Prevention of recurrent stone is possible for most patients. This sites aims to promote prevention as best we can.
Six articles present the essentials of prevention in a form aimed directly at patients. These articles link to others on the site but not to peer reviewed research.
The Five Steps to Stone Prevention contains the essentials. How to be an Effective Kidney Stone Patient concerns how patients can make their stone prevention care most efficient and effective. Two articles on how to read stone lab reports enable patients to evaluate their own progress.
They are based on my primary hypothesis which rules this site: In a person forming new stones supersaturations are too high with respect to the crystals in the stones forming. Therefore prevention is to lower those supersaturations.
The Deeper Articles
All of the other articles linked below are fully referenced to the primary peer reviewed literature. They are like medical reviews but written with a minimum of jargon so they can be read by non physicians. But they adhere to the same scientific rigor I bring to my standard research publications.
Fred Coe MD
This link takes you to a drawing which shows all the articles linked to each other in their natural relationships. Each article name is a link to the article. You can use this to read the site functionally. The red articles are the backbone of the site and outline the main factors for stone prevention. The blue articles support and expand upon the red ones. This is a new feature. I have checked all the links. If you find something wrong let me know.
The articles on science and medicine listed below do not appear on the drawing as they are not directly related to prevention but rather to a desire to share my thoughts on this subjects with those who might care. They are discussed on the Site Logic page which also shows this site map.
Quick links to Articles – Perfect for Browsing
|Hypercalciuria in General||The Low Oxalate Diet
|Idiopathic Hypercalciuria||Oxalate Physiology||Use of Supersaturation|
|How Salt Works||Science of Supersaturation|
|Salt Stones and Bones||Why Use 24 Hour Urines?|
|Thiazide to Prevent Stones|
|Stones Themselves||Ureteroscopy||Michelle and Pat||CaOx Stone Formers|
|Supersaturation||Phosphate Stone Formers|
What is New Right Now
With considerable trepidation, I unfurl my first and certainly very unpolished video offering. The good part of the articles on this site is their devotion to scientific accuracy and referencing from PubMed. The bad parts are their opacity, length, and difficulty. I have long been a public lecturer and decided that video offerings might be a valuable add on. There is more room, I think I speak better than I write, and it seems to me one video can summarize and complement a group of written articles, so I did this one. It covers crystal formation, how crystals are made, and where in the niches and crevasses of the kidney they actually form. Its message is my usual one: Prevent crystals and you prevent stone disease. This is a beta version. I know it has some errors in it. I also know it lacks refinements I need. But, refinements and corrections will come. Let me know.
The second in this series of stone forming phenotypes, the calcium phosphate stone formers are less numerous than the calcium oxalate stone formers, but perhaps more worrisome, and certainly more complex. There are two types, those whose stones contain any brushite – an unusual form of calcium phosphate in stones, and those whose phosphate is only hydroxyapatite – the mineral found in bones. This latter group is to a large extent composed of young women, for reasons we do not know. Phosphate stones are likely than the calcium oxalate variety to be numerous, and often produce nephrocalcinosis, a mixture of small stones and tissue calcium deposits. Nephrocalcinosis, in turn, is often labelled medullary sponge kidney simply on radiological grounds, even when the distinctive lesions of MSK are not necessarily present. Likewise, phosphate stone patients can appear to have renal tubular acidosis because of nephrocalcinosis and because RTA and phosphate stone patients both produce a more alkaline urine than do normals, or patients with calcium oxalate stones. All in all, this is a complex form of calcium stones, challenging for clinicians and often very trying and concerning for patients with it. The article is long and difficult, so you might want to watch this video by way of an introduction.
Here is the most common kind of stone former, described in such detail as one can muster up at this time. They are simple to diagnose: Stones containing a preponderance of calcium oxalate, no uric acid, struvite, cystine, brushite, drugs, or rare organic materials, and exclusion of any systemic disease as a cause of stones. More or less, these patients are stone disease as it is seen in primary care and most urology practices. Of the millions of stone formers most are like this. The trials for prevention of calcium stones have mainly used these patients as a majority of subjects. However common they may be, and easy to define, they are complex in the way that they make stones, and it appears that there may be not one but perhaps two kinds of idiopathic calcium oxalate stone former. Because of modern flexible ureteroscopy the types of idiopathic calcium oxalate stone former will soon be told apart during stone removal surgery, and patients and their physicians confronted with a variety they may not fully expect. This article sums up what is known, as best as I can manage. If you would like a movie preview of the article, here it is.
