PREDICTING RENAL OUTCOME IN IGA NEPHROPATHY

Immunoglobulin A (IgA) nephropathy, the most common form of glomerulon ephritis worldwide, is characterized by a heterogeneous clinical cours e. In this study, multivariate analysis was performed to identify hist opathologic and clinical features that most accurately predict adverse outcome from a dataset of 148 individuals with IgA nephropathy who un derwent renal biopsy at our institution between 1973 and 1995. A semiq uantitative scoring system was developed for assessment of six glomeru lar, eight interstitial, and six vascular histopathologic features of IgA nephropathy. Glomerular and interstitial proliferative activity wa s evaluated by immunostaining archival biopsy specimens with Mib-1, an antibody directed against the Ki-67 antigen. Kaplan-Meier survival an alysis was performed, with renal failure being defined as onset of dia lysis or transplantation. A number of clinicopathologic factors were u nivariately associated with adverse outcome, including elevated serum creatinine levels; the presence of hypertension; proteinuria; componen t and total histopathologic scores; and positive glomerular or interst itial Mib-1 scores. The total glomerular score, consisting of the arit hmetic sum of each of the six component scores, was the strongest hist opathologic predictor of adverse outcome. Total interstitial and vascu lar scores also provided more prognostic information than did individu al component scores. By multivariate analysis, high total glomerular s cores, increased serum creatinine levels at diagnosis, and younger age were significant (P < 0.01) independent predictors of renal failure. Our studies provide a rational basis for the inclusion of composite hi stopathologic scores in clinical intervention studies of patients with IgA nephropathy and other glomerular disorders.