to pass them and he gave me a prescription of Flomax and a pain med. While we’re not 100% sure they are uric acid stones–my family history may point in that direction. My question is, with a PH of 6 would I benefit from potassium citrate supplements?

    • Fredric L Coe

      Hi Jon, Yes. The pH was in a single spot sample, whereas 24 hour urine pH may be a lot lower. But despite the virus you can get 24 hour urine testing which is done by mail. Litholink is running, and if your physician orders testing, they send out a collection kit and you mail back a sample. No virus exposure. Why not do that? Regards, Fred Coe

  7. Carol T

    A month ago I had a CT abdominal scan for another issue (found to be clear) but some small kidney stones were seen, the largest of which is 3mm. I have no symptoms and have been drinking a lot of water every day since the finding, hoping to flush them out. The doctor says there is no need for treatment or follow-up unless symptoms emerge. I’d like to try to prevent any further formation and would be very grateful if I could be advised as to whether potassium citrate (or anything else) would be worth taking.

    • Fredric L Coe

      Hi Carol, I have to disagree with your physician – rather rare for me. If you indeed have multiple stones in your kidneys you should be evaluated as to their cause and treatment directed at the cause(s). This is my best summary of what to do. Regards, Fred Coe

  8. Pat Scully

    Thank you for this very interesting article. I recently became interested in supplementing with potassium citrate after listening to a podcast interview by David Asprey (promoter of the Bulletproof ketogenic diet) with the recently deceased Dr. Richard L. Veech. In that interview, Dr. Veech stated that ketosis can precipitate gout because ketosis decreases elimination of uric acid, and Dr. Veech recommended that, if one was on the Keto diet, one should buy potassium citrate to allow the body to secrete uric acid. I recently was on the Keto diet and developed gout in the distal knuckle of a finger. Although I have no significant pain, the knuckle is quite swollen and red. I have no kidney stones that I know of. I have since switched to a more vegetable- and fruit-centric diet and greatly reduced foods with high purine content, but the gouty knuckle remains. I am wondering if that means I still have a high uric acid load and whether supplementing with potassium citrate might cure or reduce the gouty knuckle. Thank you again for your article.

    • Fredric L Coe

      Hi Pat, Measurement of serum uric acid is the easiest way to resolve the gout issue – if it was gout. One cannot know unless crystals were aspirated from the joint and identified as urates. A 24 hour urine will tell you if you produce too much uric acid. As for potassium citrate, it will not affect your present joint. Regards, Fred Coe

  9. Jody

    Hi, Dr. Coe. Let me start by thanking you for all the informative help you’ve made available to the public in regards to kidney stones.
    I am currently dealing with having passed my first stones 80% uric acid 20% oxalate. My 24 hr urine study showed my only problem was with 5.3 ph. I Had been on keto diet for 6 months prior to passing the stone (and still have one parked in other kidney) and really did not eat veges as I should have been, so mostly purines, Nor had i been a big hydrator (tho I am now (96oz a day), and Urologist says to immediately go on potassium citrate for life.
    My question is this. Shouldn’t the doc have waited to see if I went back to a regular diet, with the 96 ounces of water I now drink, to see if the ph would balance out? And then, if ph didn’t rise, to then try a more alkaline diet with the 1/2 cup of lemon juice a day that I read is equal to daily doses of pharmacological therapy (I wont use the artificial sweetner aspartame they use in crystal light, tho I will use the crystal light “Pure” because the sweetner they use in there is stevia, but don’t know if the citric acid count is the same). to see if that would help first before putting me on a med for life?

    • Fredric L Coe

      Hi Jody, Given a uric acid stone you surely have the problem arising from low urine pH. Of course you should try higher urine volume and a more normal diet before committing to potassium citrate. If urine pH remains low on repeat testing, five servings of fruits and veggies is a good idea. If that is no good – and it may be inadequate – lemon juice is not my favorite. The fruit is too acid, and much of the citrate is in the form of citric acid that will not raise urine pH. Crystal light is reasonable. If you do not want it or it is not enough, perhaps you will need only 2 10 mEq K citrate pills a day, which is not bad. But do not leave the pH below 6 as the stones can grow rapidly. Regards, Fred Coe

  10. Viktor

    Hello Dr Coe,
    I just had a 6mm non obstructing Calcium Oxalate kidney stone removed from my ureter thru ureteroscopy. I have another 1mm stone in my other kidney. I had 2 24hr urine samples analyzed by litholink and below are the readings:

    Day one/two results:
    Calcium Oxalate Saturation: 2.27/2.02 Standard range 6-10
    Calcium Phosphate Saturation: 0.14/0.10 Standard range 0.5-2.0
    pH,24Hr,Urine: 5.664/5.594 Standard range 5.8-6.2
    Citrate, Urine: 868/772 Standard range >450mg/24hr
    Calcium, Urine: 172/144 Standard range <250mg/24hr
    Uric Acid, Urine: 604/571 Standard range <800mg/24hr
    Uric Acid Saturation: 0.61/0.65 Standard range 450mg/24hr) and starting Potassium Citrate raises this further will it cause any issues?

    Concern 2) I read online in a medical journal that “Calcium oxalate supersaturation is independent of urine pH, but calcium phosphate supersaturation increases rapidly as urine pH rises from 6 to 7. Calcium oxalate stones form over an initial calcium phosphate layer….”
    Will not increasing my Urine pH using potassium citrate not make me vulnerable to more Calcium Oxalate kidney stones?

    Also, I read Urine pH <6, creates UA stones. Treated with alkali. My Uric Acid (Uric Acid, Urine: 604/571 Standard range <800mg/24hr). My stone was calcium oxalate, do I need potassium citrate?

    Thank you

    • Fredric L Coe

      Hi Victor, Your urine values do not confer risk of calcium oxalate stones. You left off urine oxalate, perhaps that is a problem. At 5 liters of urine volume you have no supersaturations so no stone risk. Since you formed calcium oxalate stones I deduce you have changed diet, fluids etc since having the stones removed, and therefore the labs cannot tell us why they formed. But you know what was present before, and I hope you will avoid that in the future. As for urine pH, it is not relevant for calcium oxalate stones even though they form on plaque. Before, when you were forming stones, I imagine your SS for CaP was above 1, which is more than enough. As for potassium citrate, in your present state why would you? Your urine citrate is high. Just do not go back to what you were. Regards, Fred Coe


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