HYPERCALCIURIA

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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.

Overview

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.

Sarcoidosis

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

69 Responses to “HYPERCALCIURIA”

  1. Pieter Botha

    Dear Dr. Coe

    I had so many kidney stone that I can not remember anymore. I am 53 years old and had my first stone at the age of 14 years with many fractures over the years before and after 14 years of age. 5 years ago I was diagnosed with osteoporosis and low Vit D with a slightly lowered kidney fuction and polyarthritis. I drink Calcifirol once a week and my Vit D is in the normal range. I was also diagnosed with the HLA B27 gene due to the joint pain that I had. Everybody thought that this was the problem dispite that the inflammation counts were normal. About a year ago, I was diagnosed with renal calcium and potassium leak after insiting on a test, and put on thiazides. I was also diagnosed with Metabolic Acidosis and Idiopathic Polycythemia. For the last few months, I had venesections, which I was told that it would relieve the pain. I was initially on Fosavance but for the last year on Aclasta. My PTH is normal and so are the minerals in my blood. I use Caltrate Plus and from time to time Slow-K when I am getting cramps. I have bone pains and kidney pain everyday and I find that a bit of exstra magnesium relieves the pain for a while but not always. Bone pain is in the upper long bones and in the lower distal third of the bone. All of them can sometimes pain but in most cases it is just one of them, alternating to the others from time to time. The most frequent bone that pain, is the left femur. The sacrum also pain constantly. NSAID’s does not make any differensce to the pain. I excersice regular through my whole life and I avoid to much protein and salt. I also don’t eat sugar and very little starch and I eat a lot of assorted raw vegetables everyday. My mass is 85 kg and I am 1.8m tall. My homone levels are in normal rage for my age. My recent Bone Density scan showed little improvement in my left femur neck and lumber vertebra, but a 6.8% decrease on my right femur neck from a year ago. From what I see from my own research, is that metablic acidosis, joint pain, bone pain, polycythemia, renal calsium and potassium leaks, low vit D and magnesium all interplay with each other. None of the specialist that I visited made any connection between them. If this is a chain reaction and is a true inverance by me, how do you break the chain. I have spend a lot of money on my problem, without benifit. I would appreciate it if you could give me some pointers on what the problem might be and what to do about it. I understand that you have not examined me and it would be difficult to make a proper informed diagnosis. At the moment I am desperate as the interventions that I had, don’t seem to work.

    Kind regards,

    Pieter

    Reply
    • Fredric Coe, MD

      Hi Pieter, You have what sounds like something with a name but there is not enough detail for me to try to place that name. If you would like to send all of your results I would try to interpret them for your physicians and you, not on the web but in a private note. As I am a university professor, I can do this as a courtesy. I may not be successful. Regards, Fred Coe

      Reply
  2. Kerri

    My daughter who is 8 recently had blood in her urine with no other physical symptoms of a uti. We ended up at a nephrologist who did a 24 hour urine and said she is spilling a lot of calcium in her Urine. She said she will need to be on meds rest of her life. Dr believes it’s a genetic cause as I have had kidney stones many times and my mom and grandma. Me, my mom and grandma all had other alarming physical symptoms as well and have not found a diagnosis. Have you found any autoimmune diseases that cause hypercaluria? What type of doctor should we all see now to find if there is a genetic cause,,a geneticist?

    Reply
  3. Donnie Lambert

    Just would like to add, she has tested negative for hyperthyroidism, malignant neoplasm and sarcoidosis. Thank you for your review of my comments.

