Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery

Abstract

Background and objectives: AKI is a serious complication after cardiac surgery. Although high urinary concentrations of the tubular protein uromodulin, a marker of tubular health, are associated with less AKI in animal models, its relationship in humans is unknown.

Design, setting, participants, & measurements: A post hoc analysis of a prospective cohort study of 218 adults undergoing on-pump cardiac surgery between 2004 and 2011 was conducted. Multivariable logistic and linear regression analyses were used to evaluate the associations of preoperative urinary uromodulin-to-creatinine ratio with postoperative AKI (defined as a rise in serum creatinine of >0.3 mg/dl or >1.5 times baseline); severe AKI (doubling of creatinine or need for dialysis) and peak postoperative serum creatinine over the first 72 hours.

Results: Mean age was 68 years, 27% were women, 95% were white, and the median uromodulin-to-creatinine ratio was 10.0 μg/g. AKI developed in 64 (29%) patients. Lower urinary uromodulin-to-creatinine ratio was associated with higher odds for AKI (odds ratio, 1.49 per 1-SD lower uromodulin; 95% confidence interval, 1.04 to 2.13), which was marginally attenuated after multivariable adjustment (odds ratio, 1.43; 95% confidence interval, 0.99 to 2.07). The lowest uromodulin-to-creatinine ratio quartile was also associated with higher odds for AKI relative to the highest quartile (odds ratio, 2.94; 95% confidence interval, 1.19 to 7.26), which was slightly attenuated after multivariable adjustment (odds ratio, 2.43; 95% confidence interval, 0.91 to 6.48). A uromodulin-to-creatinine ratio below the median was associated with higher adjusted odds for severe AKI, although this did not reach statistical significance (odds ratio, 4.03; 95% confidence interval, 0.87 to 18.70). Each 1-SD lower uromodulin-to-creatinine ratio was associated with a higher adjusted mean peak serum creatinine (0.07 mg/dl per SD; 95% confidence interval, 0.02 to 0.13).

Conclusions: Lower uromodulin-to-creatinine ratio is associated with higher odds of AKI and higher peak serum creatinine after cardiac surgery. Additional studies are needed to confirm these preliminary results.

Keywords: Animals; Cardiac Surgical Procedures; Cohort Studies; Female; Humans; Kidney Function Tests; Models, Animal; Odds Ratio; Postoperative Period; Prospective Studies; Regression Analysis; Uromodulin; acute kidney injury; adult; cardiac surgery; creatinine; renal dialysis; tubular function; uromodulin.