Clinical Care and Research Propel Nephrology Division

When Jochen Reiser, M.D., Ph.D., the Peggy and Harold Katz Professor of Medicine and vice chair for research in the Department of Medicine, joined the Miller School four years ago as chief of the Division of Nephrology and Hypertension, the division boasted an excellent clinical program with a strong focus on kidney transplantation.

Transplant nephrologists managed patient care at Jackson Memorial Hospital, one of the nation’s busiest kidney transplant centers. Renal specialists directed four dialysis clinics and one of the state’s largest peritoneal dialysis programs. The fellowship program trained the next generation of nephrologists, including six faculty members, and the pioneering interventional nephrology program, the first at an academic center, was attracting international observers.

But today, even as the division continues to grow clinically, it is becoming as well known for research aimed at unlocking the mechanisms of chronic kidney disease that affects 26 million Americans as it is for the top-notch care it provides to 250-plus new kidney transplant recipients, 2,000 post-transplant patients, 450 dialysis patients and scores of lupus and other patients annually.

And that’s entirely by design. Under the novel administrative model Reiser proposed for running an academic nephrology division when Miller School Dean Pascal J. Goldschmidt, M.D., and Marc Lippman, M.D., the Kathleen and Stanley Glaser Professor and Chair of Medicine, recruited him from Harvard to build a comprehensive, multidisciplinary, academic medical enterprise, the division has struck a self-sustaining and enviable balance between research and clinical care.

Divided into seven complementary sections – Basic and Translational Research, including drug discovery, Clinical Nephrology, Interventional Nephrology, Fellowship Training, Clinical Practice Outreach, Clinical Research, and the Nephrology Service at the Miami Veterans Affairs Medical Center – the division is designed to accelerate the development of therapeutic alternatives to dialysis and transplant while continuing to provide and improve the kind of care for which it has long been renowned.

“If we really want to change the life of a kidney patient we need to start bridging the gap between a really good discovery and industry picking it up,’’ said Reiser, who leads the division’s basic and translational research arm, The Peggy and Harold Katz Family Drug Discovery Institute. “This is an effective way to get our novel scientific insights translated into the clinic to optimize patient care.”

Under the Katz Institute umbrella, Reiser and investigators like Christian Faul, Ph.D., assistant professor of medicine, cell biology and anatomy, and Vineet Gupta, Ph.D., assistant professor of medicine, biochemistry and molecular biology and founding co-director of the institute, are teaming up with clinicians to understand kidney diseases on a molecular level and develop novel assays and compounds that can be used to develop kidney-cell specific therapeutics.

“Fifty years ago, dialysis made nephrology the most exciting discipline in internal medicine. All of a sudden, people with kidney failure didn’t have to die,” Reiser said. “Now, 50 years later, dialysis and transplant are not the best solutions – on average, dialysis keeps you alive for several more years, and transplant is expensive and has organ shortages and failures – yet we still don’t have really good drugs to treat patients. That’s why we had the idea of creating this structure that can serve as an outlet to clinical trials and industry.”

Under that structure, every section in the division has undergone considerable growth and notched numerous milestones that contribute to the overall mission.

Among them:

For two years in a row, the division earned a spot in U.S. News & World Report’s national rankings of best hospital nephrology and hypertension programs, climbing into the top 3 percent of all divisions in the nation in last year’s evaluation, based on reputation, patient survival, safety and other care-related factors.

NIH-funded research increased from $100,000 to more than $15 million and clinical and basic science researchers have published ground-breaking studies in a number of top-tier journals. Last summer, in a study published in Nature Medicine, Reiser and his team identified the first circulating factor known to start the process of focal segmental glomerulosclerosis – scarring of the kidney that causes about 25 percent of all cases of nephrotic syndrome.

A few weeks earlier, Tamara Isakova, M.D., M.M.Sc., assistant professor of medicine, and Myles Wolf, M.D., M.M.Sc., associate professor of medicine and director of the division’s clinical research, published a study in The Journal of the American Medical Association that found that elevated levels of fibroblast growth factor 23 (FGF23), the hormone that prompts the kidney to excrete phosphate, is a predictor of mortality and the development of end-stage renal disease in patients suffering from chronic kidney disease. Wolf and Faul soon followed that study with another in The Journal of Clinical Investigation that showed the same hormone induces heart disease in patients with kidney disease.

Under David Roth, M.D., professor of medicine, director of clinical services and medical director of Kidney Transplantation, the clinical faculty has doubled to serve the growing number of patients with chronic kidney disease. Today, more than 30 division specialists deliver a wide range of inpatient and outpatient services at University of Miami Hospital, Jackson Memorial, and the Miami VA, and see about 1,400 new referrals for kidney transplants and more than 900 patients on the waiting list annually.

“Unfortunately, kidney disease is a growth industry,” said Roth, one of the first nephrologists in the nation to manage the care of transplant patients, a role once filled almost entirely by transplant surgeons. “That’s largely ascribable to the growth in the elderly population, and the number of diabetics. The leading cause of kidney disease in this country is now diabetes.”