This is a first for the site, and perhaps it should have been a feature long ago. After all the generalizations and reviews there is something wonderful about a single instance that contains all the elements of a topic in the kind of instructive detail we can get only in life itself. Pat – who has permitted me to use his name and data – forms calcium stones and has idiopathic hypercalciuria and a job that makes hydration a problem. For treatment I wanted to use low sodium diet to lower his urine calcium excretion and if possible avoid thiazide diuretics just because of his job which is outside and in summertime poses serious heat loads. MIchelle, his wife, created a reliable low sodium diet for him as proven by multiple follow up tests and that reduction of sodium lowered urine sodium and stone risk, as one might expect. I asked her to share her experience in doing this, and she responded with this wonderful article. It helps that she is a professional writer! I am indebted to Michelle and Pat for their story, and I hope you like it.
There is no doubt that urine oxalate excretion is an important factor in calcium oxalate kidney stone production, and that excretion is a very complex outcome of transport in the gut and kidney tubules and, of course, diet calcium intake. We have devoted a lot of energy to refining food oxalate lists and making a reasonable diet plan for oxalate. Here, we have taken on the harder task of reviewing the complex movements of oxalate from food into urine. The intestines not only absorb oxalate from food into the blood, they can secrete oxalate back out from blood into the gut lumen from which it is removed in the stool. The kidneys remove the net of diet oxalate absorbed minus that secreted by a process of filtration and subsequent renal cell reabsorption and secretion of that filtered oxalate. It is as though evolution has handled oxalate like a real hot potato: keep control of how much oxalate the kidneys need to remove and keep control of the blood oxalate concentration. This seems prudent – if one dares to speak this way about evolution – as oxalate can crystallize in blood as it does in urine and both processes can be dangerous. The new work on oxalate transport does not now directly translate into new tests or treatments for patients, but surely will. So I and my brilliant colleague Dr Hatim Hassan – who is the real expert here – have written about the future in medicine. Because the article is very complex and may not get a lot of readers – scared off – I have made a tiny movie to introduce it by way of encouragement.
We promised to make a table of the comments we received, and a first draft of it is now in the article. The overwhelming answer thus far is that most people who answered do not use these devices. A surprising lot of responders liked just plain old jugs – containers of water to carry around or have ready as pre-measured amounts. The largest group just expressed no interest in fancy new products or anything else, preferring to find their own ways. This is not science, even science of polling. But it does suggest a lack of passion within a group of stone forming people willing to put up answers or write an email back. We hope for more comments.
When I wrote the original article in 2014 limitations of proteomics seemed the main obstacle. This new work by Dr Frank Witzmann shows us the other side of the problem. A master of the modern proteomic techniques, with them Frank shows that the number of unique proteins in just two human calcium oxalate kidney stones is over 1,000. If inadequacy of technique stymied us two years ago, inadequacy of intellect – at least of mine – stymies at least me, now. What to make of so many proteins! What are they doing there? Which ones matter in stone genesis? We have the methods, we have stones to work on, but what shall we ask? As always, the magic is in the vision.
This is an article that can be written only by the readers of this site. We are not product testers nor do we do market surveys. But given how many fluid and diet apps one can find on the web and also given how many people come to this site every month we should be able to get a good idea about which ones seem of value. The benefit of accumulating your experience in comments to this very brief article accrues to all of you who come here. Whether you use an app or not crowd sourcing of a kind can tell us all which ones seem really good, and we can all use that knowledge. There are almost no words in the article, but as the results come in – in other words if you will share – we will count up by app in a table or so, ongoing. As for smart bottles, there are only a few on the market, but we should be able to get an idea about them if you will share. So, here it is: A blank slate for everyone to write on so everyone can benefit. Please share.
This little goodie started with my partner Dr Anna Zisman who to wanted us to have a simpler format for patients to follow in looking at their 24 hour urine lab reports. Answer five easy questions and get back a list of what you have to do with fluids and diet. Try it. Let me know if it works. If not, can you help make it better?
Well, here it is, the last pillar in the foundation. My goal is to enable patients to achieve successful stone prevention and I believe this requires a partnership with their physicians, a partnership in which they play a very active individual role. Patients after all are the ones who can manage diet, fluid intake, and life demands, only they can assure that 24 hour urine collections are representative of normal life, and, frankly, only they can decide on a life of long term prevention. Stones being rarely fatal and usually not a cause of progressive kidney disease, patients can elect prevention or not, and their physicians are in a role more like attorneys and accountants than authoritarian directors of events. But as in Eden, one can expect proper choices only if one has provided full knowledge, which I have set out to accomplish. By proper I mean most suitable to patients given full knowledge, for some may not care to exercise themselves so much as I think they must to be successful, whereas others may consider the work of prevention slight indeed compared to the consequences of continued stones. In any event, this article is the end of that cycle of enablement I can manage, and I put it here, as in all writings, as the chef puts out her best effort – to face the indifferent judgement of the gourmet.
