TY - JOUR
T1 - YKL-40 associates with renal recovery in deceased donor kidney transplantation
AU - Puthumana, Jeremy
AU - Hall, Isaac E.
AU - Reese, Peter P.
AU - Schröppel, Bernd
AU - Weng, Francis L.
AU - Thiessen-Philbrook, Heather
AU - Doshi, Mona D.
AU - Rao, Veena
AU - Lee, Chun Geun
AU - Elias, Jack A.
AU - Cantley, Lloyd G.
AU - Parikh, Chirag R.
N1 - Publisher Copyright:
© 2017 by the American Society of Nephrology.
PY - 2017/2
Y1 - 2017/2
N2 - 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.Wemeasured 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 ofDGF, 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.
AB - 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.Wemeasured 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 ofDGF, 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.
UR - http://www.scopus.com/inward/record.url?scp=85020328386&partnerID=8YFLogxK
U2 - 10.1681/ASN.2016010091
DO - 10.1681/ASN.2016010091
M3 - Article
C2 - 27451287
AN - SCOPUS:85020328386
SN - 1046-6673
VL - 28
SP - 661
EP - 670
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 2
ER -