Background: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid\nProgression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated\nglomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse\nEvents of Anti-HIV Drugs (D:A:D) study from 2004 to 2011.\nMethods: Two definitions were evaluated; RP definition A: An average eGFR decline (slope) =5 ml/min/1.73 m2/\nyear over four years of follow-up with =3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute\ndecline =5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline =5 ml/min/\n1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two\nand three years� follow-up. The percentage with and without RP who went on to subsequently develop incident\nchronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated.\nResults: 22,603 individuals had baseline eGFR =90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with =4 years�\nfollow-up and =3 measurements/year experienced RP under definition A; similar proportions were observed when\nconsidering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP\ndefinition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three\n(n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years� follow-up. For RP definition A, 13 (12%) individuals who\nexperienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2%\nand specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD.\nConclusions: Our results suggest using three years� follow-up and at least two eGFR measurements per year is most\nappropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with\nthe known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however,\nit can be used alongside other renal measurements to early identify and assess those at risk of developing CKD.\nFuture analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.
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