The lovely courtyard with its gorgeous buildings all made of limestone blocks quarried a century ago in Indiana is a city block away from the medical school and hospital buildings where we practice, but I put it here to give a sense of context. I an my colleagues practice kidney stone treatment and prevention as physicians, but also as faculty of a very great university. And in that mixture of medicine and university life is the story of the kidney stone program, or at least part of it.
I am Fred Coe, the founder of the kidney stone program at UC. I put my picture here so you will know who wrote this introduction.
I began the stone program in 1969 as an assistant professor of medicine at the University of Chicago stationed at Michael Reese Hospital which was then a 1000 bed teaching hospital affiliated with the university. I had no formal training in the kidney stone field but was instead trained in the laboratory of Dr Donald Seldin, University of Texas Southwestern Medical School, Dallas, in the physiology of sodium and water. I became interested in stone prevention and founded the kidney stone evaluation laboratory which is still a central feature of our program. I have been an NIH funded scientist more or less since 1976 in the kidney stone research area, and continue in research to today. In 1995, along with Joan Parks and John Asplin – described below – I founded Litholink Corporation to provide kidney stone laboratory services to physicians in the US who could not otherwise obtain the kind of quality our UC program has always provided. We sold the company to LabCorp in 2006 and it has continued its excellent services as a subsidiary of that corporation to this day. I have founded this site partly as I founded Litholink and this program: to bring to the largest possible constituency the means for managing kidney stones. I have made my Google Scholar page public which shows the published work I have contributed to.
Dr. Elaine M. Worcester
Dr. Worcester is Professor of Medicine in Nephrology. She and I have worked together for many years. At the beginning of her career in Nephrology she worked in my laboratory as a post doctoral fellow where she did two distinguished research projects. She accepted a position at University of Wisconsin, Milwaukee, where she worked with Dr. Jacob Lemann, one of the leading mineral metabolism researchers of the 20th century. We were fortunate to get her back to the University of Chicago in 2000. Dr. Worcester has taken over directorship of the Kidney Stone Evaluation Laboratory and is the principal investigator (PI) of our National Institutes of Health Program Project grant in kidney stone research. She is among the leading investigators in kidney stone disease, and is an accomplished clinician concerning all aspects of nephrology and, of course, kidney stone prevention. Her major research during the past 10 years has concerned the biological mechanisms of hypercalciuria, the high urine calcium losses that raise risk of the common calcium kidney stone and also predispose to a serious kind of bone disease in some people. The work is performed on humans in the clinical research center and the protocols she created are the engine of the research which continues to the present day.
Dr. Anna Zisman
Dr. Zisman joined us as an faculty member in 2010 and is an Assistant Professor of Medicine, in nephrology. Before that she was a postdoctoral fellow in nephrology and worked with me and Dr. Worcester learning the specialty of kidney stone medicine. She is among the most talented young physicians in the Department of Medicine, recently honored with the distinguished departmental award as best young clinician. Her research concerns renal physiology of patients with reduced kidney function, and is highly related to the work Dr. Worcester and I do. Dr. Zisman took over directing the stone practice, and has done much to improve the patient experience and maintain the highest standards of quality. We are very fortunate to have this talented young consultant with us.
Dr. Glenn S. Gerber
Dr. Gerber is professor of surgery at University of Chicago, and Director of Endourology as well as the Urology residency program and student clerkship. Many of our patients have received care from him. Likewise, he has referred many of his surgical patients to us for stone prevention. He has published 134 research papers. Many concern the common urological problem of prostatic enlargement, lower urinary tract obstruction, prostate cancer and laparoscopic surgery. He published three basic science papers with Dr. Worcester on experimental hyperoxaluria which delineate two unique tubule lesions from in vivo crystallization. With Dr. Zisman he runs a joint Urology Nephrology teaching conference which involves fellows and house staff from both medicine and surgery and is very well attended. Surgeons obtain a knowledge of the medical aspects of kidney stone formation, the nephrologists some insight into stone urology and particularly how to read radiographs of kidney stones with the kind of precision and insight that surgeons require for their work.
