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. Lisa

    Hi Dr. Coe,
    I had surgery in May for a calcium oxalate stone (my 3rd kidney stone incident but first analyzed). I finally had a 24 hour urine ordered here in Toronto. My results are:
    Calcium per day 12.2 mmol/d
    Citrate per day 7.5 mmol/d
    Creatinine per day 13.3 mmol/d
    Magnesium per day 9.3 mmol/d
    pH 5.5
    Phosphorus per day 29 mmol/d
    Potassium per day 35 mmol/d
    Sodium per day 75 mmol/d
    Urea per day 359 mmol/d
    Uric acid per day 3.5 mmol/d
    volume 5.792 l

    Bloodwork
    calcium 2.4 mmol/L
    Chloride 104 mmol/L
    Creatinine 49 umol/L
    Ionized Calcium 1.24 mmol/L
    Magnesium 0.79 mmol/L
    Phosphorus 1.19 mmol/L
    K+ 4.0 mmol/L
    PTH intact litho – cancelled
    Sodium 139 mmol/L
    Total CO2 26 mmol/L
    Urea 2.8 mmol/L
    Uric Acid 154 umol/L

    They have not shown any oxalate amount even though I saw it on the requisition and I don’t know why the PTH was cancelled. I am hoping to see a nephrologist after I have completed my 2nd 24 hour urine. I am just wondering what I should be asking him/her once I do get in to see them. It looks to my like I have hypercalciuria but I don’t yet know why. Thanks for any help/suggestions you can give me.
    Sincerely,
    Lisa

    Reply
    • Fredric L Coe

      Hi Lisa, You do have a high urine calcium and normal serum calcium, suggesting precisely the condition in the article you post on. The PTH would be unneeded given the normal serum calcium. Omission of oxalate is a mistake as it can be high in any stone former, and should be measured at least once for safety. I know that Canadian health systems function on statistical assessments of cost/benefit, and also prides itself on evidence based decisions. But here the system is wrong. Rare people have very high urine oxalate levels AND incidentally high urine calcium, and the former can cause kidney disease. Given it is rare but dangerous one should always look at least once at 24 hour urine oxalate excretion. Overwhelmingly, it will be unremarkable, but even so. insist on at least one measurement. Idiopathic hypercalciuria is familial, certainly genetic, and strongly improved by low diet sodium and if needed thiazide diuretics. Here is my very favorite article on treatment. Regards, Fred Coe

      Reply
      • Lisa

        Thank you so much for replying. I re-checked my online results a few days later and the oxalate amount showed up at 556 umol/d which shocked me because I’ve been following your and Jill Harris’ Kidney stone prevention diet for almost 6 months. I will be doing another 24 hour urine next month and then hopefully seeing a nephrologist so I will discuss this with them. Much appreciated.

        Reply
        • Fredric L Coe

          Hi Lisa, So high a urine oxalate usually means diet calcium is not high enough, or calcium is not timed well to meals that contain high oxalate foods, or some very high oxalate foods are being eaten, or there is an underlying issue raising oxalate absorption or even production. Consider these alternatives with your physicians and perhaps you and they can sort out the cause – everything has a cause. Regards, Fred Coe

          Reply
  2. Vasiliki Anderson

    Hi Dr. Coe,
    I was just diagnosed with IH based on two 24 hour urine tests and the blood test. My level of calcium in urine is 390 and calcium/creatine ratio is 365.
    I am 62 and have never had any stones. Moreover, there is absolutely zero history of stone-forming anywhere in my family. I was tested because my bone scan showed osteoporosis in my hip femurs: 2.5 & 2.7 Z scores.
    The endocrinologist of course prescribed Hydrochlorothiazide 12.5 Mg daily, but I am interested in avoiding this medication if at all possible. For one thing, I have quite low blood pressure to begin with, and also I would be much more inclined to treat the root cause rather than the symptom. So I am wondering about your advice on diet and any other things I can do. (I have always exercised with weights and am very active so I don’t think I can do much more with that). My diet is very healthy, but I may be eating quite a bit of protein.
    I really appreciate any guidance you can provide.
    Thank you so much.

