IDIOPATHIC HYPERCALCIURIA (IH)

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VIDEO: About 27 minutes with a break at 15 minutes

Perhaps the most common abnormality among calcium stone formers, idiopathic hypercalciuria (IH) causes calcium kidney stones and can lead to bone mineral loss and fracturing bone disease. Proper treatment requires a high calcium intake, a low sodium intake, moderation of very high protein intakes, avoidance of refined sugar loads, and – not rarely – use of diuretic drugs which can lower urine calcium losses, prevent stones, and protect bones.

Why The Bathers?

Bone seems, to me, a bather in a bathtub. Calcium flows in from faucets – the GI tract – and out down the drain – the kidneys – as they regulate serum calcium – the height of the water in the tub. I realize the bather does not take up or lose water, but if you ponder the image awhile you may see in it what I see.

The Large Bathers (1884-87) of Renoir and The Large Bathers (1900-1906) of Paul Cézanne both reside in the Philadelphia Museum of Art, and I, though I love them both, could choose just one.

Toward the end of summer, surrounded by gardens, I chose the beguiling Renoir. In winter, the gray stones of my university might have swayed me toward Cézanne’s distant, dark, and brooding goddesses.

What is Idiopathic Hypercalciuria?

What is Hypercalciuria?

As hypertension is defined by blood pressures that associate with stroke, heart failure, and heart attack, hypercalciuria is defined by urine calcium excretions that associate with stones.

PQ RISK VS URINE CALCIUM LOW AND MEAN OVERPLOTTED.jpg

Increasing urine calcium losses associate with increasing risk of stones in two cohorts of women – red – and one of men – blue. Urine calcium is along the horizontal axis in six bins. The average relative risk of forming stones is marked by the tops of the bars. A value of 1 means no higher than among people with urine calcium below 100 mg/day – the reference population.

The lower 95th percentile of risk is at the bottoms of the bars. When the bottom of a solid bar lies above one, which is the case for all bars from 200-249 mg/d on, increased risk is very likely present. So the threshold of hypercalciuria is 200 mg/d both sexes.

Diet was not controlled, so we do not need special diets to diagnose hypercalciuria using this criterion.

As the urine calcium rises, risk – top of the bar – rises in smooth progression.

What Does ‘Idiopathic’ Mean?

The overwhelming majority of hypercalciuric stone formers have none of the many diseases that can raise urine calcium excretion. Their urine calcium exceeds 200 mg/d for no obvious reason – idiopathic, arising of itself, without overt cause.

Normal Calcium Excretion

normal uca male anf female.png

Since 1900 scientists have collected 24 hour urine samples from people in clinical research units, perfect collections, and measured urine calcium. I collected all such values I could from published papers – a tiring exercise. Here is my yield of values from normal adult men (blue) and women (red).

The threshold of clinical hypercalciuria, 200 mg/day, resides at about the 75th percentile: 25% of normal people are above it. But stone formers are perhaps 7-10% or less of the human population. So hypercalciuria raises stone risk, but not everyone gets the stones.

Likewise, stone disease is familial, but IH alone does not fully explain why. Presumably other inherited factors matter.

Decades ago we used the 95th percentiles of these two distributions, at about 275 and 325 mg/d of calcium for women and men, to define ‘hypercalciuria‘. No doubt such high values confer risk of stone, but they are too high for clinical use. They remain useful in research to define people with extremely high urine calcium values.

Hypercalciuria Raises Supersaturation and May Promote Plaque

Supersaturation produces and enlarges crystals and therefore stones. We now have superb evidence that rising supersaturation associates with rising stone risk. Calcium oxalate and calcium phosphate supersaturations rise smoothly with urine calciumleaving no doubt that urine calcium raises risk of calcium stones via increasing supersaturation.

Many calcium stones form on plaque, tissue deposits of calcium phosphate crystals in human renal papillae. Plaque abundance rises with urine calcium excretion, and a plausible theory, vas washdown, links them.

Idiopathic hypercalciuria is Hereditary

FAMILIAL NATURE OF IHFamily Studies

I am not sure if we were the first, but here is our evidence from 1979. 

The arrows point to the stone formers whose families we studied. Filled symbols are men (square) and women (circles) with IH,  asterisks mark children, open symbols did not have IH, and dashed people are deceased. About 50% of immediate blood relatives had IH, in successive generations. Others have also found IH heritable.

IH might look like a simple dominant trait from one abnormal gene, but it results from a number of genes. Incidentally, urine calcium is not the only stone forming trait that appears genetic. Urine citrate appears to be, as well.

