Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation-A Prospective Cohort Study

Abstract

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30-0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54-13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723-0.848] to 0.813 [95%-CI 0.755-0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.

Keywords: Tamm-Horsfall-protein; delayed graft function; ischemia-reperfusion injury; kidney transplantation; uromodulin.

Figure 1

Mean serum uromodulin values [ng/mL] from pretransplant to follow-up (up to 120 days after transplantation) compared to the mean serum creatinine [mg/dL] in the total cohort and in patients with and without delayed graft function (DGF).

Figure 2

Multivariable receiver-operating-characteristic (ROC) curve analysis evaluating models including established risk factors (recipient age and body-mass-index (BMI), dialysis vintage, cold ischemia time, deceased vs. living donation, expanded criteria donors) for the prediction of delayed graft function (DGF) without (A) and with preoperative serum uromodulin (B).