    Reply
    • Fredric L Coe

      Hi Vasiliki, IH produced bone disease and you can do well with reduced diet sodium and high calcium diet. THe ideal diet sodium would be about 50 – 60 mEq (about 1500 mg/day or less), and diet calcium about 800 to 1000 mg. If the low sodium diet is not enough one can add a very low dose of thiazide to it, low enough to prevent too much side effects. If the disease progresses, standard bone treatments are not unreasonable, including bisphosphonates and newer agents. Regards, Fred Coe

      Reply
      • Vasiliki Anderson

        Thank you for the speedy and helpful reply! Since you didn’t suggest low protien intake, can I assume that is because I am not at risk for kidney stones, just bone mineral absorption? Thank you!
        Your generosity of time is a true gift to people like me seeking to understand this disease better.

        Reply
        • Fredric L Coe

          Hi Vasiliki, No; low protein diet is not a good idea. You want about 1 gm/kg/day, a normal intake. Fred

          Reply
  3. Emily

    Dear Dr Coe,

    I came across your website because you diagnosed my maternal grandmother with hypercalciuria many years ago when she was having kidney stones, and she has described what a difference your work made for her. I have recently passed a calcium oxalate stone myself, and I am currently having further investigations into the cause, which is what led to my recent interest. My mother and other family members have also had kidney stones, and several family members suffer from low bone mineral density/osteoporosis. Therefore, it was really interesting to read about the stone and bone links and the relevance of family history. I am currently feeling quite unwell even though there are no more stones present on ultrasound, and my serum calcium concentrations have been normal on the three occasions they have been checked over the past few months. However, I did have a raised parathyroid hormone level with normal serum calcium, and I have other symptoms of hyperparathyroidism (fatigue, excessive thirst, finding it difficult to concentrate, feeling slightly dizzy). My calcium levels were not checked after fasting, although in one occasion I had had very little to eat beforehand. I am currently waiting for a bone density scan. Can you suggest any other investigations that might be useful for exploring the cause of my stones and other symptoms? I would be happy to send more detailed results if you are willing to look at them. If so, it might be easier to send them via email if there is an email address I can contact you on.

    Many thanks in advance for any advice.

    Best wishes,
    Emily

    Reply
    • Fredric L Coe

      Hi Emily, Idiopathic hypercalciuria is genetic and causes stones and a form of bone disease. Obviously I would suggest 24 hour urine testing along with fasting am bloods to be sure about serum calcium. I suspect you have IH, and also perhaps low calcium diet or low vitamin D as a cause of high PTH with normal serum calcium. This kind of normal calcium increased PTH is secondary and without known symptoms of its own. If you wish to write to me personally I can look up my records of your grandmother. If she is still alive ask her permission and also send my regards. Regards to you, as well, Fred Coe

      Reply
      • Emily

        Dear Dr. Coe,

        Thank you so much for your quick reply and your offer to look into this for me. I will send your regards to me grandma. She speaks very highly of you and I’m sure she’ll be pleased to hear from you. I will also ask for her permission regarding accessing information from her records. Is there an email address that would be okay for me to contact you on? If you would prefer not to share it on here, I could contact your department and ask them if that’s okay?

        Thank you again,
        Emily

        Reply
  4. John Scott

    From recent tests my 24 h urine calcium is 338 mg/d and bone density T-score of -1.7 at right total femur(low bone mass). I am allergic to sulfamethoxizole(hives on forearms). Is there an option for my apparent I.H. other than thiazide diuretics ?

    Reply
  5. Carol Wenmark

    Dr Coe,
    I sent you all my test results back in January and you said I had secondary hyperparathyroidism due to vit d deficiency. Saw my endochronologist and she agreed. Since taking 4000 in of vit d and 800 mg calcium my PTH was 31 and calcium was 9.8. Was tested a month later in March 2018 and PTH was 36 and calcium was 9.7. Just saw my endochronologist today after blood work and my PTH was 64 and calcium 9.2. I am on a low salt diet and high water intake. My vit d25 OH was 49 then 61 and now 84. I was told to back off on vit d to 2000 iu and stop taking calcium. My kidneys are full of tiny stones and this situation concerns me the most because things haven’t gotten better for two years. Would appreciate advice on what to do about stones.

