Long-term kidney and patient outcomes in pure versus mixed lupus membranous nephritis

Abstract Objective Pure membranous lupus nephritis (pMLN, Class V ISN/RPS) is traditionally considered less aggressive than mixed forms of MLN (mMLN, Classes III/IV ± V ISN/RPS). Only two trials have compared the outcome of these two forms of MLN, with inconclusive results. In this retrospective multicenter study, we assessed and compared the short and long-term outcomes of pMLN versus mMLN. Methods Patients diagnosed with pMLN or mMLN on their first kidney biopsy were included. The main outcomes were complete renal response after 1 year, sustained complete response, relapse rates, chronic kidney disease (CKD)-free survival, and the composite outcome of kidney failure/death-free survival. Results Of the 195 patients included, 96 (49.2%) pMLN had milder immunological features of active LN at baseline compared to 99 (50.8%) with mMLN. At kidney biopsy, the NIH activity and chronicity indices were lower in patients with pMLN (P < 0.001). Moreover, they received less intensive immunosuppressive treatment (less i.v.-steroids, lower use/earlier withdrawal of the immunosuppressive regimen). Both groups achieved similar rate of responses, relapses, and kidney survival over follow-up. Kidney Failure (KF)/death-free survival was significantly lower in pMLN compared to mMLN (P = 0.026). In a Cox-model adjusted for baseline kidney function and induction immunosuppressive regimen, mMLN retained an 80% lower risk of KF/death compared to pMLN (P = 0.0384). In a subgroup analysis, crude survival differences between pMLN and mMLN were confirmed only in patients biopsied before 2000. Conclusion This study challenges the long-standing view of pMLN as a generally benign condition, suggesting that less intensive treatment of pure MLN may have contributed to less favourable hard outcomes in the long-term.