CALCIUM PHOSPHATE STONES: Causes and Prevention

Me

Full Video – 19 minutes; Brief Video – 10 minutes

Unlike Zeus, or Athene, Janus did not come to Rome from Greece but from myths about a person living early in Roman history and later deified. Janus – deity – presides over beginnings and endings, gateways and doors, invariably dual in nature.

What is dual here?

Calcium stone formers are dual. A minority arise from systemic diseases we must screen for. Each systemic disease has its own universe of causes and treatment decisions. A majority are “idiopathic”, systemic causes have been excluded.

Idiopathic calcium stone formers are dual. They have no systemic cause of calcium stones. Most form calcium oxalate stones. A minority, more women than men, form calcium phosphate (CaP) stones.

Idiopathic calcium phosphate stone formers are dual. Most have hydroxyapatite (HA, like bone mineral) as their stone calcium phosphate. Some have brushite (Br, calcium monohydrogen phosphate) in their stones. These latter have more kidney damage than HA CaP stone formers, and are a special high risk group of patients.

Both kinds of CaP stone formers need special attention. That is why I have written this article for them.

Basic Facts about Phosphate Stone Formers

Phosphate Stones Damage Kidneys

Phosphate stones, HA or Br, can grow faster and larger than calcium oxalate ones. Calcium phosphate crystals invade kidney tissue – so called tubule plugs. Tissue damage is common, as is Nephrocalcinosis from plugging – often misdiagnosed as medullary sponge kidney. Kidney tissue damage is worse with Br than HA stones. Potassium citrate, a common stone prevention, may not be appropriate as a treatment because it raises urine pH.

Alkaline Urine Causes Phosphate Stones

Stone phosphate replaces oxalate when urine is too alkaline. Kidney and GI tract physiology raise urine pH, especially in women. Diet is not the cause of higher urine pH. Diet will not reliably lower the pH, and we have no specific drugs to do it, either. So although treatment uses the same tactics as for the more common calcium oxalate patient, it must follow a different strategy.

How Stone Analysis Distinguishes CaP from CaOx Stone Formers

Only CaOx and HA Present

If the average stone mineral composition of all available stones for a given patient is above 50% calcium oxalate, the patient is considered a calcium oxalate (CaOx) stone former. If the average calcium phosphate content is above 50% the patient is considered a calcium phosphate stone former.

The average must be computed using 0 – for example, given CaOx/CaP percentages of 100/0, 0/100, 40/60, the correct classification is 140/3 vs 160/3 or 46% CaOx vs 53%, and so a CaP stone former.

Uric Acid, Struvite, Cystine Also Present

If uric acid, struvite, or cystine are present we name the patient for that constituent. A patient who forms mixed stones – for example, 60% calcium phosphate/20% struvite 20% CaOx is called a struvite stone former. The reason is that these stone types have special causes and treatments. 

Any Brushite Present

Brushite is very uncommon in human kidney stones, and associates with large tubule plugs and more severe tissue damage. So when any stone contains brushite we classify the patient as a brushite stone former even though brushite is a minority of stone mineral.

Sex and Age

Single Clinic Experience

Percentages of Cases

CaptureThe table shows ‘CaP’ as cases where HA or brushite was the stone phosphate crystal (in early years we did not distinguish). CaP(b) are CaP stone formers with only HA, no brushite in any stone.

CaP predominate among females (a and b superscripts denote outsize high frequencies). Brushite does not show this difference a statistical level of significance. CaOx stone formers predominate among the total of all cases. Brushite patients are least common.

Sex vs. Percent CaP in Stones

The same study furnished this nice graph showing the sexes as the percent of stone CaP increases. The bulk of patients have very little CaP in stones (tall bars at the left of the graph). These are the common CaOx stone formers, mainly men (% female, dots, right axis about 25%). But when CaP percent is 20 – 50% in stones, women and men are nearly equal.Capture 2

This graph blurs the sex distinction because we used stone CaP% from both brushite and hydroxyapatite. Today, I would have left the brushite to one side, which would have made the female preponderance among those with high stone CaP% more marked – because the sex ratio for brushite stone formers is closer to 1.

National Laboratory Findings

The Mayo Clinic kidney stone analysis laboratory analyzed 48,446 stones in 2010, and of these 43,545 were the first submitted to the lab for that person. From these stones, they report the distribution of stone type by sex and age. I have made a graph from Table 2 of their publication.

Population Sex Ratio

stone rates and male to female stone and population ratios from Lieske

The general population contains more males than females at younger ages (blue dots). By age 30-39 the two sexes are present in equal numbers. Thereafter, as men predecease women, their blue dots slump downward.

For all ages combined, the ratio of men to women is just under 1 (last blue dot at right).

Stone Former Sex Ratio

The blue bars show male to female ratios among stone formers. Remember this is counted from the sex of the person whose stone was analyzed. A survey based on symptomatic rates of stone passage, by contrast, might give different results altogether.

