A Good Place to Start

VIDEO 1: RISK FACTORS (17 min).

VIDEO 2: EVALUATION (13 min) AND TREATMENT (13 min).

The videos review the chapter and emphasize the main points. I would start with them.

Salt Ponds

The featured image shows salt harvesting from evaporation ponds.

The sea is salty and like our blood holds its salts in solution. But if you channel the sea into ponds, and balance things so the sun evaporates water faster than new water can enter, the remaining water overloads with sodium chloride. It crystallizes out of solution as sea salt. Workers collect it for us to season our food with.

Is it not an apt picture?

Our Blood is the Sea, our Kidneys Make the Pond

Mostly the Salts Stay in Solution

Our kidneys filter the salts and water of our blood into their millions of fine tubules. Like the sun they take back the water, unlike the sun they also take back much of the salts.

Mostly they are balanced, these takings back, so the final urine can dissolve its salts.

Stones Arise from Imbalances

If you ask me to say what makes stones form, I must answer that something has disturbed the balance, leaving not enough water to dissolve the salts, as in the ponds drying out under the sun.

Which salts, you might ask? After all, we are not ponds and our kidneys remove many small molecules.

Those salts, I would answer, that have made the stones.

Precisely those. Usually calcium oxalate and calcium phosphate.

The 24 Hour Urine is Our Pond

In it we measure losses of salts that can become stones, and the volume of water to dissolve them. We need the full day because things vary, with sleep and food, and all of what we do in life. Each is snapshot of our pond for one day. Which salts, how much imbalance, all this comes from our daily samples.

Abnormal Excretions Cause Stones

In our urine, excesses of calcium or oxalate excretion, or insufficiency of citrate excretion or of water are proven independent risk factors

that predict new onset of stones. Since stones cannot cause these abnormal excretions, and the abnormal excretions can cause stones, this association is equivalent to cause.

By independent I mean that the effect of each is significant when the effects of the other factors are adjusted for mathematically using common statistical techniques.

In cohorts of women (red) and men (blue) followed over decades, risk of forming stones rose smoothly with urine calcium or oxalate (upper left and upper middle panels), and fell with increasing citrate and urine volume (lower left and middle panels).

The mechanisms causing high urine calcium and urine oxalate are well known. Means for lowering them, likewise, and such lowering is known to reduce new stone formation.

Risk from low urine volume is most obvious below 1.25 liters per day (lower middle panel), a scanty volume. By 2 liters a day risk from low volume is gone.

Supersaturation is the Word for Overloading the Pond

Crystals produce kidney stones, and supersaturations produces the crystals. Modern laboratories can measure the supersaturations in 24 hour urine collections along with the key components in the urine that control the supersaturations.

As you might expect, supersaturation is a powerful predictor of whether people will become stone forming patients. The two right panels of the graph show how supersaturation with respect to calcium oxalate (top) or calcium phosphate relate to risk of stones. (Note that common supersaturation urines for calcium oxalate are 3.3 times higher than these older style supersaturation ratios. Your report will almost always use the newer units. So risk begins above 3 and rises smoothly up to 12 or more).

Given the stone crystals and the supersaturations you can gauge treatment goals from a simple maxim: In a patient who is producing new stones, urine supersaturation with respect to the crystals in the stones forming is too high.

Ideally one will lower supersaturation by improving all factors that raise it. But one must avoid a common and obvious fallacy. Water alone can lower urine supersaturation – think about rain and the pond. But water alone, without proper testing and as a sole remedy is a poor idea under all circumstances and to me anathema.

Ideal Treatment Improves All Abnormalities

Given a patient may have any one of these four abnormalities, and that they act independently, the ideal treatment strategy will attempt to improve each one to achieve synergy. It is often more practical to partly reverse multiple abnormalities than to rely on improving only one. For example, possibly extremely high urine volume might reduce stones even if urine calcium and oxalate remain high. But lesser volume would be sufficient if these two excretion rates were each moderately reduced.

When treating hypertension, as an example, one tries to achieve some weight loss, some increase in exercise, some reduction in sodium intake, and some increase in potassium intake, and then use medications as needed. The alternative, medications alone, or just exercise, would create a potential for side effects – too tired from exercise, or drug side effects in this case – which synergy would avoid.

