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

167 Responses to “HYPERCALCIURIA”

  1. Cori LaRocque

    Dear Dr. Coe,
    I am a 56 year old female with osteoporosis and a history of calcium oxalate kidney stones. I first consulted with an endocrinologist for my osteoporosis early in 2016. He had me do a 24h urine collection and found my calcium excretion was too high at 284 mg on a reference range of <=199 mg. He started me on chlorthalidone 25 mg and Potassium CL ER 20 MEQ. Since 2016 I’ve had six 24h urine calcium tests ranging from 190 mg to 258 mg with an average of 221mg. My serum potassium has decreased from a pretreatment level of 4.4 mmol/L (range 3.5 mmol/L to 5.2 mmol/L) to an average value of 3.6 mmol/L despite the potassium supplement and my efforts to increase potassium consumption in foods. In addition, the osteoporosis has worsened significantly with my spinal T-Score going from -1.9 in Oct 2015 to -3.2 in Aug 2019 (-16%) despite concurrent treatment with raloxifene for nearly 2 years.
    My questions are these:
    1 Is potassium chloride the best form of potassium for someone with osteoporosis or would a different form such as citrate would be better?
    2) In a situation with low serum potassium levels, would it be beneficial to lower the chlorthalidone to 12.5 mg or perhaps stop all together? It’s my understanding that low potassium levels can create an acidic environment which would be detrimental to bone health.
    3) I’m trying to follow the high calcium/low sodium diet you outlined for bone mineralization but find it very hard to track the actual sodium consumption I’m getting. Are there lab tests that can be done to determine if I’m achieving the low sodium goal?
    I’m trying to educate myself on this as much as possible and your informative articles have been a blessing to me. Thank you for sharing your wealth of knowledge!
    Best regards,
    Cori L.

    • Fredric L Coe

      Hi Cori, I assume you have idiopathic hypercalciuria, and it is fomenting bone mineral loss. Thiazide is effective in maintaining bone mineral, but only if diet sodium is not high – the only way to know diet sodium is to measure urine sodium, guessing never works. If you have a low urine sodium and decent diet calcium and use chlorthalidone and bone mineral loss progresses you should be taking a bone directed medication. The choice of such medication is beyond this site, but a simple bisphosphonate usually works as a first agent. As for potassium, both the chloride and citrate forms are fine, and the choice depends on the urine citrate and pH. If the citrate is low, potassium citrate may be the better choice, but it will raise urine pH and risk for calcium phosphate stones. Citrate is lowered by potassium depletion, so take enough potassium to raise serum levels to normal for at least several months before making the 24 hour urine measurement. Regards, Fred Coe

      • Cori LaRocque

        Dear Dr. Coe,
        Thank you for your response, it is much appreciated. I will work with my endo to get the potassium levels up to normal and then test the citrate. I had tried alendronate for the OP back in 2017 but had a severe allergic reaction so bisphosphonates are off the table for me which limits the choices significantly. My U24 sodium was 107 mmol/day (range 41-227). If I did the math right that’s 2461 mg of sodium vs. 1500 mg recommended. So I need to address that with dietary changes. I don’t add a lot of salt but I’m thinking a salt substitute is potassium chloride, that would help with reducing sodium and increasing potassium – both of which I need. Thanks again for helping me understand!
        Cori L.

        • Fredric L Coe

          Hi Cori, If your bone mineral falls below a safe level your physicians have a much larger array of medications to stabilize it beyond bisphosphonates. Just be sure to follow up with them and I am sure they will do what is needed to prevent fractures. Potassium chloride salt substitute is not a bad idea so long as the taste is reasonable for you. Regards, Fred Coe

          • Cori LaRocque

            Dr. Coe, Thank you again for your response. I tried the salt substitute and it’s really not too bad. I’m hoping it will help to raise my serum potassium level. I really had no idea how much sodium was in my diet but I see now from reading labels that some foods have a tremendous amount. I’m glad to have a path forward and very much appreciate your help in understanding this complex subject.
            Cori L.