In childhood, men have slightly more stones than women (blue bar is above 1.0). In the teen years and up to age 39, women predominate over men (blue bars are below 1.0). After age 40 men predominate, until at age 90 and more, in this and perhaps most things, the sexes come into a near perfect alignment. Averaged over all of life, men have more stones, which appears to be because of their midlife excesses (Height of the ‘ALL AGES’ bar above 1.0).

The fraction of all stones formed (red dots; scale along the right axis) for both sexes combined is highest from age 20-69, with only a small fraction in childhood or old age.

Types of Stones

sex and age vs stone type from lieske

The men are on top, women on the bottom of the picture to the left.

Stones were classified using the system I have used on this site. Uric acid in any amount meant the stones were classified as uric acid stones, and likewise for any struvite or cystine.

CaOx stones preponderate among both sexes over all ages, except in women between ages 20 – 39 stones were about half CaOx and HA. With age, HA stone frequency fell in both sexes, so that most men, and most older women (over 40) have CaOx stones.

Brushite stones, in both sexes, are very uncommon. You can see them as triangles along the bottom of both graphs.

Over age 50, uric acid stones become a significant concern in both sexes.

Struvite stones, which always arise from infection with bacteria that possess urease, are more common in women than men, a fact known for ages.

The Mystery of Brushite

Brushite stones are rare but should be rarer still. I have written a whole article on brushite because it is so important and yet so evanescent. It forms first of all crystals in human urine. If pH is not too high, oxalate steals away its calcium atoms so it vanishes. If pH is high, HA does the same, and brushite vanishes.

Why, then, are there any brushite stone formers?

I do not know nor does anyone I know of. It is an open question that seems obscure but whose answer might well lead to some new understanding of how stones form.

The Importance of Brushite

Being the first crystal to form, brushite supersaturation is crucial for stone prevention, a fact not intuitive but worthy of special emphasis. Rare in stones, vanishing in most urine, yet brushite supersaturation is foremost in importance for clinicians and patients. The goal is a supersaturation below 1, so brushite cannot form. For those who want to know more about why, please look at the parent article.

Time and Shock Wave Lithotripsy

We (left hand figure below) and others have noted an increasing percent of CaP in stones over the past 30 years. In women (black dots) CaP percent is always higher than in men, but it has risen in both. For those of a quantitative bent, the time trend of stone CaP tested by ANOVA with post hoc contrasts was significant for both sexes, and women were higher than men throughout.

In the publication, we found a relationship between CaP cappercent vs decades from parks phosphate paperpercentage and numbers of shock wave lithotripsy procedures. Use of potassium citrate, however, did not seem to increase stone CaP.

The number of shock wave procedures per patient adjusted for the number of stones and the years of stone disease rose with the percent of CaP in stones (Panel A of the figure below to the right) and the percent of CaP likewise adjusted for number of stones and duration of stones and sex rose progressively with the number of shock wave procedures (Panel B of figure to the lower right).

Not shown here, but of interest, the number of shock wave treatments was higher among BRSF than HASF suggesting a link between shock wave treatment and brushite stones.

One might infer from this set of graphs that the advent of shock wave lithotripsy caused the increase in phosphate stones, and there is nothing to contradict the idea. In fact, the very physiology of phosphate stone formation and the effects of shock waves on kidney swl and stone capfunction strongly support that idea as I shall show you.

Mechanisms of Phosphate Stone Formation

High Urine pH

As expected, percent CaP in stones (upper left panel of the figure below) rises with CaP SS. I have shown elsewhere on this site that stone crystals parallel urine supersaturations.

Because CaP SS depends powerfully on urine pH one expects and finds (upper middle panel) that urine pH tracks very closely with stone CaP percent. Urine calcium, volume, phosphate, and citrate excretions (remaining panels) had no important relationship to stone CaP percent. 

But take a look at the urine calcium excretions (Upper right panel). They are very high on average. This is because a high fraction of all calcium stone formers have genetic (idiopathic) hypercalciuria. Risk for stone forming begins at a urine calcium of 200 mg/d in both sexes.

determinants of phosphate stones sixplot

So you can think of CaP stones as a two hit model.

Genetic hypercalciuria promotes calcium stones, and urine pH controls the fraction of phosphate in the stones. High CaP SS and CaP stones require a urine pH significantly above 6 as shown in the upper middle panel.

Kidney Tissue

Plaque and Plugs

CaOx stones can be produced as overgrowths in interstitial HA deposits, called plaque.

Idiopathic CaP stone formers, and patients with stones from bowel disease, ileostomy, renal tubular acidosis, and primary hyperparathyroidism, form stones on plaque but also on plugs of HA that fill and damage the last millimeter or so of the nephron, the inner medullary collecting ducts and ducts of Bellini.

Although we are not certain, I think it is fair to say that the plugging of CaP stone formers is because more CaP crystals form in urine and can produce plugging. In a recent article I trace out how calcium phosphate actually forms, how it is a rapid process compared to calcium oxalate, and therefore more able to make plugs during the short times it takes for urine to pass out of tubules into the renal pelvis.