Among the division’s clinician-scientists investigating diabetes and kidney disease, Alessia Fornoni, M.D., Ph.D., assistant professor of medicine and director of the Diabetic Nephrology Clinic, is focused on characterizing the molecular mechanism responsible for kidney disease as a complication of diabetes. She is also developing personalized approaches to understanding each patient’s kidney disease, and created the personalized cellular assays used in a UM study published in Science Translational Medicine that identified patients who have increased susceptibility to post-kidney transplant complications.

Under the co-direction of Arif Asif, M.D., professor of medicine and a leader in the burgeoning field of interventional nephrology, and his successor and protégé, Loay Salman, M.D., assistant professor of medicine, Interventional Nephrology opened its first off-campus center last year to provide care to dialysis patients with complications related to their vascular access, through which they receive the life-sustaining treatment that filters waste from the blood three times every week.

A vital resource for an estimated 900 dialysis patients in south Miami-Dade County, the UHealth Vascular Access Center in Palmetto Bay is also a model for building collaborative partnerships with community physicians. Absent the access center, community nephrologists would have to send dialysis patients with dysfunctional vascular access to the hospital or a distant locale for interventional care. That process typically delays dialysis and often contributes to morbidity and mortality.

Asif, who is heading to Albany, New York, to become a division chief, and Salman also have published extensively in their field and helped to improve the care of kidney disease patients. For instance, they helped define the appropriate treatment for dialysis patients who need pacemakers or other cardiac implantable electronic devices, and they identified the source of cells that build up in the access circuit and cause the most common access dysfunction, neoentimal hyperplasia, lesions that limit the flow of blood and disrupt dialysis.

“Now we are studying the cell type and characteristics for targeted and maybe preventive therapies in the future,” Salman said.

Building more bridges to colleagues in the community, Reiser recently created a Practice Outreach section, directed by Jorge Diego, M.D., assistant professor of medicine and medical director of one of the University’s four dialysis clinics. An expert in kidney and infectious diseases, including HIV, Diego is creating new opportunities for shared work between academia and private practitioners.

Led by Oliver Lenz, M.D., associate professor of clinical medicine, the nephrology fellowship program is among the largest in the country, attracting 350 applicants a year and offering comprehensive training at UMH, Jackson and the VA. Over the past three years, the program has expanded from four to five two-year fellowship positions and added two third-year fellowships, one for transplant nephrology, headed by Giselle Guerra, M.D., assistant professor of clinical medicine and director of the Living Kidney Donor Program, and another in interventional nephrology, directed by Asif. A four-year research-track fellowship is also in the works.

Lenz, whose specialty includes cardiovascular complications in patients with chronic kidney disease, said he’s hopeful the growing basic science and clinical research enterprises will attract more fellows interested in becoming investigators or teachers. “The dedicated faculty members at the participating institutions have made this a very successful clinical training program,” he said. “Now we have the opportunity to move to the next step, develop training grants and combined academic/clinical tracks.”

Under Wolf’s leadership, the clinical research section is also fertile ground for training and career development, with investigators participating in single- and multi-center clinical trials supported by government and industry, as well as many observational studies that complement and integrate with the efforts of the Katz Institute.

Through his team’s work, Wolf has helped advance the understanding of how abnormal mineral metabolism can harm patients with kidney disease, particularly the role of FGF23 as a potent risk factor in the progression of kidney disease.

“In population studies of patients with end-stage renal disease, early-stage chronic kidney disease, and even transplant patients, higher FGF23 are linked to greater risk of death,” Wolf said.

Other clinical investigators are involved in transplant research, or in research on lupus, the autoimmune disease that often affects the kidney. Gabriel Contreras, M.D., M.P.H., professor of medicine and director of Inpatient Acute Dialysis Services at Jackson, has been the Miami-site principal investigator on numerous NIH-funded studies, including one published in The New England Journal of Medicine last year that uncovered an effective therapy for patients with lupus nephritis, a debilitating kidney disease linked to lupus.

The newest recruit is Julia Scialla, M.D., M.H.S., assistant professor of medicine, who joined the faculty in 2011 after completing nephrology training at the Johns Hopkins University School of Medicine. She studies how the reduced capacity of kidney patients to excrete acid generated by diet affects their risk of accelerating the progression of their disease to end-stage.

Working with the divisional leadership at UM, Leopoldo Raij, M.D., professor of medicine, director of hypertension and chief of the Nephrology-Hypertension Section at the Miami VA, is trying to bridge research opportunities on both sides of the campus. He’s also supporting the VA’s effort to launch its own kidney transplant program, further solidifying Miami as a hub for kidney transplantation.

A nationally recognized hypertension researcher who remembers his VA lab being the first in the division, Raij has made significant contributions to understanding how hypertension accelerates the development of both atherosclerosis and kidney disease. Directly linking research and clinical care, he and his team found that agents used to treat hypertension also can protect the kidneys and cardiovascular system.

Today, Raij, who was honored with the American Heart Association’s prestigious Irving Page Alva Bradley Lifetime Achievement Award in 2009, is delighted with how well integrated the division’s clinical care and research missions are, and looks forward to more pivotal discoveries. “It’s exciting,” he said. “Since we are all working on the mechanisms of disease, what we do is almost automatically translatable.”

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