  2. Julie Cole MD

    Hello Dr Coe, I am a patient with osteoporosis and idiopathic hypercalciuria (hx of stones in the past)… I also happen to be a radiologist. In addition, I’ve had a problem with obesity for many years, with many episodes of significant weight loss and weight gain. I’m about to undergo bariatric surgery (sleeve gastrectomy). I have seen many docs for opinions on how to treat my osteoporosis and hypercalciuria; and recommendations have varied from evista to bisphophonates to prolia (as well as thiazides, which I cannot tolerate due to hypokalemia). I’m confused as to best course of treatment; especially since I expect to lose more weight after surgery (hurting my BMD); AND I will have to take PPIs for some period of time after surgery (?hurting my BMD as well). I have sought opinions from nephrologists, endocrinologists, and rheumatologists, from UPenn and Columbia (where I saw John Bilezikian, whom I remember from when I was at P&S). Can you weigh in with any opinion; and/or could you recommend someone who could address BOTH my bone and kidney issues? (PS I also have psoriatic arthritis, on Humira, but I don’t *think* that has any bearing on this problem). THANK YOU. -Julie Cole

    • Fredric L Coe

      Hi Dr Cole, This article on idiopathic hypercalciuria is complex but well within your reach as a physician. The bone disease appears to arise from reduced renal tubule calcium reabsorption and bone mineral lability – some from increased tissue vitamin D effects. High calcium diet coupled with low sodium – 50 – 60 mEq/d is ideal – to increase renal calcium reaborption is the only diet regimen that can bring bone balance to neutral in perimenopausals and by extension – no trials – in IH. Very low doses of thiazide like drugs – I like chlorthalidone 12.5 mg daily – also promote bone mineral retention. Hypokalemia is minimal when diet sodium is low as I mentioned, otherwise it is very annoying. The PPI drugs are not ideal for bone, but perhaps their use can be transient. If needed bone active drugs are best on a background of high diet calcium low diet sodium and therefore added not in place of diet. Of course the diet + CTD will lower urine calcium (and oxalate) and is well known as a way to reduce stones. Regards, Fred Coe

  3. Natalia M

    This is very interesting article, doctor Coe. Thank you.
    I am a year and a half post parathyroid adenoma surgery, 45 year old female, lost two glands and a half of the thyroid. I also have Hashimotoe and on thyroid medication (T3 + T4). It took 5 months to bring my serum Ca to normal after the surgery and hypocalcemia symptoms were severe. Now, after 6 months of normal life the symptoms have returned (mostly tingling and cramps) with low serum Ca (2.05 -2.09 mmol/L), normal PTH (shows activity, but doesn’t get above midrange), and at this time very high urine Ca. I was taking 1500mg of Ca citrate and 5000 IU of D3 for the last 6 months daily, feeling great, but when hypocalcemia symptoms returned my GP advised to raise the dose to 3000 mg with no improvement (this is when he tested 24hr urine and found out that Ca is x2 from the highest number in range (14.8 mmol/day with low phosphate). There are thoughts that the supplements just not being absorbed and I may have kidney issues and/or remaining parathyroid’s activity is not sufficient, even though it tests as “normal”. I reduced Ca supplements to 600 mg a day and retested in few days, so urine Ca dropped to 8.75 mmol/day, but serum Ca is still low ( but did get up from 2.08 to 2.12 mmol/L with PTH 3.4 pmol/L), vitamin D is in midrange. My GP wants to put me on thiazide, but my blood pressure is already on the lower side and I don’t consume much sodium. Serum Mg, K, phosphate and sodium are normal, bone scan last year – normal. Is there any known way to bring serum Ca up other than this medication? What other tests are recommended to confirm whether I may or may not have a renal reabsorption problem? I want to make sure I am diagnosed correctly. Thank you.

