Program Description of Nephrology and Hypertension Fellowship Training Program

History

Georgetown University Medical Center takes pride in education, and the Nephrology and Hypertension Fellowship Program program has benefited from a generation of extraordinarily successful leaders: George E. Schreiner (nephrology), Proctor Harvey (cardiology), Saul Katz (pulmonary medicine), Charles Hufnagel (cardiac surgery), and Edward Pelligrino (medical ethics).

The Nephrology Fellowship Program at Georgetown was begun in the 1960’s by George Shreiner and has since trained over 200 Nephrology fellows. Past trainees include many leaders in the field: James Balow, Howard Austin, John Maher, Shaul Massry, Jack Moncrief, Brendan Teehan, James Winchester, Gary Abuelo, Arleen Chapman, John Curtis and Dominick E. Gentile. In 1994, Georgetown University created the Schreiner Chair of Nephrology and hired Christopher S. Wilcox, M.D., Ph.D. to fill it. A passionate advocate of research and clinical training, Dr. Wilcox served as Division Chief and as Director of the Nephrology Fellowship Program from 1994-1999, promoting the clinical program, fellowship training, the research program, and clinical investigation.

The research component of the training program was further extended by Jason Umans, MD, PhD, the Nephrology fellowship director who in 2001 obtained a research training grant from the National Institutes of Health. With the assistance of this grant, the fellowship program was increased from two to three or more years to permit development of research projects. During this time, Dr. Umans built enduring links with the established training programs at Georgetown in Clinical Pharmacology and Therapeutics, and with the General Clinical Research Center at Georgetown. He also established ties with the National Institutes of Health, including access to a comprehensive course on the essentials of clinical investigation and research ethics. Today, Dr. Umans works primarily through the MedStar Research Institute at our sister campus of MedStar Health, Inc. at the Washington Hospital Center, although he maintains a clinical research program at Georgetown.

Shakil Aslam, MD, who specializes in hypertension, cardiovascular disease and oxidative stress in chronic kidney disease (CKD), assumed the directorship of the Nephrology Fellowship Program in 2006. Under Dr. Aslam’s direction, the clinical and research components have become more deeply interwoven with a new NIH training grant that was awarded in 2007. The program seeks to cultivate intellectual skills through attentive mentorship, critical reading of scientific literature, analysis, writing and reporting of research data, oral presentation of research in small groups and larger forums, and frequent interaction with an encouraging but critical group of training faculty and visiting scientists.

Today’s Program

An applicant for fellowship may now apply through a two-year clinical research track or a three-year basic research track.

The first fellowship year in either track focuses heavily on clinical training. Toward this end, Georgetown has a strong clinical program in the Division of Nephrology and Hypertension. Our daily inpatient nephrology census has grown to an average of 20 to 40 patients with 30-40% of these patients in the medical and surgical intensive care units including patients with kidney, liver, pancreas, and small bowel transplantation. There are seven outpatient clinics that offer a wide range of nephrology and hypertension patients. In addition, our in-center and home hemodialysis and peritoneal dialysis programs provide full exposure to all forms of renal replacement therapies for ESRD patients. The enlarged clinical program thus provides a rich range of clinical experience for fellowship training.

Our fellows also rotate through the Nephrology Renal Transplant Service at the Washington Hospital Center (WHC) for one (or occasionally two) months. The WHC has the world’s largest acute cardiovascular admitting program, and performs more than 150 renal transplants annually. Although the nephrology training programs at Georgetown and Washington Hospital Center are separate, both hospitals share MedStar Health, Inc. as their corporate parent, and WHC fellows attend weekly scientific and clinical didactic lectures and our monthly renal biopsy conferences.

• Clinical Research Track

The second year of clinical research track training exposes the fellow to clinical investigation. In recent years, a joint venture with DaVita, Inc., has given us the medical directorship and part ownership of the four DaVita outpatient dialysis units in Washington, DC. This has been important to our clinical research training program for two reasons:

1. It has provided us with valuable resources to expand and re-equip our research laboratories and to help maintain a fully funded clinical research program.

2. It has helped us to develop a large and growing population of our own end stage renal disease (ESRD) patients, which facilitates recruitment of research subjects.

Clinical studies include oxidative stress in CKD, plethysmography and ultrasound for vascular compliance and endothelial function, MRI/MRA with the GCRC research magnet, four chamber Mulvany myography and a novel perfusion myography to study human microvessel function ex vivo.

There are now six other areas of developing clinical investigation: Vascular calcification in ESRD, vascular compliance as a predictor of preeclampsia, mechanisms and treatment of oxidative stress in CKD, novel mechanisms to diagnose renovascular hypertension, defects in dopamine regulation in essential hypertension, and microvascular dysfunction and repair in patients with polycystic kidney disease.

