HIV-associated nephropathy (HIVAN)
- Christina M Wyatt, MD
Christina M Wyatt, MD
- Associate Professor
- Icahn School of Medicine at Mount Sinai
- Paul E Klotman, MD
Paul E Klotman, MD
- President, CEO, and Executive Dean
- Baylor College of Medicine
HIV infection has been associated with both acute kidney injury (AKI) and chronic kidney disease (CKD). (See "Overview of kidney disease in HIV-positive patients".)
HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS [1-3], although HIVAN may also occur in patients with less advanced HIV infection or acute seroconversion [4,5]. Histologically, HIVAN is a collapsing form of focal sclerosing glomerulosclerosis (FSGS) (picture 1), accompanied by microcystic tubular dilatation and interstitial inflammation .
Issues related to HIVAN will be discussed in this topic. An overview of kidney disease in patients with HIV infection and discussions of electrolyte abnormalities, dialysis, and transplantation in HIV-positive patients are provided elsewhere. (See "Overview of kidney disease in HIV-positive patients" and "Electrolyte disturbances with HIV infection" and "Human immunodeficiency virus and dialysis" and "Solid organ transplantation in HIV-infected individuals".)
The pathogenesis of HIV-associated nephropathy (HIVAN) is hypothesized to involve several factors:
●Infection of kidney epithelial cells by HIV and expression of HIV genes within infected kidney cells
- Gardenswartz MH, Lerner CW, Seligson GR, et al. Renal disease in patients with AIDS: a clinicopathologic study. Clin Nephrol 1984; 21:197.
- Pardo V, Aldana M, Colton RM, et al. Glomerular lesions in the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101:429.
- Rao TK, Filippone EJ, Nicastri AD, et al. Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med 1984; 310:669.
- Winston JA, Bruggeman LA, Ross MD, et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001; 344:1979.
- Levin ML, Palella F, Shah S, et al. Hiv-associated nephropathy occurring before HIV antibody seroconversion. Am J Kidney Dis 2001; 37:E39.
- Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int 1999; 56:2203.
- Dickie P, Felser J, Eckhaus M, et al. HIV-associated nephropathy in transgenic mice expressing HIV-1 genes. Virology 1991; 185:109.
- Kopp JB, Klotman ME, Adler SH, et al. Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci U S A 1992; 89:1577.
- Bruggeman LA, Dikman S, Meng C, et al. Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression. J Clin Invest 1997; 100:84.
- Dickie P, Roberts A, Uwiera R, et al. Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy. Virology 2004; 322:69.
- Kajiyama W, Kopp JB, Marinos NJ, et al. Glomerulosclerosis and viral gene expression in HIV-transgenic mice: role of nef. Kidney Int 2000; 58:1148.
- Hanna Z, Kay DG, Rebai N, et al. Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice. Cell 1998; 95:163.
- Husain M, Gusella GL, Klotman ME, et al. HIV-1 Nef induces proliferation and anchorage-independent growth in podocytes. J Am Soc Nephrol 2002; 13:1806.
- Bruggeman LA, Ross MD, Tanji N, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection. J Am Soc Nephrol 2000; 11:2079.
- Ross MJ, Bruggeman LA, Wilson PD, Klotman PE. Microcyst formation and HIV-1 gene expression occur in multiple nephron segments in HIV-associated nephropathy. J Am Soc Nephrol 2001; 12:2645.
- Kopp JB, Smith MW, Nelson GW, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 2008; 40:1175.
- Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329:841.
- Kopp JB, Nelson GW, Sampath K, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 2011; 22:2129.
- Papeta N, Kiryluk K, Patel A, et al. APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. J Am Soc Nephrol 2011; 22:1991.
- Estrella MM, Wyatt CM, Pearce CL, et al. Host APOL1 genotype is independently associated with proteinuria in HIV infection. Kidney Int 2013; 84:834.
- Atta MG, Estrella MM, Kuperman M, et al. HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics. Kidney Int 2012; 82:338.
- Ross MD, Bruggeman LA, Hanss B, et al. Podocan, a novel small leucine-rich repeat protein expressed in the sclerotic glomerular lesion of experimental HIV-associated nephropathy. J Biol Chem 2003; 278:33248.
- Kaufman L, Hayashi K, Ross MJ, et al. Sidekick-1 is upregulated in glomeruli in HIV-associated nephropathy. J Am Soc Nephrol 2004; 15:1721.
