Risk factors for ESRD in HIV-infected individuals: traditional and HIV-related factors

Abstract

Background: Despite improvements in survival with human immunodeficiency virus (HIV) infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with the development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals and compare ESRD risk by estimated glomerular filtration rate (eGFR) and proteinuria levels.

Study design: Retrospective cohort study.

Setting & participants: 22,156 HIV-infected veterans without pre-existing ESRD receiving health care in the Veterans' Affairs medical system between 1996 and 2004.

Predictors: Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin <3.5 mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and eGFR were identified using the Veterans' Affairs electronic record system.

Outcomes: ESRD was ascertained by the US Renal Data System.

Results: 366 cases of ESRD occurred, corresponding to 3 cases/1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5-2.4), diabetes (HR, 1.7; 95% CI, 1.3-2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7-2.7) were associated independently with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/μL (HR, 1.5; 95% CI, 1.2-2.0), HIV viral load ≥30,000 copies/mL (HR, 2.0; 95% CI, 1.5-2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5-2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8-2.5). Compared with persons without chronic kidney disease, defined as eGFR >60 mL/min/1.73 m(2) and no proteinuria, lower eGFR and higher proteinuria categories were associated jointly with exponentially higher ESRD rates, ranging from 6.6 events/1,000 person-years for persons with urine protein excretion of 30-100 mg/dL and eGFR >60 mL/min/1.73 m(2) to 193 events/1,000 person-years for persons with urine protein excretion ≥300 mg/dL and eGFR <30 mL/min/1.73 m(2).

Limitations: Results may not be generalizable to female and nonveteran populations.

Conclusions: In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for chronic kidney disease staging is most effective for stratifying the risk of ESRD.

Figure 1. Risk Factors for ESRD Stratified by Race

Multivariable model adjusted for baseline age, race, body mass index, baseline eGFR, baseline urine dipstick, baseline hypertension, diabetes, cardiovascular disease, CD4 lymphocyte count, HIV viral load, hepatitis C infection, hypoalbuminemia (serum albumin <3.5 mg/dL), and receipt of ACE inhibitor. Abbreviations: ACE inhibitor (angiotensin-converting enzyme inhibitor); eGFR (estimated glomerular filtration rate); ESRD (end-stage renal disease).

Figure 2. CKD Staging by Risk of Progression to ESRD

ESRD rate per 1,000 person-years stratified by baseline eGFR and proteinuria (measured by urine dipstick). Severity of CKD shown by intensity of shading (no CKD vs mild, moderate, and severe CKD). †Multivariate-adjusted hazard ratios for ESRD adjust for baseline age, race, body mass index, baseline eGFR, baseline proteinuria, baseline hypertension, diabetes, cardiovascular disease, CD4 lymphocyte count, HIV viral load, hepatitis C infection, hypoalbuminemia (serum albumin <3.5 mg/dL), and receipt of ACE inhibitor. Abbreviations: ACE inhibitor (angiotensin-converting enzyme inhibitor); CKD (chronic kidney disease); eGFR (estimated glomerular filtration rate); ESRD (end-stage renal disease).