Objective: Proliferative (WHO III/IV) nephritis in systemic lupus erythematosus (SLE) is a severe disease manifestation for which treatment with cyclophosphamide and high dose corticosteroids is generally recommended. We investigated the effect of this standard treatment on renal histopathology and clinical and serological findings to determine if the therapeutic response could be predicted by these variables.
Methods: We studied 18 patients with SLE and proliferative nephritis in whom repeated renal biopsy was performed after termination of induction therapy with cyclophosphamide and corticosteroids. At the time of renal biopsy, renal function and albuminuria were determined and analyses of anti-dsDNA, anti-C1q, and the complement factors C1q, C3 and C4 were performed.
Results: At repeated biopsy, 6/18 patients still had renal biopsy findings of WHO III/IV, 3 had transformed to WHO V, while 9 exhibited histopathological remission (WHO I/II). In the 9 patients with WHO III-V at the repeat biopsy, all but one patient had low C1q levels at the time of first biopsy and 5/9 at the repeat biopsy. In the 9 patients with WHO I/II at repeated biopsy, 4/9 had low C1q at first biopsy and none at the repeated biopsy (p = 0.0054 and p = 0.017 vs WHO III-V at repeat and first biopsy, respectively). Albuminuria > or = 0.5 g/day combined with low C1q levels at repeat biopsy predicted persistent histopathological activity (WHO III-V).
Conclusion: Despite aggressive immunosuppressive therapy, 9/18 patients still had active proliferative or membranous nephritis at a second renal biopsy. Serum C1q levels at both first and repeated renal biopsies were found to be a predictive marker of the histopathological outcome.