I do not know if Edvard Munch (1863 – 1944) had Lot’s wife in mind, but I do and thought this an apt image.

She crystallized, perhaps into calcium carbonate, hence my putting her here at the beginning of our sojourn into the vast territories of calcium metabolism and the hypercalciuric states. If I were to single out one condition that dominates stone disease prevention because of sheer commonness and reliable means of treatment it would be this one.

I have put off the crucial topic of hypercalciuria for the first year of this site because I wanted to build a proper foundation.

We now have good materials about stones and stone crystals, supersaturation, and certain critical treatments such as potassium citrate and high fluid intake.

It is time to tackle the problem of high urine calcium itself, what happens when it is high, why it might be high, what levels pose stone risk, and how it is best treated so far as we know.

This article lays out the relationships between urine calcium and stone risk, names the important causes of high urine calcium in stone forming people, and the other problems high urine calcium may be related to.

It is an introduction: Long, but brief in comparison to what is a major component of stone disease and its clinical management.

What is Hypercalciuria?

Stone Risk

To me the most immediate definition is about stones: At what level of urine calcium is the risk of new stone onset increased?

The best information to date arises from long term longitudinal data contributed by two cohorts of nurses and one of physicians exploited by Dr. Gary Curhan. In each cohort, some people became stone formers, and most did not. Gary obtained 24 hour urines in a cross section from all three cohorts, and was able to relate the level of urine calcium excretion to the risk of forming stones.

PQ RISK VS URINE CALCIUM LOW AND MEAN OVERPLOTTED.jpgAlong the horizontal axis urine calcium excretions are groups into 6 bins; above each bin the relative risk of becoming a stone former is presented for the two nurse cohorts (all women, and in red bars) and the physician cohort (all men and in blue bars). The dashed line is at 1, meaning the baseline of risk for the population which was at taken at <100 mg/day of urine calcium loss.

The relative risks are given in the manuscript as an average (mean) value and an upper and lower 95% confidence limit. But I am showing only the lower 95% confidence limit (solid bars) and means (lighter bars).

For example, in the 100-149 bin the mean relative risk for the first of the two female (red) cohorts is 1.26 (plotted up from 1 as a light bar), the lower limit is 0.84 (plotted down from 1 in a solid red bar) and the upper limit is 1.91 (not plotted).

I am after a measure of risk that is robust: In which bin is it very likely that risk is increased above the 100 mg/day baseline?

For me, that is when the lower limit for the relative risk is above 1. 

For example, the value of the lower 95% risk confidence limit of the 100-149 bin, in the first of the two nurse cohorts – 0.84 – does not connote a high likelihood of significant risk compared to 100 mg/day of urine calcium.

On the other hand, risk is very likely present above 200 mg/day of urine calcium, because the lower 95% limit is above 1 in all three cohorts. Of interest, women and men do not seem to differ, so this one criterion applies to both sexes equally.

Also of interest and great importance, there is a dose response.

Higher and higher urine calcium levels are associated with higher and higher relative risk. This is good supportive evidence of a causal connection and best seen by the position of the means which are at the tops of the bars..

The direction of causality is not determinable from observation, but I vote for higher urine calcium causing stones not that being a stone former somehow raised urine calcium.

My vote is because of the other science.

This site has belabored the point that supersaturation drives crystallization, and stones are made of crystals. In preparation for this new series of articles on urine calcium I have gathered the main articles on the stones themselves and on supersaturation into a pair of ‘walking tours’ which present them in context and with with commentary. These are the foundational articles upon which the effects of urine calcium and other urine constituents can be assembled to produce a reliable picture of how stones form and how they can be prevented.

Here, I simply note that higher urine calcium loss will increase average urine calcium concentration for any given urine flow rate, and higher calcium concentrations will in general produce higher SS values for calcium phosphate and calcium oxalate and therefore higher risk of stones. So hypercalciuria, to me, and for good reasons, is almost certainly a cause of calcium stones via increase of SS which is the prime measure of the energy that drives crystallization.

Upper End of the Normal Range

A valid and alternative definition of hypercalciuria is that it consists in very high urine calcium excretion, and a way to gauge the meaning of ‘very high’ would be values at the upper end of the normal range. This idea of the ‘upper end’ is usually taken as above the upper 95% of values encountered in surveys of people without known diseases.

The Curhan data actually give a reasonable measure of this ‘upper end’ from the means and 95% limits of the non stone formers in the three cohorts. The lower dot marks the position of the lower 95th percentile of bar plot for calcium limitsurine calcium for the two nurse cohorts and the physician cohort. The upper dot gives the upper 95th percentile (two standard deviations above the mean for those technically inclined). The intervening bars are for visual effect.

For those who want to study hypercalciuria, as an example, and want a reliable gauge of who is ‘really high’ the three figures are 374 372 and 351 mg/day for the three groups.

Older Conventions

Using smaller and less well selected populations, many investigators have derived somewhat different upper limits for defining hypercalciuria. For example urine calcium excretions above 250 mg/day or above 4 mg/kg body weight are common as in this typical kind of research publication. In our own reviews we have frequently used 250 mg/day for women, 300 mg/day in men, and 4 mg/kg body weight either sex as upper limits to define hypercalciuria.