Dr. Murray Favus
Although he does not directly work on kidney stone prevention, Dr. Favus sees a number of our stone patients, and we see a number of his patients who he treats for bone diseases. So he is in a special category here. A professor of medicine in the Endocrinology section of the Department of Medicine, Dr. Favus began collaborating with me in 1974 at Michael Reese hospital and together we have co-authored 37 scientific papers as well as several multi-author textbooks. Although we both study aspects of mineral metabolism, as does Dr. Worcester, Dr. Favus early on branched off into osteoporosis and related bone diseases wherein he has achieved international recognition. He created the UC bone program which serves a number of our kidney stone patients. Partly the overlap is because age and the ill advised low calcium diets stone patients often decide to follow produce bone disease. But largely the overlap is intrinsic. The most common abnormality of calcium stone formers is hypercalciuria to which I alluded in my opening remarks. Hypercalciuria leads to a complex bone disease that resembles osteoporosis but is not, rather it is something altogether different and hard to treat. Dr. Favus collaborates commonly with Drs. Worcester and Zisman and I in the treatment of such patients here. Murray collaborates closelyl with Dr David Bushinsky, who is Professor of medicine and Section Chief of Nephrology at University of Rochester medical school. Together with Murray, David has discovered critical new mechanisms thagt govern calcium regulation in bone and kidney relevant to human hypercalciuria.
Our dedicated and invaluable staff
Tony began working with us as chief laboratory technician in 1985 and is a mainstay of our program. He is the person our patients meet when they bring in their 24 hour urine collections. He runs or supervises the running of all of our samples from patients. In particular, we are among the very few laboratories that provide high precision serum calcium measurements for our patients using atomic absorption technology. Tony runs all those assays, and achieves the kind of results that have allowed us to diagnose primary hyperparathyroidism faultlessly in our stone forming patients for many decades and thereby bring about a cure. When we do our clinical research center research patient studies as part of our NIH grant, it is Tony who, along with Kristin and Shen, sees to getting the complex protocol done, and all the samples of blood and urine into the laboratory and properly assayed. It would be difficult for me to envision our program without Tony. Personally, Tony is all sunshine, never a complaint, and always something nice to say.
Kathy began working with us in 2008 and is the voice of the program. I hesitate to guess how many patients she has spoken to but certainly it is by now in the thousands. She is the person who tells our patients what we do, and how they can do what they need so we can help prevent their stones from recurring. She does so many specific things to bring about a successful visit here for each patient one is best off just saying it is a complex business to connect patients into so highly a specialized program as ours, and she does it beautifully. Kathy says, “Working with the patients is the best part of my day” and I believe it. She comes to clinic, sometimes, and when the patients get to meet her they are just delighted. ‘Oh, so that’s who Kathy is! Now I know what she looks like. That’s the voice I hear on the phone every time I call.’
Shen joined us only a year ago to work with Kristin on our research. We study patients in our clinical research center in order to better understand the mechanisms of hypercalciuria. In this work, we feed people with hypercalciuria, and normal controls, too, three meals a day for one day and two the next and measure how the kidneys control calcium balance. The work itself is very hard because it requires many samples of blood and urine all precisely timed. The nurses in the center do the collecting and timing, and the samples come to our kidney stone laboratory where Shen has a main responsibility for the measurements. Like all research, there is an endless labeling and sample preparation, loading samples into instruments, and getting results into the computer for analysis, which she does. Without her care and thought the work would be lost altogether. Shen is a charming and soft spoken person who is always cheery and happy to chat about the day.
The Scientists of Indigo
As clinician scientists concerned with kidney stone disease, Dr. Worcester and I work with a number of other scientists. Our joint work is funded by the an ongoing program project grant (NIH NIDDK P01 56788) and we have worked together for so long – 15 years or more – that this bi-city group has taken on its own identity which I have called ‘INDIGO’. As listed below, a number of scientists in the PPG work at Indiana University, Indianapolis (IUPUI), whereas the others work at University of Chicago (UC); thence the name Indigo.
