THE TIME-DEPENDENCE OF LONG-TERM PREDICTION IN LUPUS NEPHRITIS

Objective. To assess the clinical, laboratory, and renal biopsy predic tors of long-term outcome in lupus nephritis and to investigate the ti me-dependence of these predictors. Methods. Eighty-seven lupus nephrit is patients were studied retrospectively for the outcomes renal failur e and fatality due to renal involvement. In addition to a conventional Cox model analysis, a new generalized time-dependent analytic approac h was developed and used to assess the time dependence of a predictor variable's importance. Results. The mean followup time was 11.9 years. Renal failure (n = 19) was significantly predicted by measures of ren al function (abnormal serum creatinine levels, proteinuria, duration o f prior renal disease) and immunologic activity (elevated DNA binding, hypocomplementemia, and thrombocytopenia), by overall lupus disease a ctivity measures (le Riche index, Lupus Activity Criteria Count), and by the activity index, the tubulointerstitial index, and the amount of subepithelial deposits on renal biopsy. In general, the laboratory pr edictors were significantly better prognostic markers in the early yea rs after biopsy, the disease activity measures were best in the later years, and the biopsy variables were significant predictors over the e ntire observation period. In contrast to the renal failure outcome, th e best predictors for death not directly related to lupus nephritis (n = 17) were the extent of comorbid diseases (principally vascular dise ases), older age, and the chronicity index. All three predicted well o ver the extended observation period. Conclusion. The major predictor v ariables for renal outcomes and nonrenal outcomes are distinct. The ti me-dependence of the predictive ability of some variables may be impor tant in managing individual patients. The new generalized time-depende nt analytic technique may have widespread application in studies to id entify prognostic factors for established disease or risk factors for the development of disease.