Association of an early postoperative immune frailty index with a 6-month composite of infection and acute rejection in older kidney transplant recipients

Early infections and rejection remain common in older kidney transplant recipients, yet early postoperative immune vulnerability is difficult to quantify using routine clinical data. In a single‑center prospective cohort, we enrolled kidney transplant recipients aged ≥ 65 years who reached a defined post‑transplant month‑1 landmark (day 30 ± 7) with laboratory assessment available. An Immune Frailty Index (IFI) was calculated from eight routine measures: absolute lymphocyte count, neutrophil‑to‑lymphocyte ratio, CD4 count, CD8 count, CD4/CD8 ratio, serum IgG, C‑reactive protein, and albumin. The primary endpoint was time to first occurrence of a composite of clinically significant infection or biopsy‑proven acute rejection after the landmark through 6 months post‑transplant. Multivariable cause‑specific Cox models were used, with competing‑risk sensitivity analyses and bootstrap internal validation. Among 597 recipients, median age was 67 years (IQR 65–71) and 60.6% were men. Median IFI was 0.25 (IQR 0.13–0.38). The composite endpoint occurred in 181/597 (30.3%) recipients (159 (26.6%) infections, 41 (6.9%) rejections, and 19 infections + rejections). Higher IFI was associated with higher composite risk (adjusted hazard ratio [aHR] per 1 SD, 1.27; 95% CI 1.14–1.41; p < 0.001) and infection (aHR 1.31; 95% CI 1.17–1.47; p < 0.001), whereas the rejection association was exploratory and imprecise (aHR 1.12; 95% CI 0.89–1.41; p = 0.33). Adding IFI modestly increased optimism‑corrected discrimination relative to the clinical covariate model (C‑index 0.67 to 0.72; Δ = + 0.05); this comparison did not include month‑1 maintenance drug exposures. The associations were materially unchanged after additional adjustment for month‑1 tacrolimus trough concentration and dose, mycophenolate dose, and corticosteroid dose in the dominant triple-therapy subgroup (composite aHR 1.24; 95% CI 1.11–1.39; infection aHR 1.28; 95% CI 1.13–1.44). A pragmatic month‑1 IFI was associated after multivariable adjustment with higher 6‑month adverse outcomes in older kidney transplant recipients, driven primarily by clinically significant infections; no clear rejection association was observed. The study does not establish age specificity, individual‑level clinical utility. External validation and impact studies are needed before clinical use.