Dr. Mike Borofsky authored a favorite article on this site – Pain from Kidney Stones. Now, he has authored our first article on stone urology, meaning the urological surgeries used for treatment of stones in the kidneys and urinary tract. Ureteroscopy is fast becoming the preferred approach, outstripping shock wave lithotripsy and percutaneous lithotripsy. This is because the instruments for ureteroscopy offer superior optics and are flexible and small enough to get from the urethra up into the kidneys and into all of the crevices of the kidneys where stones form and lodge. Armed with tiny but powerful laser fibers, the new ureteroscopes permit surgeons to fracture stones in the kidneys and turn them into mostly harmless dust that passes silently for days or weeks thereafter, or into small fragments they take out during the procedure leaving not a speck behind. It is a brilliant time to be a young urologist and use these marvelous instruments to do what would otherwise require a far more complex and risky procedure (percutaneous nephrolithotomy) or depend upon an indirect and often incompletely effective one (shock wave lithotripsy).
These two articles cover the main stone types, and this new one on uric acid parallels the prior one on calcium stones. Like the calcium stone article it is meant for patients, although physicians might like some of the nuances. The purpose is not to make patients into their own physicians but to enable them to understand their own stone forming abnormalities. My ruling hypothesis is that patients want prevention, and will embrace and implement the changes needed with more enthusiasm and endurance if they fully understand the goals. LIkewise if they can themselves follow the effects of their efforts on stone risk factors they will believe that what they are doing has real meaning. I know that hypotheses are for disproving, and I know someone may well do a prospective double blind randomized trial, some day, to test mine. Right now, I believe in the idea because of Eden whose resident twosome were not just told about the tree but exactly why they should not eat of its fruit. I know it is an unfortunate comparison, given the outcome, but much effort was expended on education. My source for the details, apart from the Hebrew Bible, is Milton, J: Paradise Lost; Books V – Viii.
This site is meant to promote prevention and my current hypothesis is that enabling patients to read their own 24 hour urine tests with a professional eye will help achieve that aim. It is not an easy task. Lab reports, even the best of them, are dazzling arrays of numbers in often mysterious units. Even physicians have some work to do. But numbers are numbers and people can read them if they have the code. Here I have parsed out the main numbers for the calcium stones: Volume, calcium, oxalate, sodium, citrate and pH. Because this is the first article on reading this kind of report I also discuss collection quality, conversion of units – some labs report, as an example, calcium in mg/24 hour, others in mmol/24 hour, even mEq. So I introduce the simple conversions needed to use what I have written for a report with different units. Likewise I introduce how urine creatinine can be used to estimate collection quality. The supersaturation come at the end, as they should, being the final summary of everything. The tone is about that for trainees in nephrology or urology I have often worked with but with jargon elided and a focus on lab results per se. Those interested can follow the links into the thickets of the site which hold enough to satisfy most appetites. The main purpose is to enable patients to cast a cold eye on their own problems and on the results of treatment efforts so that in the event saturations can be effectively reduced and stone recurrence with them.
The thiazide type diuretics are able to reduce new stone formation and are an important part of stone prevention regimens. Here is all about these drugs: The trials that show they work; How they work; What they do for bone: Certain precautions in their use. To give a pill to someone is to throw a seed on unprepared ground – it is a sterile and doomed enterprise. All the features of prevention from diet and fluids and lifestyle come first, so that what one can do with them is being done. Then the drug will be most useful. And, you will know by the fall in urine supersaturation achieved. Whatever it was when stones were forming is too high, and real treatment means it has been reduced. After all that can be done without thiazide has been done, there will no doubt be residual supersaturation lowering needed, or one would not use the drug. The marginal benefit of the pill can be assessed by the extra fall in supersaturation it produces. Which supersaturations? Those related to crystals in the stones forming.
This is my letter to the world. For months I have been reading on social media the miseries and pains of huge numbers of patients and have come to realize how critical it is to put forward a simple plan in hopes of getting more prevention accomplished nationwide. This site reaches a lot of people every month, so perhaps this brief but accurate and complete five step prevention plan will catch on and help prevent the widespread suffering I have been reading about. This plan is meant to go with a companion article from a few months back that helps patients organize for their medical stone prevention visits.
