Introduction Therapeutic options that allow a substantial time off-treatment and prevent progression to kidney failure in patients with IgA nephropathy (IgAN) are limited. Mezagitamab, an anti-cluster of differentiation (CD) 38 monoclonal antibody, may deplete plasma cells that produce galactose-deficient IgA1 (Gd-IgA1), thereby stabilizing kidney function. Methods This multicenter, open-label, single-arm, phase-1b study evaluated mezagitamab in combination with stable background therapy. Eligible participants had biopsy-proven disease, proteinuria, and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min per 1.73 m2. Participants received subcutaneous mezagitamab 600 mg once weekly for 8 weeks, then 600 mg every 2 weeks for 16 weeks. The primary end point was the percentage of participants with adverse events (AEs) through week 96. Results Seventeen participants enrolled. There were no serious AEs, study discontinuations because of AEs, grade ≥ 3 infections, or opportunistic infections. Rapid reductions were observed in serum IgA, IgG, IgM, and Gd-IgA1, with a sustained depletion in Gd-IgA1, but partial or complete recovery in IgA, IgG, and IgM by week 96. Proteinuria rapidly decreased within weeks, and at week 96 the urine protein-to-creatinine ratio (UPCR) was reduced by a model-based mean change from baseline of −53.4% (95% confidence interval [CI]: −72.6 to −20.7, n = 13). Hematuria resolved in 60% of participants with baseline hematuria. Renal function remained stable at week 96 (model-based mean change from baseline in eGFR: +3.2 [95% CI: −1.1 to +7.5; n = 13]). Conclusion Mezagitamab was generally well tolerated in patients with IgAN. Stable kidney function was observed through week 96, with reductions in proteinuria, hematuria, and Gd-IgA1, approximately 1.5 years after the last dose of mezagitamab.
As the prevalence of chronic kidney disease (CKD), end-stage kidney disease, and kidney transplantation continues to rise, these patients are increasingly undergoing elective surgical procedures. This unique population presents significant clinical challenges due to extensive comorbidities, heightened cardiovascular risk, and high susceptibility to acute kidney injury (AKI). In patients with advanced CKD, an episode of perioperative AKI can exhaust renal reserve, often precipitating a transition to acute or chronic dialysis. This review provides a comprehensive framework for perioperative risk assessment from a nephrology perspective. Beyond standard cardiovascular evaluation, we examine kidney-specific nuances, including AKI prediction models for cardiac and non-cardiac surgery and the perioperative management of hypertension and anemia. Furthermore, we detail specialized care for hemodialysis (HD), peritoneal dialysis (PD), and transplant recipients, including the optimal timing of dialysis and the management of perioperative medications. Distinct considerations for PD patients, such as the risk of peritonitis, dialysate leakage, and wound dehiscence following abdominal surgery, are addressed. By integrating these strategies, providers can mitigate complications and improve outcomes in this high-risk surgical cohort.