Animals

Dr. David Bushinsky bred rats with the highest calcium excretions. Urine calcium rose for the first 40 generations, and thereafter seems at a near plateau. So the trait is breedable.

ghs uca progression-14-07-25 c

These animals form calcium stones and develop a more severe bone disease than normal rats if diet calcium is not ample. So they well mimic human IH.

We humans did not breed ourselves for IH. Something about the trait must have conferred a benefit during evolutionary time.

Children

We had the opportunity to collect 24 hour urine samples from large numbers of boys and girls who were brothers and sisters of children with kidney stones, and also from children in families where none of the children, their parents, or other relatives were known to form stones.

Urine calcium excretions of siblings with more than two stones (left panel of the figure) are highest – farthest to the right. Next highest – second from the right – were siblings with 1 – 2 stones. Siblings with no stones were even lower, third from the far right.

Children from families with no kidney stone history were lowest – most leftward – and almost none had above 200 mg/day of urine calcium loss.

The four bars in the right hand graph say the very same thing. Mean values of urine calcium, shown by the top of each bar, rose progressively with stones.

This is expected if IH is genetic and causes calcium stones.

Hypercalciuria with Hematuria

Hypercalciuria in children not rarely causes hematuria found on routine screening. Loin pain with hematuria is a common syndrome ascribed to crystal passage. IH can raise urine supersaturation and higher supersaturations promote crystals. Hematuria can be familial because it is due to IH and crystals or stones. In adults, unlike children, hematuria can be from malignancy so proper evaluation, even in stone formers, requires imaging and considerable care. 

Bone Disease

There Is Bone Disease in Stone Formers

Epidemiology of Fractures

This figure, from people living in Rochester, Minnesota, shows the cumulative incidence of vertebral fractures among those who had a symptomatic stone (irregular line) and the expected fracture rate nihms271156f1 bone fractures in stone formersbased on the entire population (the smooth line) between 1950 and 1974. The excess of fractures was not observed for hip or forearm.

Bone Mineral Density

Reduced bone mineral density is a general finding in stone formers. Table from Sakhaee paper on bone

Among 2,052 patients assembled from 20 separate studies, between 31% and 65% had some reduction of bone mineral density (Table). Although not remarkable for fractures in the Rochester study, the radius was most affected.

The authors of this review did not conclude that IH caused the low bone density of stone formers. I infer it played an important role, however, because IH can promote bone mineral loss (detailed in the next section) and thiazide diuretics – well known to lower urine calcium in IH – appear to reduce bone disease.

Prospective Bone Mineral Observations

ASPLIN BMD VS UCA

Another reason I make this inference is that the magnitude of urine calcium loss predicts future loss of bone mineral. 

We measured bone mineral density in a number of stone formers with IH, collected 24 hour urine samples, and then re-measured bone mineral density three years later.

When change in bone mineral by three years (vertical axis) is plotted against the urine calcium loss at time 0, (horizontal axis), the trend – highlighted by 68% containment ellipses – points downward: More urine calcium loss at the beginning, more bone loss by three years. A majority of people with urine calcium above 200 mg/d lost bone mineral over three years, whereas those with values below 200 mg/d tended to gain bone mineral.

How Does IH Raise Urine Calcium?

The Extra Calcium Can Come From Diet

qplot of percent calcium absorption IH and N from balance plots for gibbs lecture control file using balance data file in CKD ca and p balances folder

In the balance studies from which I derived normal calcium excretions, scientists fed subjects a fixed diet and measured all food calcium eaten and all calcium lost in the stool. The difference between calcium eaten and calcium lost in the stool is net calcium absorbed into the blood.

Typically measurements are made in 6 day blocks after a few days to equilibrate with the diet, so subjects participate for perhaps 8 – 10 days. I have aggregated the calcium absorption measurements that match the urine calcium excretions I already showed you.

Normal men and women (orange) absorb about 18% of diet calcium. I combined the sexes because they have almost identical values. Women and men with IH – the blue curve – absorb much more calcium, about 30%.

You might ask how calcium absorption can be negative – points to the left of the vertical 0 absorption line. It is because salivary glands, pancreas, liver via the bile, and perhaps the ileum secrete calcium from blood back into the bowel lumen. When diet calcium is less than this ‘endogenous secretion’, stool calcium loss exceeds what is eaten.

An early theory held that IH arose from over absorption of diet calcium: High absorption, more calcium comes into the blood, the kidneys lose it – done. This theory led to decades of low calcium diet as a treatment for stones. No one knew such diets might cause fractures.

The Extra Calcium Can Come From Bone

A Glucose Load Causes Bone Mineral Loss

Years ago Dr Jack Lemann did this informative study. He measured urine calcium excretion (vertical axis) then gave glucose or sucrose (table sugar) to normal people, calcium stone formers, and relatives of calcium stone formers.

jack NEJM pictureCompare the control (left of the big arrows) calcium excretions of the normal subjects to the stone formers: 5 of the stone formers have control values above all but the highest normals. The relatives of stone formers are even higher – and this is fasting, before the sugar load!

