Medicine - Medicine - Infectious Diseases
Natural history of chronic kidney disease in HIV-infected and HIV-seronegative individuals in Rakai, Uganda
We selected a random sample of HIV-infected participants who were enrolled in 1994 and were believed to have stored sera available from _ 2 study visits. We randomly selected a sample of HIV-negative participants from the same communities who were age-and sex-frequency matched to the HIV-infected subjects. For each participant, we measured creatinine concentration from the first and last available sera using a rate-based enzymatic assay from Roche Diagnostics, which was calibrated using isotope dilution mass spectrometry traceable standards. GFR was estimated using the abbreviated Modification of Diet in Renal Disease (MDRD) equation . We defined GFR categories according to the National Kidney Foundation guidelines , with normal, mildly reduced, and moderately reduced GFR corresponding to >90, 60 to 89, and <60 mL/min/1.73m2, respectively. We oversampled HIV-infected participants in order to assess changes in GFR with greater precision in this group. We used the Fisher’s exact test and the Wilcoxon rank sum test and continuous variables, respectively, and log-binomial regression  to calculate unadjusted and adjusted prevalence ratios (PR) of mildly and moderately reduced GFR. We used person-time analysis and Poisson regression models to assess incidence rate rations (IRR) of transition from a higher or a lower GFR category. In year 2 of the project we completed all necessary laboratory testing on stored specimens from the Rakai cohort. We evaluated earliest and latest glomerular filtration rate (GFR) in 1202 HIV-infected and 664 age- and sex-matched HIV-negative individuals from the Rakai District of Uganda. At baseline, we found that 8.4% of HIV-infected and 4.7% of HIV-negative individuals had mildly or moderately reduced GFR (P=0.002). During follow-up, the rates of decline to a lower GFR category were of 32.4 and 20.3 per 1000 person-years in HIV-infected and HIV-negative subjects, respectively (P=0.019). An initial manuscript was rejected by the journal AIDS, but the manuscript has subsequently been accepted as a brief report in JAIDS. Finally, results from the study are being used as preliminary data in an R01 grant that is in preparation (Maria Wawer, PI) to examine comorbidity (including kidney disease) and functional status in a cohort of 1) HIV-negative, 2) HIV-positive but not yet on ART, and 3) HIV-infected and on ART subjects (500 per group) in Rakai, Uganda. This study will build directly on our results by measuring proteinuria and novel measures of kidney function in this cohort.
Ronald H. Gray, MD, MSc; William A. Clarke, PhD; Mohammed G. Atta, MD, MPH; Steven J. Reynolds, MD, MPH