Here is your page. If you want specific help managing diet and fluids for stone prevention, put your questions up on this page and Jill Harris will answer you. If there are medical aspects of the question, I will help provide an answer.
Another article by Jill, this one on a problem that plagues calcium oxalate stone formers. How do you actually lower oxalate intake and still manage a healthful diet replete with salads and vegetables? The answer is not so complex. Reliable lists from experts reveal a very large number of safe alternatives, and Jill shows how to plan the three meals of a day in a tasty and safe way. The article links to the lists themselves and offers a summary of the worst foods in a new and compact format. While food oxalate is and will remain a vexed problem in terms of analysis variability, the general range of oxalate contents in a food serving is reasonably well known, and this article puts such information to use.
Jill Harris has written among the most popular articles on this site, and here is her lucid, charming, and helpful approach to eating a diet that is low enough in sodium to really help prevent stones and bone mineral loss, and, as an added benefit, lower blood pressure. This site has long detailed articles about sodium, but they cannot do what Jill has done here – simply say how to do it, how to lower your salt intake and keep it low. I have no doubt this will become another of Jill’s classics, and be read by thousands of people who will benefit from her wisdom, experience, and utter practicality.
Two good trials support lower sodium diets as a way of reducing new calcium stone formation and of protecting bones from calcium loss. The physiology behind these trials is detailed in the articles on idiopathic hypercalciuria and salt. In Italy at least, and in men with calcium stones and idiopathic hypercalciuria, a diet low in sodium, moderate in protein, and high in calcium leads to less stones than low calcium diet alone, and in fact to a rather low new stone recurrence rate. Among postmenopausal women, a high calcium low sodium diet brings bone mineral balance into the positive range: Bones add mineral. Neither trial is comprehensive in covering men and women, young and old, US vs. Italian cuisine, but they are the only ones we have of this quality, they are consistent with the science we have, and convincing. To me they are enough to recommend low sodium diet, moderation of diet protein, and high diet calcium for calcium stone formers with idiopathic hypercalciuria, recommend this kind of diet without reservation pending what I hope will be more trials which cover a wider range of patients and of ages. It is this kind of additional trial we really need in the US right now, substantial, bearing on really important diet interventions, and arising out of a sound scientific base.
No one wants to be a kidney stone patient in the first place, but although physicians provide the means for prevention, patients can do a lot before and after a visit to make prevention happen. This article tells you how best to prepare for and use the limited and precious time you have with your physician. It gives you a method to implement the treatment program your physician offers. Although I wrote it for patients, physicians may enjoy it, too. This article is not based on my long experience as a kidney stone clinician. It is utterly practical in intent, and although what I say in it will never be tested in a trial I have published my outcomes and show the main findings: Those who stay in treatment with us do very well indeed, so the approach seems sound.
The article is long and important and too difficult. I have added bold summaries. You can read these and decide if you wish to plunge in further. The main points are that IH is a risk for both stones and bone disease. An implied point is that IH is a complex exaggeration of normal physiology, not a disease, so adjustments of diet may be of unique value. The article mentions but does not detail these changes, which are coming soon.
Idiopathic hypercalciuria may well be the most complex and important issue in all of medical management of calcium kidney stones. It arises within the elaborate systems that regulate calcium metabolism and produces both a risk of stone formation and of bone disease with fractures. IH is strongly familial, almost certainly genetic in origin, and present in children as well as adults. Treatments used include high calcium – moderate protein – reduced sodium diet, moderation of dietary sugar loads, and potassium citrate, and thiazide type diuretics, each of which act through different and reasonably well characterized pathways which cannot be understood without a knowledge of how IH works in the first place. Unlike stones themselves, supersaturation, or citrate, each a very large and important topic, IH cannot be presented well – at least by me – in separated linked articles but only in one article that carries its many intersecting physiologies along side by side and uninterrupted. Being a long and comprehensive article, foundational for this site and – to me at least – for comprehension of the whole topic of pathogenesis and treatment of nephrolithiasis, this article is not necessarily meant to be read all at once but rather used as a resource. I will cover the treatments of IH later on, in separate articles.
The site is taking a new turn, from stones themselves, supersaturation, and kidney tissue to the causes of high supersaturation. Among these high urine calcium is a major factor and a common object of treatment. This first article about hypercalciuria introduces some of the many stone forming diseases that cause it, or are thought to cause it: Hyperparathyroidism, normocalcemic primary hyperparathyroidism, secondary hyperparathyroidism, familial hypocalciuric hypercalcemia, renal tubular acidosis, MSK, very uncommon genetic diseases, and calcium supplements and vitamin D. Likewise, this article introduces idiopathic hypercalciuria (IH), the familial, genetic, and very common condition of calcium stone formers which might indeed be the main identifiable cause of stones in a majority of people. From now on and for a considerable period articles will center around this topic.
