학술논문
Uromodulin to Osteopontin Ratio in Deceased Donor Urine is Associated with Kidney Graft Outcomes
Document Type
Academic Journal
Author
Mansour, Sherry G.; Liu, Caroline; Jia, Yaqi; Reese, Peter P.; Hall, Isaac E.; El-Achkar, Tarek M.; LaFavers, Kaice A.; Obeid, Wassim; Rosenberg, Avi Z.; Daneshpajouhnejad, Parnaz; Doshi, Mona D.; Akalin, Enver; Bromberg, Jonathan S.; Harhay, Meera N.; Mohan, Sumit; Muthukumar, Thangamani; Schröppel, Bernd; Singh, Pooja; El-Khoury, Joe M.; Weng, Francis L.; Thiessen-Philbrook, Heather R.; Parikh, Chirag R.
Source
Transplantation. Jul 27, 2020
Subject
Language
English
ISSN
0041-1337
Abstract
BACKGROUND:: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. METHODS:: Primary outcomes: all-cause graft failure (GF) and death-censored graft failure (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month eGFR. We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and graft failure contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II (MHCII) in mouse macrophages. RESULTS:: Doubling of UMOD increased dcGF risk (adjusted hazard ratio (aHR) of 1.1 (95% CI: 1.02-1.2)), whereas OPN decreased dcGF risk [aHR 0.94 (95% CI: 0.88-1)]. UMOD:OPN ratio ≤ 3 strengthened the association, with reduced dcGF risk [aHR 0.57 (0.41-0.80)] with similar associations for GF, and in the test dataset. A ratio ≤ 3 was also associated with lower DGF [aOR 0.73 (95% CI: 0.60-0.89)] and higher 6-month eGFR [adjusted B-coefficient 3.19 (95% CI: 1.28-5.11)]. UMOD increased MHCII expression elucidating a possible mechanism behind UMOD’s association with GF. CONCLUSIONS:: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation. TRIAL REGISTRATION NUMBER:: NCT01848249