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Background: This study examines the association between microalbuminuria and the development of proteinuria among HIV-infected persons., Methods: A total of 948 subjects provided urine samples for albumin, protein and creatinine measurements semiannually. Microalbuminuria was defined as an albumin-to-creatinine ratio of >30 mg/g. Proteinuria was defined as a protein-to-creatinine ratio of > or =0.350 mg/mg. The progression from microalbuminuria to proteinuria was described., Results: At baseline, 69.4% of the subjects had no detectable proteinuria, 20.2% had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria and proteinuria were more likely to be black (P=0.02), have lower CD4 cell counts (P=0.02 comparing subjects without abnormal urine protein excretion to subjects with microalbuminuria; P=0.0001 comparing subjects with microalbuminuria to subjects with proteinuria), and have a higher HIV RNA level (P=0.08 and 0.04, respectively). Among 658 subjects with normal urine protein, 82.7% continued to have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed proteinuria. Subjects without baseline proteinuria (i.e. either normal protein excretion or microalbuminuria) who developed proteinuria were more likely to have microalbuminuria (P=0.001), a lower CD4 cell count (P=0.06), and a higher plasma HIV RNA (P=0.03) than those who did not progress to proteinuria. In multivariate analysis, only microalbuminuria remained associated with the development of proteinuria (odds ratio 2.9; 95% confidence interval 1.5, 5.5; P=0.001)., Conclusion: Microalbuminuria predicts the development of proteinuria among HIV-infected persons. Because proteinuria has been linked to poorer outcomes, strategies to affect microalbuminuria should be tested.