Two Related Articles: Supersaturation, and patients with persistent low urine volumes.
Joan Parks describes a not uncommon problem, patients with low urine volume that does not or cannot increase, and tells about it in a humane and personal way. Her article ostensibly concerns the paper we never wrote about about this kind of patient, and it is true we never did write it. But along the way she says much of what we probably would have said in that more formal genre. After 40 years of witnessing the travails of the Low Flows it is not hard to describe them and what can be done to help. Joan is retired; check out her novels.
Being a central issue in stone disease, many articles concern supersaturation and it is hard by now to extract from them a single coherent story. I have made the attempt here, in the form of a walking tour that takes us from one to another in what I think is a reasonable order and with what I hope is a useful tour guide’s overview. I did another of these tours, for Stones Themselves, and you might find the two go well together.
This word is old – 1934 – and simple: Calcium deposits in kidney tissue. Clinically it has for decades meant calcium deposits in kidney tissue as seen on CT scans or other means of visualization. Now, with common use of high resolution ureteroscopy it means calcium deposits in kidney tissue which can be stones or tissue deposits, and the two need to be distinguished by direct observation. During ureteroscopy stones can be removed and tissue deposits seen for what they are. It is now a word that leads to action: a particular kind of action that is likely the best one for patients. Is that not a wonderful progress in medicine?
It is time to move on into the deep cold waters of calcium physiology, hypercalciuria, and bone disease in stone formers, and therefore into the problems of sodium – table salt. Here is my contribution. This will be an article no one fully agrees with because salt intake has such powerful and dramatic effects on the kidney, blood pressure, and mineral metabolism that research and the research community are vast and often controversial. Even so, I am confident here, and will defend my contribution as reasonably valid. If you wish to understand calcium, you will have to grapple with sodium, and this is a good place to start.
You can look up any topic in the Quick Links. But perhaps, sometimes, you might like to come on a tour with me, from place to place, visit a few articles in a proper order so they tell a story. I have put the first one together; see if you like it. There will be more.
Dr. Michael Borofsky tells us How to Diagnose and Treat Medullary Sponge Kidney
Mike is a man of energy and talent. Here he tackles a big issue for many patients: Just what is Medullary Sponge Kidney, how do we diagnose it properly, and what about treatment? In response to his article on pain we received many inquires about MSK and this post is a direct answer to many of the questions. It is overdiagnosed, but we have only become aware of that fact with the advent of widely used high resolution endoscopy to treat stones. With such endoscopes the abnormalities of MSK are easily seen and it is apparent that radiological diagnoses can be very wide off the mark.
If there is any one thing stones do which creates fear and loathing it is to cause pain, pain of such magnitude and character as to have become legendary, famous for millennia. To me, as a kidney stone expert, I think they do other things more dire, even, but pain will do as a major concern. Here, we have a brilliant young specialist in kidney stone surgery offering a thoughtful and rather elegant article on how the pain is produced. He specially deals with a controversy: can so called ‘non obstructing – innocent – stones cause pain? Do some of these stones warrant removal? What people feel is linked to what is happening inside the kidneys and urinary system in a clear and interesting way. What is happening is an acute obstruction of the kidney which, if we had only one, would be obvious as acute kidney failure. Because the other kidney is quite able to support the body unaided we never need to notice how serious the loss of function is on the obstructed side. Everyone who encounters stone pain, in person or in a relative of friend will devour every word Mike has written. This article is foundational in that it speaks to the very nature of how stones cause illness, and transient kidney injury as they pass.
Certainly our most popular writer, Jill offers this article to the beleaguered patients faced with a 24 hour urine collection jug and all that goes with it. Compassionate, smart, experienced, and a fun writer, Jill tells everyone why, in very blunt terms, and how – not so simple. I cannot imagine anyone involved with stone prevention who will not like and use this contribution.
