Urine Alpha-1-Microglobulin Levels and Acute Kidney Injury, Mortality, and Cardiovascular Events following Cardiac Surgery

Introduction: Urine alpha-1-microglobulin (U alpha 1m) elevations signal proximal tubule dysfunction. In ambulatory settings, higher U alpha 1m is associated with acute kidney injury (AKI), progressive chronic kidney disease (CKD), cardiovascular (CV) events, and mortality. We investigated the associations of pre- and postoperative U alpha 1m concentrations with adverse outcomes after cardiac surgery. Methods: In 1,464 adults undergoing cardiac surgery in the prospective multicenter Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury (TRIBE-AKI) cohort, we measured the pre-and postoperative U alpha 1m concentrations and calculated the changes from pre- to postoperative concentrations. Outcomes were postoperative AKI during index hospitalization and longitudinal risks for CKD incidence and progression, CV events, and all-cause mortality after discharge. We analyzed U alpha 1m continuously and categorically by tertiles using multivariable logistic regression and Cox proportional hazards regression adjusted for demographics, surgery characteristics, comorbidities, baseline estimated glomerular filtration rate, urine albumin, and urine creatinine. Results: There were 230 AKI events during cardiac surgery hospitalization; during median 6.7 years of follow-up, there were 212 cases of incident CKD, 54 cases of CKD progression, 269 CV events, and 459 deaths. Each 2-fold higher concentration of preoperative U alpha 1m was independently associated with AKI (adjusted odds ratio [aOR] = 1.36, 95% confidence interval 1.14-1.62), CKD progression (adjusted hazard ratio [aHR] = 1.46, 1.04-2.05), and all-cause mortality (aHR = 1.19, 1.06-1.33) but not with incident CKD (aHR = 1.21, 0.96-1.51) or CV events (aHR = 1.01, 0.86-1.19). Postoperative U alpha 1m was not associated with AKI (aOR per 2-fold higher = 1.07, 0.93-1.22), CKD incidence (aHR = 0.90, 0.79-1.03) or progression (aHR = 0.79, 0.56-1.11), CV events (aHR = 1.06, 0.94-1.19), and mortality (aHR = 1.01, 0.92-1.11). Conclusion: Preoperative U alpha 1m concentrations may identify patients at high risk of AKI and other adverse events after cardiac surgery, but postoperative U alpha 1m concentrations do not appear to be informative.