Abstract

Introduction Graft failure remains a major clinical challenge to improving long-term outcomes in kidney transplant recipients (KTR). Early identification of KTR at higher risk of graft failure is key to potentially improve this outcome. Epidermal growth factor (EGF) is involved in kidney tissue proliferation and integrity, with a reduction of its urinary excretion being associated with early fibrotic processes and a wide range of kidney diseases. We aimed to investigate whether, in KTR, urinary EGF (uEGF) is prospectively associated with graft failure. Methods In this prospective cohort study, KTR with a functioning allograft for at least 1-year were recruited and followed-up for three years. uEGF was measured at baseline by ELISA in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of graft failure was assessed by multivariable Cox-regression analyses and its predictive ability by C-statistic. Results In 706 patients, uEGF/Cr ratio at enrollment was 6.43 (IQR, 4.07–10.77) ng/mg. During follow-up, 41 (6%) KTR developed graft failure. uEGF/Cr ratio was inversely associated with the risk of GF (HR 0.68, 95% CI 0.59‒0.78; P<0.001), which remained independent of adjustment for several potential confounders including immunosuppressive therapy, human leukocyte antigen mismatch, estimated glomerular filtration rate and proteinuria. C-statistic of uEGF/Cr ratio for graft failure was 0.81 (P<0.001) and when added to urinary protein excretion significantly improved its predictive ability (C-statistic from 0.76 to 0.81; P<0.001). Conclusions In KTR, uEGF/Cr ratio is independently and inversely associated with the risk of graft failure and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising biomarker for clinical uptake postkidney transplantation.