I think that the Curhan values are ideal for clinical practice. People with calcium stones and urine calcium levels above 200 mg/day have increased risk from their urine calcium and one aspect of their treatment can be to reduce urine calcium.

That is to say, physicians look at all possible factors that may be increasing risk in a patient, sort them out and select for treatment those most promising and practical to treat. Among them will often be urine calcium and Curhan has given us good targets and criteria.

For research, I am more flexible. Strictly speaking the 95% upper limits are a kind of ideal, but if you want to understand mechanisms that raise urine calcium one might be better served by selecting cohorts with a range from high normal to very high. These are research design decisions, and all I mean to say here is we have decent ideas about normal ranges and stone risk, and it is possible from them to derive appropriate approaches to clinical research on hypercalciuria.

Diseases That Cause Hypercalciuria in Stone Formers

Let me be clear about goals here. Each of these diseases will get its own articles, or perhaps many articles, so this is not meant to be a proper exposition but merely an introduction.

For this reason referencing is light and I mainly make assertions which are commonplace and can be found in any textbook or review article. When I get to the diseases one by one I hope to offer considerably more than is commonplace.

Primary hyperparathyroidism (PHPT)

About 3 – 5% of calcium stone formers have this curable disease, on average, so its detection is crucial for proper patient care. As a reference I have used my own publication because it contrasts patients with this disease to ordinary stone formers, is available as a free pdf, and, perhaps, because I wrote it.

One or more of the parathyroid glands enlarges and produces an excess of parathyroid hormone (PTH). PTH signals kidney cells to retain calcium by reabsorbing a higher fraction of calcium that is filtered by the glomeruli. It stimulates production of the active form of vitamin D (calcitriol) and that in turn increases the efficiency of GI absorption of calcium from foods. Finally PTH increases bone turnover so more calcium than normal leaves the bone and can be lost in the urine.

The increased bone calcium loss and increased GI calcium absorption are balanced by increased urine calcium losses, and these can be very impressive. The high urine calcium losses raise urine supersaturation with respect to calcium oxalate and calcium phosphate so stone risk rises and patients with this disease not uncommonly present themselves as stone formers.

High rates of mineral loss from bone cause bone mineral depletion, and bone disease is well known to occur. If the disease is cured in a timely way bone healing is expected.

The action of PTH to increase the fraction of filtered calcium that is reabsorbed causes blood calcium to rise. The increase is often modest.

Being rarely malignant, the enlarged parathyroid glands can be removed surgically with expectation of a cure, so this disease is a curable cause of kidney stones and bone disease.

The diagnosis depends upon finding high urine calcium excretion, a serum calcium concentration above normal for the laboratory making the measurement, and a serum PTH value which is not suppressed below the normal range.

However, there are a few cautions that must be considered always. Even if everything I have just said is true, there are artifacts that lead to mistakes in diagnosis and could lead to unnecessary surgery. All thiazide type diuretics can raise serum calcium, so testing needs to be done after 2 weeks off the drug. Lithium can raise both serum calcium, serum PTH and even urine calcium, so is a real fooler. Hyperthyroidism, including that induced by too much thyroid hormone replacement, can raise serum and urine calcium although it does suppress serum PTH. The serum for PTH must be the one for the calcium – same blood draw for both, and must be drawn fasting overnight. 

The relationship between PTH and serum calcium is often misunderstood. The calcium balance systems are elaborate and tend to be self regulating, so increased PTH secretion leads to increases in serum calcium and calcitriol both of which, through negative feedback on the glands, bring PTH down toward or even to normal, but never below normal. Therefore PHPT is diagnosed when the serum calcium is above normal and the PTH is not below normal.

Here are the serum and urine calcium values from the PHPT cases in our publication – all proven surgically – shown in large dots, normal people (medium dots) and thousands of points from stone formers without any systemic diseasephpt two plot of serum urine calcium before and after treatment – fine spray of tiny dots (common stone formers). The vertical dashed lines are the normal range for blood calcium in our kidney stone laboratory, the horizontal line is just below the level where stone risk from urine calcium begins (200 mg/day).

The patients all had serum calcium values above normal but many were just slightly high. Urine calcium was a lot higher than in ordinary stone formers, but even in those the plume of fine dots rose far above 200 mg/day. Note that some normal people had values above 200 mg/day.

After surgical cure (right panel) the PHPT cases, normals, and treated common stone formers who had no systemic disease all contracted into a small region, but not a few urine calcium values were above the fateful 200 mg/day limit still.

The curves outside the boxes show the distributions; see how the hyperparathyroidism points (dashed lines) spread out far above those for normals and ordinary stone formers, then fall back with surgical cure.

Normocalcemic Primary Hyperparathyroidism

Properly speaking this would be high urine calcium excretion, normal blood calcium, and reasons to think that an abnormality of parathyroid gland function was responsible for the high urine calcium – which is the only abnormality. One such reason could be an elevated level of serum PTH, and such levels are encountered from time to time. Another could be blurring of the true upper limit for serum calcium; not all laboratories are equally crisp. A third could be, and this is speculative, that along the course of PHPT glands might lose their normal CaSR responsiveness, so that PTH levels are no longer down regulated normally by serum calcium. In another article I will explore this problem. Right now, I believe it is wiser to wait for hypercalcemia before committing to neck surgery in hopes of cure and treat the hypercalciuria as if it were idiopathic hypercalciuria – see below. PHPT will ultimately declare itself in most cases. The reference in the link above is supportive of my suggestions because the authors expect elevated serum calcium in PHPT, as I do.

