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Data on the incidence and prognostic significance of renal dysfunction in HIV disease are limited.To determine the incidence of proteinuria and elevated serum creatinine in HIV-positive and HIV-negative women and to determine whether these abnormalities are predictors of mortality or associated with causes of death listed on the death certificate in HIV-positive women.The incidence of proteinuria or elevated serum creatinine and mortality was assessed in a cohort of 885 HIV-positive women and 425 at-risk HIV-negative women.Women from the general community or HIV care clinics in four urban locations in the United States.Creatinine of ≥1.4 mg/dL, proteinuria 2+ or more, or both. Deaths confirmed by a death certificate (92%) or medical record/community report (8%).At baseline, 64 (7.2%) HIV-positive women and 10 (2.4%) HIV-negative women had proteinuria or elevated creatinine. An additional 128 (14%) HIV-positive women and 18 (4%) HIV-negative women developed these abnormalities over the next (mean) 21 months. Relative hazards of mortality were significantly increased (adjusted relative hazard = 2.5; 95% confidence interval: 1.9–3.3), and there were more renal causes recorded on death certificates (24/92 (26%) vs. 3/127 (2.7%), p < .0001) in HIV-infected women with, compared with those without these renal abnormalities.Proteinuria, elevated serum creatinine, or both frequently occurred in these HIV-infected women. These renal abnormalities in HIV-infected women are associated with an increased risk of death after controlling for other risk factors and with an increased likelihood of having renal causes listed on the death certificate. The recognition and management of proteinuria and elevated serum creatinine should be a priority for HIV-infected persons.