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. Estimated 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 sustained 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.
Uzzo, M., Mescia, F., Scott, J., O'Brien, J., Galesic, K., Genovesi, S., et al. (2026). Kidney Outcomes in ANCA-Glomerulonephritis According to Induction Immunosuppression and Histopathology. KIDNEY INTERNATIONAL REPORTS, 11(3), 1-12 [10.1016/j.ekir.2026.103776].
Kidney Outcomes in ANCA-Glomerulonephritis According to Induction Immunosuppression and Histopathology
Genovesi, Simonetta;La Manna, Gaetano;
2026
Abstract
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. Estimated 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 sustained 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