Secondary Hyperparathyroidism

Being so caught up in the maintenance of a normal serum calcium, the parathyroid glands will react to any threat with increased or decreased PTH secretion as required to restore that normal value. Low calcium diet, vitamin D deficiency, GI diseases with calcium malabsorption for any reason, chronic kidney disease with its odd form of calcium aberrations, all these will and do cause increase of PTH secretion and raised serum PTH levels. None of these are hypercalcemic states, and most have a low urine calcium loss. Stones may be present but for reasons other than parathyroid abnormalities, and often other than level of urine calcium. For example, acid urine pH from kidney disease can cause uric acid stones; high urine oxalate from bowel disease can cause calcium oxalate stones. All I mean to say here is that isolated increase of serum PTH with low or even normal urine calcium and normal or low serum calcium levels are usually not an occasion for parathyroidectomy, but call for a diagnosis of their own. As I have by said to excess, this is an issue that deserves more than an introduction. The link for normocalcemic primary hyperparathyroidism is useful for this topic and the one below.

Familial Hypocalciuric Hypercalcemia (FHH)

High serum calcium with low urine calcium excretion – below 100 mg/day is common – is almost never primary hyperparathyroidism but rather a mutation of the PT gland CaSR that raises its sensitivity so serum calcium can be low, serum PTH normal, and urine calcium quite low. When FHH patients have stones the stones are not due to high urine calcium but some other cause, and most importantly parathyroid surgery is a mistake.


In my long experience I have seen far less than 1% of calcium stone formers present with this condition. A reputable source of information about Sarcoidosis fails to mention kidney stones so far as I could see.

Briefly, sarcoidosis is a disorder of the immune system and the cells which proliferate and enlarge lymph nodes, liver, spleen and other tissues produce calcitriol. So the physiology is that of unbalanced high calcitriol production.

As I have mentioned above, calcitriol increases GI calcium absorption, so food calcium entry into the blood increases. I have not mentioned but say now that calcitriol increases net bone mineral losses mainly by reducing bone production. Calcitriol is a steroid hormone and like many steroids acts on the nuclei of cells. It acts on parathyroid cells to shut down production of PTH so tubule reabsorption of filtered calcium is reduced as compared to primary hyperparathyroidism.

The increases in bone mineral loss and GI calcium absorption raise urine calcium excretion as in hyperparathyroidism. Because PTH is suppressed below normal, serum calcium may not rise or when it does so rises only slightly at first.

This means that in many instances suppressed serum PTH may be the only laboratory clue to sarcoidosis as a cause of hypercalciuria and stones. Clinically sarcoidosis is often diagnosed from its signs and symptoms, as noted in the reference from the National Heart and Lung institute. I have had cases which I diagnosed de novo being without obvious signs otherwise because of suppressed PTH with very high urine calcium and even elevated serum calcium.

Serum calcium rises when the flows of calcium from bone and GI absorption are very marked or when the efficiency of renal calcium removal falls.

This latter can occur because of calcium itself. It can reduce water and salt conservation and therefore reduce the blood volume and therefore filtration. Any reduction will tend to increase serum calcium, and increases in serum calcium will reduce filtration and water losses, so a kind of unhappy cycle begins. How calcium acts to reduce calcium reabsorption and that it also acts on filtration itself comes later, not in this article but in those perhaps months from now.

CYP24A1 Deficiency

Vitamin D3 is made in the skin or consumed in pills, and in the liver converted into 25 hydroxy (OH) vitamin D (25(OH)D3). The enzymes responsible for the conversion are called CYP2R1 and CYP27A1.

25(OH)D3 circulates and is itself biologically active, but has a larger fate. Some is converted by kidney cells into 1,25(OH)2D3 (calcitriol for ease of writing and reading) and it is this molecule which more powerfully activates tissue responses in the GI tract, kidneys, bone, and – as already mentioned – parathyroid cells. The enzyme which activates 25(OH)D3 to calcitriol is called CYP27B1.

CYP24A1 is a general purpose inactivator of 25(OH)D3 and calcitriol. It converts the former into inactive molecules in liver. In kidney it converts calcitriol into other inactive molecules. If this degrading enzyme is deficient because of mutations, calcitriol levels increase as in Sarcoidosis, and one gets a similar picture of high urine calcium suppressed serum PTH and high normal to high serum calcium, with kidney stone formation as a consequence of the high urine calcium.

This is a rare condition; in my lifetime of practice I have encountered only 2 cases I know of.

Vitamin D and Calcium Supplement Excess

Certainly, these OTC materials are associated with increases of urine and even serum calcium, especially noted in menopause when their use is prevalent. Causality is not certain. For example, serum 25(OH)2D3 levels between 20 (a low number) and 100 (a high number) were not associated with kidney stones in a small sample of 2012 people. However in a large trial, it appeared that calcium supplements, not food calcium, might be specifically a risk for stones. Calcium supplements might be a particular hazard in people prone to high urine calcium excretion by their genetics.