- Gharavi AG, Ahmad T, Wong RD, et al. Mapping a locus for susceptibility to HIV-1-associated nephropathy to mouse chromosome 3. Proc Natl Acad Sci U S A 2004; 101:2488.
- Abbott KC, Hypolite I, Welch PG, Agodoa LY. Human immunodeficiency virus/acquired immunodeficiency syndrome-associated nephropathy at end-stage renal disease in the United States: patient characteristics and survival in the pre highly active antiretroviral therapy era. J Nephrol 2001; 14:377.
- US Renal Data System (USRDS): USRDS 2004 Annual Data Report: Atlas of End-stage Renal Disease in the United States. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, 2004.
- Schwartz EJ, Szczech LA, Ross MJ, et al. Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease. J Am Soc Nephrol 2005; 16:2412.
- Lucas GM, Eustace JA, Sozio S, et al. Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study. AIDS 2004; 18:541.
- Berliner AR, Fine DM, Lucas GM, et al. Observations on a cohort of HIV-infected patients undergoing native renal biopsy. Am J Nephrol 2008; 28:478.
- Williams DI, Williams DJ, Williams IG, et al. Presentation, pathology, and outcome of HIV associated renal disease in a specialist centre for HIV/AIDS. Sex Transm Infect 1998; 74:179.
- Lescure FX, Flateau C, Pacanowski J, et al. HIV-associated kidney glomerular diseases: changes with time and HAART. Nephrol Dial Transplant 2012; 27:2349.
- Bigé N, Lanternier F, Viard JP, et al. Presentation of HIV-associated nephropathy and outcome in HAART-treated patients. Nephrol Dial Transplant 2012; 27:1114.
- Ramsuran D, Bhimma R, Ramdial PK, et al. The spectrum of HIV-related nephropathy in children. Pediatr Nephrol 2012; 27:821.
- Han TM, Naicker S, Ramdial PK, Assounga AG. A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa. Kidney Int 2006; 69:2243.
- D'Agati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol 1998; 18:406.
- Barisoni L, Kriz W, Mundel P, D'Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 1999; 10:51.
- Atta MG, Choi MJ, Longenecker JC, et al. Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. Am J Med 2005; 118:1288.
- KDIGO. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl 2012; 2:209. http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf (Accessed on December 23, 2013).
- Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58:e1.
- Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 59:e96.
- Yahaya I, Uthman OA, Uthman MM. Interventions for HIV-associated nephropathy. Cochrane Database Syst Rev 2013; :CD007183.
- Szczech LA, Gupta SK, Habash R, et al. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney Int 2004; 66:1145.
- Atta MG, Gallant JE, Rahman MH, et al. Antiretroviral therapy in the treatment of HIV-associated nephropathy. Nephrol Dial Transplant 2006; 21:2809.
- Cosgrove CJ, Abu-Alfa AK, Perazella MA. Observations on HIV-associated renal disease in the era of highly active antiretroviral therapy. Am J Med Sci 2002; 323:102.
- Kirchner JT. Resolution of renal failure after initiation of HAART: 3 cases and a discussion of the literature. AIDS Read 2002; 12:103.
- Scheurer D. Rapid reversal of renal failure after initiation of HAART: a case report. AIDS Read 2004; 14:443.
- Kimmel PL, Mishkin GJ, Umana WO. Captopril and renal survival in patients with human immunodeficiency virus nephropathy. Am J Kidney Dis 1996; 28:202.
- Wei A, Burns GC, Williams BA, et al. Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition. Kidney Int 2003; 64:1462.
- Burns GC, Paul SK, Toth IR, Sivak SL. Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy. J Am Soc Nephrol 1997; 8:1140.
- Eustace JA, Nuermberger E, Choi M, et al. Cohort study of the treatment of severe HIV-associated nephropathy with corticosteroids. Kidney Int 2000; 58:1253.
- Smith MC, Austen JL, Carey JT, et al. Prednisone improves renal function and proteinuria in human immunodeficiency virus-associated nephropathy. Am J Med 1996; 101:41.
- Post FA, Campbell LJ, Hamzah L, et al. Predictors of renal outcome in HIV-associated nephropathy. Clin Infect Dis 2008; 46:1282.
- CLINICAL MANIFESTATIONS
- Differential diagnosis
- TREATMENT AND FOLLOW-UP
- Overview of medical therapy
- - ART and HIVAN
- - Renin-angiotensin system inhibition
- - Glucocorticoids
- Routine chronic kidney disease care
- Dialysis and transplantation
- SUMMARY AND RECOMMENDATIONS