    Reply
    • Fredric Coe, MD

      Hi Carol, I already responded to your labs. I am confused about the sequence = I presume the many tiny stones were there before. If they are new, that is a real worry. I suggested a full evaluation for the cause of stones and think that is essential. What interests me is why your serum calcium fell – had you lowered your calcium intake before the blood draw? Are the bloods all fasting? If not, they can be very misleading as PTH falls with meals and serum calcium rises. Regards, Fred Coe

      Reply
      • Carol wenmark

        Dr Coe, Are my stones caused by the secondary hyperparathyroidism or are they a completely separate issue and not related to SHPT.

        Reply
        • Fredric Coe, MD

          Hi Carol, Secondary hyperparathyroidism does not cause stones. It is a response to some drive for more PTH: vitamin D deficiency, low calcium diet, reduced kidney function, intestinal calcium malabsorption. Often stones ’cause’ it because people avoid diet calcium – always a mistake as it will not prevent stones. Regards, Fred Coe

          Reply
  6. Carol wenmark

    Dr Coe…I emailed you in January and based on my lab results you believed I had secondary hyperparathyroidism. My endochronologist came up with the same due to Vit D deficiency. She raised my Vit D to 4000 in and calcium to 800 mg/day. I am on low salt diet and about 90 oz water/ day. Since implementing these changes, here is my recent blood work.
    D25 OH. CAL. PTH
    2/23/18 49. 9.8. 31
    3/27/18. 61. 9.7. 36
    10/1/18. 84. 9.2. 64
    I am concerned because my kidneys are still loaded with tiny stones. There has been no change in stones for two years. I have never been able to collect a stone. I also don’t know why the PTH has gone up to 64. Should I be seeing a nephrologist for stones?.
    Thank you,
    Carol

    Reply
    • Fredric Coe, MD

      Hi Carol, I notice the serum calcium is lower. Have you reduced your calcium intake or changed the kind of calcium foods?? Given multiple stones you should want a full evaluation. Here is my favorite article about the subject. Regards, Fred Coe

      Reply
      • Carol Wenmark

        Coe,
        I would appreciate if you could look at my current testing. I’m still in limbo as to my diagnosis. Finally passed two kidney stones and they were both calcium oxalate. I took Jill’s course and have been on the low salt, low sugar diet, high water intake since last summer. I am now on the low oxalate diet for the past month. Nephrologist said that he still thinks I have primary HPT. He said a urine calcium over 400 is most definitely PHPT. I can’t figure out why my urine calcium went so high. I’m taking a cal supplement 800 mg/day. I do eat a lot of calcium in my diet. Am I getting too much? Vitamin d is i2000iu/day. My blood tests were non fasting.
        My nephrologist wants to put me on hydrochlorothiazide and do another 24 hr urine in three months. I don’t know if I sent this so you can see my recent test results. If I didn’t send them correctly please tell me how to get them to you.
        Sent from my iPaimage1.JPG
        image2.JPGimage3.JPG

        Reply
        • Carol Wenmark

          Forgot to tell you that I still have many stones. My nephrologist requested that I contact you about my test results before going on thiazide. Thanks so much.

          Reply
        • Fredric Coe, MD

          Hi Carol, I am always happy to help but this is a slightly unusual issue – to intervene in a real clinical decision as opposed to simply offering routine technical information about 24 hour urine findings. If your nephrologist would actually want my advice concerning your medical management, S/He would need to contact me and send me the materials deemed pertinent. I would then respond to him/her as well as to you. It is the better way to do this, with a proper relationship. Warm Regards, Fred Coe

          Reply
      • Carol wenmark

        Here are my last three test results from litholink.