Proper Testing Is Essential for Proper Practice

All Stone Formers Deserve Serum and 24 Hour Urine Testing

It is obvious that the only documented risk factors for stone are found in 24 hour urine, so this measurement is the bedrock of stone prevention. Systemic diseases that cause stones often alter serum chemistries, and they must be diagnosed from those alterations. 

Inadequate Testing Can be Dangerous

A few causes of stone disease, such as severe hyperoxaluria can destroy kidneys. Others like primary hyperparathyroidism or renal tubular acidosis can do the same. Other rare but dangerous inherited diseases lurk in any kidney stone population. They require both serum and 24 hour urine testing.

Consider that idiopathic hypercalciuria can be very severe and lead to both stones and bone disease. One cannot know without a 24 hour urine collection. Elevated serum calcium can mark for primary hyperparathyroidism, or simply benign familial hypocalciuric hypercalcemia. So one needs a 24 hour urine here as well. Low urine citrate as a cause of stones is simply unknowable without a urine collection. 

Arguments Against 24 Hour Urine Testing are Specious

Cost, difficulty, and futility are all common arguments against urine testing, and none of the three convince me. Add to this that all people fear and detest surgery. Surgery is a nightmare one hopes to avoid. If testing can reduce surgery by even a small amount, testing is a virtue.

Surgical Costs Dwarf Those of Proper Testing

A common 24 hour urine with fasting blood sample costs a few hundred dollars – say three hundred for an upper end estimate. A kidney stone surgery, ureteroscopy for example, costs – about eight to ten thousand dollars, to which one must add lost work and the debilitating effects of general anaesthesia, postoperative pain, stents, infections, and postsurgical visits to physicians. Shock wave lithotripsy costs as much or more as shown in the same reference. At these rates, 30 to 40 24 hour and blood testing panels match one surgery discounting the personal losses.

Difficulty of Collection Stops Few Patients

In my decades of managing patients with kidney stones almost none have demurred to collect – pilots, surgeons, busy and successful business people, teachers. I could also point out that modern commercial vendors all provide convenient collection kits and instructions. But no one could make the case better than my partner Jill Harris did in her spirited article on this topic. 

Personalized Kidney Stone Prevention

Stone Analysis is Crucial

Assuming stones are forming or have formed, everything branches off of stone analysis.

Uric Acid in Stones

Uric acid stones form mainly because an overly acid urine raises supersaturation so powerfully nothing can reliably prevent more stones but alkali to raise pH and make the urine less acid. Uric acid stone can be pure or admixed with calcium oxalate crystals. In either event, treatment must include alkali to prevent more uric acid. If your stones contain uric acid, follow this link. 

Cystine in Stones

Cystine stones form only when genetic abnormalities of renal cell transporters allow a vast excess of this amino acid into the urine. Treatment is high specialized. Stones can grow very large and rapidly. Supersaturation can be measured but only in a few laboratories. Like uric acid stones, cystine stones can contain calcium phosphate crystals, but prevention of cystine crystallization is paramount and takes primary importance. If your stones contain cystine, follow this link. 

Struvite in Stones

Struvite, magnesium ammonium phosphate, forms in humans only because of infection with organisms that hydrolyse urea to ammonia and carbon dioxide. Struvite can be the only stone crystal or can become part of any stone. Treatment has nothing to do with diet or the usual stone medications. Struvite stones are essentially infected foreign bodies within kidneys, and cure requires a mixture of thoughtful surgical management and use of antibiotic drugs. 

Calcium Stones

The mass of patients will form calcium stones unmixed with uric acid or struvite. Out of this mass physicians – patients cannot do this

themselves -must cull the small fractions with systemic diseases that cause stones but produce illness  beyond stones and require special and often very complex management.

Serum and Urine Testing

The tubule disorders are recognized from serum abnormalities, sometimes paired with specific 24 hour urine findings. Renal tubular acidosis and primary hyperparathyroidism are particularly related to stone disease. Both require both serum and 24 hour urine abnormalities for diagnosis.