Distinctions Among the Three Idiopathic Calcium Stone Formers

We have table from ha br caox comparison paperpublished selected laboratory and tissue findings of CaOx, brushite and HA stone formers, in an attempt to clarify differences in how stones form, and amounts of tissue injury.

Numbers are small because each patient had been studied with intra-operative imaging of the renal papillae and papillary biopsy: 11 CaP (HASF), 25 BR (BRSF), and 30 CaOx (ICSF) stone formers.

As expected, urine pH was higher in the BRSF and HASF than in the ICSF, as was supersaturation (SS) for CaP. Incidentally, urine calcium (Ca) was also higher in both CaP groups than in the ICSF.

Mainly CaOx and BR stone formers formed plaque, and mainly CaOx SF form stones on it. About 8% and 6% of papillary surfaces were covered with plaque in ICSF and BRSF but only 0.8% among the HASF. CaOx stone formers had an average of 10 stones/patient attached to plaque, vs. only 3 plaque stones in 25 BRSF and 6 in 11 HASF stone patients: 10/ CaOx patient  vs 0.12/brushite patient and 0.54/HA patient. These are 80 and 18 fold differences, respectively!

Plugging (‘deposits’ in the table) was absent in ICSF, but common in BRSF and HASF. Plug size averaged 1.6 mm2 in BSRF but only 0.4 mm2 in HASF – a 4 fold difference. The number of plugs was 3 times higher in HA vs. Br patients: 12 vs. 3/mm3 of tissue volume. BRSF formed fewer but much bigger tubule plugs.

Calyx dilation (a abnormal finding) estimated during surgery was higher in HASF than in the other two groups, and papillary injury (papillae are the parts of kidneys inside calyces) higher in both phosphate groups than in ICSF.

In the kidney cortex, far from where stones form, many CaP stone formers had scarring (TIF, tubular interstitial fibrosis) vs. very few CaOx patients. Brushite patients had most cortical damage.

So phosphate stone formers have injury involving the papillae and cortex, whereas CaOx stone formers have almost none.

Why is Urine pH High?

Being Female

I wrote a whole article on how women raise their urine pHThey do it by absorbing from their food a higher fraction of its alkali content. No sense copying all that here, it is better to read the article. High GI alkali absorption is not easy to treat. Those alkali are nutrient – anions that cells metabolize to get energy. 

Being Young

We used a massive database of kidney stone formers to ask what happened to urine pH in men and women with age. The answer is it falls, in both sexes (women are circles, men triangles).

Why is a long story. We could exclude gain in BMI, loss of kidney function, and GI alkali as reasons, but could not find the reason itself. In fact, GI anion absorption rose with age, as if to offset the falling pH.

Here the important fact is on the graph – higher pH in women and in youth are an obvious cause of more CaP stones.

Shock Wave Lithotripsy (SWL)

No practical experiments permit us to measure effects of SWL on urine pH in humans.

For these reasons we turned to an animal model: The farm pig whose kidney is much like that of a human, and likewise is similar in size.

In these animals we could shock one kidney, and then compare the treated to control side at time intervals after the treatment, the untreated side being a perfect control as both kidneys are bathed by the same blood.

SWL Raised Urine pH.

Urine pH from the treated kidneys was 0.18 pH units higher than the control, meaning SWL had increased urine pH (first line of table under ‘Basal’).

SWL Damaged Kidney Tubule Function

There was a lot more.

Urine flow, and excretion of bicarbonate, potassium, chloride, sulfate, calcium, magnesium, sodium and oxalate all were higher from the treated side (bolded). This means that shock wave treatment affects tubule handling of multiple molecules, presumably because of injury.

table 2 from swl paperWe could find these abnormalities up to 90 days after shock wave. The control kidney reduced its losses in compensation so blood remained entirely normal.

Bicarbonate Losing Raised the pH

The higher urine pH could have been due to damage of final urine acidification in the collecting ducts or to high delivery of bicarbonate from higher up in the nephron so that acid secreted lower down was neutralized by a flood of bicarbonate.

To tell these apart we gave the pigs an acid load that lowered their blood bicarbonate and therefore filtration and downstream delivery (‘Acid load’ columns). Acid load brought urine pH and almost all other measurements to equality between the shocked and control kidneys (loss of bolding).

The tissues from the pigs showed widespread injury to the thick ascending limbs, and you can read the paper for details.

SWL Can Raise Urine pH by Damaging Kidney Tubules

The meaning of the work is clear.

After shock wave treatments the treated kidney may excrete excess calcium and produce a urine of higher pH than it would otherwise do. The effects are precisely those needed to produce calcium phosphate crystals. From the bladder urine, which mixes urine from both kidneys, one could never know this was happening.

It is possible that the advent of shockwave lithotripsy has contributed to the rise in CaP stones, and I hope that further science sorts out whether this hypothesis is false or true.