Distal Renal Tubular Acidosis

I have referenced our paper not out of community pride but because it is the only one which describes the papilla and separates stones from nephrocalcinosis. In a massive surgical practice at the Kidney Stone Center at Indiana University we could find only 5 cases on whom we have operated and obtained research information about the papillary tissues.

All five had the expected reduction of serum bicarbonate with increased serum chloride (no elevated anion gap), alkaline urine pH, and reduced serum potassium – from the obligatory bicarbonate driven kaluresis. Several were hypercalciuric.

RTA from our paper showing stones at pnl and deposits in tissueOf interest, most of the calcifications seen on radiographs were, at surgery, removable stones as opposed to crystals embedded in the renal tissues.

You can tell this from the x rays in the upper two panels. Before percutaneous nephrolithotomy nephrocalcinosis was dramatic; afterwards, few calcifications were present.

In the middle left panel you can see stones in the calyces during surgery, and in the right middle panel you can see the papilla after the stones were taken out. It has some calcifications in the tissue which are plugs in tubules. These plugs are shown by a micro – CT of a tiny biopsy from the papilla (lower left) and in a histological section (lower right)

Stone cultures were positive, perhaps because these patients had many prior procedures for multiple stones.

Deposits of calcium phosphate crystals affected virtually all of the Bellini ducts and though each deposit was small plugging on average replaced much of the papillary tissue. Despite this, kidney function as measured clinically was not remarkably abnormal, and the cortex of the kidneys not remarkably damaged.

In 1980 I presented our only 6 patients with stones and distal RTA out of over 1,000 stone formers to date, of whom 4 were from one family. They all had low bicarbonate and high chloride in their serum, as expected, an alkaline urine pH, and were unable to lower the urine pH with an acid load. Only one was convincingly hypercalciuric.

The essence of dRTA in stone formation is this: By inheritance or because of Sjogren’s syndrome, SLE or other immune mediated diseases the ability of the collecting ducts to lower urine pH normally is diffusely impaired, not in the patchy way one might expect from tubule plugging with crystals but throughout the medulla and papillae. High tubule fluid pH and, when present, hypercalciuria raise supersaturation with respect to calcium phosphate and diffuse plugging occurs with considerable damage and loss of tissue.

Perhaps because of its diffuse nature, dRTA does appear to lead to overall reduction of renal function if enough cases can be found and comparisons made to other forms of stone disease. In this study we had 1,856 patients with stone analyses and renal function, as well kidney function by disease and stone typeas diagnoses, all from our Kidney Stone Prevention Program at University of Chicago – the program that brings you this website.

Measured creatinine clearances are shown as means with standard errors for all stone types on the left, and by diagnostic category on the right. Note that RTA, cystinuria, obesity bypass patients, and a miscellany of other rare disorders (like sarcoidosis and CYP 24A1 defects) shared a distinct reduction of renal function, whereas the common calcium stone types without systemic diseases, and even primary hyperparathyroidism (HPT), had no reduction compared to normal (N). ID refers to idiopathic hypercalciuria, people who have high urine calcium losses without obvious disease.

What does all this mean?

Distal RTA is very uncommon, colorful, easily diagnosed by blood abnormalities, family history of like diseases, and the presence of immune diseases. The label RTA may be misapplied to patients with many calcium phosphate stones because they produce an alkaline urine pH; that is not true RTA, but how phosphate stone formers are.

More Rare Genetic Mutations

These conditions are almost always evident in childhood, very rare, and not what a clinician in the practice of stone prevention expects to encounter. However every once in a while they do show up. The best reading source for all of the genetic hypercalciurias is OMIM, the wonderful online library that is free to everyone. In reading the tiny blurbs below keep in mind that almost no stone formers have these rare diseases, that those who have them present typically as ill children, even infants.

Bartter Syndromes 1-3

These are gene defects of transporters in the thick ascending limbs of the loops of Henle (In case you forgot or never knew the nephron segments this article has a nice picture). There is hypercalciuria but also a picture that resembles lasix use because lasix acts on this segment. Urine losses are high for sodium, potassium, and chloride, and people with these diseases are prone to low blood pressure if they do not get enough sodium replacement. The blood bicarbonate is high, potassium is low.

Bartter Syndrome 5.

There is excessive signalling of the cell surface calcium receptor (CaSR) which produces a lasix like picture but because of the specific problem serum calcium is low and so is serum magnesium. The parathyroid glands are regulated by serum calcium via via the CaSR which is the reason for the low serum calcium level.

Autosomal dominant hypercalciuric hypocalcemia

The CaSR is altered genetically but the specific alteration causes a more marked change in serum calcium than in thick ascending limb function, so the serum potassium and bicarbonate can be normal. These two diseases BS 5 and ADHH are essentially on a spectrum and resemble each other.

Dent Disease 

A genetic mutation in a chloride transporter leads to hypercalciuria and, in males especially, progressive kidney disease. The serum values are normal apart from reduced kidney function.

Medullary Sponge Kidney

Given the nephrocalcinosis and many stones, one might think MSK is a cause of extreme hypercalciuria, but that is not the case. Among our 12 cases that were proven to be MSK during surgery and with papillary biopsy, the average urine calcium was 250 mg/day, just above the Curhan threshold for significant risk. SS values for calcium oxalate averaged 7 and for CaP 1.3, values scarcely above those encountered within normal populations or among common uncomplicated calcium stone formers.