Last fall the American College of Medicine published two regrettable articles detailing faulty and unfounded ‘guidelines’ for primary care and general internists to use in their care of kidney stone formers who desire prevention of more stones. Beyond the commonplace disdain of guideline authors for specialist expertise, these guidelines essentially take the position that because not proven effective in prospective trials simple determination of stone composition and of 24 hour urine chemistries are not useful and should not be obtained. Given the whole content of this very site I could not fathom how these odd ideas made it into an august journal like the Annals of Internal Medicine. Moreover, I cannot imagine how one would contrive a randomized prospective trial of stone analysis or 24 hour urine testing that could get by ethics committees and be acceptable to patients: Exactly how would you explain to a patient that one might not want to know what her stones were made of or what was wrong in his urine that might promote stones? Which patients would be willing to be treated by physicians so ignorant of their disease, and for how long would patients tolerate treatments fashioned in such willful ignorance? Here, Dr, David Goldfarb, an expert in this field and advocate for honest patient care shares his views as he expressed them to the College in a letter that should find its place in the Annals of Medicine. Arrogance and naivete are poor substitutes for wisdom, he points out, and it is finally the patients who suffer.
The very central testing mechanism for stone prevention, the 24 hour urine has been a long standing center of controversy and misunderstanding. Here I review its importance in assessment of supersaturations and the key urine risk factors for kidney stones, the pitfalls in its use, and the controversial matters of how many to obtain and why one really needs to collect for 24 hours. Most especially I point out that without such testing modern kidney stone prevention is impossible. The accompanying email is helpful as a guide for reading.
This is an excellent introduction to cystinuria for patients by Dr. Anna Zisman. It is the first article about rare stone diseases, and meant to be a straightforward introduction for patients and their families. We will present more detailed materials over time.
It is not enough to make a site about one disease unless that one disease can lead us to a greater intellectual world. This site now has a number of articles about science and medicine which use stone disease as an example and a source of richness. I have been shy about them for a larger audience and so placed them on the Site Logic page. But after some thought I have decided to place them everywhere. Many patients, many doctors, and I would hope all scientists have the education and interest to peruse these articles: Why hide them? Science and Medicine are married, in their way, and what that way consists of is important right now, in a world of confusion about medicine and its place in society.
Urine can tolerate considerable supersaturations before permitting crystals to form. How does this occur? This article describes the one measurement of tolerance that ever was proven to discriminate between stone formers and normal people, meaning it is a measurement that is probably pointing to a vulnerability permits stones to form in some people. Unfortunately the measurement has never been practical to produce for medical practice, so patients cannot benefit from it. But a new analysis of the results of two papers published decades ago points to two molecules that may confer tolerance: Citrate, and inorganic pyrophosphate. Citrate has had center stage here for months, as it should. Pyrophosphate has not, but perhaps needs to be. If these two small molecules together are so important, perhaps they point to some new way drugs might be used or fashioned for prevention. Read it.
Potassium Citrate: The Contributions of Dr. Charles Pak
It is always as though scientific findings are just there, but it is people who produce them as if by a kind of magic of imagination. Potassium citrate has occupied this site for months, and Dr. Charles Pak, a friend and respected scholar did some of the best work on the drug. Especially, Charles worked with industry to obtain a usable pill version of the supplement, and wrote for physicians so they would know to use it. After so much about the medicine, how wonderful to put him forward for all his achievements, in this public place.
They can prevent new calcium oxalate stones, but what do these pills really do? The citrate in the pills does not simply appear in the urine, bind calcium, inhibit crystals and prevent stones. What happens is a lot more interesting. Our diets impose an acid load which the kidneys must remove, and in the course of that removal they conserve citrate. Acid removal uses a massive renal biology which we activate lifelong because of how we eat. The pills neutralize all or some of that acid and reverse that biology. As it reverses, citrate is no longer conserved and is lost in the urine. Perhaps few medications are so well understood as citrate, and probably few have such extreme effects on renal functioning.
Physicians determine what to do for stone prevention, but how to do changes in lifestyle, fluids, and foods concerns common but intricate details about very practical everyday matters. Jill Harris has volunteered to do this page for us. Her two articles, on how to drink and kinds of fluids are very popular on this site. Ask your own questions. See what other people ask. Add Comments.
Although it is too early to be sure about numbers, an appreciable fraction of calcium stone formers have not only stones but crystal deposits within the kidneys themselves. The million or so nephrons that make up the normal human kidney eventually drain through about 200 terminal ducts that open into the renal pelvis, so called ducts of Bellini (BD). It is there that calcium phosphate plugs form. These plugs result in tissue injury, with loss of the normal lining cells and inflammation around the plugged duct. Exactly how these plugs relate to the actual stones which patients form and pass is not completely known. Possibly stones begin as tiny growths over the open ends of the plugged ducts. But whatever their relationship to stones, these plugs are damaging kidney tissue and their prevention is consequently important.
