Urinary Epidermal Growth Factor/Creatinine Ratio and Graft Failure in Renal Transplant Recipients: A Prospective Cohort Study

Manuela Yepes-Calderón, Camilo G Sotomayor, Matthias Kretzler, Rijk O B Gans, Stefan P Berger, Gerjan J Navis, Wenjun Ju, Stephan J L Bakker, Manuela Yepes-Calderón, Camilo G Sotomayor, Matthias Kretzler, Rijk O B Gans, Stefan P Berger, Gerjan J Navis, Wenjun Ju, Stephan J L Bakker

Abstract

Graft failure (GF) remains a significant limitation to improve long-term outcomes in renal transplant recipients (RTR). Urinary epidermal growth factor (uEGF) is involved in kidney tissue integrity, with a reduction of its urinary excretion being associated with fibrotic processes and a wide range of renal pathologies. We aimed to investigate whether, in RTR, uEGF is prospectively associated with GF. In this prospective cohort study, RTR with a functioning allograft ≥1-year were recruited and followed-up for three years. uEGF was measured in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of GF was assessed by Cox-regression analyses and its predictive ability by C-statistic. In 706 patients, uEGF/Cr at enrollment was 6.43 [IQR 4.07-10.77] ng/mg. During follow-up, 41(6%) RTR developed GF. uEGF/Cr was inversely associated with the risk of GF (HR 0.68 [95% CI 0.59-0.78]; P < 0.001), which remained significant after adjustment for immunosuppressive therapy, estimated Glomerular Filtration Rate, and proteinuria. C-statistic of uEGF/Cr for GF was 0.81 (P < 0.001). We concluded that uEGF/Cr is independently and inversely associated with the risk of GF and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising marker for use in clinical practice.

Keywords: creatinine; epidermal growth factor; graft failure; renal transplantation..

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Participant flow diagram.
Figure 2
Figure 2
Kaplan–Meier curves by tertiles of uEGF/Cr on graft failure. Tertile 1: 8.80 ng/mg. P value was obtained from the log-rank (Mantel cox) test. uEGF/Cr, urinary epidermal growth factor/creatinine ratio.
Figure 3
Figure 3
ROC curve of uEGF/Cr for graft failure. During a follow-up of 3 years, 41 (6%) patients developed graft failure. GF, graft failure; uEGF/Cr, urinary epidermal growth factor/creatinine ratio; UAE, urinary albumin excretion; UPE, urinary protein excretion.

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