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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 GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (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 GF 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 in mouse macrophages., Results: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [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 β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II 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., Competing Interests: S.G.M. supported by the American Heart Association (18CDA34110151) and Patterson Trust Fund. P.P.R. supported by epidemiology consulting from COHRDATA related to dialysis outcomes. This study received grant/research support from Merck, CVS and initiated grants from Merck to the University of Pennsylvania to support the THINKER (kidney), USHER (heart), and SHELTER (lung) trials of transplanting organs from donors with Hepatitis C into Hepatitis C negative recipients. It initiated grants from CVS to the University of Pennsylvania to support studies of medication adherence. I.E.H. received NIH grant support from NCATS (UL1TR002538 and KL2TR002539). T.M.E.-A. received grant support from NIDDK and US Department of Veterans Affairs. M.D.D. obtained the salary support from NIDDK. S.M. received grant/research support from NIH (NIDDK/NIAID/NIHMD/NIBIB) and consulting fees from Angion Pharmaceuticals. A.Z.R. received NDAs with Pliant Therapeutics and xMD Diagnostics, advisory board of Escala Therapeutics. C.R.P. received consulting fee from Renalytix and grant/research support from National Institute of Diabetes and Digestion and Kidney Diseases, National Heart, Lung, and Blood Institute and Data Safety and Monitoring Board of Genfit, Abbott. M.N.H. received grant support from NIH/NIDDK. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)