We noticed the same in our much earlier paper on MSK diagnosed in the era of intravenous pyelography. We have already mentioned that among our two MSK series serum levels showed none of the abnormalities of renal tubular acidosis (low bicarbonate and potassium) and urine pH was not high (6.1 in our recent series). Ductal and clinical stones were on average calcium oxalate, not calcium phosphate. We believe the stones form in the stagnant recesses of the collecting duct cysts, abetted by a very modest bias of urine calcium excretion above the normal median value. This is what one expects when supersaturated urine is trapped in place, and supersaturation inevitably expresses itself in gradual crystallization.

Idiopathic Hypercalciuria (IH)

What is It?

In those two words you can find the major preoccupation of my life as a clinical investigator. To the mechanisms responsible for this common abnormality I have devoted my energies since I first began, in 1969.

The reference in the link above is to a review by my colleague Dr. Elaine Worcester whose brilliant research has clarified how the kidney goes about raising the urine calcium in this condition.

IH is not a disease.

It is a stone risk.

And that risk can be ascertained in any given person from the Curhan data in the first figure in this article.

People with high urine calcium excretions who do not have any of the diseases I have mentioned, or any of the others I have not – for pity and reasonable length of this article – mentioned thus far, have hypercalciuria that is ‘idiopathic’, of or from themselves or itself if you wish. They are the top of the mark among normals.

No red or green line separates IH from normal. Just as high blood pressure is a risk factor for stroke and heart disease, hypercalciuria is risk factor for disease – stones and bone disease, which is why I have devoted to its study so much of my life.

Being one end of the human distribution, IH may be found in your next door neighbor, or even your spouse and you would not know unless they are tested. And they will not be tested unless they get stones, or bone disease, or their family members get these diseases. If testing is done nothing will be found but high urine calcium, enigmatic, distinctive yet bland, but bespeaking a complex physiology.

Where Does the Extra Calcium Come From?

In the named diseases, hypercalciuria comes from bone and food calcium, and the same is true for IH. It has to be so, there are no other sources. But IH is not a disease, so we are seeing in IH a magnification of the usual losses of bone and diet calcium in urine, meaning that one or both of these must be increased. Certainly, as I will show in other articles, diet calcium is absorbed more efficiently in IH than in normal people. But bone mineral can be lost in excess, and bone disease can result.

It is for this reason, Dr. David Bushinsky, a distinguished bone and mineral investigator and internationally recognized authority in calcium metabolism, has proposed that every stone clinic is a bone clinic. Stone formers have the potential to develop bone disease if not properly cared for. Though their stones are an immediate reason for attention and a prime focus of care, bone health is also an inescapable concern.

How Can The Urine Calcium Be Lowered?

Toward the lowering of urine calcium and consequent prevention of stones – and preservation of bone mineral – we have some useful trials using thiazide diuretic type drugs. Likewise, some trial evidence favors reduction of diet sodium intake, to which I have alluded without presenting evidence.

Why Are We Ending Here?

It could seem ungracious to end here, without more details about IH or the many named hypercalciuric diseases, but this article is already very long, and what remains is a massive amount of information. I plan for many articles on hypercalciuria, the named diseases that cause it, and especially on IH itself because of its central role in stone disease and because it is a personal interest of mine and of those I work with.

Here I mean merely introductions, as at a cocktail party.

It seems probable to me that in doing right by this topic the articles on this site could double in number, although that may be an overestimate.

Check by from time to time, and you will find more.

Regards, Fred Coe

26 Responses to “HYPERCALCIURIA”

  1. DAVID

    With recurrent bladder stones 60% CAOX-COM and 40% CAOX-COD, what are the likely causes and prevention?

  2. Mousa

    I studied your great article. it was very interesting to me while I’m not in medical field.
    My 3 years and 8 months old girl has recurrent kidney stone ( 3 times up to now after dissolving stones by poly citrate). we tested her TSH, T4,IGFI, 25OH D3 in blood and urine calcium/creatinine ,uric acid/ creatinine . T4(9.63 microg/dL),TSH(0.86 mIU/L) results was normal but she’s got deficient 25OH vitamin D3 ( 21.62 ng/ml in one lab and 17.6 in another lab) and both Calcium/cr(0.31) and uric acid/cr(2.15) are high in urine random test. Our doctor prescribed hydrochlorothiazide and polycitrate latter to dissolve two 1.4 mm stones in her kidney.
    Also Endocrinologist doctor prescribed around 900 IU/day Vitamin D3 supplement(3 types of syrops) .
    I asked from her nephrologist doctor whether vitamin D3 defficiency can lead to higher calcium in her urine or not and he replied there is no relation between the two.
    please help us to find our daughter recurrent stone root cause .

