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.

Uromodulin: more than a marker for chronic kidney disease progression

“…These data are interesting as unlike other studies which have measured uromodulin in KTR [34,42 ▪ ,43], this cohort focused on the donor kidneys. To explain the higher risk of adverse kidney outcomes with higher uUMOD, the investigators demonstrated that a truncated, nonpolymerizing form of uUMOD induced major histocompatability II expression in bone marrow-derived mouse macrophages, which may have a maladaptive effect on graft function due to an immunostimulant effect [41 ▪ ]. However, given that the vast majority of uUMOD is polymerized, whether this explains the discrepant findings of this study in comparison with others is unclear.…”

“…Significantly, sUMOD levels 24 h after transplantation were not associated with DGF. A second larger study of 1298 KTR evaluated the association between deceased donor uUMOD with risk for all-cause graft failure and death-censored graft failure (dcGF) and DGF at 6 months post-transplantation [41 ▪ ]. In contrast to epidemiologic data in nontransplant studies, higher uUMOD levels were associated with increased risk of graft failure, dcGF, and DGF.…”

The Perspectives of Biomarkers in Predicting the Survival of the Renal Graft

“…They determined serum uromodulin pre-KT and 24 h after KT. The serum uromodulin was not higher in DGF patients (72). Recent studies regarding uromodulin are controversial; therefore, it is hard to establish its potential role in predicting the graft survival.…”

Role of Uromodulin in Salt-Sensitive Hypertension

“…64 Circulating UMOD has been shown to be an effective parameter for monitoring kidney function in transplant patients. Higher pretransplant circulating UMOD levels were found to be associated with lower odds for delayed graft rejection, 67 whereas in renal transplant recipients, lower circulating UMOD levels are associated with a higher risk of failure or rejection. 68,69 In recent years, the clinical value of UMOD has extended beyond being a renal pathophysiology biomarker.…”