Each period was 20 minutes, so this experiment went on for 2 hours. The higher urine calcium with sugar must come from bone – there was no calcium in the sugar drink. It came from bone in normal people and in those with IH but the latter lost far more calcium than the former. Though fasting they had higher urine calcium losses.

In a separate experiment, Lemann proved that the kidneys themselves caused calcium loss from sugar by reducing their conservation of the calcium they had filtered out of blood.

Low Calcium Diet Causes Bone Mineral Loss

We persuaded nine normal people and 27 stone formers with IH to eat a very low calcium diet – 2 mg/kg body weight – for 9 days, and on days 7-9 we collected 24 hour urine samples and measured lcd picturecalcium losses.

The diet went well; most people ate what we asked (middle panel). The normals (the 9 people to the left on the plot) lost in their urine less than 2 mg/kg of calcium daily – lower panel, to the left, so the difference each day between what they ate and lost was positive (upper panel, all normal points were above 0).

The patients were different. Many lost more calcium in their urine than they ate, and did so most of the time. This was bone mineral lost in the urine.

On such a low intake surely everyone was losing bone mineral because the fraction of diet calcium that is absorbed into the blood is far below 100%. I just showed you that it is about 18% in normal people and 30% for people with IH.

But those with IH were more flagrant than the normals. Because their urine contained more calcium than they ate we could prove bone mineral was lost.

In IH Urine Calcium Usually Exceeds Net Calcium Absorbed

On the horizontal axis of this figure, calcium absorption is the difference between calcium eaten and lost in the stool. Urine calcium is on the vertical axis. People with IH are red large dots, and normal people are blue microdots.

Each point compares calcium absorbed in a day to calcium lost in the urine. If urine calcium is higher than calcium absorbed (points to the left of the diagonal line of identity), bone mineral is being lost in the urine. Those to the right the opposite – bone is gaining mineral.

At a net calcium absorption of 150 mg/d or more, a majority of the normal points lie to the right of the diagonal line – urine calcium is less than calcium absorbed. Bone mineral is stable or increasing.

Idiopathic hypercalciuria points all lie left of the diagonal line, negative bone mineral balance, until net absorption rises over 300 mg/d. It takes a huge amount of calcium absorption to overcome the tendency of IH people to lose bone mineral.

Bone Calcium Retention vs. Diet Calcium

Perhaps a more practical way to envision these balance data is to plot calcium retention – net calcium absorbed minus urine calcium excreted – against diet calcium intake.

At diet calcium intakes above 500 mg/day, the average retention (the jiggly blue line) for normals passes through 0, meaning that their bone mineral stores will, an average, be stable. Higher calcium intakes make the normal average rise so that by 1,000 mg/day retention vs calcium intake in mg per day with smoother means red is IH blue is normalsa majority of normal points are above 0.

Among the IH subjects (red), retention rises with diet calcium intake, but the average – red line – never passes through 0. Some points do lie above 0, meaning that not all IH subjects will share the general high risk of bone mineral loss, just as some normal points lie below 0 even at high calcium intakes. But on average, at all reasonable calcium intakes, IH appears to hamper bone mineral retention.

What Have We Learned?

Low calcium diet is not ideal for normal people and a disaster for those with IH. Given IH, even a liberal calcium intake will not achieve stable bone mineral balance for the average person.

These balance data lay latent in papers published from 1900 through until even recent times. Using a different and sophisticated way to assess bone mineral balance, Lieberman and his colleagues showed as early as 1965 that IH reduced bone mineral stability. Yet low calcium diets remained a common treatment for stone disease for more than a decade thereafter.

IH Kidneys Release Excess Calcium 

Filtered Calcium

Calcium gets into the nephrons of the kidneys by filtration from blood. If you do not know about filtration, use this link to learn about it. 

Each of the 2 million nephron units we possess in our two kidneys has a glomerular filter that filters water, sodium, calcium, phosphate, oxalate, and thousands of other small molecules and ions out of blood into the long tubules that process the filtrate into urine. 

Reclaimed Calcium

The process we care about here is reclaiming filtered calcium back into the blood. Normal people excrete about 2% or less of filtered calcium, those with IH excrete 4% to 5% or more.

Here are a few numbers. We filter about 150 liters/d. The filtrate contains about 40 mg/l of calcium: 40×150 = 6,000 mg/d of calcium. Of that 2% is 120 mg/d, 4% is 240 mg/d, 5% is 300 mg/d. So the differences in percent excreted account for the range of calcium between normals and stone formers.