    Best Regard

    • Fredric Coe, MD

      Hi Mousa, It sounds like your daughter has hypercalciuria and the drug is not inappropriate. Did they check the urine oxalate? What were her stones made of? Was she screened for cystinuria? It is important to be sure about everything. If the stones are calcium oxalate they will not dissolve, and probably that is also true for calcium phosphate. As for vitamin D levels, low ones to not play a role in stone production. Regards, Fred Coe

  3. Amy Wallaker

    I have recently been diagnosed with IH non stone former. I have osteopenia according to DEXA scan. Have had hip replacement surgery and cervical neck fusion both orthopedic surgeons said I have soft bones. Had PE after hip replacement surgery currently on warfarin. Dr recommendsaid 25mg of hydroclorothiazide.Apprehensive?

    • Fredric Coe, MD

      Hi Amy, Very low diet sodium and 1200 mg diet calcium would help as would protein intake no higher than 1 gm/kg/day = 24 hour urine PCR gives this figure – and avoidance of sugar loads are a good base. The diuretic – I prefer chlorthalidone 12.5 mg – is on top of that so the dose can be low and potassium wasting minimal. You should consult a bone expert – bone directed drugs may he helpful – outside the scope of this site right now. Regards, Fred Coe

  4. Margaret

    Very informative article…I am an ongoing stone maker and have been doing blood work for the last 5yrs at U of M. Dr’s are baffled because I continually have high PTH which they thought in the beginning was cause from my Vitamin D being so low(9) they put me on prescription vitamin D got my level up and my PTH went up so they no longer will put me on the high dosage of vitamin D. In Dec 15, my urine calcium tested at 501 so they suspected Primary Hyperparathyroidism and sent me for an Ultrasound, Sestamibi Scan and 4D Cat scan all of which were negative. U of M surgeon said thats not uncommon to see negative scans so he ordered 3 consecutive days of blood work testing my ionized calcium, PTH and regular calcium..everything came back normal except my PTH was in the 90’s. My question is does could I possibly have a renal calcium leak and would this cause my PTH to be elevated? Also, could I my body be excreted calcium out through my urine in order to keep my blood levels normal? Thank You for your help.

    • Fredric Coe, MD

      Hi Margaret, So you have a high PTH normal blood calcium levels, and very high urine calcium levels. I also believe your may be an active stone former from what you have said. All idiopathic hypercalciuria has an element of reduced renal calcium reabsorption, so the old idea of a ‘renal leak’ which may have originated with me long ago, no longer matters. What does matter is your treatment. I would think very low sodium diet proved by very low urine sodium would come first – try for 65 meq or 1500 mg. That may bring your urine calcium down. Be sure and maintain a high diet calcium – 1000 mg is ideal. If thiazide is needed one uses it with low sodium. The goal is to lower supersaturation, which will reduce stones. The High PTH is interesting but not my main concern given the normal blood calcium levels – if you have primary hyperparathyroidism under it all that will become obvious with time. Regards, Fred Coe

  5. Trish McClain

    Dr Coe

    I was wondering if you were going to talk about RTA in infants
    And children. I found out infants a year old and under were being diagnosed
    Also the parents did not have kidney disease in their families. I thought RTA
    Was inherited or the result of the conditions you mentioned. I was not aware it was idiopathic. AlSo these parents are being told there children may grow out of it. Is that even possible? They are going to give them Polycitra in an effort to reduce or stop stone formation. I know pediatric nephrology is another subspecialty I don’t understand this . Also these parents want to have more children I would be terrified I would have another child with RTA. Is there. Genetic testing that can help. Them? Is it costly

    Tpl Th’ve Are. Thin Ist

    • Fredric Coe, MD

      Hi Trish, I will be writing about RTA somewhat later on. It is hereditary, in multiple forms, and therefore can begin in childhood. There are forms that can wane with age. RTA affects growth and therefore treatment in children is very important. IN general genetic testing is not widespread but many of the genes are known and can be sampled in individuals on a research basis. Diagnosis of RTA is generally obvious, and the condition is very uncommon. Regards, Fred Coe

  6. Laura Bousada

    Dear Dr. Coe,
    I myself cannot make heads nor tails out of these results. I can read them of course but to write them all out I no longer have the length of concentration that would take. You asked me about a few of my levels so I sent my labs all to Celia and she has written them all down. Some (the first set) are from 2013 and earlier. The second batch from 2014, 2015. I know that my sodium has gone way down but I am missing some values that you asked for.
    Values Chart of 2013:
    13/10/27 24 HR URINE
    Calcium 3.6 mmol/d – ref. <3
    Sodium 108 mmol/d – ref. < 100
    13/10/28 Serum
    K 3.3 mmol/L – ref 3.5-5.1
    CI 102 mmol/L – ref 96-107
    HCO3 31 mmol/L – ref 21-32
    CA ++ 2.28 mmol/L – ref 2.2-2.5
    Na 139 mmol/L – ref 136-145
    pH Urine 7.5
    Volume 24 hr 1.38 L
    Citrate Urine 3.3 mmol/d – ref 0.8-6.0
    CO2 31 mmol/L – ref 21-32
    CA Urine 2.34 mmol/d – ref 2.12-2.52
    Oxalates 287 mmol/d – ref <320
    K 3.4 mmol/d – ref 3.5-5.1
    CA Ionized 1.14 mmol/L – ref 1.15-1.32
    K 3.5 mmol/L – ref 3.5-5.1
    CA 238 mmol/L – ref 2.12-2.52
    CI 100 mmol/L – ref 98-107
    CO2 30 mmol/L – ref 21-32
    AnionGap 8 mmol/L – ref 5-12
    Na 137 mmol/L – ref 136-145
    SO what you have above is all nice and organized by Celia. I hope you will be able to tell me something about this.
    Very Best Wishes
    Laura Bousada