High Kidney Ammonia Production

Ammonia Production Regulates Urine pH

Kidneys excrete acid by making ammonia that can carry acid (protons) into urine without lowering urine pH. They also excrete acid by titrating urine phosphate, which does lower urine pH. If ammonia production goes down, from kidney disease, for example, urine pH has to fall so acid can be lost on phosphate.

Ammonia production relates itself to body acid load – from food and metabolism – so that the average urine pH is just around 6. But what would happen if regulation were abnormal so more ammonia than normal was made for a given bodily acid load?

Urine pH would rise.

CaP Stone Formers Make More Ammonia

The graph shows urine ammonia excretion from normals, and CaOx and CaP stone formers studied eating the exact same diet in a research center.

Fasting, all three groups are the same (left panels). Food increased urine ammonia in male CaP patients (#). Fed, the female CaP stone formers produce more ammonia than female normals (*, top right panel). So do the female CaOx stone formers. Ammonia production is governed by body acid load, which we measure as GI anion and urine sulfate – a residue of metabolic acid production. When we adjust ammonia for acid load (lower right panel) CaP stone male and female stone formers remain high compared to same sex normals.

We suspect the high urine pH that causes CaP stones arises in part from high ammonia production, perhaps an inherited trait.

Low Urine Citrate

Many articles on this site explore the powerful effects of citrate to bind calcium and inhibit calcium crystal growthIn these closely 

studied men and women we could document a uniquely low urine citrate of CaP stone formers vs. normal people.

Low Citrate in CaP Stone Formers

Food increased urine citrate is normal women and all three male groups (#). With food, CaP stone formers of both sexes have urine citrate excretions below their same sex normal counterparts (*, upper right panel) as did female CaOx stone formers.

As is well known, citrate is lower in normal men than women (compare black bars; we did not choose to compare the sexes statistically).

Adjusted for GI alkali and urine sulfate, (lower right panel) low citrate is concentrated among male CaP and female CaOx stone formers. Normal men remain below normal women.

Male CaOx stone formers have abnormally high urine citrate with and without adjustment for systemic acid balance.

Abnormal Kidney Cell Citrate Handling

Alkali loads, most famously potassium citrate, raise urine citrate and is an established stone preventionCitrate also raises urine pH, because the alkali appears in urine as bicarbonate. That is why potassium citrate is not an ideal treatment against CaP stones, and why we have for decades needed a controlled trial to see if it works or makes things worse.

But here we have a high urine pH coupled with low urine citrate, in male CaP and female CaOx and CaP stone formers. That points to something wrong with kidney cell regulation.

We measured serum citrate and glomerular filtration so we could calculate the fraction of filtered citrate excreted (FE Citrate), shown in the upper right panel of the graph at left.

FE citrate is low in female CaOx and CaP stone formers and in males with CaP stones. This means that CaP stone formers are reabsorbing abnormal amounts of citrate back from the filtrate. It is used by kidney cells to produce metabolic energy.

Adjusting for GI alkali absorption (lower right panel) removes the female abnormalities but makes the male one even more prominent.

That male CaOx stone formers have abnormally high urine citrate excretion with normal FE citrate is because their serum citrate concentration is higher, a fact for which we had no explanation.

CaP Stone Formers Have Proximal Tubule Abnormalities

Citrate reabsorption and ammonia production are linked in the proximal tubules of the kidneys as part of overall kidney regulation of bodily acid base balance. In general alkali loads raise urine pH and urine citrate, and reduce ammonia production, whereas acid loads do the opposite.

Here we have high pH and high ammonia production coupled with low urine citrate, more marked in male CaP patients but detectable among the women as well.

It is as though the cells perceive a need to produce more acid excretion (ammonia) and conserve potential alkali (citrate is metabolized to bicarbonate), but there is no need. So urine pH rises and converts calcium stones to their phosphate forms. The cause(s) of these proximal tubule abnormalities are not known.

Incomplete Distal Renal Tubular Acidosis (dRTA)

A Questionable Disorder

Some have proposed that CaP stone formers have high urine pH and low citrate as part of “Incomplete renal tubular acidosis”. In proof, when given extra acid they may not reduce urine pH as low as normal people. In my primary article on dRTA, I present contemporary evidence that acid loading creates a continuous spectrum of urine pH responses, even among normal controls, so it is not a good basis for diagnosis. It seems better to say that CaP stone formers have abnormal proximal tubule functions, and make those the focus of new science.

Heterozygotes of Familial dRTA

With one exception, hereditary dRTA arises from gene disorders of the main proton transporters or of carbonic anhydrase itself, and these disorders are in general recessive. They are recessive because you need two defective genes to knock out a transporter whereas one good gene copy will maintain function.

Of course dRTA causes massive CaP stones and kidney disease. But heterozygotes – meaning one good and one defective gene – from families with dRTA if studied in detail, may not lower urine pH normally. These might be diagnosed as ‘incomplete dRTA, because in fact that is what they are.

