Predictive value of renal pathology in diffuse proliferative lupus glomerulonephritis

Abstract

We tested the value of the activity (AI) and chronicity (CI) indices devised by Austin et al as predictors of outcome in lupus patients with diffuse proliferative glomerulonephritis (DPGN). Four renal pathologists independently scored the AI and CI on 84 renal biopsy specimens from patients with lupus DPGN followed for 109 ± 74 weeks (mean ± SD), and the mean score was compared to the development of renal failure and to adverse outcome (combined data for renal failure, death and predefined clinical stop points). Receiver operator characteristic curves were derived from a series of 2 x 2 tables in which one variable was renal failure or adverse outcome and the other variable was AI or CI dichotomized by a cut-off point. Over the entire range (0 to 10) of the CI there was no value that separated patients who developed renal failure from those who did not. The ROC curve analysis indicated that the sensitivity and specificity of the CI were too low to allow it to function as a good test. Once patients entering renal failure were identified, the mean CI approached but did not reach a significant difference when compared to the mean CI of those who did not go into renal failure (4.38 ± 0.42, mean ± SE vs. 3.19 ± 0.23, P = 0.0620). The CI did not predict the adverse clinical outcomes. There was no cut-off value of the CI which separated patients who had an adverse outcome from those who did not, and this result was confirmed by ROC analysis. As a group, the patients who reached an adverse outcome had a higher CI (4.12 ± 0.37, mean ± SE) than those who did not (3.2 ± 0.24), but this difference was not significant (P = 0.3944). In this population of patients with the histologic diagnosis of DPGN, there was no value for the AI over its entire range (4 to 22) that predicted either renal failure or adverse outcome. The mean AI was not different either for those who developed renal failure and those who did not (11.24 ± 0.48, mean ± SE vs. 11.35 ± 0.47, P = 0.7257) or for those with and without an adverse outcome (11.41 ± 0.44, mean ± SE vs. 11.27 ± 0.50, P = 0.7061). This finding indicates that the degree of inflammation required for the diagnosis of DPGN is alone predictive of outcome. Since the histological indices did not improve the predictive value of the standard histological classification (ISKDC/WHO) in this group of patients with DPGN, we recommend holding in abeyance therapeutic decisions based upon the CI until its predictive value is independently confirmed.