Abstract
INTRODUCTION: Recurrent Ig A nephropathy (IgAN; rIgAN) after kidney transplantation is heterogeneous and lacks a guideline or a standard treatment. We evaluated the efficacy and safety of telitacicept as an add-on therapy for rIgAN with persistent proteinuria in kidney recipients. METHODS: In this prospective, single-center, single-arm cohort study, 25 kidney transplant recipients with biopsy-confirmed rIgAN received add-on telitacicept 240 mg subcutaneously weekly for 12 weeks, then every 2 weeks until week 28. Primary end points were 24-hour urinary protein (24h-UP) and urine albumin-to-creatinine ratio (UACR). Secondary assessments included remission, kidney function, laboratory parameters, and mechanistic biomarkers. RESULTS: Twenty-two participants completed the follow-up. At week 28, 24h-UP and UACR decreased by 51.6% and 62.7% (both P < 0.001), respectively. Complete and partial remission rates were achieved in 47.6% and 57.1% of patients, respectively. Serum albumin increased significantly, whereas serum creatinine (SCr), estimated glomerular filtration rate, and hemoglobin remained stable. Circulating galactose-deficient IgA1 (Gd-IgA1) and asialoglycoprotein receptor (ASGPR) levels declined; Ig levels also decreased, in line with B-cell inhibition and on-target pathways suppression. No treatment-related severe adverse events were reported. The most common adverse events were mild injection site reactions and transient infections. CONCLUSION: Add-on telitacicept was associated with marked proteinuria reduction and a favorable safety profile in kidney transplant recipients with rIgAN and persistent proteinuria, supporting its potential as a therapeutic option.