Where Along the Tubule?

Review the Proximal and Distal Tubules

Each kidney tubule resembles a woman’s hair – long as a long hair, and that thin. Down the center of the hair is its lumen through which the filtrate passes to become urine, and where calcium is reclaimed.

Go back to the filtration article and check out the tubule picture. Pay special attention to the proximal tubule. In the proximal tubule calcium is reclaimed in parallel with sodium. In the distal tubule – on the picture in the link – calcium can be reclaimed independent of sodium.

Urine Calcium Follows Urine Sodium

This picture illustrates the basis for recommending a low sodium diet to lower urine calcium in IH.

It shows how urine calcium (vertical axis) rises as urine sodium (horizontal axis) rises. The rise is far steeper among stone formers with IH (blue) than in normal people (red). Circles show experiments – diet sodium was deliberately altered. Triangles show observations – diet sodium and urine calcium varied on their own.

Urine Calcium and Sodium are Linked in the Proximal Tubule

As you eat more sodium, urine sodium goes up so output balances intake. One way the kidney accomplishes this balance is that filtration rises with higher sodium intake. Another is that reclamation of water and sodium in the proximal tubule (the part nearest the glomerular filter) goes down – more sodium and water flow downstream in the nephron. Calcium goes with it, the two are linked by the way that part of the nephron works.

For this reason, the steeper slope of urine calcium vs. urine sodium in IH must arise from abnormalities further downstream from the proximal tubule. We cannot presently identify where or how this happens.

What Can We Do With What we Know?

We can shut down filtration and increase reclamation of sodium in the proximal tubule. Both will reduce urine calcium by reducing delivery of calcium downstream. Lowering diet sodium does both, reduces filtration and increases proximal tubule sodium reclamation. The latter is usually more prominent than the former.

Thiazide diuretics do the same. They increase reclamation in the proximal tubule.

Once you understand this, you understand why reducing diet sodium and taking thiazide are two ways to do one thing. So the more you limit diet sodium the less you need thiazide, or at least the less dosage you need. On the other hand, if you take thiazide and eat a lot of sodium, the sodium will undo the effect of the drug.

What Happens to Bone?

Diet Calcium Must Be High

All this gives some insight into why IH appears to reduce bone mineral.

When we eat, the kidneys release calcium into the urine, normals and IH alike. But IH patients release a lot more calcium, depending on their sodium intake. If the diet has adequate calcium in it, bone can get its share even if more than normal is lost in the urine. If the diet is not so adequate, less than 1,000 mg/d, bone may not get its share even in normal people. Given IH, diet calcium must be quite high, at least 1,000 to 1,200 mg. But that cannot be sufficient as I have shown you. Even at such high calcium intakes, bone balance in IH is usually negative.

Diet Sodium Must be Low

The only present remedy for renal calcium wasting in IH is to lower delivery out of the proximal tubule. Low diet sodium, thiazide, ot both can do it. We presently have no other means that have proven effective.

The Combination of High Diet Calcium and Low Diet Sodium Can Preserve Bone Mineral

The best proof of this is one study showing that in perimenopausal women the combination of low diet sodium and high diet calcium can promote bone mineral gain. 

The women each ate all four of the diets shown along the horizontal axis: high and low calcium (Ca) and sodium (Na). Specifically, the sodium levels were 1600 and  4400 mg/day, and low and high calcium (518 and 1284 mg/day. 

On the vertical axis is calcium in mg/d. The colors say if ‘calcium’ on the vertical axis is calcium absorbed (blue), secreted by the GI tract (red), lost in urine (gray), and bone balance (black).

Low calcium diets were hopeless. High calcium diets with high sodium led to high absorbed calcium (blue) but also high urine and GI endogenous secretion losses (‘ENDOFEC’): red and gray bars point downward. Reducing diet sodium lowered the urine loss (gray bar was less down) and also – surprise – less GI calcium secretion (red bar is less down).

The net result is good for bone. This one combination drove bone mineral balance positive (Black bar above 0). 

Before we leave this powerful demonstration, look back on urine calcium (gray bars). The high calcium low sodium diet gave the very same urine calcium as the low calcium high sodium diet. In other words, the women could raise their diet calcium from 500 to nearly 1300 mg/day and yet by lowering diet sodium to 1600 mg/day keep urine calcium unchanged.

What Makes Calcium Go In or Out of Bone?

Blood is saturated with respect to the initial phases of bone mineral, so called early hydroxyapatite forms. Likewise bone has considerable circulation, so that the outer layers of bone can be in physicochemical equilibrium with the blood. In isolated bone reduction of calcium phosphate supersaturation leads to physical dissolution of bone mineral.

