OBJECTIVE: In the United States, kidney dysfunction is prevalent in almost 30% of HIV-infected patients and is an independent predictor of mortality. Proteinuria and elevated serum cystatin C (eCysC) are used as markers of kidney disease in the general population; however, the prevalence of these markers in HIV-infected adolescents is largely unknown. METHODS: This study includes 304 HIV-infected adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort, an observational study of adolescents recruited from 13 US cities. Clinical and demographic characteristics of participants were evaluated as correlates of proteinuria, a urine protein to creatinine ratio of ≥200 mg/g. Select univariate predictors were assessed to determine the association with urinary protein excretion and serum cystatin C in multivariable linear regression models and proteinuria and eCysC (eCysC ≥ 75th percentile) in multivariable logistic regression models. RESULTS: Overall, 19.1% of the participants had proteinuria, whereas 23.7% had an eCysC. Low CD4 T-lymphocyte counts (<200 cells/mm) were significantly associated with a greater urine protein to creatinine ratio in linear models and with proteinuria in logistic regression models. CD4 T-lymphocyte counts <500 cells/mm were significantly associated with a greater serum cystatin C concentration in linear models and with eCysC in logistic regression models. CONCLUSIONS: Proteinuria among HIV-infected adolescents in the REACH cohort was approximately 2-fold greater than healthy US adolescents. Both proteinuria and eCysC are associated with CD4 T-lymphocyte counts. Further studies investigating early markers of kidney disease and the association with immune status and inflammation in HIV-infected adolescents are needed.