The research of our PPG concerns formation of calcium kidney stones, and here at UC Dr. Worcester and I are are specially focused on the role of high urine calcium excretion (hypercalciuria) in causing such stones. Hypercalciuria is familial and almost certainly genetic, found in about 1/2 of the immediate relatives of patients who have the trait. During the past 10 years we have worked out some of the mechanisms by which the kidneys create such high urine calcium losses, and how at least one important treatment for hypercalciuria – thiazide diuretic drugs – exerts its effects.
Many scientists are crucial to the success of Indigo, but 4 are at the very heart of it: Drs. Andrew Evan, Elaine Worcester, Jim Lingeman, and I. We are the core group who wrote the PPG application and renewals, and essentially designed the shape of the work. As I have mentioned, Dr. Worcester is now the PI of the NIH Program Project.
Having introduced those scientists who are clinicians and several of the Indigo scientists using their doctoral prefix, I found I could simply not persist in this naming as I went through what we all do together as scientists. It is always first names. So I have shown everyone below with their titles but drop those titles in the little blurbs about each as it seemed a more fit way of speaking.
Dr. Andrew Evan (IUPUI)
Andy is rightly considered among the greatest living experts on the handling and interpretation of calcified kidney tissue. He is an accomplished anatomist and scientist, and had led our work on kidney stones into new areas that no other group has so far been able to enter. When Indigo began, we had a lot of knowledge here and worldwide about the driving forces for crystal formation, but little knowledge concerning how stones actually form in human kidneys. To find out how they formed, Andy had to work out new methods and adapt old ones to study tiny biopsies taken from human kidneys during stone surgery. Having done this, he proceeded to essentially create the atlas of figures showing human stone formation, and thereby transform this field of science and human disease. Andy was the founding PI of another PPG, concerned with the renal effects of shock wave lithotripsy, and saw that PPG through three funding cycles and a vast array of publications. So, throughout the years of Indigo, with all that has required, he supervised an entire separate group of scientists, published with them, and radically improved understanding of what shock waves can do to kidneys.
Dr. James Lingeman (IUPUI)
A master surgeon, Professor of Surgery, and director of the kidney stone surgery unit at IUPUI Jim pioneered in the intraoperative study of human kidneys of stone forming patients and was essentially the surgical counterpart of Andy Evan in the new work from Indigo. One can say without question that none of the new work on human kidney stone formation could have been accomplished without Jim’s uncanny ability to do what had never been done before with respect to intraoperative human surgical research. During stone surgery Jim perfected methods for visualizing the sites of stone formation, and obtaining tiny tissue biopsies from those sites and sites without stones in order to permit Andy to study the differences in the tissues and the exact manner in which stone crystals find their lodgings in the kidneys. In this work, it is as though Jim and Andy were one investigative unit, of remarkable ability. With Andy, Jim has been a major part of the shock wave lithotripsy PPG. In fact, it was Jim who understood the importance of studying shock wave effects on kidneys and brought Andy into the kidney stone field.
Dr. Kristin Bergsland (UC)
Kristin joined our group at UC in 2006 and is the technical director of the Kidney Stone Evaluation Laboratory. She has created many of the special assays we need for our research and keeps the stone evaluation laboratory one of the most accurate and reliable in the institution. She is a key part of our research program and an author on many of our publications. Before coming here, Kristin was a senior scientist at Litholink Corporation, now a part of LabCorp. While there she was PI of 3 NIH grants over a 10 year period. I can say our research program could not function without Kristin. More importantly than her scientific executive abilities, Kristin has given considerable thought to the molecules that make up the organic matrix of stones and especially their relationship to the innate immune system. She directs one of the Cores in our NIH Program Project grant. We certainly expect Kristin to contribute posts in the future.