    • Fredric Coe, MD

      Dear Laura, Thank you for sharing your information so others can perhaps benefit from thinking about the implications of the results. Let me make clear that my analysis is strictly technical, in that your physicians are responsible for your care and anything I say is from the numbers plus a few facts I know in addition: you are taking amiloride and indapamide and might be taking potassium citrate, and your stones are calcium phosphate – I do not know if the form is apatite or brushite. On 10/27/13 your urine calcium was mildly increased despite your diuretics and well controlled sodium of 108 mmol/day; your blood showed reduced potassium and increased CO2 content because of indapamide and despite amiloride. Calcium was normal. These are common results in treated idiopathic hypercalciuria; the potassium depletion is a problem because it will lower urine citrate. On 9/14/15 the urine pH is very high at 7.4. On 12/7/14, the volume very low at 1.38 liter/day, the blood remains essentially the same, and surprisingly urine citrate molarity and excretion exceeds calcium meaning I suspect you were taking potassium citrate. Urine oxalate is unremarkable. On 2/5/15 the blood is essentially unchanged – calcium is missing a decimal = 2.38 – and the slight reduction of [Ca] is from the metabolic alkalosis – high blood pH – from potassium depletion and diuretics. The urine is not provided. You seem to have a common condition which is being treated in the way I would favor but you are making stones actively, as I understand it. There are no supersaturations, perhaps because your health system does not provide them, but the one pH and the low urine volume make me quite sure your urine is supersaturated with respect to calcium phosphate as brushite. I would think that you would be better served with potassium chloride which might allow the urine pH to fall a bit, and by vastly more water – 3.5 to 4 liters – so that stones can stop. I see no alternatives provided you are indeed still forming stones. The serum potassium should be brought up – it is too low. I am sure your physicians have said all this already and will find my remarks of little value, but if they encourage you to raise your urine volume greatly I suspect stone activity will fall. Fred Coe

  7. Tasha Williamson

    I found this article to be extremely informative. Sadly since being ill my cognitive abilities have suffered so I will need to read it again. I struggle with to high calcium output in my urine and sometimes high in my serum. My PTH is all over the place. The PTH issues and high Urine calcium out put have been on going for a couple years but only recently I have had a couple tests showing higher serum calcium. My nephrologist said he suspects idiopathic but after reading this I’m a little confused. Once again thank you very much for your very informative article and I will be certain to read it again. I have also given my GP the information to join as she was very interested as was the student doctor with her last appt.

    • Fredric Coe, MD

      Dear Tasha, If your serum calcium is elevated above the normal values for the laboratory, and your serum PTH values are not suppressed below normal, and – very importantly, your urine calcium is clearly elevated, and you are NOT on drugs that can raise the serum calcium such as thiazide type diuretic drugs or lithium, then you may well have primary hyperparathyroidism. But if these specific features are not all met, I would not be satisfied with that diagnosis. I imaging your physicians already know all this and are acting in accord with what they know. Whatever the underlying diagnosis, if you are forming new stones, stones not present on prior CT scans, then your urine has too high a supersaturation for you and the supersaturations with respect to the crystals in your stones need to be lower. Regards, Fred Coe

      • Tasha Williamson

        Thank you:) I don’t take any diuretics. They gave me gout. Do other than ranitidine for the terrible heart burn I take pain medication and recently started Synthroid. I’m not a big stone maker. I pass lots of sand and have nephrocalcinosis. I pass larger stones only once or twice a year yet my kidneys are on agony always. I don’t understand. It and wish I could feel better. I appreciate you taking your time to help to educate us. Thank you

        • Fredric Coe, MD

          Dear Tasha, The sand means your urine is supersaturated with respect to the crystals in the sand. Have you had the sand analysed? You should. If diuretics give you gout perhaps the sand is not calcium but uric acid. The latter has an orange color sometimes. Passage of sand can cause kidney pain and back pain, and needs to be stopped. The borderline serum calcium and PTH levels need to be clarified. I would begin by analysing the sand, and I would raise my urine volume a lot until the sand is never present. A target is my favorite of over 3 liters of urine until you have abolished all sand and crystal passage. None of this needs to occur. Crystals are predictable. Has your 24 hour urine chemistry been determined? Best, Fred Coe

  8. Laura Bousada

    Thank you very much for your thoughtful and helpful insights. I believe in my last 24’s my urine levels were low, and am working to get them up daily. I do have potassium citrate at home but will ask doctor if he also thinks perhaps potassium chloride would be better. I understand what you are saying when you say that without clinical knowledge this may be of limited value but it is of great value to me. You are right my doctor did put me on amiloride to help potassium wasting. I do form calcium phosphate and my doctor thinks I am very lithogenic he called it. I do have a very good nephrologist and also urologist. I just appreciate this so much as a confirmation of minds. Thank you again for taking your time and answering in such good detail.

    Best Regards,

  9. Kathleen Tega

    Thank you for the insightful article Dr Coe.

