Why Science Matters All we know more than what was said in Babylon comes from science as practiced in the West since Harvey and Galileo. Rational, modern, effective kidney stone prevention arises naturally from knowing what crystals make kidney stones and what forces drive such crystals to form. Kidney stone prevention exemplifies precision medicine at its most exacting heights. Perhaps because kidney stones do not kill us as some diseases do, patients and even some physicians fail to use the remarkable and simple tools that decades of research have provided for their prevention. I am set against such folly. Until new science can convince me otherwise and contradict the work of a generation, I stand for personalized kidney prevention specific to … Continued
Among the thousands of comments on this site, this one theme rings out. Patients Are Confused Many patients just have no idea about what to do. They suffer from confusion. They have stones, one or many. Surgeries occur, or not. CT scans show this number of stones, or that number. Physicians may say contradictory things, or things that seem contradictory. And all the while new stones may form, more pain attacks may come, and lay to waste life otherwise spent in pursuit of work and family happiness. As a way out, people seek remedies, on the web, from friends, from physicians, of course, and often they do not work. Or, they do work but seem not to. The painting, Taking the Census, by Francis William … Continued
Primary hyperparathyroidism (PHPT) is a systemic disease caused by an excess of parathyroid hormone secretion. It causes calcium kidney stones but also multiple other abnormalities, especially of bone. Here, I am concerned with that subset of PHPT patients with kidney stones. A Curable Cause of Kidney Stones Unlike most stone formers those with PHPT have a good chance at permanent cure. This makes detection of PHPT a paramount aim for patients and their physicians. As I shall tell you, PHPT raises serum calcium above normal and is detected from blood test results. The elevation of serum calcium can be slight and variable so patience and persistence matter a lot. Once diagnosed, PHPT can be cured by a surgery that modern … Continued
How kidney stones form surely offers clues to how to prevent them. But they hide those clues very well. We cannot watch them form, as in a movie. It would take too long and we have no cameras inside kidneys. Stones form hidden from sight and all we have is the final results. So, we need hypotheses about how they form. Hypotheses About How Kidney Stones Form I have said elsewhere what that word means. Hypothesis means a vision of how what our senses show us might have come to pass. But not only a vision. The vision must offer necessary deductions about the world in which we can measure things. Otherwise the vision is mere speculation, airy conjecture. Only visions that … Continued
Personalized kidney stone prevention perfectly exemplifies the goals and aspirations of this modern age of precision medicine. Nowhere than here is treatment more specific to a given patient. Computer – like and driven by exacting physical laws, stone crystals respond to forces we can quantify in homely but surprisingly informative 24 hour urine collections. Crystal specific, patient specific treatments work. They reduce stone formation. And, they foster long term adoption by patients who can understand their basis and therefore believe in the treatment as more than some vague nostrum or imagined remedy thrown out to them by a busy and distracted practitioner. The featured image shows salt harvesting from evaporation ponds. Saltwater evaporates in sunlight, overloads with sodium chloride that crystallizes … Continued
Do Supersaturations Match Kidney Stones? This is a story about how well the supersaturations we measure in 24 hour urines reflect the average supersaturation in the kidneys of patients, whether supersaturations match kidney stones – match the crystals stone contain. If they do match well, we can trust supersaturations as our guide to treatment. If stones and supersaturations do not match well, what value can supersaturation measurements have? They could mean nothing. Stones form over months or even years. Can a few frames tell us about a movie? It is also a story about my own past because Joan Parks and I did the work over 20 years ago. Though old, human observational data do not go out of date. The stones and 24 … Continued
Our newest venture – the Kidney Stone Prevention Course. It arose from this idea: Kidney stone prevention depends a lot on proper diet and fluids, which patients control. This site tells people what that diet and what those fluids should be, but not how to eat that diet or drink those fluids in real life. They have to learn how. So we built the kidney stone prevention course to help them learn. Just as Raphael imagined generations of brilliant minds come alive together in The School of Athens (Raphael, 1509 -1511; Apostolic Palace in the Vatican.), we – on a vastly lower plane of existence – imagined and have, in the kidney stone prevention course actuated the knowledge on this site into real life. … Continued