        Vol 24 sscaox. Ca24. Ox24. Cit24. SSCaP. Ph. So UAE. Ua24. Date
        3.38. 3.99. 373. 27. 684. 1.74. 6.944. 0.05. 0.561. 1/7/19
        3.80. 2.37. 171. 26. 300. 0.52. 6.398. 0.17. 0.651. 11/26/17
        250. 3.09. 247. 18. 645. 1.60. 6.963. 0.05. 0.478. 7/27/17

        Here are my last three PTH, calcium and Vit. D,25-OH
        1/15/19. 46. 9.9. 68
        12/31/18. 33. 9.7. 61
        10/1/18. 64. 9.2. 84. Lowered vit d to 2000iu from 4000 after this test.
        Sorry I sent this in three different emails. My nephrologist values your opinion. Thank you.
        Carol

        Reply
        • Fredric Coe, MD

          Hi Carol, just looking at numbers, serum calcium levels seem normal so primary hyperparathyroidism is not a realistic idea. It all looks like idiopathic hypercalciuria. Regards, Fred Coe

          Reply
      • Carol wenmark

        A few more results…sodium is 56, mg24 is 167, cr24 is 1005 on current 24 hour urine. Sorry I sent this in a few emails. Thank you, De Coe

        Reply
        • Fredric Coe, MD

          Hi Carol, the low sodium should have lowered urine calcium; I do not know what 167 is. Regards, Fred Coe

          Reply
          • Carol Wenmark

            167 is urine magnesium. All other numbers were good. Ca24/cr24 was 371. Can”t understand why my calcium is so high. I stopped taking calcium pills and get my 1200 mg in food. Appreciate you so much.

            Reply
            • Fredric Coe, MD

              Hi Carol, Idiopathic hypercalciuria, if that is what you have, raises the urine calcium. If low sodium diet does not bring it down, and your blood calcium is really normal, then meds are in order. Regards, Fred Coe

              Reply
  7. Lulu

    Hi I am a 50-year-old post menopausal woman postmenopausal since 45 years old I have a high urine calcium read out I’ve had multiple lithotripsy and multiple incidences of kidney stones and my renal doctor wanted me to start thiazides. I however do not want to start any type of water pills because I’ve been reading about the adverse affects of them especially on the heart . I started taking Rice bran in food in the morning and at night but I don’t take any calcium supplements. My calcium level was low but my vitamin D level was extremely low and I don’t know what the differences between those two and I am currently having severe pain in my hips and my shoulders. I don’t know what else to do

    Reply
    • Fredric Coe, MD

      Hi Lulu, Rice bran and low calcium diet may lead to bone mineral loss. Your best treatment is very low sodium diet to keep your urine calcium down, and a high diet calcium for your bones. Low vitamin D is very bad for bones and I am sure your physician will want to raise it. If your serum calcium is low – as you suggest – the vitamin D deficiency and low diet calcium absorption may be causing serious problems your physician will want to remedy promptly. Regards, Fred Coe

      Reply
  8. Janet Hanway

    Dr. Coe, I was diagnosed with primary hyperparathyroid disease in August of 2017 and had a parathyroidectomy on 3.5 of my 4 parathyroid glands at Yale New Haven hospital. I have also had very high CA reading in my 24 hour urine tests and am diagnosed with osteoporosis. My 24 hour urine tests have consistently been high and in the neighborhood of 387 or so. While my PTH reading fell to normal after my surgery, it is now a high reading again of 86. My bone density test has deteriorated to the following: The L1-L4 BMD has a T-score of -2.8, the L2-4 BMD has a T-score of -2.8 and the L1 BMD has a T-score of -3.0. The femur BMD T-score is -1.5, the femur neck BMD T-score is -1.9. My doctor has tried decreasing my urine CA through drugs such as chlorthalidone or hydrocholorthiazide but I do not tolerate them. One raised my potassium level and I did not feel well with the other. He is now trying me on a low level of potassium citrate (10MEQ, 3 times daily) to see if I can tolerate it and improve the urine CA level. In addition but unrelated, I have Hashimoto disease of my thyroid. He is asking that I get tested for kidney stones due to the high urine CA level. If the potassium citrate does not work, do you have any other suggestions for approaches to address the high urine CA and osteoporosis issue as my osteoporosis continues to progress even though I am very careful with my diet and do strenuous weight lifting twice a week.