CaP Stone Formers are Not Like Incomplete dRTA

Unlike our CaP stone formers, urine ammonia is low in dRTA and heterozygotes from families of dRTA, when compared to their acid load – urine sulfate. Urine ammonia is never high. I suspect that some CaP stone formers have high urine pH because they are indeed heterozygotes of dRTA. Low ammonia may be a way to separate them from the high ammonia of routine CaP stone formers.

Risk of Conversion From CaOx to CaP Stones

Some patients gradually increase their stone CaP percent, often enough to alter their classification to CaP stone former. The opposite, conversion from CaP to CaOx stones must be very uncommon, as we have no cases to report. We wanted to know how to detect risk of conversion.

Who We Studied

From 4767 patients in our program, we collected all CaOx stone formers who had two or more stone analyses and clinical follow up data (445 patients). From these we selected all who had a last stone CaP% at least 20% higher than that of the first stone (62 patients). Men and women were combined because we had so few cases.

Of these 62 cases, 26 had had three initial (pre-treatment) 24 hour urine studies before they passed the stone whose CaP percent was at least 20% higher than their first stone. We labeled these transformers with prior laboratory work – labs before they transformed – as ‘TP’.

the 26 converting patients with pre conversion labs TC group

For controls we chose 181 patients whose first stones were >90% CaOx and who increased their stone CaP percent <20% between the first and last stone.

This figure shows the 26 TP cases and the 181 controls.

CaP% Was High at the beginning

Even though their initial stone CaOx percent was >50%, the 26 TP cases (black circles, upper left panel) had an average stone CaP of 10% before treatment, whereas it was much lower in the controls – who never added significant CaP.

During follow-up (upper left and middle panels) the 26 TP (black circles) increased their stone CaP markedly (average 10% to 79%, top left). The controls (gray triangles) hardly changed (-0.6% for controls, 69% change, for TP, upper middle panel).

Higher Urine pH Increased CaP SS

Urine pH and CaP SS before treatment and before conversion (upper right panel and lower left panels) and during treatment (lower middle and lower right panels) were higher in TP (black circles) than controls. CaP SS rose because we used potassium citrate as part of our treatment program.

SWL May Have Played a Role

ESWL associated with conversion: 112 of the 136 total cases with no ESWL procedures were controls, whereas only 21/41 cases with >2 ESWL were controls (X2=17, p<0.001). Furthermore, a predominance of ESWL procedures preceded the final stone (not shown here but shown in the paper), meaning ESWL could have been a causal factor.

Who is at Risk?

When stone CaP is above 10%, average 24 hour pH is as high as 6.3, or CaP supersaturation is above 2 before treatment risk of increasing stone CaP may be high. More than 2 ESWL procedures likewise. Given these risk factors in a CaOx SF perhaps one is prudent to treat as if CaP stones were already forming, so as to possibly prevent further stone CaP accumulation.

Prevention of Calcium Phosphate Stones

The objective is to lower CaP SS – reported with respect to brushite – below 1.

The main modifiable factors are urine volume, and calcium and citrate excretion. Because we cannot lower urine pH, the most crucial factor, we have to use what is left to achieve our goal. Likewise, because citrate regulation is abnormal in CaP stone formers, use of potassium citrate may not raise urine citrate so much as it raises urine pH, and therefore this otherwise valuable treatment can be ineffective.

Fluids

Relative calcium stone risk falls to 1 (no excess risk) at about 2.3 l/d of urine volume. Given the limitations of our treatments, I usually strive for 2.5 l/d spread out over the waking hours. This is an achievable goal if patients understand why it is important for their stone prevention.

Reduced Calcium Excretion

Genetic hypercalciuria is very common among calcium stone formers. If we understand that relative risk of stones rises above 1 at a urine calcium of 200 mg/d, both sexes, our goal is to reduce urine calcium to or below that point.

Reduced Diet Sodium

Multiple articles on this site detail the power of diet sodium to control urine calcium and bone calcium balance. The US diet recommendations for sodium are 100 mEq (2300 mg)/day as a tolerable upper limit, and 65 mEq (1500 mg)/day as ideal. These values concern blood pressure and bone rather than kidney stones. But if we achieve an ideal diet sodium it will lower urine calcium as well as defend blood pressure and bone mineral. So I have no reservations about promoting the ideal diet sodium, but also am prepared for compromise in this fast food dominated world.

Reduced Diet Sugar

As for diet sodium, I have written extensively about sugar as a factor that raises urine calcium, abruptly after the sugar load and with proven increase in supersaturations. Once again, US guidelines call for reducing sugar intake, and there is no benefit to anyone from eating refined sugar in any form. So I am shameless in my zeal to encourage patients to eat as little of it as possible.

Thiazide

Drugs of this class lower urine calcium about 80 to 100 mg/d below the level predicted by sodium intake. They act in part to increase proximal tubule calcium reabsorption. They are trial proven agents to reduce calcium stone recurrence. We have shown thiazide drugs lower urine pH, a possible benefit.

