Jeffrey B. Kopp, M.D. : NIDDK

Jeffrey B. Kopp, M.D.



KIDNEY DISEASE SECTION
NIDDK, National Institutes of Health
Building 10, Room 3N116
10 Center Dr.
Bethesda, MD 20892-1268
Tel: 301-594-3403
Fax: 301-402-0014
Email: jeffreyk@mail.nih.gov

Research Website:


Education / Previous Training and Experience:
Dr. Kopp graduated from Harvard College (1975), University of Pennsylvania Medical School (1980) and completed training in Internal Medicine and Nephrology at the University of Washington (1987). He came to the NIH in 1987, working in the National Institute for Dental Research until 1995 and the National Institute for Diabetes and Digestive and Kidney Disease since that time.. He is a consulting nephrologist at the NIH Mark Hatfield Clinical Research Program and oversees a basic and clinical research program investigating mechanisms of focal segmental glomerulosclerosis. Dr. Kopp is a Commissioned Officer with the US Public Health Service, holding the rank of Captain. He is the Chair of the Physicians Professional Advisory Committee (2007), which advises the Surgeon General on issues relating to professional practice and personnel (www.usphs-ppac.org). He is Deputy Operations Chief of the PHS-1 Rapid Deployment Force, a 105-person medical team that deploys for disasters and other events that pose a threat to public health. He co-chairs the Emergency Preparedness and Biodefense Interest Group at NIH, which sponsors monthly talks relating to natural and man-made threats to public health (www.nih.gov/sigs). Dr. Kopp holds an appointment as Adjunct Professor of Medicine at the Uniformed Services University of the Health Sciences. Honors include NIDDK Directors Award (for service in Baton Rouge during Hurricane Katrina). USPHS awards include Unit Commendation, Commendation, and Crisis Response Service Award. Dr. Kopp serves on the Editorial Boards of the American Journal of Nephrology, the American Journal of Physiology (Renal) and Biomed Central Nephrology. He co-chaired the 2005 Basic Science Conference of the American Society of Nephrology, Why Kidneys Fail: Translating basic mechanisms into novel therapies. He has served on various NIH study sections and FDA advisory committees. He has authored over 130 papers and book chapters.


Research Statement:

Dr. Kopp is a principal investigator within the Kidney Disease Section of the Metabolic Diseases Branch. Work in his laboratory focuses on the study of focal segmental glomerulosclerosis (FSGS). FSGS occurs in several forms, including idiopathic FSGS, FSGS in association with HIV-1 infection, and FSGS occurring as a consequence of glomerular hyperfiltration due to reduced renal mass. FSGS is characterized by accumulation of glomerular extracellular matrix protein (fibrosis), with progressive loss of kidney function.

(1) FSGS Genetic Study: In collaboration with nephrology investigators around the country and with Dr. Cheryl Winkler, NCI, NIH, we are collecting DNA samples from patients with idiopathic and HIV-associated FSGS. We are studying candidate genes and will initiate a random genome scan based on linkage disequilibrium. Link to trial

(2) FSGS Pathogenesis Study: We are pursuing the hypothesis that viruses other than HIV may cause FSGS and are analyzing blood, urine, and kidney biopsy samples for the presence of multiple candidate viruses. Link to trial

(3) FSGS Permeability Factor Study: Patients with FSGS may develop recurrent FSGS following renal transplantation; this occurs in about 20 percent of patients. Recurrent FSGS has been linked to a plasma factor, which has been characterized by our collaborator, Dr. Virginia Savin of the Medical College of Wisconsin. We are preparing a protocol in which we will measure permeability factor. We will recruit patients with recurrent FSGS in a transplanted kidney, or who have lost a transplanted kidney to recurrent FSGS and are on dialysis. We will also recruit patients who wish to have FSGS permeability factor levels determined prior to transplantation. In patients with high FSGS permeability factor levels, we will examine the efficacy of plasma exchange to reduce the factor and determine both the rate at which the factor returns and the correlation between the return of the factor and proteinuria. Further, we will study the role of additional medication, such as cyclophosphamide, to suppress production of the permeability factor. In related studies, we will use molecular techniques such as expression profiling in attempt to identify the factor. Link to trial

(4) Podocyte Dexamethasone Study: Patients with minimal change disease or FSGS may respond to oral steroids (usually prednisone), and some enter complete remission. Paticularly for patients with FSGS, this may require many months of daily therapy, which has substantial toxicity. We are enrolling patients who have received <8 weeks of steroids in an open label trial of intermittent oral dexamethasone therapy lasting 12 months. We will determine whether this regimen is effective and whether it has less toxicity compared to standard doses of steroids. Link to trial

(5) FSGS Pirfenidone Study: Patients with steroid-resistant FSGS are eligible for a trial of an anti-fibrotic agent, pirfenidone. The trial is open label (no placebo) and involves one year of treatment. Analysis involves comparing the rate of GFR decline during a baseline period and while receiving pirfenidone. In preliminary analysis, pirfenidone slowed GFR decline by approximately 35%, an effect size compared to ACE inhibitor therapy along and greater than angiotensin receptor blocker alone. Link to trial

(6) Retinoids for podocyte diseases: Animal studies suggest that retinoids reduce proteinuria and fibrosis and act to promote podoctye differentation. We are recruiting patients with minimal change nepropathy, focal segmental glomerulosclerosis, or collapsing glomerulopathy who have proteinuria >3.5 g/d and estimated GFR >25\ ml/min/1.73m2. The trial is an open label trial of isotretinoin over 24 weeks, with a possible extension to 48 weeks. Link to trial.