    Reply
    • Fredric Coe, MD

      Hi Janet, Given that you are at Yale, I hesitate to mention the possibility, but perhaps you have recurrent primary hyperparathyroidism; you seem to have had multi gland disease, and the high PTH and stubborn high urine calcium + failure of bone mineral to increase are most compatible with that possibility. Is your serum calcium perhaps even trivially above normal?? Have they done ionized calcium to check? Hypercalciuria is common after cure of PHPT as we and others have reported, but rising PTH and worsening bone disease are not expected. Perhaps your physicians might consider this idea, if they have not already done so and abandoned it as being unlikely. Regards, Fred Coe

      Reply
  9. Barb Blue

    Hi Dr. Coe. I am 59 year old post menopause woman. I had my first stone 2/18 with laser lithotripsy. Took Jills wonderful course and follow the diet vigilantly. My last 24 hr urine in May had all good parameters EXCEPT urine calcium was 351. My first 48 hr collection had calcium of 221 and 295–we figured out that my sodium intake was a little too high–and have resolved that issue. 1) Why would my urine calcium jump so much this time?
    Today is my first day of hydroclorothiazinde — 25mg– and I will repeat urine in 2 weeks. Do you recommend increasing potassium intake or should I just wait to see what my urine and blood work looks like. How much of a decrease in urine calcium should I expect? How will I know if it is the medication effect when my urine calcium has been variable (221, 295, 351). My PCP did not believe I needed a bone scan. 3) Do you think I need a bone scan?
    Many thanks !!!

    Reply
    • Fredric Coe, MD

      Hi Barb Blue, Take a look at the sodium – did it increase. Likewise at the PCR – did your protein increase. Is your urine sodium low enough – below 100 and preferably about 65. Potassium citrate can wait; lower the sodium fully, keep the PCR below 1, and see what the med can do. I suspect part of the increase is you raised diet calcium. Be sure to use foods not supplements if possible. Supplements need to be with meals. A bone scan is a good idea – hypercalciuria causes bone disease. Regards, Fred Coe

      Reply
  10. Maria Jose

    Hi Dr. Coe. This is Dr. Velasco from Central Vermont.
    I wanted to ask your opinion. I have this 42 y/o woman who has been diagnosed with idiopathic hypercalciuria since 2012 at YNHH. She is on chlortalidone 25 mg a day and k supplements. Her 24 u calcium is 151, electrolytes are WNL.
    She is very frustrated about the disease and her BMD even those she is pre-menopause continues to decline. She is on low dose OCP. I have advised to eat about 0.8-0.9 g of protein a day and to be on a low salt diet. I reviewed some papers and it seems there is not much evidence about using bisphosphonates in pre-menopause woman to improve BMD or worst there is not evidence that that will improve fracture risk. Am I correct? Will you do something differently? Thank you so much.

    Reply
    • Fredric Coe, MD

      Dear Dr Velasco, The bone disease of idiopathic hypercalciuria is indeed evolving and we do not know enough. However we do know this much: Bone mineral balance will rise with low sodium/high calcium diet, and with low dose chlorthalidone. That she is on chlorthalidone and got no response suggests a problem with diet sodium, or calcium, or both. Unfortunately the data here are incomplete. My own balance study used only chlorthalidone and showed positive bone balance, but I was fortunate that calcium intake was ample. To achieve positive bone balance in IH takes a lot of diet calcium, but none of the studies also added low sodium (65 mEq/d or better). In one trial – the only one remotely related to your case – high calcium + low sodium increased bone mineral in peri-menopausal subjects. So, I would use the combine of low sodium and high calcium and CTD and also consider if she can safely continue estrogen after menopause. As for bisphosphonates, I share your concerns because IH bone disease has some low turnover features. If needed she may benefit from some of the newer MC antibody treatments if needed to ward off fractures. Regards, Fred

      Reply
      • The Patient In Question

        Hello, folks. I’m the patient in question. I was dx’d at U-C in ’06, actually, by Dr. Favus, while doing my residency. I have never formed a stone, and an U/S at U-C found no stones at that time, either. (Isn’t that strange?!) I generally keep Na<1000 mg/day, and Ca intake I obtain from 3 servings of yogurt daily, plus or minus a pile of kale or other high-Ca greens, or a couple of sardines. I experienced bone density improvement one year only, and that was a year when I was living in Indonesia, using Tums for most of my Ca, and eating an extremely low-Na diet with nearly all protein from tempeh, a fermented soy cake. After that, my spinal bone density improved. It worsened after I returned to the States, and I've wondered why ever since.

