title: YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation.
abstract: Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant.
authors.affiliation: Program of Applied Translational Research, Department of Medicine and.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Puthumana
authors.affiliation: Program of Applied Translational Research, Department of Medicine and.|Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: Hall
authors.affiliation: Renal-Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Reese
authors.affiliation: Section of Nephrology, University Hospital, Ulm, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schröppel
authors.affiliation: Renal and Pancreas Transplant Division, Saint Barnabas Medical Center, Livingston, New Jersey.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Weng
authors.affiliation: Program of Applied Translational Research, Department of Medicine and.
authors.forename: Heather
authors.initials: H
authors.lastname: Thiessen-Philbrook
authors.affiliation: Department of Medicine, Division of Nephrology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Mona D
authors.initials: MD
authors.lastname: Doshi
authors.affiliation: Program of Applied Translational Research, Department of Medicine and.
authors.forename: Veena
authors.initials: V
authors.lastname: Rao
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island; and.
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island; and.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.affiliation: Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Cantley
authors.affiliation: Program of Applied Translational Research, Department of Medicine and chirag.parikh@yale.edu.|Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.|Section of Nephrology, Veterans Affairs Medical Center, West Haven, Connecticut.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D058186:Acute Kidney Injury / Q000652:urine*; D000328:Adult; D002102:Cadaver; D000071451:Chitinase-3-Like Protein 1 / Q000652:urine*; D051799:Delayed Graft Function / Q000453:epidemiology*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D011446:Prospective Studies; D020127:Recovery of Function; D014019:Tissue Donors; D009927:Tissue and Organ Procurement
chemical_list: C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1
keywords: delayed graft function; renal function; renal transplantation