Overview of kidney disease in HIV-positive patients
- 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
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Fernando C Fervenza, MD, PhD
Fernando C Fervenza, MD, PhD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Mayo Clinic College of Medicine
With dramatic improvements in survival and disease progression in the era of combination antiretroviral therapy (ART), complications such as kidney, liver, and cardiac disease have largely replaced opportunistic infections as the leading causes of mortality in the setting of HIV . Patients with HIV are at risk for both acute kidney injury (AKI) and chronic kidney disease (CKD) , secondary to medication nephrotoxicity, HIV-associated nephropathy (HIVAN) [3-6], immune complex kidney diseases [6-10], and, less commonly, kidney disease in the setting of thrombotic microangiopathy [11,12]. In addition, the aging cohort of HIV-positive patients may be at increased risk for kidney disease related to hepatitis B or C virus co-infection [6,13,14] and comorbid or treatment-related diabetes and hypertension.
ACUTE KIDNEY INJURY
Epidemiology of AKI in HIV-positive patients — Prior to the introduction of combination antiretroviral therapy (ART), acute kidney injury (AKI) was commonly attributed to septicemia, volume depletion, or medication toxicity [15,16].
Incidence of AKI — The incidence of AKI in HIV-positive patients is higher than it is in patients without HIV. The incidence of AKI in patients with HIV has also increased over time. This was documented in a study of hospitalized adults in New York state which compared administrative data from 1995 (before the introduction of ART) to data from 2003 (after the introduction of ART) . Compared with HIV-negative hospitalized patients, AKI was documented in a significantly greater proportion of HIV-positive hospitalized patients, both in 1995 (2.9 versus 1 percent) and 2003 (6 versus 2.7 percent). Among HIV-positive patients, the proportion with documented AKI was two-fold higher in 2003, although in-hospital mortality was lower.
In a prospective study of 754 ambulatory HIV-positive patients followed at a single center, at least one episode of AKI occurred in 71 patients (9.4 percent) during a two-year period (2000 to 2002, after the introduction of ART) .
Risk factors for AKI — Some risk factors for AKI among HIV-positive patients are similar to risk factors for AKI in the general population, such as older age, diabetes mellitus, preexisting chronic kidney disease (CKD), and acute or chronic liver disease . However, some risk factors are specific to HIV. In the study of 754 HIV-positive patients mentioned above, for example, AKI occurred more frequently among those receiving ART (12 versus 4 percent) and those with an AIDS-defining illness (30 versus 7 percent) . Other predictors of AKI included low CD4 count, high viral load, and co-infection with hepatitis C virus (HCV).
- Selik RM, Byers RH Jr, Dworkin MS. Trends in diseases reported on U.S. death certificates that mentioned HIV infection, 1987-1999. J Acquir Immune Defic Syndr 2002; 29:378.
- 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.
- 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.
- D'Agati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol 1998; 18:406.
- Casanova S, Mazzucco G, Barbiano di Belgiojoso G, et al. Pattern of glomerular involvement in human immunodeficiency virus-infected patients: an Italian study. Am J Kidney Dis 1995; 26:446.
- Kimmel PL, Phillips TM, Ferreira-Centeno A, et al. HIV-associated immune-mediated renal disease. Kidney Int 1993; 44:1327.
- Balow JE. Nephropathy in the context of HIV infection. Kidney Int 2005; 67:1632.
- Kimmel PL, Phillips TM, Ferreira-Centeno A, et al. Brief report: idiotypic IgA nephropathy in patients with human immunodeficiency virus infection. N Engl J Med 1992; 327:702.
- Boccia RV, Gelmann EP, Baker CC, et al. A hemolytic-uremic syndrome with the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101:716.
- Bachmeyer C, Blanche P, Séréni D, et al. Thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in HIV-infected patients. AIDS 1995; 9:532.
- Stokes MB, Chawla H, Brody RI, et al. Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus. Am J Kidney Dis 1997; 29:514.
- Lai KN, Li PK, Lui SF, et al. Membranous nephropathy related to hepatitis B virus in adults. N Engl J Med 1991; 324:1457.
- Peraldi MN, Maslo C, Akposso K, et al. Acute renal failure in the course of HIV infection: a single-institution retrospective study of ninety-two patients and sixty renal biopsies. Nephrol Dial Transplant 1999; 14:1578.
- Rao TK, Friedman EA. Outcome of severe acute renal failure in patients with acquired immunodeficiency syndrome. Am J Kidney Dis 1995; 25:390.
- Wyatt CM, Arons RR, Klotman PE, Klotman ME. Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality. AIDS 2006; 20:561.
- Franceschini N, Napravnik S, Eron JJ Jr, et al. Incidence and etiology of acute renal failure among ambulatory HIV-infected patients. Kidney Int 2005; 67:1526.
- Choi AI, Li Y, Parikh C, et al. Long-term clinical consequences of acute kidney injury in the HIV-infected. Kidney Int 2010; 78:478.
- Wyatt CM, Kitch D, Gupta SK, et al. Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine. J Acquir Immune Defic Syndr 2014; 67:36.
- Wikman P, Safont P, Del Palacio M, et al. The significance of antiretroviral-associated acute kidney injury in a cohort of ambulatory human immunodeficiency virus-infected patients. Nephrol Dial Transplant 2013; 28:2073.
