Pathogenesis and Treatment of HIV-Associated Renal Diseases: Lessons from Clinical and Animal Studies, Molecular Pathologic Correlations, and Genetic Investigations

Pathogenesis and Treatment of HIV-Associated Renal Diseases: Lessons from Clinical and Animal Studies, Molecular Pathologic Correlations, and Genetic Investigations

From George Washington University Medical Center, Washington, DC, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Abstract

HIV infection is associated with several renal syndromes, including acute renal failure. Chronic renal failure directly linked to HIV infection includes thrombotic microangiopathic renal diseases, immune-mediated glomerulonephritides, and HIV-associated nephropathy. A renal biopsy may be necessary for diagnosis. The development of HIV-associated nephropathy has been definitively linked to renal cellular infection, but the disease affects only a minority of patients, typically men of African descent. Therefore, factors determining disease expression in infected patients must now be emphasized.

The pathogenic mechanisms involved in HIV-associated renal disease remain obscure. Genetic factors, as well as renal cellular responses, mediated by HIV proteins (including an immune-activated microenvironment) capable of presenting antigen in susceptible hosts probably explain most cases. HIV-associated nephropathy has a characteristic pathologic phenotype, including glomerular, tubular, and interstitial changes, and ultrastructural findings. Infection of the glomerular epithelial cell, or podocyte, and consequent structural and biochemical changes may be pivotal in pathogenesis. The HIV-1 transgenic mouse is an important model for understanding disease pathogenesis, particularly the role of HIV proteins in mediating renal tissue injury.

Rigorously controlled randomized trials have not evaluated treatment, but corticosteroids and angiotensin-converting enzyme inhibitors have been used. Highly active antiretroviral therapy seems to have decreased the incidence of end-stage renal disease related to HIV infection and, in case reports, to have improved renal functional and pathologic outcomes of HIV-associated nephropathy. Outcomes in patients undergoing hemodialysis and peritoneal dialysis have improved, and current research focuses on renal transplantation for treatment of HIV-infected patients.

Article and Author Information

Grant Support: Dr. Kimmel was supported by grant RO1-DK-40811 from the National Institute of Diabetes and Digestive and Kidney Diseases.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Paul L. Kimmel, MD, Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, 2150 Pennsylvania Avenue NW, Washington, DC 20037.
An edited summary of a Clinical Staff Conference Grand Rounds held on 27 June 2001 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Barisoni L. Pathologic features of HIV-associated nephropathy. In: Kimmel PL, moderator. Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations.
Current Author Addresses: Dr. Kimmel: Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, 2150 Pennsylvania Avenue NW, Washington, DC 20037.
Drs. Barisoni and Kopp: Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, 3N116, Bethesda, MD 20892.