Donor Urinary Biomarkers and the Prediction of Deceased Donor Allograft Function

KEY POINTS: Combining donor urinary biomarkers with Kidney Donor Profile Index improved the ability to predict paired recipient outcomes. Donor urinary biomarkers provided additional information on donor kidney quality, thus informing the kidney transplant allocation process. BACKGROUND: Kidney transplant allocation currently relies on the Kidney Donor Profile Index (KDPI), a measure that has limitations. This study evaluated the potential of using KDPI and deceased donor urinary biomarkers to improve the assessment of organ quality and the prediction of allograft outcomes compared with KDPI alone. METHODS: Pairs of kidney recipients from the same donor transplanted between 2010 and 2013 were followed for 3 years post-transplant from kidneys procured at five organ procurement organizations. By 3 years post-transplant, concordant good outcomes were defined as both recipients having an eGFR ≥45 ml/min per 1.73 m 2 , while concordant poor outcomes were defined as both recipients experiencing graft failure (return to dialysis or waitlisted) or having an eGFR <20 ml/min per 1.73 m 2 . Urinary biomarkers (uromodulin, osteopontin, and chitinase-3-like protein 1) were measured by immunoassay using a MesoScale Device in all donors and by lateral flow devices in a subset. Discriminatory ability was quantified with the area under the receiver operator characteristics curve (AUC). RESULTS: We identified 474 donors with both kidneys transplanted and either concordant good outcomes (438; 92%) or concordant poor outcomes (36; 8%). For distinguishing concordant good from concordant poor outcomes, the AUC for KDPI alone was 0.80 (SE 0.04); the AUC for KDPI combined with uromodulin, osteopontin, and chitinase-3-like protein 1 measured by immunoassay was 0.86 (SE 0.03). In a subset of 105 donors with lateral flow device measurements, the AUC for KDPI plus three biomarkers was 0.85 (SE 0.04), compared with 0.81 (SE 0.05) for KDPI alone. CONCLUSIONS: Combining donor urinary biomarkers with KDPI improved prediction of concordant allograft outcomes, regardless of assay platform. The improvement over KDPI alone was observed both with immunoassay and with point-of-care lateral flow device measurements.