Early Experience with Sibeprenlimab for Recurrent & De Novo IgA Nephropathy in Kidney Transplant Recipients

Recurrent and de novo IgA nephropathy (IgAN) after kidney transplantation is an important cause of kidney allograft loss. Sibeprenlimab, a humanized monoclonal antibody that selectively binds and inhibits a proliferation-inducing ligand (APRIL), has been shown to reduce proteinuria by almost 50% in phase 2 and 3 trials of native kidney IgAN. However, transplant recipients were excluded from these studies. We report early clinical outcomes in four kidney transplant recipients with biopsy-proven post-transplant IgAN and persistent proteinuria despite supportive therapy who received sibeprenlimab 400 mg every 4 weeks. The main outcome of interest was change in urine protein-to-creatinine ratio (UPCR). We also monitored serum creatinine, absolute lymphocyte counts, immunoglobulin levels, and infectious complications. All four patients, including three with recurrent IgAN and one thought to have de novo IgAN, had substantial reductions in proteinuria within 4.5-7.4 months of treatment, with UPCR decreasing by 68% to 78% from baseline. Kidney function remained stable or improved in three patients, and transiently worsened in one, despite marked reduction in proteinuria, then returned to baseline. Sibeprenlimab was associated with a reduction in immunoglobulin levels, while absolute lymphocyte counts remained stable. There were no opportunistic infections, rejection episodes, or adverse events requiring discontinuation during short-term follow-up; one patient developed norovirus gastroenteritis. These cases suggest that APRIL inhibition with sibeprenlimab may be an effective therapy to reduce proteinuria in kidney transplant recipients with post-transplant IgAN. Prospective studies with longer follow-up are needed to define its safety and efficacy in the transplant setting.