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Journal article
Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes
Transplantation, v 105(4), pp 876-885
01 Apr 2021
PMID: 32769629
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 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 beta 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.
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Details
- Title
- Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes
- Creators
- Sherry G. Mansour - Yale UniversityCaroline Liu - Johns Hopkins MedicineYaqi Jia - Johns Hopkins MedicinePeter P. Reese - University of PennsylvaniaIsaac E. Hall - University of UtahTarek M. El-Achkar - Indiana UniversityKaice A. LaFavers - Indiana UniversityWassim Obeid - Johns Hopkins MedicineAvi Z. Rosenberg - Johns Hopkins MedicineParnaz Daneshpajouhnejad - Johns Hopkins MedicineMona D. Doshi - University of MichiganEnver Akalin - Albert Einstein College of MedicineJonathan S. Bromberg - University of Maryland, BaltimoreMeera N. Harhay - Drexel UniversitySumit Mohan - Columbia UniversityThangamani Muthukumar - Cornell UniversityBernd Schroppel - University Hospital UlmPooja Singh - Thomas Jefferson University HospitalJoe M. El-Khoury - Yale UniversityFrancis L. Weng - Saint Barnabas Medical CenterHeather R. Thiessen-Philbrook - Johns Hopkins MedicineChirag R. Parikh - Johns Hopkins Medicine
- Publication Details
- Transplantation, v 105(4), pp 876-885
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 10
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000639593000032
- Scopus ID
- 2-s2.0-85100715558
- Other Identifier
- 991019335232304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Surgery
- Transplantation