Primary hyperoxaluria, and hyperoxaluria from bowel diseases, dangerous diseases that can cause kidney failure, are diagnosed from high 24 hour urine oxalate excretion and cannot be otherwise recognized. Bowel disease is recognized clinically, but 24 hour urine testing is required to assess both urine oxalate excretion and other secondary abnormalities that can cause stones and kidney disease. 

Idiopathic Calcium Stones

Evaluate 24 Hour Urine and Treat Abnormal Risk Factors

Urine Calcium

High urine calcium in these patients arises from idiopathic hypercalciuria, and can be controlled with reduced diet sodium intake, avoidance of excessive diet protein intake, perhaps reduction of refined sugar intake, and, when needed, thiazide diuretic agents. Adequate diet calcium is needed to reduce risk of bone mineral loss.

Urine Oxalate

Urine oxalate above 25 mg/d can be treated with adequate diet calcium, that reduces oxalate absorption, and reduction of diet oxalate intake to below 200 mg/d using lists of high oxalate foods. Of these, spinach, rhubarb, nuts, seeds, and pepper are common offenders. If diet calcium increase does not bring urine oxalate into the desired zone (<25 mg/d is ideal, <30 is acceptable), limiting diet oxalate to below 100 mg/d is a proper strategy.

Urine Citrate

Low urine citrate, below 400 mg/d raises stone risk because citrate binds urine calcium in a soluble complex and directly inhibits formation and growth of calcium oxalate and calcium phosphate crystals. Five servings of fruit and veggies provides about 120 mEq/day of potassium alkali that can raise urine citrate. If needed, potassium citrate can be added as a specific treatment. 

Urine Volume

One hardly need mention that urine volume below 2 – 2.25 liters a day needs extra fluids to achieve that goal.

The Kidney Stone Diet

The elements common to the three main risk factors beside urine volume are reduced diet sodium, sugar, and protein – to permit adequate diet calcium without raising urine calcium, adequate diet calcium for bones and to block diet oxalate absorption, and fruits and veggies to provide diet potassium alkali. These are highlighted in the large upper box.

These five diet elements all correspond to present healthy diet recommendation for all US citizens, and should be advocated by all physicians for all patients unless otherwise limited by underlying diseases. Since idiopathic calcium stone formers are almost by definition free of systemic disease, it is a desired diet in general. The diet has been tested in one prospective trial and more trials are much needed. 

Specific treatments, thiazide like diuretics, potassium citrate pills, and low oxalate diet are noted under their respective abnormalities. A strategy for beginning treatment with diet and adding drugs as needed is outlined here. 

More is Wrong Than Just Stones

Having stones is burden enough, especially the dreaded surgery they can entail. But epidemiologists have discovered links between stone formation and risk of hypertension, bone disease, stroke, heart attack, and kidney disease including even renal failure and dialysis. The links between stone forming and these other major diseases are not as yet obvious, but the message obvious. Physicians need to treat the patient, nor just focus on preventing stones.

The kidney stone diet, being in line with best present recommendations for all US citizens, is a reasonable choice for all stone formers because aimed at reduction of risk for all of the above mentioned disorders. Even if the problems of stone formers transcend those of normal people, so that a healthy diet does not suffice, it can do no harm, and may do some element of good.

Why Not Just Lots of Water?

Consider the least threatening possible scenario, an idiopathic calcium stone former who has had only one stone – a kind of baseline kidney stone disease. Being such a common and large group why not simply treat them with lots of fluids, do a single 24 hour urine for safety, and save more refined treatment if water fails?

That Has Been Tried

Before you read what follows brush up on supersaturation. 

Of ninety nine people who formed one calcium oxalate stone and drank so much they produced 2.6 liters a day of urine, 12 formed one or more new stones in five years (Group 1). Among one hundred more just like them who produced only 1 liter of urine daily 27 formed one or more new stones during the same time.

As expected water reduced supersaturations. SS CaOx was 9.9 in the low flow and 2.6 in the high flow group. SS CaP was 1.58 in the low and 0.48 in the high flow group. Excellent and predictable results.

In passing the authors note that before the trial, at baseline, patients had lower urine volumes than their non stone forming subjects. One might surmise from this that habitual low urine volume played a role in causing their stones. But that is observation, not hypothesis testing.

Water Is Not Enough

Surely water works. Stones were less with lots of it.