    • Frederic L Coe

      Hi Natalia, I suspect that perhaps some PT tissue was removed with your thyroid or that during the surgery blood supply to one or both of the remaining glands was compromised. That there is some PT hormone in your blood is a very good thing. I imagine the low urine phosphate is because the high oral calcium load is blocking phosphate absorption. The inadequate PTH prevents normal renal conservation of calcium, of course. With time – perhaps a lot of time – the remaining PT tissue may enlarge so you have a better balance between oral calcium intake and renal losses. Now your main risk is stones from the high urine calcium. You and your physicians are doing the right thing: use supplements only as needed, try to lower diet sodium to the maximum possible, measure urine sodium – do not guess – and strive for <50 mEq (1500 mg Na) or even less. I would move supplements away from meals so you are sure to absorb phosphate better – cells need it. Here is some additional PT physiology for you. Regards, Fred Coe

  4. Jan Parfit

    I am a 79-year old Caucasian female with a history of corticosteroid use for polymyalgia rheumatica (for 18 months, starting at 80 mg) and osteoporosis. I have been treated with Fosamax 70 mg for 2 years (2006-08) followed by Reclast infusions in 2009, 2010, 2017, and 2018. (I refused to have it from 2011-16). I am scheduled for another Reclast infusion on March 29. A 3-mm kidney stone was noticed on a CT scan in 2002, 2003, and 2004 when looking for a cause to RBCs in my urine. Because of the stone, I was selected for a 24-hour urine test in the Nurses Health Study (I’m a member of the 1976 cohort). It showed a calcium level of 328, with a comment of “Hypercalciuria. Suspected problem is hypercalciuria nephrolithiasis.” Despite treatment, my osteoporosis seems to worsen and my fracture risk is now at 51%. In preparation for the next Reclast infusion, I had a 24-hour urine test, which showed a calcium level of 424. Blood vitamin D level was 61.9, PTH 15.0, albumin 3.7. This was nonfasting and I was taking my usual medications and supplements. Blood work showed a Tandem-R Ostase of 5.5, down from 6.5 two years earlier. I assume this means my bone turnover is low because of the Reclast; so I keep old bone but don’t make new bone? My osteoporosis is managed by a rheumatologist. I seems that the local endocrinologists don’t treat it or don’t take Medicare. Because the hypercalciuria hasn’t been addressed and my osteoporosis is worse despite treatment, I made an appointment to go to the Mayo Clinic in MN for consultation with an endocrinologist who does treat osteoporosis. My question is this: Do you think I should postpone the Reclast infusion until I have been seen by the endocrinologist? It seems to me that I have other issues contributing to bone loss and may need a different type of intervention. For that reason I believe I should wait. Thank you.

    • Frederic L Coe

      Hi Jan, You have hypercalciuria with a very low serum PTH. Idiopathic hypercalciuria famously causes bone disease, but there are other causes as well. Mayo is excellent in general. Dr Raj Kumar is a remarkably brilliant physician scientist there and I would try to get him to see you. He towers over most other people in the field. You can say I said this, and perhaps that will help. Regards, Fred Coe

  5. David Hamm

    Hello Dr. Coe, My wife has repeatedly had calcium oxcalate stones and I’m musing on the subject. I’m wondering, do you know of any link between circulating calcium and high-impact exercise (like running)? I’m wondering if there’s any signaling that would alter the uptake or release of calcium from the bones, or from dietary calcium to the bones. Thanks!

  6. Khalid


    In March 2011, I was diagnosed as Osteoporosis patient. I am male and 51 years of age as of toady. Results of BMD was: Left Hip T Score -1.9, Z Score -1.6 (femoral neck T Score -2.8 & Z Score -2.2) SPINE: T Score -3.4 and Z Score -3.2.
    I was given the treatment of Aclasta Injection (once every year) during last five years to strengthen the bones.
    To investigate the reason for osteoporosis, examination of parathyroid scintigraphy with sestamibi was done June 2013 and the results was as follows:
    “radionuclide parathyroid scintigraphy with sestaMIBI revealed no evidence of functioning parathyroid adenoma in neck or mediastinum.
    Te results of recent (Nov 2018) Dexa Scan revealed further deterioration in bone and the result was as follows:
    Left Hip T Score -1.9, Z Score -1.6 (femoral neck T Score -2.6 & Z Score -1.9) SPINE: T Score -3.6 and Z Score -3.3.
    ( Please note that in Feb 2015, results of Femoral neck was T Score -1.7 and Z Score -1.0)
    Now recently (Dec 2018) doctors have advised me to undergo the following lab tests:
    Urine calcium 679
    Urine creatinine 2.4
    Creatinine clearence 166.8
    Serum Creatinine 0.8
    Serum Phosphorus 4.0
    Serum TSH 0.345
    Plasma PTH 66.2
    Serum 25- Hydroxy Vitamin D 24.2
    Plasma Glucose Fasting 136
    Whole blood Hb1C 7.4

