Early Prediction of Acute Kidney Injury after On-Pump Coronary Artery Bypass Grafting by Quantification of Urinary Timp-2 and Igfbp-7 Protein Levels Compared to Serum Creatinine and Urea Concentration

Introduction: Acute kidney injury (AKI) is a common and severe complication following on-pump cardiac surgery with major implications for patient's outcome. In this observational study we compared the new urinary protein markers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP-7) ([TIMP-2]  ×  [IGFBP-7]) (Nephrocheck®) as predictors of acute kidney injury in relation to the conventional serum creatinine and urea concentrations, the clinical condition, the urine output and the glomerular filtration rate.

Methods: We investigated 50 patients at normal risk for acute kidney injury undergoing on-pump coronary bypass grafting. Serial blood and urine samples were collected and analyzed for TIMP-2 and IGFBP-7 protein concentration preoperatively, after 30 and 60 minutes of ischemic cardiac arrest and after 6, 12, and 24 hours postoperatively. The definition of AKI was according the KDIGO (KDIGO clinical practice guideline for acute kidney injury) guideline and compared with the levels of creatinine, the glomerular filtration rate, the urine output and the patients clinical and hemodynamic condition.

Results: The sensitivity on ICU admission amounted to 0.846 and specificity to 0.556. AKI occurred in 14 patients (28%) within 24 hours postoperatively. All of them represented with KDIGO Stage 1. At post-operative admission to the intensive care unit and 24 hours later [TIMP-2]*[IGFBP7] concentration differed significantly between patients with and without AKI. Mean concentrations were 0.488 and 0.385. An area under the curve of 0.725 and 0.718 was shown for those time points with cutoffs at 0.07 and 0.35. The cutoff points 0.3 and 2 cannot be confirmed in this study. In comparison to our findings the creatinine levels in these patients showed her peak value only after 32 hours.

Conclusion: The new urinary protein markers TIMP-2 and IGFBP-7 can be adjuvant in the early diagnosis and therapy at an early stage of perioperative kidney injury. The sensitivity seems to be high compared with the specificity of this new diagnostic tool which is highly dependent on several patient related conditions such as volume status, blood pressure, nephrotoxic agents, duration of surgery such as cross clamp time. Compared with the classical laboratory parameter creatinine, urea and glomerular filtration rate the result of TIMP-2 and IGFBP-7 protein levels in patients' urine could detect an impairment in renal function at an earlier stage.