Aim: Renal impairment is a relevant risk factor in acute coronary syndrome (ACS) patients. Uromodulin is a glycoprotein produced and secreted by the kidney. Patients with an impaired renal function have low Uromodulin blood levels. Low Uromodulin levels are associated with incidence of acute kidney injury (AKI) and with outcome. So far it is unknown, if serum Uromodulin levels are affected in patients suffering from an ACS and if Uromodulin is associated with outcome in the context of ACS.

Methods: We investigated serum Uromodulin levels in 209 patients (32% female, mean age 70 years) with the final diagnosis of ACS. Primary outcome measure was all-cause mortality. 32 patients died within the follow-up period. We compared baseline characteristics in patients with Uromodulin levels above and below the median including biomarkers such as low-density lipoprotein (LDL), high sensitive cardiac troponin T (hs-cTnT), and n-terminal pro b-type natriuretic peptide (NT-pro BNP). We calculated the area under the receiver operating characteristic curve (AUROC) to investigate a potential association between Uromodulin and death as well as AKI. Kaplan Meier analysis was performed to investigate the event free survival of patients with Uromodulin levels above and below the median. Cox regression analysis was carried out to further investigate the association between Uromodulin levels and outcome. 

Results: There were no differences in Uromodulin levels between men and women (p=0.622). Patients with lower Uromodulin levels were older (73 years vs. 67 years p<0.001), had a higher rate of arterial hypertension (96% vs. 81%, p=0.002) and a higher rate of diabetes mellitus (52% vs. 26%, p<0.001). Patients with lower Uromodulin levels also had higher Creatinine levels (1.32 mg/dl vs. 0.8 mg/dl), lower LDL levels (103mg/dl vs. 133mg/dl, p=0.001), and higher NT-pro BNP levels (1726 ng/l vs. 511 ng/l, p<0.001). We did not observe a significant difference for hs-cTnT levels (p=0.304).

Regarding mortality, 23 patients with serum Uromodulin levels below the median of 132.7 ng/L died, whereas only 9 patients with serum Uromodulin levels above the median died (p=0.014). Uromodulin was associated with death with an AUROC of 0.696 (Confidence Interval [CI]: 0.606-0.785). Uromodulin was also associated with the incidence of AKI with an AUROC of 0.656 (CI: 0.535-0.776). This association was more pronounced than the association between the estimated glomerular filtration rate and AKI (0.455 [CI: 0.312-0.597]), without reaching statistical significance (p=0.051).

We observed a significantly lower event free survival in patients with Uromodulin levels below the median in the Kaplan-Meier analysis (p=0.034, Figure 1). High serum Uromodulin levels were associated with a lower risk for all-cause mortality with a Hazard ratio of 0.50 (CI: 0.36-0.69, p<0.001). 

Conclusion: To the best of our knowledge, we are the first to report that serum Uromodulin levels are associated with mortality in ACS patients. As risk stratification is crucial in ACS patients, Uromodulin might help to identify high risk patients in the presence of ACS. Further, Uromodulin seems to be a strong risk predictor for AKI and therefore might by a useful additional biomarker at presentation to identify ACS patients at risk for AKI and therefore higher risk for mortality. 

Figure 1. Kaplan-Meier Estimator in patients with an acute coronary syndrome stratified by serum Uromodulin median (132.7ng/L, p=0.034)