Do you need a low oxalate diet? Who does? Who does not? How can you tell? I chose the gorgeous painting by Raphael that hangs in the Musée Condé Chantilly because three surpasses one. Who Needs Low Oxalate Diet? Most of all, those whose stones contain calcium oxalate crystals and urine oxalate enough to promote such stones. Less so those with systemic diseases – bowel disease, malabsorption syndrome, bariatric surgery, and primary hyperoxaluria – that raise urine oxalate. Their diseases require many treatments, only one of them low oxalate diet. Therefore, I write here for only patients without a systemic cause of stones. Do Your Stones Contain Calcium Oxalate? If your stones contain little or no calcium oxalate crystals, and urine oxalate itself poses no danger to your kidneys, low oxalate … Continued
Would anyone bet against water to prevent stones? Here is the first of new articles that highlight stone treatments in a simple format. These new articles were provoked by what patients asked for, and by Freakonomics. Because patients asked for clear answers about treatments, I lifted ‘water’ out of my long article on treatment of calcium stone formers, and simplified the style so the main points stand out. I also suggest betting, something we all understand. Freakonomics offers a three part podcast about the woeful state of medicine. Doctors, they say, rely on received wisdom, poor clinical trial design, and bad data. At the end I ask you to vote if we kidney stone physicians suffer from these three defects, and by how much. Voting sharpens the mind, or should. … Continued
My Question Tell me what you want next on this site; that is my question. I have been writing this site – with the able help of my co-authors – since July 2014, and have reached what I might call a kind of plateau. Much of what I came to say about the most common kinds of kidney stone patients is said. Because the main work is done for the moment I have come with my question to you. The readership of the site has grown from 50 people in the first month to a present running average of 55,000 – 58,000 people monthly, depending on the season, and many of the visitors read quite a bit each. People find the site valuable, … Continued
It was a comment by Dr. Robert Perlman, a friend and brilliant scientist in the field of evolutionary medicine, that set me off on what I can only call a historical and scientific pilgrimage, a pilgrimage to the beginnings of the modern guidelines. At the end of my most recent article on the guidelines and our present stone fomenting diet, he pointed out that the US diet guidelines are so influential and the new ones so helpful in management of kidney stone disease we all must question who creates them, and how. The guidelines must have, he implies, the kind of elaborate and winding history one expects from a succession of governmental committees which, howsoever well served by volunteer scientific experts, can be subverted – by money, by … Continued
I have summarized the scientific evidence that low intakes of diet calcium and potassium and high intakes of refined sugar and sodium and protein raise risk of stones and loss of bone mineral. I have pointed out that the recommended US diet specifically seeks to correct all five of these risks and we should recommend it to all of our stone patients unless contraindicated by some specific problem. But I have not as yet shown to what extent we as a nation eat a diet deficient in calcium and potassium and excessive in refined sugar, sodium, and protein. In other words I have not as yet quantified the extent of the problem that stone forming patients face. Here is evidence from a large body … Continued
A Remarkable Concordance From 1980 to now the US government has published diet recommendations for the American people. Gradually and over time these have become quantitative and specify amounts of critical nutrients such as calcium, sodium, refined sugar, protein, and potassium – as alkaline anions in mainly fruits and vegetables. The goals are reduction of osteoporosis, hypertension, obesity, and diabetes. I shall call this the Ideal US Diet. Surprisingly, though aimed at stone prevention and management of bone disease from idiopathic hypercalciuria, decades of kidney stone research have identified precisely the same diet. Even more surprising, the Diet Against Systolic Hypertension (DASH) diet resembles the current Recommended US Diet, and stone researchers have found a reduced risk of stone disease in people who eat ‘DASH – … Continued