But why so many stones? Of one hundred random people 12 people will not make one or more new stones in five years drinking so much water as to achieve a urine volume of 2.6 liters daily. This would be 2.4 percent per year or 24 percent per decade. Even if limited to adult years this would produce stone rates approaching 75 percent in a population of high fluid drinkers.

For the controls, who drank less, the numbers essentially double.

More is wrong than water could right. Given the risk factor studies I have already presented, this is an expected outcome.

In fact, in Table 4 of the water treatment article in the link above, hypercalciuria was at least one of the reasons for higher relapse. Baseline, before anything was done, the urine calcium levels of those destined to relapse was higher than those who did not 233 vs.336 mg/d and 249 vs. 313 in the high fluid and low fluid groups, respectively; p<0.001 for those into statistics. So those destined for a bad outcome had idiopathic hypercalciuria, a well known personal risk factor. 

This Was Water Under Ideal Conditions

Above all else, these patients were supervised so that water treatment was as good as it can ever be. The cost of such supervision was underwritten by the grants that supported this trial. Outside the umbra of a subsidized program, adherence to such high fluid intakes will be less ideal.

Multiple Stones Predict Higher Relapse on Treatment

This figure shows the treated patients in a number of published trials. The details can be found in the parent article. 

The abbreviations refer to the treatment modalities: K Cit means potassium citrate; chlorthalidone, indapamide are thiazide like diuretics, HCTZ is hydrochlorothiazide; Multi means several medications were used together; allopurinol lowers urine and serum uric acid and proved effective in one major trial against calcium oxalate stones.

As the number of stones produced before treatment goes up, from one to 10 or more (along the horizontal axis), the percent of patients who relapse during treatment rises from 10 – 12 percent to 20 to 30 percent. More or less, the percent who relapse increases proportionally to how many stones had formed before treatment.

Results for the water trial of single stone formers and my own published observations on patients who had formed a single calcium stone are at the lower left of the graph.

Stones Form Steadily Over Time

Waiting to treat a single idiopathic calcium stone former, either by the use of relatively ineffective high fluid intake alone or, in the worst

case, doing nothing at all, will on average lead to more stones. On this graph, detailed elsewhere, time is on the vertical axis and the number of countable stone events on the horizontal axis. Squares show the rate of stones per year, a rather constant number. Circles show the inevitable consequence: more time, more stones. 

So time wasted, with water as a sole remedy, or no specific treatment, will tend to increase the number of stones, and as that number increases the successfulness of even highly supervised protocol treatment as used in trials will wane.

Never Use Water Alone

I will surely not treat any patients with just water unless 24 hour and serum testing shows me that nothing at all is wrong but low urine volume. Even then I am sceptical.

The reason I am so stubborn about water and waiting is that the main force of treatment for idiopathic calcium stones – those forming in the absence of systemic diseases – is diet change. Not only that, the diet change is in the direction considered most healthy for the US population. Why would anyone force fluids on patients when much of the disordered urine chemistry can be mitigated by a healthier diet?

Maintenance Treatment

Analyse Every Stone

One might think that once we know someone forms, for example, calcium oxalate stones more analyses add little or even nothing to successful treatment. But obvious problems make that thought a poor one.

New Struvite

Every surgery poses risk of infection. As foreign bodies in the kidneys stones themselves offer lodgment to bacteria that may be passing through the urinary system. So struvite can grow over older calcium stones, or even begin on their own. The person ‘converts’ from one type of stone crystal to another. Treatment no longer stops stone growth.

Because rapidly growing, large, and laminar in appearance by x ray, struvite stones will make themselves apparent over time. But larger size means more complex surgery, and perhaps kidney injury or even sepsis from stone infection. So early detection matters.

New Uric Acid

People age, gain weight, develop diabetes and with this urine pH falls. Treatment with alkali that might have stopped uric acid production begins late, when rapid stone growth or large stone size makes uric acid come to mind. But large means harder to dissolve, perhaps impossible. That means surgery. Early detection of uric acid in stones can save future surgery.

Calcium Oxalate to Calcium Phosphate

This happens and probably matters. CaP stones most often arise over tubule plugs which means cell injury in tubules and the tissues around them. By contrast, growth over plaque, how CaOx stones form, appears less invasive. Tissues seem less injured.