Laboratory projects

(1) We have sought to identify the HIV-1 genes responsible for FSGS, using a series of transgenic mice which bear either subgenomic viral genomes or single viral genes. We have recently developed a mouse that expresses Vpr in podocytes in an inducible fashion, resulting in proteinuria and FSGS. We are pursuing the mechanisms by which Vpr induces FSGS.

(2) We are studying the mechanisms by which particular agents reduce proteinuria and reduce glomerulosclerosclerosis. These include sulodexide and retinoids

Clinical Protocols

  • Pirfenidone in focal segmental glomerulosclerosis, 00-DK-0042

  • Permeability Factor in Focal Segmental Glomerulosclerosis , 01-DK-0053

  • Genetic Analysis of Familial Keloids , 01-DK-0062

  • Pulse Dexamethasone Over 48 Weeks for Podocyte Disease, 03-DK-0226

  • Retinoids for podocyte diseases, 05-DK-0015

  • Pathogenesis of focal segmental glomeruloslerosis, 94-DK-0127

  • Genetic markers for focal segmental glomerulosclerosis, 94-DK-0133


Selected Publications:

Cho M, Hurley J, Kopp JB. Clinical trial of sirolimus for focal segmental glomerulosclerosis Am J Kidney Dis, 2006. [In Press]

Balasubramanyam A, Mersmann H, Jahoor F, Phillips T, Schubert U, Brary B, Iyer D, Smith EO, Takahashi H, Lu H, Kopp JB Effects of transgenic expression of HIV-1 protein Vpr on energy metabolism in mice Am J Physiol, 2006.

Zhang Y, Choyke PL, Lu H, Takahashi H, Mannon RB, Zhang X, Marcos H, Li KC, Kopp JB Detection and localization of proteinuria by dynamic contrast-enhanced magnetic resonance imaging using MS325. J Am Soc Nephrol (16): 1752-7, 2005. [Full Text/Abstract]

Zaragoza C, Li RM, Fahle GA, Fischer SH, Raffeld M, Lewis AM Jr, Kopp JB Squirrel monkeys support replication of BK virus more efficiently than simian virus 40: an animal model for human BK virus infection. J Virol (79): 1320-6, 2005. [Full Text/Abstract]

Orloff MS, Iyengar SK, Winkler CA, Goddard KA, Dart RA, Ahuja TS, Mokrzycki M, Briggs WA, Korbet SM, Kimmel PL, Simon EE, Trachtman H, Vlahov D, Michel DM, Berns JS, Smith MC, Schelling JR, Sedor JR, Kopp JB Variants in the Wilms'' tumor gene are associated with focal segmental glomerulosclerosis in the African American population. Physiol Genomics (21): 212-21, 2005. [Full Text/Abstract]

Cho ME, Kopp JB Fabry disease in the era of enzyme replacement therapy: a renal perspective. Pediatr Nephrol (19): 583-93, 2004. [Full Text/Abstract]

Dickie P Roberts A Uwiera R Witmer J Sharma K Kopp JB Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy. Virology (322): 69-81, 2004. [Full Text/Abstract]

Kitiyakara C, Eggers P, Kopp JB Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States. Am J Kidney Dis (44): 815-25, 2004. [Full Text/Abstract]

Yo Y Braun MC Barisoni L Mobaraki H Lu H Shrivastav S Owens J Kopp JB Anti-mouse mesangial cell serum induces acute glomerulonephropathy in mice. Nephron Exp Nephrol (93): e92-106, 2003. [Full Text/Abstract]

Kim JM Wu H Green G Winkler CA Kopp JB Miner JH Unanue ER Shaw AS CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science (300): 1298-300, 2003. [Full Text/Abstract]

Shigehara T, Zaragoza C, Kitiyakara C, Takahashi H, Lu H, Moeller M, Holzman LB, Kopp JB Inducible podocyte-specific gene expression in transgenic mice. J Am Soc Nephrol (14): 1998-2003, 2003. [Full Text/Abstract]

Shigehara T Zaragoza C Kitiyakara C Takahashi H Lu H Moeller M Holzman LB Kopp JB Inducible podocyte-specific gene expression in transgenic mice. J Am Soc Nephrol (14): 1998-2003, 2003. [Full Text/Abstract]

Kimmel PL Barisoni L Kopp JB Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations. Ann Intern Med (139): 214-26, 2003. [Full Text/Abstract]

Kimmel PL, Barisoni L, Kopp JB Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations. Ann Intern Med (139): 214-26, 2003. [Full Text/Abstract]

Kitiyakara C Kopp JB Eggers P Trends in the epidemiology of focal segmental glomerulosclerosis. Semin Nephrol (23): 172-82, 2003. [Full Text/Abstract]

Barisoni L Kopp JB Update in podocyte biology: putting one''s best foot forward. Curr Opin Nephrol Hypertens (12): 251-8, 2003. [Full Text/Abstract]



Page last updated: December 15, 2008

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