Medullary sponge kidney (MSK) is more spoken about than witnessed, and more witnessed than accurately diagnosed. This patient adds to the 12 we have described in our publication, and adds also in having a very long and evolving history with one of us (FLC). We write for a general audience yet hope to include a level of detail that satisfies physicians and scientists. Here, we may fail of clarity to the one audience or of a sufficiency to the other because the disease is complex. But withal, the evolution of diagnosis and care for this person so educates and the surgical anatomy and histopathology so instructs we have chosen to share the experience. What is it we are sharing? MSK is a Unique Disease MSK is remarkably specific in … Continued
Recently we presented what we think of as The kidney stone diet, meaning a unitary diet platform suitable for idiopathic calcium stone formers in otherwise good health. The story of that diet and the implications it has for stone prevention deserve perhaps a bit more commentary than we allowed for in the original article. The lovely image – Hendrick van Cleef, The Building of the Tower of Babel hangs in the Kröller-Müller Museum. He (1525 – 1589) is one of a family of famous painters and much admired for his brilliant textures and colors. Babel was to keep us aware we are divine. The Narrow Winding Path Over many decades, kidney stone researchers have gradually recognized what the ideal kidney stone diet might be. They did … Continued
If we put together everything on this site about diet for kidney stone prevention we get a reasonable and consistent image of one basic pattern. It is more or less what is ideal for idiopathic hypercalciuria and for reducing urine oxalate. It is the diet that has been used in the one major trial of diet for stone prevention. It accords with modern recommendations for the health of the American people. More or less, after all is said, there is only one diet plan that meets the needs for kidney stone prevention and we have called it ‘The Kidney Stone Diet.’ Of course, we are speaking of the diet for treatment of idiopathic calcium stones. Stones from systemic diseases, like bowel disease, primary … Continued
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.
Some of us overdo things with shakes and powders, some with 2 pound steaks. Others love sweets too much and don’t eat much protein. Like all the diet factors in stone and bone disease, protein intake is complex. Certainly, we all need protein in our diet but how much? Experts debate the best course, and patients wonder what to do. Abraham van Beijeren was, by the way, little recognized in his day but now considered a major painter of ‘luxuries’ like this standing roast. I chose it, as opposed to others more brilliant, because it looks modern – I have seen something like it on my own dining room table. In preparing this article I have made considerable use of the analyses performed by professor … Continued
Here are all the trials for prevention of idiopathic calcium stones, and my personal approach to using their results in clinical stone prevention. The whole site thus far has been built to support this article, which is the capstone of the enterprise. To highlight its importance I have made it header type larger.
Beside the usual references, I provide spreadsheets that contain all of the trial stone data with links to the original articles and PDF images of the articles. I also provide spreadsheets of stone risk data from the trials that I use in my analysis of the physiological responses to treatment. So this is a definitive as I can make it. I have left the two preceding videos in red because they are the steps up to this article, and perhaps people might want to view them in preparation. The two prior articles on phenotypes that come before the videos are also preparatory to this final presentation.
I say final because with the full presentation of all of the trials we have more or less covered the entirety of idiopathic calcium stone disease and need to move on to other stone types and to the systemic diseases that cause stones.
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.
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.
CLINICAL FINDINGS A man in his fifties formed his first stone in the early 2000’s and his last 6 months ago. There was a single passage event a year or two after the first stone at which time he was given hydrochlorothiazide 25 mg daily. A right SWL procedure was performed 1.5 years ago because of a stone attack, and potassium citrate 10 mEq twice daily was added in treatment. A right sided URS procedure was performed 8 months later but was not completed because of bleeding. A right URS 6 months ago is said to have left his right kidney stone free, but some stones were seen on the left. I did not have images to review when I saw him. He believes that all of … Continued
CASE 1: A Stone Former. As you will see, this is a person with considerable numbers of stone attacks who has certainly produced large stones in the past, but he posed major problems in deciding if stones were active and is therefore a perfect place to start. His many laboratory abnormalities are just wonderful for thinking about stone pathophysiology.
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.
