Deceased donor urinary DKK3 associates with future allograft function following kidney transplantation

Abstract

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/creatinine ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Pre-nephrectomy uDKK3/crea levels were 100x higher in deceased than in living donors (9888 pg/mg versus 113 pg/mg, p<0.001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n=68) or above (group B, n=65) median. The primary endpoint of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 ml/min/1.73 m2) compared to group B (44.2 ml/min/1.73 m2, p=0.0139). Second, the composite clinical endpoint consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modelling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of -4.282 ml/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, urinary DKK3 may serve as a non-invasive, donor-dependent biomarker for assessing organ quality and future allograft function.