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J Clin Med. 2019 Oct 13;8(10). pii: E1673. doi: 10.3390/jcm8101673.

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

Author information

1
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. manueyepes@gmail.com.
2
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. c.g.sotomayor.campos@umcg.nl.
3
Department of Internal Medicine, Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. kretzler@umich.edu.
4
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. r.o.b.gans@umcg.nl.
5
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. s.p.berger@umcg.nl.
6
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. g.j.navis@umcg.nl.
7
Department of Internal Medicine, Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. wenjunj@med.umich.edu.
8
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. s.j.l.bakker@umcg.nl.

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.

PMID:
31614925
DOI:
10.3390/jcm8101673
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