As I see things, all of stone disease concerns the balance between the opposing forces of supersaturation and kinetic retardation of crystallization. The former is better understood and more tractable because easily measured and commercially produced for clinical care. The latter is not fully understood in term of the molecules responsible and not commercially available as a clinical test. So of the two primary forces that control whether crystals can form, we have only supersaturation to use. Being so central, this one measurement, for each of the stone crystals, has unusual importance. These three relatively short videos cover the main elements of supersaturation: What it is, how kidneys produce it, and how it is measured and used in stone prevention. They combine with ‘How Stones Form’ to make what I think is a fine story about stone disease and a fine basis for understanding how stones are best prevented. I have gathered together in the article links to all of the supersaturation articles on the site thus far.
This is a very first for me: Recommending a kidney stone site to those who visit here. Although the internet is vast and even a casual search shows a lot of kidney stone sites, this one stand out because it has all the traits I respect. It is run by a fine and thoughtful urological surgeon with special skills in kidney stone surgery. It has very high academic, intellectual, and scientific standards. It is large and therefore has a lot of material in it whereas many otherwise good sites are small and limited. It has a distinctive tilt toward patients, and a tradition of having patients write articles on it. For people who like this site, kidneystoners.org will feel famiiar yet different enough in its emphasis that to me the sites are highly complementary. Take a look and let me know what you think.
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.
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.
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.
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.
Five Steps to Stone Prevention
Ultimately we want to prevent kidney stones. Trial data, and my own large experience correspond in this one point: Prevention is a reasonable objective that can be successfully accomplished. Here is my own approach, simplified into five steps. They correspond to the overarching theme of this entire site: Stones require crystals; crystals follow the laws of physics; the force that drives crystallization is supersaturation; commercial vendors in the US provide supersaturation measurements in 24 hour urines at a reasonable price. So the steps are indeed simple: Know the stone crystals; measure the urine supersaturations; lower those urine supersaturations for the crystals in the stones being formed; keep them low. If stones persist, lower them more. It takes physicians to initiate this process, and there are complications such as the occasional systemic diseases which must be detected and treated in special ways. But it takes motivated patients to carry out the long term changes in fluids, diet, lifestyle needed, and to take the medications provided. It is time to focus here: Prevention is better than surgery. To help, I wrote a companion article several months ago about how to organize your medical stone prevention visits so as to get the most out of them.
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.
It has always seemed to me that medical practice is a dance. One leads, perhaps, but the other does, too. If physicians know more steps, patients can prepare their parts in advance and organize their large roles in long term treatments so the final result is graceful and ultimately elegant in obtaining the best results with the least extra effort and resources. After all, it is patients who know the past and will determine the future. Here are lists for you, ways to think about time with physicians, and especially a way to think about your treatment over the long years of stone prevention. For it is years, this being a chronic and recurrent disease, years of work by you with only a rare burst of medical guidance here and there. Yet so important as rare needs preparation and curating so what transpires is not lost. What is here is my own ideal of how things should happen, how the dance is conducted – so brief, so important.
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.
This is a foundational article for the site. High rates of urine calcium excretion (hypercalciuria) will raise calcium concentration at any given urine flow rate, and therefore raise supersaturation with the calcium stone forming salts. Genetic (‘idiopathic’) hypercalciuria, simply the upper end of the normal range, is greatly over-represented among stone formers, and idiopathic hypercalciuria (IH) is a main focus of treatment for stone prevention. As well, people with IH, stone formers or not, are at risk for bone disease. This article introduces hypercalciuria: IH itself and a few of the less uncommon named diseases that cause hypercalciuria like primary hyperparathyroidism, renal tubular acidosis, and sarcoidosis. It mentions confusing disorders such as normocalcemic primary hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia. It also offers evidence linking specific levels of urine calcium excretion to risk of stones, a very important matter in deciding what needs to be treated.
Being so important, the very force that drives crystal and stone formation, supersaturation has enjoyed considerable attention on this site and it seemed time to gather the articles about it into a coherent narrative. The walking tour seems apropos as such tours visit a group of related sites and have, or should have, a guide to put each one into perspective and extract from the entire group some large and generous idea about the world from which they arose. My prior one on stones themselves attempted the same.
