Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.
Publication/Presentation Date
4-1-2021
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 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.
Volume
105
Issue
4
First Page
876
Last Page
885
ISSN
1534-6080
Published In/Presented At
Mansour, S. G., Liu, C., Jia, Y., Reese, P. P., Hall, I. E., El-Achkar, T. M., LaFavers, K. A., Obeid, W., Rosenberg, A. Z., Daneshpajouhnejad, P., Doshi, M. D., Akalin, E., Bromberg, J. S., Harhay, M. N., Mohan, S., Muthukumar, T., Schröppel, B., Singh, P., El-Khoury, J. M., Weng, F. L., … Parikh, C. R. (2021). Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes. Transplantation, 105(4), 876–885. https://doi.org/10.1097/TP.0000000000003299
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
32769629
Department(s)
Administration and Leadership
Document Type
Article