    Please review my case and advise me best treatment for my Osteoporosis problem. Pl suggest if you think that I should do more tests in the diagnostic process
    M Khalid

    • Fredric Coe, MD

      Hi Khalid, You certainly have extreme elevated urine calcium and may have bone disease from idiopathic hypercalciuria – a familial condition. I cannot review your case and advise as that is to practice medicine for someone I have never met – illegal in the US and not a good idea either. For hyperparathyroidism the key is your serum calcium which you do not mention. I presume it is normal, fasting in the morning. The scans are not helpful for primary diagnosis. Speak with your physicians about serum calcium results and if there is some known reason for your very high urine calcium. If it is otherwise unexplained idiopathic hypercalciuria might be correct and treatment is reasonably well defined. Your high serum glucose and Hba1c indicate diabetes, a cause of bone disease and hypercalciuria – overall that may be the main issue for your physicians to manage. Perhaps both IH and diabetes are important here. Your physicians need to decide all this. Regards, Fred Coe

  7. Dustin Harris

    Dr. Coe.
    I have been reading into these issues for years and your name keeps popping up. I am running out of ideas with my own issues.
    I’ve had 110 calcium oxalate stones in the last 7 years. 2-3 a month. Serum Calcium is always normal. PTH is always normal 25-40 range. Vitamin D is deficient around 13. Urine Calcium is always high in the 400s. I have all the symptoms of pHPT, but always have to argue with Endocrine that as long as PTH is never suppressed below normal range it is HPTH. Even on HCTZ for a year my PTH never dropped. It gets worse every year and I am tired of fighting the Doctors. Do you think it could be something else or is it safe for me to assume hyperparathyroidism.

    • Fredric Coe, MD

      Hi Dustin, I gather your serum calcium is always normal, PTH normal, urine calcium high – this is not primary hyperparathyroidism. It is probably idiopathic hypercalciuria and incompletely treated. Surgery for PT disease is NOT an option. Regards, Fred Coe

      • Dustin Harris

        I just reread my statement and I didn’t fully explain the serum calcium, sorry for the confusion. I’m in my late 30s. My serum calcium has been jumping all over the place but the majority are 10.1 to 10.4. Sometimes it drops to the mid 9s but pth is always steady. I am otherwise healthy, I have been active duty Army for 16 years now and this all started after a deployment to Balad, Iraq. The last two years it has been getting worse and I am fighting chronic fatigue, headaches, and have been spacing out mentally. I told my Doctor that it feels like I am slowly dying and I just the kidney stones to stop so I can get my life back. I don’t feel that it is as simple as IH.

  8. Laura

    Hello and thanks for reading!

    I had two stone episodes 15 years apart. In 2003 I had two stones in each kidney. I had EWSL on both kidneys but it did not break up the stones in the left kidney, so one was removed and one was left there. 15 years went by and I ended up in the ER with a 6mm, 9mm, and 2mm calcium oxalate/phosphate stones. I had a stent and then uteroscopy, lithotripsy and basket removal of the two larger stones. The 2mm remains in the left kidney.

    I had two 24 consecutive 24 hour collections done. My volume on day 1 was 2.49 and it was 2.82 on day two. Other results were:

    Day 1
    Vol 24 SS CaOx Ca 24 Ox 24 Cit 24 SS CaP pH SS UA UA 24
    2.49 4.31 276 23 388 0.63 6.010 .41 0.508

    Vol 24 SS CaOx Ca 24 Ox 24 Cit 24 SS CaP pH SS UA UA 24
    2.82 3.31 174 26 506 0.60 6.381 0.20 0.585

    All of my dietary factors were within normal range and the only normalized value that was out of range was ca/cr 24 of 265 on the first day.