Given that kidneys supersaturate the urine by conserving water, no treatment can be more immediate and direct than to drink more water than one needs so the kidneys can excrete it and in the process dilute the urine salts – which is to lower supersaturation. Alas, there are many patients who cannot or will not drink enough water, and it is these Joan Parks writes about in this article. Over our 40 years of collaboration very many patients with the problem of persistent low flow have come through our stone program at UC, but Joan and I never wrote a paper about them so much of what we found is buried in their charts. By way of redress, Joan has conjured up a lot of details that we think people will find valuable, even though they have not been shaped into the formal character of a scientific paper.
Not a few of you have heard this word and wondered what it meant for your health and management. Here is what it means. On the one hand, crystal deposits in kidney tissue. On the other, the name radiologists use when they see calcified regions overlying your kidneys, regions that are not clearly free stones but could be stones or tissue mineral. They really cannot tell with great precision. They never could. Modern high resolution ureteroscopy can tell, and surgeons everywhere have adopted this wonderful technology into common practice. You need to know this. Those of you who carry the diagnosis of nephrocalcinosis will all benefit from modern surgical visualization as opposed to indirect means of radiology.
If you want a comprehensive view of what kidney stones are and how they are made, I have put together various of the articles in this by now rather large site to make up a kind of story, or narrative, or, as I like to think of it, a walking tour. Read in the order I suggest, and take a look at the few narrator comments and I promise a nice overview of the topic. More will come if people seem to like this format.
Dr. David Goldfarb has taken on the American College of Physicians concerning the flawed guidelines they have promulgated for prevention of kidney stones. I have criticised these guidelines – for fluids and medication use – in two prior articles. My criticisms were about their intellectual failings and naivete concerning medical practice. His are broader because in addition to their intellectual and medical flaws they were published against the advice he gave as a peer reviewer of the articles. Furthermore, as he points out, they do not properly acknowledge the guidelines of the American Urological Association, which represents the main body of physicians who actually take care of stone patients. The AUA guidelines contradict those of the ACP and, in my opinion, and his, properly so. This matters to you as patients. If your doctor has been told something is good and proper, by physicians promoted as experts by the ACP, he or she may act accordingly, and that may not be good for your care. Read what Dr. Goldfarb says, and likewise what I have said about this matter.
Get ready. We have covered stones, supersaturation, stone risk, potassium citrate, and more, but now we are coming to a central mystery – a pivotal issue in whether or not treatment will work or not. Calcium is the first name of most kidney stones, and the calcium in stones comes mainly from the urine. So the urine calcium is a big deal. Yet it is sodium chloride, humble table salt, that strongly controls how much calcium is in the urine. Genes play a role, protein, too, lots of factors. But salt intake is so modifiable, so amenable to change it has a massive role in treatment. Here is my best on the subject. I hope you like it.
This is the essential basis for modern kidney stone prevention. I review its limitations, and how much information it provides on the pattern of stone risk factors for a given patient. Also, I show how much variation within a day hides in the 24 hour averaging and what you should do about it, and point out why you need at least two 24 hour urines before treatment. If you have signed up for my emails, read the one for this article because it explains how it is put together and best read.
I have no illusions this will have mass appeal, but the topic is important and many patients may have an interest in how medicine and science work together in general and in this disease as a particular example. Unlike the rest of this site where I am redacting and elaborating well known themes, here I am forced into originality by the general poverty of writing on the subject. For those who like this kind of writing, the Site Logic Page is its natural home. For those who do not – no doubt a vast majority – pass by.
This article will take you for a ride and offer you some surprises.
It is about how urine resists crystallization, a property summed up in the forbidding term ‘Upper Limit of Metastability.’
But don’t be scared off.
The ULM is a powerful concept that will help you understand the real issues in stone prevention.
And, at the end of the article, you will find that quite possibly it is not the mysterious and giant collection of urine proteins which protect us against crystals but perhaps our familiar citrate molecule in league with another small molecule, inorganic pyrophosphate which is a close relative of the bone sparing and common bisphosphonate drugs.