  10. Laura Bousada

    Dear Dr. Coe,
    Thank you for your latest educational and entertaining article on hypercalciuria. I thoroughly enjoyed reading it, and your witty and fun writing style. My I just add that Celia is my sister, and her intelligence and thoughtful inquisitiveness has been a godsend to me and all of us in our MSK group.
    My question is twofold. Does citrate diminish stone crystalization in all types of stone formers’? So even me with calcium phosphate?
    Next, I do not have high urine calcium. But I am hypokalemic, and have high urine pH. I have nephrocalcinosis, and RTA. How is this even possible if I dont even have high urine calcium? I used to but do not any longer. Thank you for this site, these articles and mostly your kind answers.

    • Fredric Coe, MD

      Dear Laura, Well, I guess between you and Celia we have a powerful family force! Citrate has never been tried formally in calcium phosphate stone formers, a matter I have repeatedly brought to the attention of my research colleagues: It is time! But the NIH is not usually willing to spend precious and limited research money on trials, which can be very costly. Industry will not because potassium citrate, though pricey, is a kind of commodity. As for your urine calcium, I gather it is below 200 mg/day, the lower level of risk in the Curhan data I just put up in my last article. Be sure this is true. If it is above 200 mg, an easy way to lower it is reduced sodium – check out your 24 hour urine sodium. Now, the low serum potassium. I gather you are not taking any form of diuretic for stone prevention; all of them reduce potassium levels. If you are not, and your blood level is low, is there enough potassium in your urine – at least 40 mEq/day? If so, you really are wasting potassium. If not, there may be other reasons. All patients with calcium phosphate stones have alkaline urine pH – that is how to make such stones. But RTA is when the blood bicarbonate is below normal and the urine is alkaline – both at the same time. Is your blood bicarbonate low? Ask yourself – and your test results – the answers, and if you like put up another comment with the numbers, so we can try to be helpful. Warm regards to you and Celia, Fred Coe

  11. Celia Mac Donald

    I agree with you Fredric, a massive amount of info but hopefully our MSK members will find the time to read! You list many different causes of hypercalciuria, some of each may be present in our MSK support group members, in particular RTA and autoimmune diseases, also diagnosed with MSK!
    In your paragraph on MSK you say, in your study with 12 patients (we have thousands of MSK members!) “none showed abnormalities of RTA, low potassium or high pH”, although we do have many members with all these lab results, some with very severe hypokalemia! We have both members who make calcium phosphate/brushite stones (which need to be surgically removed) and members who make, not frequent, BUT rapid daily, weekly, monthly calcium oxalate stones. All diagnosed with MSK.
    I have a feeling we are dealing with much much more than MSK as though “just” MSK was an underdiagnosis? Maybe we should be renaming this new disease? With MSK Plus or Hyper MSK? Each patient different, with different symptoms, thus different causes.
    In your paragraph on IH Idiopathic Hypercalciuria, you say “it is not a disease but a stone risk”. How do we know if some of our MSK members suffer from IH? And if they do, have been diagnosed with MSK and nephrocalcinosis, have been making stones for years, have continuous uti’s/kidney infections, IC, hematuria, have been reduced to a very low quality of life due to chronic pain, fatigue, depression, anxiety, reason for which they were forced to give up their jobs, in these cases (so many of them!) I would call it a disease! A very serious one which their doctors are not taking seriously enough! As always, thank you for listening Fredric!

    • Fredric Coe, MD

      Dear Celia, You are a very thoughtful and valuable voice, so thank you for your helpful comments. Of course we have reported few cases of MSK, but these are surgically proven, so we are sure that MSK is present. In that tiny sample we found what we found. Our group has spent the past 15 years – and considerable of your taxpayer dollars via NIH – gradually defining the various types of stone formers using a combination of intra-operative imaging, histology of tiny biopsies, and physiological studies. Brushite stone formers, for example, can have nephrocalcinosis and look like MSK on CT scans; so can RTA. But at surgery they do not have MSK. Accelerated stone formers, with vast numbers of stones, are uncommon but we have reported on them. What I plan to do is gradually write up all of these kinds of stone formers, for everyone who reads this site, with references, as always, and hope that things sort out. That there are so many patients in your group is important because as the site gets more details – it takes a lot of time to write these things up!! – perhaps patients and their doctors will be able to sort themselves out, even contribute to our work, if possible. As for IH, it causes diseases, lot of them, in kidney and bone, but it is itself just one end of the distribution of values found among people. Those with the highest urine calcium losses are prone to develop stones, often severe, nephrocalcinosis, and all of the miseries you have amply documented. But you would be surprised how many normal people have IH and never know it. Strictly speaking, 5% of all people have urine calcium excretions far above 300 mg daily, but only a small fraction get stones. How many get bone disease, and how much IH is part of postmenopausal osteoporosis are presently controversial issues and of research interest. Thank you so much for your thoughtful writing and your contributions to this site. I appreciate both very much. Regards, Fred Coe

  12. Marguerite Galiardo

    I enjoy reading your articles rekidney stone formation. Very informative. Thank you!

    • Fredric Coe, MD

      Dear Marguerite, thank you very much for your comment; it is encouraging that people find this site useful and enjoy it. Best, Fred Coe


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