It seems not unreasonable that tiny reductions in blood calcium phosphate saturation can occur when kidneys release calcium into the urine at a rate that exceeds diet calcium absorption. The loss of bone mineral from simple sugar ingestion may well be an example of this effect. Of course bone is regulated by myriads of hormone signallers, but short term mineral balance could be affected by physical forces. This is an area that deserves research.

I should say that in presenting this conjecture about bone it is just that. Furthermore I doubt it is sufficient as an explanation. But it shows at least one plausible connection that can be demonstrated in isolated bone, and perhaps in humans.

In another article, as yet unwritten, I will take up the larger issues of bone and kidney in IH, and show the deeper science that is now available.

What Should We Do?

Kidney Stone Prevention

Without doubt, reduced diet sodium and refined sugar are valuable in all people with IH. Although I did not demonstrate it here, a high diet protein load raises urine calcium and is best brought into the normal range of 0.8 – 1 gm protein/kg body weight/d. Protein intake is calculated from urine urea excretion as the protein catabolic rate (PCR) and best quality kidney stone testing vendors present it on reports.

Bone Disease

Provide Adequate Diet Calcium

Diet calcium must be adequate, 1,000 to 1,200 mg/d. Without concomitant control of diet sodium this alone would raise urine calcium and kidney stone risk. But when combined with low sodium it will not. Multiple proofs of this statement exist. I just showed you one in the lovely four way bone experiment.

Measure Bone Mineral Density

US insurance practices exclude bone evaluation in large swathes of stone forming populations. But bone mineral scans are not very expensive compared to the eventual costs of fractures. A useful medical buying guide places the bone mineral density scan cost to uninsured people at about $200.00, and mentions that in May prices can be lower because it is national osteoporosis month. The price usually includes a simple medical interpretation.

The Kidney Stone Diet

The proper diet for prevention of the common calcium stone arises almost totally from the requirements to treat IH: reduced diet sodium, refined sugar, and protein, and adequate calcium for bone. The last of these, high diet calcium plays another role in stone prevention by lowering urine oxalate. That is fully described in other articles

As well as stone prevention and the protection of bone, this diet is thought beneficial for reduced risk of hypertension and vascular disease, to which stone formers seem unduly prone. 

Because it accords with general diet recommendations for the entire US population, I can recommend its use without hesitancy for stone formers and, incidentally, all the rest of us, too. 

169 Responses to “IDIOPATHIC HYPERCALCIURIA (IH)”

  1. Sandra White

    Hello Dr. Coe, Thank you for sharing your valuable knowledge online on Hypercalciuria. I had 2 kidney stones in 2018. One passed and 1 was removed from my right kidney. So far been lucky not to have another one. My urologist ordered a 24 hour urine test recently and found my calcium level elevated. All results were in normal range, including volume, except the following:
    Calcium 243 mg (550 mg)
    Sodium 161 mmol (50-150 mmol)
    I take Levothyroxine 100 mcg and my TSH level is 0.821 which is within range but the lower side of normal limits. I have been checked for Parathyroid and the PTH level was 26 pg. My Vit D level is slightly low so I take 1600 IU in a multi vitamin that does not contain calcium. My question is could lowering my levothyroxine to 88 mcg as long as I stay under 4.0 ulU/ML help lower my urine calcium? I read that hyperthyroidism can increase calcium so my thought was I might be benefited with a lower dose of Levothyroxine.
    Other noted information/thoughts: Last 5 months have had several cortisone injections (spine/hip) trying to figure out groin pain, which ended up being a torn hip labrum. Cortisone causing elevated calcium? I’ve been under high stress from the pain for over a year until recently, maybe elevated cortisol might be contributing to calcium? Also, up until recently have been taking Hydrocodone 5-325. Codeine or acetaminophen effecting calcium?
    Just trying to see if an outside factor could be causing the elevated calcium so I don’t have to take medication to lower my calcium. Any thoughts would be greatly appreciated. Thank you so much!

    Reply
    • Fredric L Coe, MD

      Hi Sandra, Possibly the steroids raise your urine calcium. But surely the high diet sodium plays a role. If you lowered it to 2000 mg or better 1500 mg/d urine calcium will fall to normal – in all likelihood. No meds. The role of sodium is in the article if you want the details Regards, Fred Coe