    Reply
  4. Donnie Lambert

    My daughter is special needs at age 50, and is post menopausal. In 2015, I took her to the ER, and found she had three kidney stones. She has never had kidney problems or stones prior to that time. They dissolved with 0.4mg of Tamsulosin. No other stones have been identified. Since 2015, she has had three 24 hour urine tests, which shows high urine calcium counts above 300, and drop in Urine PH at 5.369. Latest test was done in Sept. 2017. She is hypercalcuric, and has been showing she is hypercalcuric since the first test in 2016. In Oct. 2013, she had a count of 9 on a D3 test. The doctor prescribed 4,000IUs of Vitamin D3 supplements. She was re-checked in January 2014 and her D3 level had risen to 29. She was told to continue on the 4,000 IUs a day of Vitamin D3, and was not re-checked until recently in June 2017. Her level of D3 was measured at 97 even though she has had no Vitamin D3 supplements during at least the last 6 -10 months. She has been referred over to a Nephrologist, who has placed her on a low dose of Hydrochlorot 12.5MG, lemon or lime water and a Mediterranean diet. She has been on low sodium since 2015, water has been increased from 64 oz. of water per day, and now upwards of that amount to 2.5 liters, and low oxalate foods as well. I am not questioning the current Nephrologist’s method of treatment, But I do feel such a large dosage of Vitamin D3 supplements prescribed by her primary doctor over a year and a half without followup is what led to the stones and current high uric acid levels leading to hypercalcuria. The urologist or nephrologist are not the doctors who prescribed the vitamin supplements. Could I be wrong about the high dosage of Vitamin D3 supplements over a year and half as being the culprit for the hypercalcuria?

    Reply
    • Fredric Coe, MD

      Hi Donnie, Your daughter had high urine calcium since 2016, but all we know is that her vitamin D level was 29 in 2014 and 97 in 2017. I gather her D level is now 93 which is very high. I presume blood calcium levels are normal. I assume the stones occurred in 2015 and led to the urine testing. So: 2013, D was 9; placed on 4000 units of D. 2014, D level was 29. 2015 three kidney stones, urine calcium high. 2016 and 2017 I presume high urine calcium found; 2017 vitamin D measured at 97. Possibly the high vitamin D caused the high urine calcium, possibly it was high anyway. The best approach is much like what your physician is doing: low sodium, chlorthalidone, water, and wait for the D to go back down. When it does, one will know what it contributed to the high urine calcium. Regards, Fred Coe

      Reply
  5. Joe

    Hello,
    I have been treated for Vitamin D deficiency for 6 months and only now have tested my 24hour urinary calcium, serum calcium and PTH. Urinary calcium came back at 15.21mmol/d (High), along with high PTH (8.1mmol/L), but normal calcium (2.28mmol/L) [it might possibly be even a bit lowish]. My serum creatinine was in the normal high range and urinary creatinine was high.
    Could it be consistent with still-being-treated Vitamin D deficiency to still have high PTH, high 24hr urinary calcium and lowish normal serum calcium. Those 3 simultaneously seem paradoxical.

    Reply
    • Fredric Coe, MD

      Hi Joe, The urine calcium is majestic. But a high urine creatinine for your body weight means overcollection may have inflated the value. One possibility – assuming all other tests are normal – is idiopathic hypercalciuria with vitamin D deficiency showing up as vitamin D is repleted. YOu do not mention your vitamin D level. I would get it measured as well as your 1,25 d level which I imagine will be high. The other possibility is that you have primary hyperparathyroidism with incompletely treated vitamin D deficiency and as the latter is fully corrected serum calcium will rise above normal. Regards, Fred Coe

      Reply
  6. Shannon

    Hi Dr. Coe,
    I have had multiple kidney stones on my left side only, for the past 8 years. All have come back as Calcium Oxalate. I am 46 years old and have a family history of stones. For the past 6 months I have kept to a whole foods ketogenic diet to help control migraines (with good success). Have been told by previous doctor to increase fluids and avoid high oxalate foods, however the stones kept forming.

    My new urologist ordered a 24 hr. urine test and bloodwork and I’ve been sent a copy of the results to review before my follow-up appointment next week. Two values came back out of range and I’m curious if there is a link between them.

    On the urine test the Calcium was 624 mg (pH 6.4, volume 4L, citrate 1276mg, sodium 156, mag 228, Ox 21.1, Uric acid 436, phos 880, Creatinine 1080).

    On the blood work my-out-of-range value was Eosinophils at 2.8 x10E3/uL (mag 2.1, PTH 30, Phos 3.3, WBC 7.6, RBC 4.36, Neutrophils 2.3, Lymphs 2.1, Baso 0.0, Granulocytes 0.0, Uric Acid 4.7, Creatinine 0.55, sodium 140, potassium 4.2
    chloride 96, calcium 9.2).

    I have read elevated eosinophils could be related to Sarcoidosis, however I have no physical concerns/complaints beside trying to figure out my recurrent stone issues. I also understand that Sarcoidosis is relatively rare.

    Thanks for any insights and for your wonderful, educational work. Best regards!
    -Shannon

    Reply

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