Further clinical research opportunities are available through our collaboration with Vasilios Papademetriou, MD, the director of hypertension and interventional cardiology at the Washington Department of Veterans Affairs Medical Center (VAMC), directs our Divisional Hypertension Research Clinic, in addition to his large, funded VA research program. Thus, Georgetown can offer fellows an opportunity to care for a large population of patients with hypertension and renal disease in intervention trials (including LIFE, HOPE, VALUE, VALLIANT, and ALLHAT).

• Basic Research Track

The second and third years of the basic research track are devoted to closely supervised and mentored research in basic sciences in one of the several labs in the division. We have built an integrated research program at Georgetown that is centered on renal mechanisms of hypertension and damage. One part, co-directed by Christopher S. Wilcox, MD, PhD and William J. Welch, PhD, focuses on renal microcirculatory hemodynamics, oxidative stress, nitric oxide (NO) and vasoconstrictor arachidonate metabolites. A second part, co-directed by Kathryn Sandberg, PhD and Pedro Jose, MD, PhD, focuses on molecular mechanisms regulating G-coupled receptors, gender and age differences in renal and cardiovascular disease and defects in dopamine signaling in hypertension.

Basic science research training is directed by William J. Welch, PhD, who has daily interaction with the fellows during their laboratory experience. Our recently renewed fellowship training grant by the NIH provides funding for the fellows during their second and third years of basic research. Fellows are required to spend at least 80% of their time in the labs working on their projects. Our fellows present their findings at national and international meetings on a regular basis. Most of the findings from their work are published in high quality peer-reviewed journals. This experience is of paramount importance for securing jobs in academic nephrology, and helps prepare our fellows to set up independent research as junior faculty.

In terms of research, our goal in Nephrology and Hypertension is to prepare physicians and scientists to undertake independent investigation in renal and hypertensive disorders and in the basic biology which underlies normal and aberrant kidney function or blood pressure (BP) regulation. We emphasize the application of cutting edge basic research techniques to health related problems of renal and hypertensive diseases that include studies of renal mechanisms of blood pressure and volume homeostasis, receptor regulation, vascular physiology and pharmacology, angiogenesis, vascular remodeling and rarefaction, intracellular signaling mechanisms, oxidative stress, effects of gender and pregnancy on vascular function, molecular genetics, gene silencing and interactions between vasoactive factors in the kidney.

Research opportunities currently available to trainees include areas of renal microvascular physiology, micropuncture and microperfusion, gene transfer and gene silencing, whole animal studies of electrolyte and BP homeostasis, studies of free radical chemistry, site-directed mutagenesis of G-coupled receptors, cell signaling in renal tubular endothelial and VSMCs, functional studies of microvessels from systemic organs and the kidney, angiogenesis, rarefaction and vascular remodeling, in and ex vivo gene silencing, intravital microscopy of microvessels, fluorescence microscopy for radicals, renal oxygenation with O2 and CO2 sensitive microelectrodes, mouse micropuncture physiology, BP telemetry in conscious rats and mice, micropuncture studies of tubuloglomerular feedback, proximal glomerulotubular balance, and unidirectional Na+ fluxes in rats and mice, real time PCR, capillary zone electrophoresis with laser induced fluorescence to assay mediators in tubular fluid, and rat and mouse models of hypertension, aging, renal failure and diabetes.

THE GEORGETOWN ACADEMIC ENVIRONMENT

Georgetown, MedStar and the Cardiovascular-Kidney Institute

The Georgetown University Medical Center comprises a nationally ranked School of Medicine, School of Nursing and Health Sciences, and the Lombardi Comprehensive Cancer Center. It is a $120 million medical research enterprise with over 400 principal investigators. The Division of Nephrology and Hypertension is a busy, faculty-staffed, inpatient and outpatient program at Georgetown University Hospital backed by four outpatient dialysis units in which Georgetown faculty serve as the medical directors, a continuous ambulatory peritoneal dialysis (CAPD) program, and a pioneering regional home dialysis program. Every full-time faculty member in the Division has 100% funding for his/her salary either from research sources, clinical income and clinical research, or clinical income.

Georgetown University Hospital is one of seven hospitals and other healthcare services in Washington, DC and Baltimore that comprise MedStar Health, Inc. MedStar Health is a $2.9 billion non-profit healthcare organization with 23,000 employees, and 4,600 physicians care for 145,000 inpatient admissions, more than one million outpatient visits a year, and over 1,000 clinical trials.