I have often argued to use diet as much as possible before adding thiazide to avoid drug side effects. But phosphate stones are not easy to prevent, so far as I have observed, and they damage kidney tissue. Moreover, we have no trials – none. These patients may have been in trials but are doomed to perpetual minority status unless specifically a focus.

So I am not shy about adding thiazide after perhaps only one to two efforts at diet control, should CaP supersaturation remain above 1.

Why NIH has yet to fund a calcium phosphate stone prevention trial escapes me. I cannot imagine how this has not been a priority.

Potassium Citrate  

This drug will lower urine calcium below the level predicted by diet sodium intake. It may raise urine citrate excretion. But It may also raise urine pH.

Being as it is therefore able to raise or lower CaP supersaturation, I do not so much avoid using it as view it with a cold eye.

If thiazide is not attractive to a given patient I will try citrate and watch the effect on CaP supersaturation. CaP supersaturation is the final resultant of whatever changes it induces in urine calcium, pH, and citrate. If it indeed lowers CaP supersaturation, I am prone to use it but with appropriate 24 hour urine followup and an inextinguishable skepticism.

Reduced Diet Oxalate

I am aware that calcium oxalate in stones matters, and that even high phosphate stones often contain that crystal. If urine oxalate is high enough to confer risk – above 25 mg/d in both sexes – I make appropriate diet recommendations.

But patients cannot do everything all at once, so I generally put most emphasis on the calcium phosphate side. The exception is when urine oxalate is quite high – above 40 mg/d, for me – whereupon I do what I can with diet.

Monitoring Treatment

The objective is to lower CaP supersaturation below 1 in the 24 hour urine, and that is what I aim to achieve.

If fluids are enough, so be it. If not I add more treatments more or less as in the paragraphs above. Lacking trials, this is the best we can do. I watch supersaturation for calcium oxalate as a secondary endpoint, and if it is high enough to promote risk – above 3 – I attempt to lower it by reducing diet oxalate.

Monitoring is crucial. What we try to do may not be done because patients cannot or will not do it, so we have to know when to try another approach.

Put another way, for stone prevention, especially calcium phosphate stones, deliberation is reality.

I wish to thank Dr John Asplin for his careful reading of this article and suggestions for improvement. 

 

 

115 Responses to “CALCIUM PHOSPHATE STONES: Causes and Prevention”

  1. Christoph Schwarz

    Hallo Dr. Coe
    I see only few patients with recurrent CaP (mostly apatite) kidney stones in our clinic.
    If those patients have nephrocalcinosis additionally,we search for hereditary diseases of calcium and phosphate metabolism.
    But, in the literature there is sparse information on the stone composition in such diseases. So it is not clear if those patients have CaOx or CaP stones (or both)

    Do you have information on stone composition in hereditary hypercalciuric/hyperphosphaturic diseases?
    Do you think it makes sense to screen for hereditary diseases of CaP metabolism in patients with recurrent CaP stones and nephrocalcinosis?

    Kind regards
    Christoph

    Reply
    • Fredric L Coe, MD

      Hi Dr Schwartz, Phosphate stone formers form tubule plugs that can mount up to look like nephrocalcinosis on CT. Images during URS are the most reliable, for me, in assessing stones vs plugging. Our most recent – small samples, immense detail – of CaP stone formers show what appears to be a dysregulation of renal NH4 production with an associated increase of citrate reabsorption – higher urine pH lower citrate. I suspect this is heritable. There is a sex difference as well, men CaP SF having the more marked NH4 disorder. All of the patients we have studied in detail have idiopathic hypercalciuria, which is genetic and polygenic enough no one has as yet even found workable clinical gene markers. As for the less common single gene diseases, in my own work I rarely find them. I do family history in everyone and in a few instances have uncovered forms of dRTA but our clinic does not have routine genetic screening. Best, Fred

      Reply
  2. Lisa

    Dr. Coe, I’ve seen ionized calcium test mentioned, should all stone formers have that tested and what benefit is ionized over a regular calcium blood test? Also since my lab does not show on my 24 hour urine PCR, ammonia, sulfate, chloride, and urea nitrogen can they be figured out from the supersaturation values that are listed on my 24 hour urine? I can only use this lab because of insurance and Quest but I’ve read that Quest doesn’t show many of the values either. As long as the supersaturations are listed along with other routine values like calcium, vol, ox, citrate, etc is it okay to not have those others listed above? Thank you for your valuable time.

    Reply
    • Fredric L Coe, MD

      Hi Lisa, Ionized serum calcium is sometimes used in diagnosis of primary hyperparathyroidism.It adds little. The article discussed the crucial problems of fasting morning samples and a need to make many measurements if the values seem high. As for QUEST, their stone product is mediocre, and there is no way to get the missing information. Lacking them, at least try to keep total protein intake to about 1 gm/kg body weight/day, which is what PCR tells us. I am not sure about the SS values either, but you want them as low as possible. Regards, Fred Coe

      Reply
  3. Alicia T.