        Here's my question, Dr. Coe: would it be helpful to add Ca supplements atop my yogurt intake? Perhaps Ca citrate, recheck bone density in a year? From past experience, I know my urinary Ca rises when I use supplements, but I'm unsure whether that would negatively affect bone density. I'm not worried about stones. I'm extremely worried about my spine.

        Reply
        • The Patient In Question

          IN other words, might my poor spine vacuum up extra Ca if I provide it, given that I don’t seem to form stones (knock on wood)? Could I safely bump Ca to, say, 1500 mg/day and see what happens?

          Reply
          • The Patient In Question

            I would also welcome insights as to why my hip bone density improved, 2018 vs 2012, but spine worsened. Why would these two types of bone be going in different directions?

            Reply
            • Fredric Coe, MD

              Hi Again, The bone disease of IH can be focal, and I do not know why. Sorry, Fred

              Reply
              • Lily

                Hi there, I’m 19 and have had kidney stones since the age of 11. Currently I have one 9 mm stone in the lower pole of my left kidney as well as a 4 mm stone in the middle. Although both are non obstructing I’ve been getting a lot of pain in my left kidney..what can I do to alleviate this? Also, my nephrologist put me on potassium citrate and said my diet was fine. My blood calcium levels fluctuate from 9-10.1. Is there a chance this could be due to my parathyroid? My 9 mm stone grew from 2 mms in January to 9 mm in late April. The 4 mm stone was not there on the last scan I had in March. Why am I producing stones so fast?

              • Fredric L Coe

                Hi Lily, your variable blood calcium does suggest primary hyperparathyroidism, and you should be sure and get proper testing for it. Pain from non obstructing stones is not uncommon, and we do not as yet know if more surgery will improve it. Regards, Fred Coe

          • Fredric Coe, MD

            Hi, I suspect you might settle at about 1200 – that was the trial. Those women were peri-menopausal, so not like your condition, but it is all we have. If you keep the sodium low enough, try 1500 mg calcium but check the urines. Consider a very low dose of chlorthalidone 12.5 mg daily as an extra – it can raise bone mineral balance. Regards, Fred

            Reply
        • Fredric Coe, MD

          Hi Patient in Question, I gather you have idiopathic hypercalciuria and its associated reduced bone mineral density. Your experiment in Indonesia with very low sodium diet and extra calcium resembles the one – yes only one – actual trial concerning effects of sodium and calcium intake on bone balance – in this article. I believe the very low sodium was important and perhaps the Tums. Here, with some bone loss, I would consider using supplements – the best way is with larger meals – that was how the trial went – along with the lowest possible diet sodium. I would use 24 hour urine testing to be sure of the sodium, hard to gauge. Your urine calcium rise with diet calcium is entirely a function of the corresponding sodium intake and consequent fractional excretion of sodium, so the lower the better. Regards, Fred

          Reply
          • The Patient In Question

            Thank you for your reply , Dr. Coe. I will try these ideas. I’ve been on chlorthalidone for 12 years now, and it has not really helped–hence my and Dr. V’s frustration and search for new approaches. (Would you mind removing my name from your reply?)

            Reply
            • Fredric Coe, MD

              Hi Patient in Question, perhaps your diet sodium is high enough to offset the effects of the medication. If bone mineral retention cannot be otherwise maintained bone directed meds may ultimately become your best alternative – I think you know that. Fred

              Reply
              • The Patient in Question

                Please remove my name from your previous reply. My diagnosis is now linked to my real name on search engines.

              • Fredric Coe, MD

                OK, I think I did that. Fred

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