Founded by Dr. Christopher S. Wilcox, Chief of Nephrology at Georgetown, the Cardiovascular- Kidney Institute has been incorporated by the Georgetown University Board of directors to promote interdisciplinary training and research in cardiovascular/kidney/metabolic disorders. It will integrate key investigators in basic science and clinical departments. The Cardiovascular Kidney Institute spans Georgetown University, the Washington Hospital Center and its Medical Research Institute /Cardiovascular Research Institute; the Department of Veterans Affairs Medical Center, the National Children’s Hospital, and the National Institutes of Health to develop large interdisciplinary groups that will provide shared mentorship among key scientists and selected fellows to broaden their research opportunities.

Research Links with National Institutes of Health

The superb faculty and research environment of the National Institutes of Health is only 20-30 minutes from our Georgetown campus. Several years ago, our Chief of Nephrology and Hypertension, Dr. Christopher Wilcox, enjoyed a part-time sabbatical at the NIH where he developed active collaborations with Peter Choyke, MD, PhD (Chief of MRI, Division of Radiology) to develop a new method to diagnose, at one visit, renal artery stenosis by magnetic resonance angiography (MRA) and functional renovascular disease by a captopril MRI renogram. He studied catalytic antioxidants in collaboration with pioneers in this field, James Mitchell, PhD (Director of Radiation Oncology) and Murali Krishna, PhD (senior scientist) at the NCI. A recent manuscript with K. Patel as a first author was coauthored with this NCI group who provided superb direction to our fellow (research fellow). Another collaboration with Juan Saavedra, MD, PhD (Director of Neuropharmacology, NIH), a world expert in brain receptors, resulted in an invitation for Chagria Kitiyakara, MD, (research fellow) to spend six months in Dr. Saavedra’s laboratory developing new methods to study central thromboxane receptors. He later returned to the NIH to take a further year of post-doctoral training with Jeff Kopp, MD in the division of nephrology. Collaboration with Jurgen Schnermann, PhD (Laboratory of Kidney and Electrolyte Physiology) who is the pioneer of mouse micropuncture, led to the training of Nori Kawada, MD, PhD, (research fellow) who has now established the techniques in our laboratory.

National and International Research Collaborations

Georgetown faculty in Nephrology and Hypertension have developed active collaborations with other leading universities nationally and internationally to widen the scope of research and training opportunities. We have recruited faculty for Georgetown, and have trained fellows from several universities:

The University of Osaka in Japan (nephrology director Enyu Imai, MD, PhD, who is a world leader in gene transfer into the kidney). Nori Kawada, MD, PhD was recruited from Osaka as a nephrology fellow and is now an assistant professor with his own grant in our division. We have coauthored several manuscripts with Professor Imai and he has been a visiting professor on three occasions.

The University of Guangzhou in China (division director, Professor Jiaming Yu, MD, PhD, a leader in clinical studies of nephrotic syndrome). Dan Wang, MD, PhD was recruited from Guangzhou as a research fellow and is now an assistant professor in our division.

The University of Naples in Italy (division director, Professor Gianni Capasso, MD, PhD, an expert in renal micropuncture). A current research fellow, Carla Panico, MD, was recruited from Naples as a post-doctoral scientist. Dr. Welch and Dr. Capasso are her advisors for her PhD.

Ramathibodi University Hospital, in Bangkok, Thailand (division director Vasant Sumethkul, MD, PhD, a world expert in oxidative stress) is an ISN sister institution. Chagriya Kitiyakara, MD was recruited as a research fellow, and became instructor before returning as Associate Professor of Nephology.

University College London, UK (Professor Patrick Vallance, MD, PhD; Professor Robert Unwin, MD, PhD; Professor James Leiper, MD world experts in NO, ADMA and nephron function.) We have active research programs and publications with this group.

The University of Aarhus, Denmark (director Michael Mulvany, MD, PhD) and the University of Copenhagen, Denmark (director Svend Strandgaard, MD, PhD) who are pioneers in microvessel physiology. We recruited Dan Wang, MD, PhD, from Copenhagen as a postdoctoral fellow. She is now an assistant professor in our division. We have an active collaboration with these groups with joint publications and will send a fellow (Dr. Nouri) to train with Dr. Mulvany in culture myography.

We also have active collaborations within the USA with University of Michigan at Ann Arbor (Bert Pitt, MD and Rajiv Saran, MD, leaders in clinical studies of aldosterone and oxidative stress) with whom we have a collaborative NIH grant for a clinical study of aldosterone blockade and CVD under review; and the University of Maryland (Tom Pallone, MD, PhD, an expert in renal microvariolar physiology in the medulla), who has helped train our research fellows and junior faculty Dan Wang, MD, PhD, and Yifan Chen, MD, PhD.