      Reply
  2. Charles Ellis

    Hello Fred,
    I am grateful to receive your very useful mailings — thank you. You diagnosed my condition as idiopathic hypercalciuria, and your recent article reminded me of your advice over the years to consume an adequate amount of calcium and to be mindful your other dietary recommendations. Calcium consumption for me means plain yogurt and non-fat milk. You recommend consumption of at least 1,000 to 1,2000 mg calcium daily: I’m writing you because I’d like for you to coach me about what I’m reading on the products’ labels (I’m still overseas).
    My habit is to buy containers of yogurt; quantity is 500g. The Iabel says 100g of yogurt contains 143mg of calcium. Am l right in thinking that 500g of yogurt yield 715mg of calcium and that therefore my consumption of this yogurt should be 2 containers daily? I believe you have also recommended cheese, but I usually avoid it because of fat. Fruit juice with calcium added is almost never marketed here.
    I’ll close by repeating my thanks for directing me to Dr. Giovanni Gambaro — really outstanding physician and great guy who, by the way, thinks the world of you.
    Thanks,
    Charles Ellis

    Reply
    • Fredric L Coe, MD

      Hi Charles, You are right, the yogurt will do it. I hope Italy has remained an idyll for you, and wish you well. Please send my regards to Giovanni. Fred

      Reply
  3. Stephen J Knohl

    Dr. Coe,

    Perhaps overly simplistic, but I always teach students/housestaff/fellows that any “hyperelectrolytemia” must be the result of either or a combination of impaired kidney function vs a rate of entrance into the blood that exceeds the rate of the kidney’s excretory capacity. As it relates to hypercalciuria, would it be fair to say that every cause of (ionized) hypercalcemic hypercalciuria is due to either excess GI absorption/bone resorption and the kidney is attempting to excrete the increased filtered load (i.e. “appropriate hypercalciuria”? If so, what level of ionized calcium would qualify as hypercalcemia leading to hypercalciuria (i.e. where enhanced GI absorption/bone resorption is the explanation rather than inappropriate renal loss of calcium)? Do we know this?

    Thanks.

    Reply
    • Fredric L Coe, MD

      Hi Stephen, Because your mind is clear you ask wonderful questions. Of course tubule reabsorption sets the UF level for any given combination of filtration rate and urine excretion rate. That is conservation and no way around it. So all hypercalciuric states – higher excretion – have some element of supply to keep UF calcium appropriate to GFR and tubule reabsorption. In IH we found – as you well know – reduced tubule reabsorption from about 98% in normals to as low as 95% in IH subjects, and equivalent levels of UF calcium and more or less of GFR. The fall in reabsorption is driven by nutrient, including just glucose, so bone mineral can and will make up the difference when diet calcium is lacking. I think that is a reason bone mineral can be lost. If reabsorption does not fall enough to balance a supply rise, from bone mineral dissolution or increased GI absorption, UF calcium must rise. Vitamin D excess is a good model as Jack Lemman studied it decades ago. Give an excess of 25 D to young men and urine calcium rises – a lot. PTH falls, tubule calcium falls, UF calcium is unchanged. But in real life, if GFR fell, for example, or even if sodium depletion reduced PT delivery, UF calcium could rise a lot, and itself reduce SNGFR with the infamous and dangerous and sudden hypercalcemia we all dread. Im IH, urine calcium is not high because of increased FL, we have proven that. But, tubule reabsorption is sensitive to UF calcium (no doubt calcium ion) and no doubt because of enhanced CaSR somewhere in the nephron – I vote for cortical TAHL. We have some new data on this, but have published the effect before. So things seem rather integrated: GI absorption is above normal, renal tubule calcium reabsorption is abnormally responsive to at least UF calcium – and serum calcium, too, so both balance out. We never write about this as no one asks us to do so in the reviews they invite. It is always a level below this conversation – you know, such things as ‘…when should the physician use thiazide?’ Warmest regards, Fred

      Reply
      • Stephen J Knohl

        Yep, it all makes sense while, at least for me for certain conditions, remaining a conundrum…such as the hypercalciuria seen in normocalcemic hyperparathyroidism. It would seem to me that this would simply be another designation or subtype of idiopathic hypercalciuria. It would have to be reduced TmP/GFR with secondary increases in bone resorption and/or GI absorption to maintain the UF of ionized calcium, correct?

        Reply
        • Fredric L Coe, MD

          Hi Steve, NC PHPT has always seemed a function of how well we can measure serum calcium and how many times we are willing to do it. As to phosphate, I found and published years ago that serum phosphate does indeed run low in stone formers, and it is linked to other PT functions suggesting disordered transporter regulation. Bone will one way or another maintain serum calcium if renal tubule reabsorption falls and diet is insufficient and secondary rise in PTH is inevitable. All the best and thanks for the comment, Fred

          Reply
  4. Carl J

    My doctor has recently diagnosed me with Grover’s Disease, a non-contagious skin rash that causes terrible itching and it can last for 6-12 months. On the Mayo Clinic forum site, a number of patients (with this disease) have said that eliminating dairy products has helped them significantly. Since I’ve had kidney stones 4 times, I have been on chlorthalidone (25 mg) for the past 3 years and my urologist has urged me to drink milk (I do – about a gallon a week). If I was to try and go off dairy for a month or so to see if it helped my Grover’s Disease, how would you recommend me getting sufficient calcium? Many thanks for your help.