It seems to me important to highlight not only what we can do for stone prevention, but here and there to recognize those people who have given us what we have. Charles Pak’s work was instrumental in getting potassium citrate into the real world as a treatment. He helped to establish it worked, and helped industry make a practical pill form of it. As my tribute to him I have reviewed some his most important papers on the subject. Anyone who uses the drug should care.
This article is long and complex but I think patients will want to trouble themselves to read it. It tells the story of how our diet in the US, Europe, and urban Asia imposes an acid load which the kidneys must remove. That demand forces them to conserve citrate which is a natural defense against kidney stones. The pills neutralize the diet acid, and release the kidneys from their lifelong task of compensating for how we eat. That is why the urine citrate can rise. Removing acid is a major task that affects how kidney cells work. The humble potassium citrate pills have massive and probably beneficial effects on those cells. Of course, diet could the same as the pills, but how can one pursue a diet against the tendencies of the culture? Even with a will, most of us could not get it right – the balance of food, a proper nutrition. I could not advise we try.
Here is part two: citrate slows and can even stop stone crystals from growing. It does this by binding calcium, not the calcium in the urine but calcium atoms already part of a calcium stone crystal.
By binding to structural calcium atoms, citrate interferes with the orderly arrangement of atoms that is necessary for the crystal to exist, so one can think of inhibition and binding as two aspects of one power.
Like binding itself, this is not easy material to present or read. It is like climbing a tall hill for the view. If you will follow me up, I promise a reward.
The citrate molecule in urine is thought to protect against formation of calcium stones. This thought began as reasoning from chemistry, and culminated in clinical trials which substantiate the idea. As a result manufacturers produce citrate products for medicinal use, and doctors prescribe the medicine. All this is a wonderful success story, a kind of perfection of the paradigm of translational science: From science to a treatment for patients that reduces illness from kidney stone disease. But what, exactly, is the science? Can scientists not enjoy the story of such a success, physicians derive from it a deeper understanding of the drug they so regularly dispense and patients the comfort that a perfected knowledge support the rightness of their prescribed treatment? Citrate The Molecule As … Continued
Potassium citrate, thiazide diuretic agents, and allopurinol are the three medications that have a proven ability to reduce kidney stone formation.
Because fluids are so valuable and safe, we have emphasized their use as a basic treatment for all forms of stone disease. Here, I present the evidence that potassium citrate adds protection. The evidence is in the form of 5 trials that appear well done.
Some of the background for this article was already prevented in our discussion of the costs of this drug. Likewise, that discussion presented alternative sources of alkali that should more or less mimic the protective effects of the drug despite lack of direct trial data. I say this because the drug is a simple alkaline salt.
The article is written for anyone. Physicians will fill in more blanks than patients, but patients can easily analyse the numbers.