    In June my blood calcium was 10.1, which I understand may be high for my age of 52.

    My question is about possible hyperparathyroidism, as I have other symptoms that lean in that direction. I am unsure though of the next steps to take in the investigation. I did have a negative ultrasound notwithstanding the remaining small stone.

    Thank you for any advice.

    • Fredric Coe, MD

      Hi Laura, I gather you have calcium phosphate stones and that it is unclear if you are making new ones because a stone was left behind 15 years ago after SWL; SWL scatters crystals about the kidneys that can grow into larger stones. Let’s assume new ones are forming, and you have a borderline high urine calcium and serum calcium. The best course is repeated fasting morning serum calcium measurements each with a PTH measurement – I favor at least 2 of these. If they remain at 10.1 and PTH is normal or high, PHPT is indeed a possibility. The negative ultrasound despite a CT proven stone is commonplace as ultrasound is not so sensitive. Feel free to share these thoughts with your physicians, and if they agree get the proper testing. If you do not have PHPT yet have made more stones, the increased urine calcium can be treated with low sodium diet as noted in the article and in this one as well. Regards, Fred Coe

      • Laura

        Hello, and thanks so much for your response. My primary doctor is in agreement that this should be investigated further, although my urologist felt that my values were OK, which leads me to a follow up question:

        On the second day of the 48 hour collection my values were better than the first day, and those seemed to be the ones that my urologist focused on in his interpretation of the results. However, my water intake was also better that day compared to the first day, specifically because the nurse in his office told me to push fluids throughout the collection.

        I think my question / concern about this is that the amount of fluids I pushed both days is not sustainable on a daily basis, unless I want to quit my job/life and do nothing but drink water and urinate all day and night long. So that makes my think that its not viable to expect the same results under more normal conditions with a more reasonable amount of drinking and voiding, and that the results I got from this collection are not really an indicator of how my kidneys are functioning or my risks of future stone formation.

        Did I make a mistake by increasing my fluids during the collection to an unsustainable amount? Could that have made the results less reliable? I ask because although my primary doctor is keen on looking further into this I was concerned that my urologist accepted the results as good indicators of my overall kidney function. Any light you can shed would be helpful as I decide how to proceed.

        Thanks again!!

        • Fredric Coe, MD

          Hi Laura, Indeed it was a bad mistake to distort everything just when you were testing to figure out how stones formed. How better to miss everything than make changes while testing then go back to what you do every day. Get repeat studies while at work and find out what is really causing stones. Regards, Fred Coe

  9. Jim Jones

    I have been diagnosed with renal leak hypercalciuria. I have been given triam/thiazide 25 mg once a day and it has reduced my Ca24 from 454 to 253. Seems like it is getting better. I was wondering if it ever gets better and stays better or is the thiazide going to be needed from now on?

  10. Paige T

    I wound up in the ER with a kidney stone– upon further evaluation, a CT showed several stones (some 5-6 mm) in both kidneys. Passed stone eventually– had analysis completed and showed composition of stone was 80% calcium phosphate. Had lithotripsy procedure– my post-op CT showed there are still stones in both kidneys, most smaller, some unchanged in size. Had 24-hour urine study done– urine calcium was 511 mg/24 hour. Tested PTH– levels were normal. Was started on chlorthalidone, however, it dropped my potassium significantly and quickly. Was started on a potassium supplement and was taking 100mEq/day and still was not enough to counteract how much the chlorthalidone dropped my potassium levels. Decided to discontinue chlorthalidone (and potassium supplements.) My urine calcium at 511 is quite high– should I be concerned about this? Should I go back on the medication?

    • Fredric Coe, MD

      Hi Paige, You have multiple calcium phosphate stones and very marked hypercalciuria. Be sure your serum calcium – fasting, off the chlorthalidone – is normal. Chlorthalidone is best used with low sodium diet and in a very low dose. The ideal diet is 1500 mg sodium, the dose 12.5 mg of the drug. That often works. See if your physician considers this a worthwhile variation that might help. Given so marked a hypercalciuria I am sure s/he has ruled out any systemic diseases as a cause. Regards, Fred Coe


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