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Acute kidney injury (AKI) is common among patients undergoing cardiopulmonary bypass (CPB) surgery. AKI diagnosis relies on serum creatinine and urine output which show poor sensitivity and specificity. New AKI biomarkers have not been widely adopted into clinical care due to limitations. A shortcoming of existing AKI biomarkers is lack of kidney tissue specificity. We previously described the kidney specific enzyme, myo-inositol oxygenase (MIOX), as a potential plasma AKI biomarker. In this study, we evaluated urine MIOX as an AKI biomarker in patients undergoing CPB surgery and compare MIOX with kidney injury molecule-1 (KIM-1) and neutrophil gelatinase associated lipocalin (NGAL).
Urine was prospectively obtained from 89 adult control outpatients with normal serum creatinine. 92 adult patients undergoing CPB surgery were prospectively enrolled. Urine samples were obtained within 2 weeks of surgery, within 30 minutes after discontinuing bypass, and at 3-, 6-, 12-, 18-, and 24-hours post-bypass. AKI was determined by Kidney Diseases Improving Global Outcomes criteria using serum creatinine and urine output over the first 48 hours after surgery and need for dialysis within 10 days. Urine KIM-1 and NGAL were measured by ELISA according to manufacturer’s instructions. The MIOX immunoassay used Single Molecule Counting [SMC]® technology with a rabbit polyclonal antibody for capture and a mouse monoclonal antibody for detection. Statistical analyses were performed using SAS. Wilcoxon signed rank paired test was used to compare pre-surgery to post-surgery biomarker concentrations. Independent sample comparisons were analyzed with a Wilcoxon 2 sample test.
Even though low concentrations of MIOX is present in urine of healthy controls, it was significantly elevated at 6-12 hours after CPB in patients who developed clinical AKI. This indicates that urine MIOX may have a role as a biomarker for early AKI detection. MIOX identifies CPB patients with subclinical AKI before and after surgery. Urine MIOX, KIM-1, and NGAL all increase after CPB surgery and identify patients with subclinical AKI. Further study of MIOX as an AKI biomarker and comparison with other AKI biomarkers is warranted.