I have alluded to objectives in my discussion of applied, basic, and empirical science, which was a good place for their first mention but too narrow for a proper exposition. They are in the first case an expression of need, in the second case of desire, and in the third arise from perhaps an altogether different source. Here I am concerned with objectives of applied medical science. CLASSES OF NEEDS What can be the perceived needs of medicine but treatments, prevention, tests – to aid diagnosis or prognosis, methods, techniques and devices? EXAMPLES OF EACH CLASS Consider a patient with calcium oxalate stones not due to systemic disease, ‘idiopathic’ stones. Treatments This refers to stones present; they are there and surgeons need … Continued
This post concerns guidelines just released by the American College of Physicians (ACP) concerning prevention of calcium kidney stones. In the article two specific guidelines are proposed. The first, on fluid management, is covered in another post. Here I discuss their views concerning uses of medication. The discussion here is in advance of what is already on the site. Whereas I and others have put up more than a few articles about fluids, the issue of medications has not arisen. This is because medications have always been used to alter excretion rates of three atoms or molecules in urine thought to alter risk of calcium kidney stones: calcium, citrate, and uric acid. I have not as yet set the foundation for discussion of … Continued
The American College of Physicians has published its Clinical Guidelines on dietary and pharmacological management of kidney stones in adults. My purposes are to place the results of their deliberations in clinical context and also draw some conclusions about research we might want to perform. Though only two in number, their recommendations cover virtually our entire field of practice. For this reason I thought it best to consider each of the two separately, in different posts. As a simplification, I accept the statistical analysis as correct. Partly I suspect it is correct. Partly, I am not engaged with the methods of the analysis so much as I am with how we view their results and their conclusions. The ACP Guidelines can be influential among primary care physicians. As people involved with … Continued
WHAT IS THE QUESTION? I understand that some physicians are skilled basic scientists, and that many physicians enjoy reading about basic science. But how does a knowledge of basic science benefit the patients of physicians who have such knowledge? There are two parts to this question. How can being a basic scientist benefit a physician in the practice of medicine, and how can a knowledge of the results of basic science benefit a physician in the practice of medicine. Of these two, I mean to consider only the second: How does a knowledge of basic science results benefit the practice of medicine. Of course, here, I mean practice of medicine concerned with kidney stones – the disease within the province of this site … Continued
Three Sciences of Medicine Certainly we all agree that modern medicine takes its power from science. One kind of science concerns how we can do things. Let me call it ‘applied science’ for want of a name. The other kind concerns how nature does things. This is often called ‘basic science’ or ‘natural science’. Drug development and drug trials are obvious examples of the first. Mechanisms of disease are examples of the second. These statements are so obvious I hesitate to make them, yet in such phrases as ‘evidence based medicine’, ‘basic vs. applied science’, ‘personalized medicine’, and ‘translational research’ the distinction, itself perfectly clear, can blur. If basic science seeks to learn how nature does things, empirical science seeks to … Continued
How does anyone really know the amount of fluids you need for stone prevention? Dr. Elaine Worcester and I have put together much of what is known about the topic and offer some reasonable guidelines. Our caveat: These are guidelines, but have your physician do the final decision. Not everyone can drink large amounts of fluids, and not every patient needs the maximum amount, either.
I never have been a remarkable shopper, so those who know me well might wonder at a post about prices. Even so, patients have complained and wanted alternatives to potassium citrate pills which have become too costly for them. I did a bit of web shopping for retail prices, and although they vary, even the lowest seem too high for most budgets. A very brief look at insurance plans under Medicare: Some plans just pay the whole bill; some charge $10.00 for 100 pills; some charge a percentage of retail; some do not pay. So I have put together alternatives which taken in aggregate permit everyone to piece together a replacement for all or at least some fraction of these pills whose price has become just too high.
The complex but interesting featured graphic introduces aspects of the innate immune system which is present and active in the kidney and may have a role in stone genesis. Although innate immunity in kidney is a well established area of research, the specific links to plaque and stone formation have not been explored thus far. So, my post is meant to interest people in the possibility and perhaps give rise to some new scientific research. Toll Like Receptors (TLRs) The innate immune system is an ancient system of defense against environmental threats that is found in all classes of plant and animal life. Innate immunity provides immediate, non-specific defense against infection and products of cell damage or stress. Toll-like receptors (TLRs), … Continued