    Good morning Dr. Coe,
    I have had 2 very large stones in my right kidney in the last 2 years (first was 11.65mm and second was 9.46mm) they were both broke up with Lithotripsy and after many passing of stones 4mm and below I was told I have a lot of “gravel in the bottom of my kidneys. I had a 24hr urine culture for stones and found out I have Hypercalciuria, supersaturation index – Brushite (Ca phosphate) .

    my 24 hour StoneRisk Urinalyses profile levels we as follows:
    Total urine volume – 2.92
    pH Urine – 6.8
    Calcium – 325
    Oxalate – 29
    Uric acid – 517
    Citric Acid – 660
    Sodium – 162
    Sulfate – 8
    Phosphorus – 940
    Magnesium – 90
    Ammonia – 29
    Potassium – 43
    Creatinine – 1266
    Calcium oxalate – 1.29
    Brushite – 3.14
    Sodium urate – 0.89
    Struvite – 2.12
    Uric Acid – 0.14

    This all stated after I turned 40 and had a life altering change due to a Trauma which caused PTSD and Severe Anxiety. Physically I lost 60lbs and started working out daily after being over weight for most of my life. Since the first stone I have been Hyperaware of my diet and water intake. I have been on the gallon challenge for over a year. I try to drink a gallon of water spaced out from 7am to 9pm daily. I have just learned that I am Hypercalciuric with high Brushite. I have already changed my diet to reduce my intake of beans and nuts however I do not eliminate leafy greens just try not to intake a full serving.
    Do you know of anything I can do to help prevent or limit the forming of the large stone?

    Reply
  4. Lisa

    Dr Coe,
    In your years of research have you found any info about long term use of oral contraceptives (33 years long) on stone formation or affect on 24 hour urine values?
    Why doesn’t my 24 hour urine have urea nitrogen, chloride, sulfate, ammonium, and protein catabolic rate? Is this a separate urine test and how should that be ordered? I’ve seen these in reading articles from other patients.
    I don’t understand my bone density from 2 years ago at age 49. AP Spine T score -1.6 Z score -1.2 Total left dual femur T score -1.4 Z score -1.0 Total right dual femur T score -1.8 Z score -1.3 Left Forearm T Score -1.0 Z score -1.0. Three different providers told me three different things. Is this normal?
    Thanks and learned so much from you,
    Lisa

    Reply
    • Fredric L Coe, MD

      Hi Lisa, About stones, I do not believe OCT promotes them. I suspect if estrogen use extends into menopause urine calcium will remain lower as bone mineral is better preserved. Your 24 hour urine is not from a kidney stone lab vendor as urea chloride sulfate and ammonia are needed to calculate supersaturation. Your physician may have ordered from a routine lab. I prefer Litholink as a vendor – no financial interest. At age 49 spine t = -1.6 femur t = -1.4 forearm -1; this is all from one test and one provider, just different parts of you. The T score measures deviation from peak bone mass for sex in SD units, so -1 means your value is one standard deviation below the mean for normal young women – about 67% low, a mild fracture risk. In your spine and femur risk is a bit higher than in your forearm; the first two have a higher fraction of trabecular bone the arm is cortical – outer shell of bone. Given these modest values just be sure you get enough vitamin D and diet calcium, weight bearing exercise. Regards, Fred Coe

      Reply
  5. Carol Fugel

    Dr. Coe,
    Love your work, a great source for me being Calcium Phosphate stone former. I’ve worked hard using your site and think I have accomplished some work and very compliant to make any changes needed. Drink 10-12 liquids daily, mostly all water( 12 oz coffee and milk other) and limit diet sodium and here are my 24 hour urine changes in last year.
    2019 = Cal 324, ox 23, uric acid 513, citrate 350, PH 7, volume 2.73, sodium 95, phosphorus 871, Mag 87, Ca Ox Sat 1.33,
    Brushite Sat 4.39, Sodium Urate Sat .62, uro potassium 48, uro creat 1054
    2020 = Cal 237, ox 35, uric acid 461, citrate 325, PH 7, volume 3.72, sodium 73, phosphorus 915, Mag 85, Ca Ox Sat 1.22,
    Brushite Sat 2.38, Sodium Urate Sat .25, uro potassium 41, uro creat 977
    I get all my calcium from diet, mostly dairy and my next step was to increase that to get to 1000-1200 mg day. Leary on calcium supplements but will take them if you advised to make up the difference. No problems eating dairy and like.
    Other questions, is there anything I can do to get my PH down on my own such as cranberry juice daily, Vit C, or other? I know increasing urine citrate helps with crystallization for stone prevention but was thinking it wouldn’t be advised for me to drink lemon juice because it would increase my PH or does the citrate outweigh the PH in stone formation? What is a good 24 hours urine citrate number to have? Uro Phosphorus number? Also am I okay not to worry too much about oxalate foods on a whole, I eat pretty healthy and have wheat in my diet daily from healthy cereal and bread and my biggest oxalate would be 2 measured TBS of peanut butter a day that I love and use for some protein. Is that an issue? Working hard on decreasing sugars since I use to eat too much with snack foods and chocolate. Eat lots of fruit and veggies a day and proteins are from eggs, tuna, dairy (milk, cheese, yogurt) mostly with some turkey lunch meat and very little red meats on occasion only. I find it hard to keep the protein in range for a 120 lb 50 year old woman when I don’t eat much meat! If I go by your website I’m getting that I should only have total protein under 50g a day, I tend to have in the 70’s or 80’s with my diet and little meat. Been tested for primary hyperparathyroidism and endo doc says I don’t have or any other metabolic reason for my stones. I have been studying this since I developed stones in 2018 with new R stone 2019 US and now new L stone 2020 US, one ureteral stone removed 2019 that was 70% phosphate(hydroxy and carbonate apatite) and 30% oxalate. I need guidance on what to do next since urologists locally don’t have time to educate which I understand with their schedules. He did not believe I needed meds because of their side effects and the potassium citrate raising PH.
    Thank you for your valuable time,
    Carol