Another part of the ‘deep rationale’ for citrate is its ability to inhibit formation and growth of the calcium kidney stone crystals. The citrate molecule is larger than oxalate or phosphate but has similar negatively charged oxygen atoms which bind to calcium. When they bind to calcium atoms on the surface of a calcium oxalate or calcium phosphate crystal they essentially get in the way of further growth. That citrate does this, inhibits crystal growth, is certain. How it does so at the atomic level is becoming certain thanks to remarkable instruments which can visualize events at the atomic scale. That citrate is an important inhibitor in human urine is likely, but less than completely certain because urine contains a large number of molecules like citrate which are large, contain negatively charged oxygens which bind calcium atoms in crystals, and thereby ‘get in the way of further growth.’
Part of the ‘deep rationale’ for using citrate to prevent stones is its ability to bind calcium in a highly soluble salt. By doing that citrate takes some of the calcium in urine out of circulation, makes it unavailable to oxalate and phosphate with which it might otherwise create calcium kidney stones. It is most important that the resulting calcium citrate not create yet another kidney stone crystal, and that this does not happen is because such crystals are so very soluble they will not form in urine. The chemistry is beautiful and easy to envision. I have illustrated the article with the gorgeous shapes of the citrate molecule which do, to me at least, resemble the best of art: perfect in form for the purposes at hand.
Potassium citrate salts are used for calcium and uric acid stone prevention. They have a deep rationale for their use, and reasonable trial data to support that in fact their use results in less new stones being formed. This article presents five such trials for calcium stones.
Uric acid stones are always treated with alkali, but no trials have ever been done, so far as I know. The reason seems to be that ‘everyone knows’ such treatment works.
This matter of everyone knowing that a treatment works seems odd to me because the reasoning for such a belief would appear to apply to other kinds of stone disease as well, yet trials have been deemed important and have been done. As best I can, I have tried to analyse what factors are at work in determining what ‘everyone knows’ and what, I guess, everyone does not know.
What is not in the Table of Contents is here, on this page. You can come to it as a tab on the home page or from this link. Perhaps because I know it well, stone disease seems a perfect example from which to learn about and understand how science works in and with medicine, and how medicine itself seems to work, as well. The articles rest upon examples from stone disease, but range far beyond it. They are not musings, nor self indulgences, but an effort to do what has not been done so far as I know. The page and its offerings can be ignored with no loss concerning the main uses of this site. If you are interested in the matters I have taken up there, I have made my thoughts as clear as I can and would certainly enjoy knowing yours.
Applied research is the discipline of medicine concerned with trials and their interpretations, meta analyses, guidelines, evidence based medicine, development of drugs and devices, methods and techniques. It has power and is – in relation to basic science – the actuating side of the couple. Because all science begins with its objectives, where they come from is an abiding concern, and an interesting puzzle sometimes. Here I consider the applied science concerned with treatment and prevention of the common calcium oxalate stone.
Worrisome Guidelines from the ACP
The American College of Physicians has issued new guidelines on kidney stone management. The guidelines themselves are predictable and of little interest. But as a commentary to the guidelines the College has suggested that one should consider treating kidney stones without doing kidney stone analysis, or making blood or urine measurements. These suggestions are odd at best, and would lead, if actuated, to what I consider unsafe and improper medical practice.
It is not enough to write about the science and practice of kidney stone disease. That is to slight the larger question of how science works in medicine, and in our special corner of medicine in particular. We are well situated to think about this issue as stone disease science rests upon very basic physical chemistry and material science, and reaches up into common clinical practice. Not every field of medicine and surgery has such a range. This article presents the three sciences: Basic science; Applied science; Empirical science. For each the inner workings are detailed, following especially the work of Karl Popper.
Basic science is about how nature does things, such as produce kidney stones. Some physicians do basic science. Many physicians may read about the results of basic science, and some read basic science articles though they do not do such work. But here is a different question: In what ways can the results of basic science benefit patients through the usual mechanisms of clinical practice? There seems to be some answers to this question in relation to a few examples I have drawn from management of kidney stone disease. Whether other examples give the same spectrum of answers, whether my results convince other people, and whether kidney stone disease is a good model for medicine in general are to be seen.
It is one thing to say ‘Drink a lot of fluids’ and another to justify a given amount as rational and therefore sustainable over the long run. I don’t think I would drink a gallon of fluids just because a physician told me to. I would want at least some rationale. I believe everyone is this way. Likewise, as a physician, I want to know what support I can find for any treatment, especially one that demands that my patients alter their life habits over a long time. Dr. Elaine Worcester and I have done our best to marshal evidence on this matter.