Dr. Ben Ko (UC)
Ben is an MD scientist, newly joined with us in research but not as yet as a physician for our kidney stone patients. He is an expert on the biology of kidney cell transport, especially the cells of the distal convoluted tubule. Those cells are a critical site for regulation of urine calcium excretion. Because abnormally high urine calcium excretion is a central topic in our research, having Ben with us will add very importantly to both our intellectual lives and our experimental reach. Although just at its beginning phases, his work aims at understanding the effects of sex hormones, especially estrogen, in regulating calcium and sodium transport by distal convoluted tubule cells.
Not a physician, nor a PhD scientist, nor a member of our dedicated staff, Joan is part of the structure of our program still, even though she retired 6 years ago. I put her in her own class because of her unique involvement in the foundation of the program. Joan became my research associate in 1976 and subsequently co-authored with me many dozens of papers, and one whole book. Though she was not trained in science, Joan has a flair for numbers, and an talent for computer databasing which we began using in 1980, a time when such innovations were rare indeed. I might say Joan must have transferred our precious cargo of patient data from one to another new database software at least 5 times, and it was Joan who put the detailed data from every clinic visit into the file structures from which we have drawn the tables and figures for our many clinical papers. She was funded by NIH as a researcher from 1976 until her retirement. Although retired, she still comes to clinic with me weekly and tries to keep up the data. For years, on and off, Joan wrote our patient newsletter, and I hope she will write some posts for our patients, in her lucid and frankly beautiful prose. This latter has only improved with time as she has used her new found time in retirement to write novels.
Dr John Asplin (Litholink)
John was once my post doctoral fellow and is now Medical director of Litholink Corporation, a subsidiary of LabCorp. He is consultant to our PPG and among its most innovative and brilliant experimentalists. John has worked in many areas of kidney stone research. His early work concerned driving forces for crystal formation along the nephron and the effects of urine organic stone matrix molecules. he developed what is perhaps the most useful and accurate serum oxalate measurement which permitted our research on oxalate secretion. Most especially he has collaborated with Dr. David Bushinsky exploring the physiology of an inbred strain of hypercalciuric stone forming rats whose physiology remarkably resembles that of human hypercalciuria. Because of his capacities as a scientist and especially someone who can provide critical measurements, John has had the pleasure of multiple collaborative publications in the past five years or so whose tempo, as I judge it from PubMed is increasing.
Dr. Dan Gillen (UC Irvine)
I met and began collaborating with Dan when he was a young faculty member in the Department of Health Studies. He rose quickly to Professor at UC Irvine and has published 147 papers at the time of this writing. Dan works in very broad fields of science being a brilliant mathematician and statistician; the range, even counting only recent papers includes dialysis, facial memory with aging, asthma, cancer chemotherapy, and of course mineral metabolism as a collaborator with me and Dr Worcester. I have a reasonable working knowledge of statistics, so I can marvel professionally at the quality and insight Dan brings to the data which Dr Worcester obtains in her research – for it is mainly in her research that Dan collaborates.
Dr. James Williams (IUPUI)
Jim has worked with Andy for many years, and has brought to the kidney stone research field remarkable new insights about the stones themselves. He has played an important role in both the kidney stone PPG and the shock wave lithotripsy PPG and in both has been highly productive as an experimentalist and a creative scientist. He brought into the field high resolution in vitro CT scanning as a new way to explore kidney stone structure and therefore explore how such stones might have formed and, incidentally, how they might respond to shock wave lithotripsy. He works with Andy and Jim, in both PPG groups, and also collaborates with the Mayo Clinic stone research group as well. His interests extend into radiological visualization of kidney stones and how insights from in vitro CT scanning might help increase understanding of how clinical CT imaging might become more useful in differentiating among the various stone types.
Dr. Brett Connors (IUPUI)
Dr. Connors is a highly skilled renal morphologist and an accomplished experimental surgeon specializing in urological protocols on large animals. Bret is highly trained in the anatomical sciences and routinely preforms histological analyses at the light and electron microscopic level. He is a master of the scanning electron microscope and competent in transmission electron microscopy with immuno-labeling. Bret has extensive experience in designing and performing research studies on protocols to enhance the safety of modern techniques for kidney stone removal and analysis of tissue injury to the kidney. He is presently investigating the role of several key transporters to determine their role in kidney stone formation and growth.
