α-Klotho: An Early Risk-Predictive Biomarker for Acute Kidney Injury in Patients with Acute Myocardial Infarction

Background. Acute kidney injury (AKI) was a common and serious complication in patients with acute myocardial infarction (AMI). Novel biomarkers and therapies were deficient and imperative for AKI's early diagnosis and therapy after AMI. alpha-Klotho was considered as an early biomarker and potential therapy for AKI recently. Previous studies reported that the expression of alpha-Klotho was decreased in AKI rodents, and supplement of alpha-Klotho alleviated kidney injury. Nevertheless, its effect has not been studied in patients presenting with AMI. Methods. A total of 155 consecutive diagnosed with AMI at emergency department whose eGFR >60 ml/min (*) 1.73 m(2) were enrolled in this prospective observational cohort study which conducted between May 2016 and April 2019 in Peking University People's Hospital. AKI was defined according to the KDIGO criteria in 2012. At admission, the clinical data of patients were collected and serum alpha-Klotho was tested by ELISA. The relationship between alpha-Klotho, serum creatinine, eGFR, systolic pressure, BNP, LVEF, and Hgb of AKI were analyzed and their discrimination performances were compared. The association variables were calculated (adjusted odds ratio) with a confidence interval (CI) of 95% by binary logistic regression. And, we followed up the incidence of CKD and rehospitalization after patients' discharge in one year. Our study was approved by the ethics committee (no. 2016PHB042-01). Results. AKI incidence was 17.4% (27/155) during hospitalization. Compared to patients without AKI, the AKI group had obviously higher mortality and was more female and had higher incidence of chronic kidney disease, worse cardiac function, more cardiac complications, larger doses of diuretics, and less use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker. By contrary to previous animal experiments, we found serum alpha-Klotho levels were increased significantly in AKI patients (740.2 +/- 306.8 vs. 419.0 +/- 272.6 pg/mL, p < 0.001). And, the areas under the receiver operating curves indicated serum alpha-Klotho levels had a superior discriminative power for predicting AKI after AMI compared with other risk factors (0.792, 95% CI, 0.706-0.878, p < 0.001). Meanwhile, logistic regression model indicates extensive anterior myocardial infarction, Killip classification >= 2 grade, alpha-Klotho >= 516.9 pg/mL, eGFR (decrease per 10 ml/min (*)1.73 m(2)), Hgb, and nonuse of ACEI/ARB were the risk factors of AKI after AMI. Moreover, one-year follow-up presented AMI patients developed CKD had higher alpha-Klotho levels (739.7 +/- 315.2 vs. 443.8 +/- 292.5 pg/mL, p=0.001), but no significant difference in rehospitalization. And, patients with alpha-Klotho >= 516.9 pg/ml was 6.699 times more likely to develop CKD than those with alpha-Klotho < 516.9 pg/ml (relative risk 6.699, 95% CI 1.631-27.519, p=0.007). Conclusion. Compared with traditional cardiac and renal biomarkers, serum alpha-Klotho could be a more appropriate predict biomarker for AKI after AMI in patients' eGFR >60 ml/min (*) 1.73 m(2). Higher alpha-Klotho levels are related to the development of AKI during hospitalization and suggest a higher prevalence of CKD after discharge. By contrary to animal experiments, whether the increased expression of alpha-Klotho could be a protective factor secreted by AKI after AMI, is remained to be further studied.