I have already pointed out the one trial of high fluid intake, one testing if high fluids will postpone the formation of a second stone in patients who have had only one stone. A volume of 2.26 liters was better than the low volume – about 1 liter daily – in the ‘control’ group that was not urged to drink more.
But is 2.26 liters therefore the best goal? The trial was about people with only one known stone, whereas many patients have formed multiple stones.
Our approach, lacking more trials, has been to use the fundamental physical chemistry of stone formation as a guide. Supersaturation drives crystallization and therefore stone formation. We have brought together three sets of data concerning urine volume and supersaturation, looking for the minimal urine flow at which one gets a reasonably large reduction of saturation. Likewise, we asked if time of day and meals affect fluid requirements – they seem to.
We need a trial, perhaps, for recurrent stone formers at several fluid intakes, if that can be done. Lacking that, what we present here may be among the better reviews of the matter, and a reasonable guide for patients and their doctors.
Jill Harris has written a very popular post already, about How To Drink Water. It told us how that plain essential fluid can be dressed up and fancied. Here, she goes to the next step and tackles the complicated matter of beverages, store bought and those we can make up for ourselves. She shows how to make up a day, weekend or weekday so the amounts needed get used in the context of meals and with a good balance over the whose period. Beverages that do and do not increase stone risk are highlighted as well. I view it as essential reading.
Between price increases and what appears to be cutbacks in what insurance plans will pay for, I have heard complaints from patients and physicians about the high price of this old standby treatment. The post points out where retail prices are a lot lower than average, but even the lowest ones are costly. Beverages can, however, provide inexpensive potassium alkali and I have identified what seem to be the best of them. Sodium alkali have disadvantages of physiology but marked advantages of cost, and the post offers some advice on how to use them as part of a daily alkali regimen. Between best prices, and substitutions of beverages and sodium alkali the numbers of potassium alkali pills used in a month can be greatly lowered, and that is at least one solution to what is for many a big problem.
Dr. Anna Zisman, our young and brilliant colleague, had one of her recent patients tell her about this internet remedy. The patient had actually used it on a number of occasions, on a regular basis, in fact, and seemingly gotten worse – more stones instead of less. Anna undertook a thorough review of the science concerning what lots of Coke and asparagus (yes, asparagus) might do for stones (nothing good) or for people in general (nothing good) and wrote this entertaining and ultimately most informative post. We have not so far presented our views on the information the web offers, so this is a first.
Renal Toll Like Receptors (TLRs) signal two nucleotidases which convert ATP to AMP and finally to adenosine. Kristin Bergsland offers the provocative idea that the inorganic phosphate released could raise local calcium phosphate supersaturation and thereby promote HA formation in the basement membranes of the thin limbs of the loop of Henle and in the surrounding interstitium. The signal? At least in micropuncture studies, fluid at the bend of the loop is supersaturated with respect to calcium phosphate, and crystals are known to stimulate TLRs. So one set of crystals begets another. This hypothesis has value because many of its necessary predictions are testable.
Jill Harris has written a perky and uniquely useful primer on how to drink the gallons of water physicians prescribe for their patients as a way of stone prevention. It is not so easy to keep drinking liters of water daily for years on end. Jill offers tips that help. Response to this post has been remarkable, and if you have not read it, you should.
A useful new paper shows that CT analysis of the kidney may possibly predict who will make new stones. Using standard methods that clinicians can apply in practice, a density of over 43 HU in stone free papillae was predictive of new stone formation over a 7 year period. That this was true helps support the hypothesis that common calcium stones form over interstitial plaque, as plaque would raise CT density of papillae.
We have begun a series of posts by Professor Andrew Evan, a foremost authority on the kidney tissue changes produced by kidney stones, and the manner by which stones form in human kidneys. Drs. Ross Holmes, and Andrew Evan have offered some novel comments about the process and implications for new research.
What Stones Are
The structure of the kidney stone itself. The stone crystals, and the complex matrix that holds the crystals together and affects their formation. The extreme importance of stone analysis, whether commercial analyses are accurate, and whether to analyse all stones that form in someone over time.
What is the best way to use supersaturation in clinical practice. The basic science of supersaturation as the primary force that drives all crystal formation. Patients can help their physicians determine the need for supersaturation reduction by in providing the information needed to judge if supersaturation is too high.
A personal note
Because some physicians have been curious, I have written a post on the practice of kidney stone prevention.
Let me know what you think. Suggest topics and points for some future time. Help us make this site better for you, whoever you are, because it is for others that we do this.