Ciudin et al JOURNAL OF ENDOUROLOGY Volume 28, Number 8, August 2014 Mary Ann Liebert, Inc. Pp. 1016–1021 Dr Jim Lingeman sent along a PDF of this article, which seems so useful and so germane to our current posts I decided to write about it. WHAT THE AUTHORS DID They Identified People with Prior CT Scans They did a cohort followup study of an initial 1000 people who had an CT performed between January and March 2005. From the 1000, 576 fulfilled their initial inclusion criteria which included that the CT was not performed for stone disease. Of these 177 were lost to followup leaving 362 study patients. They Measured Radiological Papillary Density In each of these 362 cases, papillary radiographic density was estimated by … Continued
Supersaturation Supersaturation names the force that makes crystals. Because it does, we measure supersaturation to understand why a patient makes stones, and we reduce risk of more stones by lowering supersaturation. Fortunately, universal and quantitative laws govern how atoms and molecules form crystals so we can calculate supersaturation and predict the risk of crystals using equations that apply everywhere, even in the kidneys and urine. Supersaturate a solution yourself, and see how it works. Supersaturate your own sugar solution Saturate Your Sugar Solution Find a heat resistant glass container, fill it with water, and stir in table sugar until no more will dissolve. You will know when no more will dissolve because extra sugar remains at the bottom even if you shake … Continued
A NEW AND USEFUL REVIEW THE FUNDAMENTAL MEASUREMENT OF STONE PROPENSITY The three Moirai, or the triumph of death, Flemish tapestry ca 1520, Victoria and Albert Museum, London, depicts Clotho, who spins the thread of life, Lachesis, who measures out the length of the thread, and Atropos, the inexorable, who cuts the thread. In book 11 of the Odyssey, Odysseus travels to the underworld where, among other matters, he learns from Tiresias his own ‘fate’; that he will return to his home and his own wife; that he will travel again to a place so far from the sea his oar will go unrecognized; and that he will die in peace, by the sea and among his own people. But he must make an offering in … Continued
Hard unwanted objects made in the kidneys, stones can cause pain, bleeding, and urinary tract obstruction. Because stone surgery often infects the urinary system, and bacteria easily infect stones retained in the kidneys, infection follow stones like a shadow. Stones surprise patients by their smallness, for all the trouble they cause, or by their largeness to think they passed through the urinary tract. But small or large, many or few, stones provoke little love. Most who form them desire no more. Yet, left to themselves, stones recur. Over half of first time stone formers form another stone within 5 – 10 years. Once recurrent, stones form – on average – every 2 – 4 years. So stone patients must pursue prevention and not imagine their … Continued
A particular manner Here and there physician friends have asked me about how I practice. But however much I have written about kidney stones, nowhere before have I told about how I practice because I feared my style might seem too odd. But it is not if you consider how narrowly I have chosen to focus. My clinical life is based on several facts. One is that doctors send me their patients and expect that I will prevent recurrent stones. That is all they want from me. This means that I can depend on other physicians to do everything else, focus on the pathogenesis of kidney stones in a particular patient and fashion for that patient a program of prevention which will … Continued
Kidney stone types Crystals make stones and their names signify the kidney stone types. Here are the names of the crystals that make the stones: CAOX, Calcium Oxalate; CAP, Calcium phosphate; UA, Uric Acid; Cystine; Struvite. The wedges on my pie chart show the relative abundances of the kidney stone types in our large population of stone forming patients. Calcium oxalate stones predominate by a wide margin in our clinic and in all others I know of. The kidney stone types, or names, matter because the whole science of stone prevention focuses upon stone crystals. Each kidney stone type creates its own unique illness and requires specific treatment. That is why we name the kidney stone types by the names of their crystals and … Continued
How bad is kidney stone analysis? I have pointed out the crucial importance of kidney stone analysis. Likewise, if possible, I analyse every stone because crystal type can change. But does this not raise the obvious question: How good are stone analysis labs? At first one might say why ask? We use labs all the time and trust them. As things turn out, stone analysis varies more in quality than serum electrolytes, or blood hemoglobin. Moreover, some stone crystals pose greater problems than others. There is a gold standard X Ray Diffraction Basiri et al recently reviewed all available papers concerning analysis of kidney stone crystals. Like prior investigators, some of whom they reference, X-ray diffraction does indeed reveal stone crystal structures … Continued
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.
There is no doubt about what I say to patients: ” Analyse every kidney stone. Bring in any stones you have tucked in a dresser drawer and get them analysed. Bring me all the analyses that have been performed on your kidney stones.” But what do I say to me, and what do I do as time goes on and more stones form or are passed? Do I analyse every kidney stone? Do you? The problem of keeping track Whenever I get a new patient, the stone analyses are at the top of my mind. How can I do anything rational about prevention if I don’t know what the stone crystals are? If there are no analyses at the first … Continued