    Reply
    • Fredric L Coe, MD

      Hi Carol, Even with a lowered urine sodium urine calcium is generous and SS for brushite – calcium phosphate – is above 1. If you are forming new stones, then either you may have to lower diet sodium even further or use a thiazide diuretic along with the diet. As for diet calcium, it is raised to lower urine oxalate but your SS CaOx is very low so a normal calcium intake in the range of 800-1000 mg from food is reasonable. The problem here is that I am not in a position to really direct your care – only your real physicians can do this, so whatever I say needs to be alright with them. If stones continue, you might want to obtain a separate consultation, which can direct your care. Regards, Fred Coe

      Reply
  6. Khansa rafi

    I have my 70% calcium phosphate stone and 30% calcium oxalate on stone analysis. I’m taking potassium citrate but it promotes high alkaline environment suitable for phosphate stones to strive in . I’m confused , should i continue with potassium citrate or not ?

    Reply
    • Fredric L Coe, MD

      Hi Khansa, An astute remark. Is potassium citrate actually appropriate for your situation. Be sure that you have been fully evaluated using 24 hour urine studies and blood as well. Usually phosphate stone formers have genetically high urine calcium excretion and treatment is other than potassium citrate. Regards, Fred Coe

      Reply
      • Khansa rafi

        Yes I’ve done my 24 hour urine analysis and had high calcium in urine with mild proteinuria and low citrate . I’ve raised parathyroid hormones too but no adenoma found on parathyroid scintigraphy and ultrasound . Dr just prescribed me calcium and vitamin D supplements to lower it . Please mention in comment the treatment plan for such case . I’m mistreated and misdiagnosed by many doctors wrong . Thanks for your informative article .

        Reply
        • Fredric L Coe, MD

          Hi Khansa, Low citrate high calcium and – you did not mention it – high urine ammonia are what we find in CaP stone formers. The proteinuria sounds like kidney problems your physician might want to consider. High PTH with normal serum calcium may be secondary, perhaps to even slight reduction of kidney function or perhaps low vitamin D. Again, your physicians need to help with this. PT imaging is usually not very informative in the absence of high serum calcium – I presume your serum calcium is normal. If it is high, that is an entirely different matter. Regards, Fred Coe

          Reply
  7. Sean

    I am a calcium phosphate former & I never stop forming them. I pass stones / sediment every 3-4 weeks. I was diagnosed with a “leaky kidney” & put on a diuretic, that I am unable to take because of my bodies reaction to sunlight while on the medication. Are there other solutions? Any nutritional advice?

    Reply
    • Fredric L Coe, MD

      Hi Sean, I imagine you have genetic hypercalciuria, and diet may suffice. Take a look at the article on that topic. If you reduce diet sodium enough you might need no drug or only a tiny dose. IDIOPATHIC HYPERCALCIURIA (IH)Regards, Fred Coe

      Reply
  8. Alyson

    I had kidney stones that were 100% calcium phosphate. My doctor is saying it’s rare and he’s not sure how to help me with these. Is there any treatment?

    Reply
  9. SC

    Hi Fred,
    I recently had a stone analyzed that was Carbonate Apatite (Dahllite) 90% and Calcium Oxalate Dihydrate (Weddellite) 10%. I am still unclear what this means.

    Reply
    • Fredric L Coe, MD

      Hi SC, It means you produce calcium oxalate stones richly admixed with calcium phosphate. The article you write on is pertinent to your situation as urine pH will be high and treatment has some special features as in the article. Regards, Fred Coe

      Reply
  10. Colette Whitfield

    I had my first kidney stone aged 59. It comprised 50% calcium oxalate and 50% calcium phosphate. Prior to this I had been suffering from persistent heartburn. My GP prescribed taking Gaviscon Advance four times daily for a few weeks which I did. Could this be the cause of this stone?

    Reply

Leave a Reply