Dr. Rajesh Handa (IUPUI)
Dr. Handa has a broad background and training in renal physiology and pharmacology with extensive knowledge in neural and hormonal regulation of the renal vasculature, glomerulus, tubular transport and cell signaling processes. His present interests are focused at understanding the biology of nephrolithiasis and endourological stone removal procedures. In particular, Dr. Handa has been developing and adapting optic biosensors to evaluate intraluminal analytes to determine their role in the development of human nephrolithiasis. He has published an extensive literature on ways to improve the efficiency and safety of noninvasive and minimally invasive procedures presently in use or under development in the treatment of nephrolithiasis.
Dr. Dan Clark (IUPUI)
Dr. Clark’s current role in the nephrolithiasis research group is to analyze patient samples for endogenous lithium levels, a measurement used to detect possible tubular defects which may contribute to the hypercalciuria characteristic of idiopathic calcium oxalate stone formers. Using a variety of analytical techniques, he is determining the level of specific proteins involved in ion transport. He is using tissues collected from selected human kidney stone forming phenotypes to shed light on the potential role of these proteins in stone formation. Dr. Clark’s special interests in kidney stone disease lie in understanding how the initial event of interstitial calcification leads to Randall’s plaque accumulation to the stage where the stones begin forming over plaque exposed to urine in idiopathic calcium oxalate stone formers. He is also interested in the mineral and protein composition of stones.
Sharon Bledsoe (IUPUI)
Sharon is a lot like Joan Parks: not a PhD scientist but someone of such skill and power in producing science one never thinks of her as anything but a full collaborator. My personal vision of Sharon is at her elaborate computer screening digital videos from the operating room, or showing us the results of some new tissue stain for a molecule we all want to see in its place in the kidney. All of the elaborate science Andy has accomplished using the human kidney biopsies has passed one way or another through Sharon’s skillful hands. And if I have given the impression that she is a merely technical wizard, let me correct matters. I have known her modify and remake endlessly so as to bring about the scientific results we all need; she is an innovator and thinker about the how of science. Sharon is an author of many papers you can find on PubMed, and in those I have also authored I will say she deserved her authorship fully.
Phil Blomgren (IUPUI)
I do not have a proper picture of the corner of the lab where Andy, Elaine, Jim, and Jim and all the others meet when the Chicago part of Indigo comes to Indy, but on the walls of that little and beloved nook are a border of journal covers that depict work Andy has participated in. A cover picture means that the editors of the journal have chosen from all the papers which will appear that week or month the one best graphic, best in being interesting to the eye, somehow depictive to an outsider about the science it represents, and, of course, best in being beautiful. It is always Phil who ultimately made that picture. Andy may have envisioned it, Sharon may have made the original, even I or someone else may have suggested it, but the final picture, the one that is beautiful because right in all of its elements, that picture, was made by Phil. Like Sharon in front of her elaborate computer I cannot imagine Phil better than at his, with a hand on the unusually large mouse he uses to control his cursor. My own picture here came to Phil who situated me in front of Botany Pond at UC, even though I was originally photographed sitting at my desk. Phil is a powerful graphic artist and photographer who has given our little world of science some aspects of beauty, and in so doing has brought the inner beauty of nature, that little bit of it that we have unearthed, into the larger world of our scientific community performing thereby his own rare and unmistakable acts of grace.
Dr. Hatim Hassan (UC)
Hatim is both an MD and PhD trained researcher who is part of the clinical faculty in the Nephrology program at UC. He is specially trained in the field of epithelial transport and works on how the intestinal tract controls the uptake of oxalate from food and the removal of oxalate from blood into the bowel lumen. He is PI of his own NIH R01 grant and unlike Elaine, Anna, Kristin, and I works with animals as opposed to human subjects. Hatim is part of our regular research meetings and I expect he will offer some posts to this site in his special area of expertise because oxalate is a central issue in human kidney stone formation.