My imagination tells me calcium phosphate stones may cause more long term kidney problems than calcium oxalate stones. If this hypothesis were true then mere observation of patients well characterized in stone composition should disclose differences in kidney function, or perhaps urine albumin loss. Perhaps blood pressure rises more. Perhaps someone might have such information.

Quite possibly potassium alkali that work well to prevent calcium oxalate stones do poorly for calcium phosphate stones. After all, they raise urine pH and a higher pH will foster the phosphate stone. No trial addresses this obvious question; one should.

How Good is Kidney Stone Analysis

Less than ideal

What happens if you make a rigorous analysis of stones, divide the sample up into parcels and send them to different commercial laboratories. What will they tell you?

Ideally they will tell you what you already know. But in fact they under reported struvite and calcium phosphate – as hydroxyapatite. They also failed in to identify brushite.

Not Utterly Unreliable

My own work with Joan Parks compared kidney stone content of CaP – as hydroxyapatite to urine pH and supersaturations obtained by 24 hour urine samples. Unlike work from centers that performed their own kidney stone analyses we relied on a multitude of commercial lab reports obtained over decades. Even so urine pH and CaP supersaturations tracked will with these commercial lab results.

A Reasonable Conclusion

As an inexpensive and indispensable tool, all of us need and use commercial kidney stone analysis. What we know prompts wariness about missed struvite – a most important stone diagnosis. But perhaps that argues for multiple analyses – more tries lower likelihood of missing the diagnosis.

Make Followup 24 hour and Serum Measurements

It would seem unnecessary to say, but sometimes this obvious maxum goes unfulfilled. There is no use to changing diet – or trying to – or adding medications if one does not assure that the changes lead to a betterment of stone risk. I think followup urine collections for diet change should be when a patient believes the diet has changed and is tolerable enough to be used long term. With thiazide or potassium citrate, I favor 6 weeks initially. For all patients, followup with testing and a clinical visit should be yearly at least until stones become a thing of the pasts.

Aids for Patients Who Have Formed Stones

I have written several articles outlining the steps to prepare for and do testing, and for obtaining the most from physician visits.

This site has a large volume of articles. This page lists all of the articles by topic.

Chapters 2 – 6 of this book give a lot of background and links to related articles.

Chapters 7 – 12 concern specific stone forming systemic diseases.

Summary of Chapter One

The miserable fragments we call kidney stones have a complex origin in the kidneys. All but one kind contain crystals without which they could not exist. The exception, protein stones, occur rarely and I do not consider them here. Stone crystals form as all crystals form, from a solution overloaded with the crystal material – supersaturated with respect to the crystal of interest.

Many Paths to Stones

Kidneys can supersaturate urine by conserving water or by increasing the amounts of insoluble salt constituents such as calcium or oxalate. They can reduce the excretion of citrate, an inhibitor or change pH. The latter can be downward, fostering uric acid or upward fostering calcium phosphate crystals.

Treatment Synergy Requires Proper Testing

Although effective and obvious, extra fluids do not reduce new stone production completely to the baseline levels of average people. Moreover, above perhaps 2 to 2.5 liters a day of urine becomes difficult to maintain. So ideal treatments employ synergies – increase of fluids and changes in calcium, oxalate, citrate, or pH of urine as indicated in any one patient. Only blood and 24 hour urine testing can tell what is indicated in any one patient, and also what treatment has accomplished.

Stone Analysis is Crucial

Since all treatments but water relate to specific crystals, prevention depends on stone analysis whenever possible. Stone crystals can change over time and I see no reason to discard stones and good reasons to analyse them. Especially, infection or uric acid stones may complicate or even replace calcium stones and be missed without analyses. Likewise for stones from drugs.

Stone Prevention is Precision Personalized Medicine

Stone prevention exemplifies the best features of precision medicine. The crystals arise from specific supersaturations we measure in simple 24 hour urine samples and can reduce with healthy diet changes and a few medications that have proven their worth in trials. No two patients are quite the same, so each needs personalized care – stone analysis and 24 urine testing along with blood tests and clinical assessment to exclude systemic diseases.