    Reply
    • Fredric L Coe, MD

      Hi Carl, Of course you can use supplements in the mean time. Use a TUM with each main meal. But also mention the chlorthalidone to your dermatologist. I have seen a lot of skin reactions to it. Regards, Fred Coe

      Reply
  5. John Daugirdas, MD

    Fred, great information, as always. I have one observation, and two questions.
    The observation pertains to the need (hypothesized, not proven, but common sense), for patients with IH to take in some calcium at a minimum (probably at least 300 mg/d if not more, EVERY day. It is very easy to take in zero calcium from the diet unless one eats dairy or green vegetables. A typical U.S. breakfast without cheese, say ham, eggs, a croissant, coffee, and orange juice, will have zero calcium. Same for lunch – say a tuna salad sandwich, and dinner (steak and potatoes with a garden salad). Lettuce has a trivial amount of calcium. A good site to look this up is https://nutritiondata.self.com/
    I have found calcium supplements to not uncommonly cause constipation, so taking in even as much as 500 mg/d of calcium from food is not easy without dairy. As urinary calcium excretion responds only partially and poorly to reductions in dietary calcium intake, I believe that it’s important to assure that there are very few or no days when dietary intake of calcium is low or absent in patients with IH. The minimum calcium intake (and days of trivial calcium intake) may be as important, or more so, than the average calcium intake.
    The second is a question: what is the role of bisphosphonates in protecting the bone against calcium reaborption ?
    And a third question/issue. Thiazide type diuretics are known to cause not only potassium depletion, but also magnesium depletion. The potassium issue can be dealt with by combining with a sodium channel blocker like amiloride, but what about magnesium? Re magnesium: and esp. in this day and age when many patients are taking PPIs such as omeprazole: Do you supplement your patients to whom you prescribe chlorthalidone with magnesium or monitor their magnesium levels?

    Reply
    • Fredric L Coe, MD

      Hi John, As always, perceptive and useful. I favor a full calcium intake of 1000 to 1200 mg/d and that means dairy products more or less. The trick is getting diet sodium down below 100 mEq/d or even lower, and I can manage that in some cases, and recommend we try in all cases. So I agree with you and even add. As for bisphosphonates, I have seen them stabilize BMD in IH patients, and they are a useful first line. But when not enough I am bold about newer agents. These patients can fracture, and fractures can be multiple. The magnesium issue is vexing and I always try to add MgO early rather than waiting for a big deficit. Unlike potassium wasting for which we have amiloride and low sodium diet, the Mg loss is hard to stop in some patients. So I monitor, and have them use OTC stuff. In manotor with 24 hour urines so I can see what is absorbed. Warmest regards, Fred

      Reply
  6. Midge Gilmour

    Thank you Dr. Coe for your research. I do appreciate it very much. I was a patient of yours when I lived in Chicago. I moved 4 years ago to retire. I followed the low sodium high food calcium diet that you prescribed for me. I make sure I drink a large amount of liquid as I live in a dry climate. I have been kidney stone free for 5 years. This year the urologist noticed a stone in my left kidney. It’s too large to pass. They offered to do a lithotripsy, but after having done two of those in Chicago with no success I refused. I’m waiting for my next appt. to see if they have to do surgery. I also need to tell you that I did have bone loss and now get bone density injections twice a year. Should I allow them to remove the stone via surgery or wait? Thanks for your time.

    Reply
    • Fredric L Coe, MD

      Hi MIdge, I remember you well. I am sorry about the new stone – that is a failure of treatment. If it is causing no pain, bleeding, obstruction or pain removal is elective. But why a new stone? Have you been able to get yearly 24 hour urine studies to be sure your diet is controlling stone risk? If not, please do that. Things change over time, and diet treatment is hazardous in a way as habits and life style are to complex. Let me know, and warmest regards to you, Fred

      Reply
  7. Kim gallagher

    I’m sure your preference would be getting your calcium from food but is calcium supplements (citracal for example) another viable option ?
    Also how much daily protein do you recommend for a 125lb woman?

