Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes

dc.contributor.authorMansour, Sherry G.
dc.contributor.authorLiu, Caroline
dc.contributor.authorJia, Yaqi
dc.contributor.authorReese, Peter P.
dc.contributor.authorHall, Isaac E.
dc.contributor.authorEl-Achkar, Tarek M.
dc.contributor.authorLaFavers, Kaice A.
dc.contributor.authorObeid, Wassim
dc.contributor.authorRosenberg, Avi Z.
dc.contributor.authorDaneshpajouhnejad, Parnaz
dc.contributor.authorDoshi, Mona D.
dc.contributor.authorAkalin, Enver
dc.contributor.authorBromberg, Jonathan S.
dc.contributor.authorHarhay, Meera N.
dc.contributor.authorMohan, Sumit
dc.contributor.authorMuthukumar, Thangamani
dc.contributor.authorSchröppel, Bernd
dc.contributor.authorSingh, Pooja
dc.contributor.authorEl-Khoury, Joe M.
dc.contributor.authorWeng, Francis L.
dc.contributor.authorThiessen-Philbrook, Heather R.
dc.contributor.authorParikh, Chirag R.
dc.contributor.departmentMedicine, School of Medicineen_US
dc.date.accessioned2023-06-12T18:22:28Z
dc.date.available2023-06-12T18:22:28Z
dc.date.issued2021
dc.description.abstractBackground: 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.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationMansour SG, Liu C, Jia Y, et al. Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes. Transplantation. 2021;105(4):876-885. doi:10.1097/TP.0000000000003299en_US
dc.identifier.urihttps://hdl.handle.net/1805/33683
dc.language.isoen_USen_US
dc.publisherWolters Kluweren_US
dc.relation.isversionof10.1097/TP.0000000000003299en_US
dc.relation.journalTransplantationen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectDelayed graft functionen_US
dc.subjectKidney transplantationen_US
dc.subjectOsteopontinen_US
dc.subjectTissue donorsen_US
dc.subjectUromodulinen_US
dc.titleUromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomesen_US
dc.typeArticleen_US
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