- Nelson MR, Katlama C, Montaner JS, et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS 2007; 21:1273.
- Zaidan M, Lescure FX, Brochériou I, et al. Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study. Clin J Am Soc Nephrol 2013; 8:930.
- 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.
- Szczech LA, Gange SJ, van der Horst C, et al. Predictors of proteinuria and renal failure among women with HIV infection. Kidney Int 2002; 61:195.
- 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.
- German P, Liu HC, Szwarcberg J, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr 2012; 61:32.
- Koteff J, Borland J, Chen S, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol 2013; 75:990.
- Becker S, Fusco G, Fusco J, et al. HIV-associated thrombotic microangiopathy in the era of highly active antiretroviral therapy: an observational study. Clin Infect Dis 2004; 39 Suppl 5:S267.
- Jotwani V, Li Y, Grunfeld C, et al. Risk factors for ESRD in HIV-infected individuals: traditional and HIV-related factors. Am J Kidney Dis 2012; 59:628.
- Estrella MM, Parekh RS, Astor BC, et al. Chronic kidney disease and estimates of kidney function in HIV infection: a cross-sectional study in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr 2011; 57:380.
- Cailhol J, Nkurunziza B, Izzedine H, et al. Prevalence of chronic kidney disease among people living with HIV/AIDS in Burundi: a cross-sectional study. BMC Nephrol 2011; 12:40.
- Emem CP, Arogundade F, Sanusi A, et al. Renal disease in HIV-seropositive patients in Nigeria: an assessment of prevalence, clinical features and risk factors. Nephrol Dial Transplant 2008; 23:741.
- 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.
- Peters L, Grint D, Lundgren JD, et al. Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients. AIDS 2012; 26:1917.
- Mocroft A, Neuhaus J, Peters L, et al. Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults. PLoS One 2012; 7:e40245.
- Lucas GM, Jing Y, Sulkowski M, et al. Hepatitis C viremia and the risk of chronic kidney disease in HIV-infected individuals. J Infect Dis 2013; 208:1240.
- Kalayjian RC, Lau B, Mechekano RN, et al. Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care. AIDS 2012; 26:1907.
- Mocroft A, Kirk O, Reiss P, et al. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS 2010; 24:1667.
- Scherzer R, Estrella M, Li Y, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS 2012; 26:867.
- Ryom L, Mocroft A, Kirk O, et al. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis 2013; 207:1359.
- Scherzer R, Gandhi M, Estrella MM, et al. A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans. AIDS 2014; 28:1289.
- Gerntholtz TE, Goetsch SJ, Katz I. HIV-related nephropathy: a South African perspective. Kidney Int 2006; 69:1885.
- Katz A, Bargman JM, Miller DC, et al. IgA nephritis in HIV-positive patients: a new HIV-associated nephropathy? Clin Nephrol 1992; 38:61.
- Foy MC, Estrella MM, Lucas GM, et al. Comparison of risk factors and outcomes in HIV immune complex kidney disease and HIV-associated nephropathy. Clin J Am Soc Nephrol 2013; 8:1524.
- 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.
- Cheng JT, Anderson HL Jr, Markowitz GS, et al. Hepatitis C virus-associated glomerular disease in patients with human immunodeficiency virus coinfection. J Am Soc Nephrol 1999; 10:1566.
- Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005; 40:1559.
- Inker LA, Wyatt C, Creamer R, et al. Performance of creatinine and cystatin C GFR estimating equations in an HIV-positive population on antiretrovirals. J Acquir Immune Defic Syndr 2012; 61:302.
- Bhasin B, Lau B, Atta MG, et al. HIV viremia and T-cell activation differentially affect the performance of glomerular filtration rate equations based on creatinine and cystatin C. PLoS One 2013; 8:e82028.
- Vrouenraets SM, Fux CA, Wit FW, et al. A comparison of measured and estimated glomerular filtration rate in successfully treated HIV-patients with preserved renal function. Clin Nephrol 2012; 77:311.
- Piédrola G, Casado JL, López E, et al. Clinical features of adrenal insufficiency in patients with acquired immunodeficiency syndrome. Clin Endocrinol (Oxf) 1996; 45:97.
- Shah GM, Alvarado P, Kirschenbaum MA. Symptomatic hypocalcemia and hypomagnesemia with renal magnesium wasting associated with pentamidine therapy in a patient with AIDS. Am J Med 1990; 89:380.
- Gradon JD, Fricchione L, Sepkowitz D. Severe hypomagnesemia associated with pentamidine therapy. Rev Infect Dis 1991; 13:511.
- ACUTE KIDNEY INJURY
- Epidemiology of AKI in HIV-positive patients
- - Incidence of AKI
- - Risk factors for AKI
- - Outcomes after AKI
- Causes of AKI in HIV-positive patients
- - Medication nephrotoxicity
- - HIV-associated thrombotic microangiopathy
- CHRONIC KIDNEY DISEASE
- Epidemiology of CKD in HIV-positive patients
- Causes of CKD in HIV-positive patients
- - HIV-associated nephropathy
- - Immune complex mediated glomerulonephritis
- - Glomerulonephritis due to hepatitis C virus co-infection
- Diagnosis and management of chronic kidney disease in patients with HIV
- ELECTROLYTE DISORDERS