    Reply
    • Fredric L Coe, MD

      Hi Kim, calcium supplements are usable but best taken with the main meals so the calcium will be absorbed along with your food. As for protein about 0.8-1 gm/kg body weight /day is ideal. Warm regards, Fred

      Reply
  8. FCormack

    Hello Dr. Coe,
    I have a question regarding management of a patient with presumed idiopathic hypercalciuria. Urine calciums ~400 mg/24 hours on multiple collections with urine Na ~100 meq. She is 62 with severe osteoporosis and calcium oxalate nephrolithiasis. Her stone disease has been stable for years but I am very concerned about her bone disease. Interestingly, she also has a diagnosis of sarcoidosis. This was based on very mildly elevated 1,25 OHvitamin D levels, hypercalciuria and chest CT findings of nodules/adenopathy over 10 years ago. Serum calcium always wnl. She was never treated for sarcoid, just monitored.

    She recently established care with me and we did not see any improvement in her calciuria on chlorthalidone 25 mg. She had significant hypokalemia and hypomagnesemia so I know she was taking it. I believe her diagnosis is most likely IH and not sarcoid. She has a strong family history of stone disease and hypercalciuria with 2 siblings on thiazides. Before starting chlorthalidone, her serum Ca, 25 OH and 1,25 OH vitamin D levels were all in normal range.
    My questions are: Why did we not see any reduction in urine calcium on chlorthalidone 25 mg daily and what would you do next? I am inclined to increase chlorthalidone to 50 mg daily and add amiloride but want to make sure I am not missing something here. I would really appreciate your insights on this case. Best, FC

    Reply
    • Fredric L Coe

      Hello Dr Cormack, You do not mention it, but I assume her PTH was not suppressed – the remaining clue to D mediated hypercalciuria. Failure to lower urine calcium despite a reasonable urine Na of 100 leaves us with only three alternatives: lower the diet sodium more, raise the dose of CTD, or begin a bone active drug to reduce bone mineral loss. Of these, I like the third best, as she may have rapidly progressive bone disease. I like the lower sodium second. I have seen rapid bone mineral loss appear this way, and the urine calcium wane over a few years as bones stabilize. A trial of a bisphosphonate is not unreasonable, or perhaps an other bone active agent. As for amiloride, I agree totally. I find 5 to 10 mg daily a big help. Regards, Fred

      Reply
      • FCormack

        Thank you so much for your prompt response and advice on this case.

        Her PTH has been high 30s-low 40s. Most recently 39 (12-88 pg/mL) with serum Ca 9.7, 25OH vit D 24.6 (20-50 mg/mL), 1, 25 OH vit D 72 (17-72 pg/mL).

        Because of quite severe osteoporosis, her rheumatologist recommended anabolic therapy (abaloparatide) to start but was hopeful we could lower urine calcium first. Historically she resisted bisphosphonates because her mother had jaw osteonecrosis. I agree that best to reconsider antiresorptive treatment at this point.

        Kind regards, Fionnuala

        Reply
        • Fredric L Coe, MD

          Hi Dr Cormack, The anabolic meds may also partition calcium into bone. If it is more desired, I would personally give a try. Fred

          Reply
  9. Rose Marie Murray

    Correction: I miscalculated my husband’s daily calcium intake. Instead of approximately 1000mg/day, it is closer to 550mg/day. My apologies. Rose Marie

    Reply
  10. Rose Marie Murray RD

    Hi Dr. Coe,

    Thank you for providing such valuable information and for offering this opportunity to ask for your advice! I hope this isn’t too much information, but I would greatly appreciate your in-put

    My husband (54 yrs old) had his first (and hopefully last) kidney stone October 31, 2019. After reading extensively on your website, I assume that he has idiopathic hypercalciurea. He has been eating a lot of sodium. It makes sense.

    I understand your dietary advice: sodium 1500-2300mg/day, Calcium 1000-1200mg/day, protein .8-1.2g/kg body wt /day, water 3 L.

    My question is to ask for clarification of your oxalate recommendation of 100mg/day for stone formers. How do I put that into perspective with the fact that his urine oxalate levels were normal (but he had been eating high oxalate prior to the stone, and then very low oxalate after the stone bc/ it was an oxalate stone) and his calcium intake meets your recommendation? Should he still try to keep dietary oxalate to 2300mg Na/day. He eats 1.1-1.5g protein/kg body weight /day.

    Reply
    • Fredric L Coe

      Hi Rose Marie, You are wise and shrewd. If his urine oxalate is normal then he is done with the oxalate diet apart from the worst foods – spinach and rhubarb, and lots of nuts, pepper, and dark chocolate. With high diet calcium from food distributed to the main meals oxalate is a minor player in people with low values of urine oxalate as you describe. The big problem is to keep the sodium low enough that his urine calcium is not too high- -so measurements are needed. Be sure everything has been measured and attended to – here is a good overview. Regards, Fred Coe

      Reply
      • Rose Marie Murray

        Thank you so very much for your response and advice. We’ll focus on lower sodium, higher calcium per your recommendations and then re-do the 24 hr urine in a couple of months.
        Best, Rose Marie

        Reply

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