Kidney Outcomes in ANCA-Glomerulonephritis According to Induction Immunosuppression and Histopathology

Introduction: Cyclophosphamide (CYC) and rituximab (RTX), alone or combined, are the mainstays of induction therapy in antineutrophil cytoplasmic autoantibody (ANCA)-glomerulonephritis. It is unknown whether the response to induction is differentially affected by kidney histopathology. Methods: This is a retrospective, multicenter study including patients with biopsy-proven ANCA- glomerulonephritis. Cases were grouped according to the Berden nephropathology classification. Esti- mated glomerular filtration rate (eGFR) recovery at 6 months was defined as eGFR increase $ 15 ml/min per 1.73 m2 or discontinuation of kidney replacement therapy (KRT); kidney failure was defined as sus- tained eGFR < 15 ml/min per 1.73 m2 or long-term KRT. Multivariable regression models were used to explore independent predictors of kidney outcomes across Berden classes. Results: The cohort included 304 patients; median baseline eGFR was 20 ml/min per 1.73 m2 (interquartile range [IQR]: 11–35). Induction immunosuppression was with CYC in 59%, with RTX in 17%, and with RTX- CYC in 24%. Overall, 50% recovered kidney function and 19.4% had kidney failure over a median follow- up of 42 months (IQR: 18–72). In the crescentic class, the RTX group had lower chances of eGFR recovery than CYC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.05–0.98, P = 0.047); the trend was similar in comparison with RTX-CYC (OR: 0.20, 95% CI: 0.03–1.19, P = 0.077). In the crescentic class, RTX monotherapy was marginally associated with increased risk of kidney failure, compared with both CYC (hazard ratio [HR]: 3.42, 95% CI: 1.03–11.35, P = 0.045) and RTX-CYC (HR: 5.33, 95% CI: 0.91–31.18, P = 0.063). No significant differences were observed in the other Berden classes. Conclusion: Patients with crescentic class ANCA-glomerulonephritis receiving RTX monotherapy may have worse kidney outcomes than those treated with CYC-based regimens. Further studies are needed to validate these results and better understand how to personalize treatment.