Are We Winning at Twinning? Persistent CNI Use in Identical Kidney Transplants.

BACKGROUND: Calcineurin inhibitors (CNIs) revolutionized kidney transplantation by reducing acute rejection rates. Identical twin kidney transplantation is the only setting in which the allograft is immunologically indistinguishable from self, yet CNI use persists. We characterized CNI utilization across end-stage kidney disease etiologies and examined whether CNI exposure was associated with reduced rejection or improved death-censored graft survival (DCGS). METHODS: We performed a retrospective cohort study using scientific registry of transplant recipients data (January 2000-August 2025). Among 255 adult identical twin kidney transplant recipients, discharge regimens were categorized by CNI use; Firth penalized Cox regression was the primary method for 10-year DCGS. RESULTS: Among recipients, 129 (50.6%) received a CNI at discharge with no decline over 25 years and use across every etiology, including glomerulonephritis (53.6%), cystic disease (80.0%), diabetes (51.8%), and hypertension (50.0%), several of which carry no recurrence or immunologic rationale. No biopsy‑proven rejections occurred within the first year. CNI use was not associated with improved DCGS in the full cohort (HR, 1.67; 95% CI, 0.72-4.13; P = 0.234) or the glomerulonephritis subgroup (log-rank P = 0.582). CONCLUSION: Half of U.S. identical twin kidney transplant recipients receive CNIs at discharge, with no utilization decline over 25 years. This practice is not supported by measurable reductions in rejection or improved graft survival and warrants clinical re-evaluation.