TIMP-2*IGFBP7 as an auxiliary identification of successful discontinuation CRRT and prediction of renal recovery in critically ill patients: a case control study

Background Cell cycle arrest biomarkers as TIMP-2*IGFBP7 are elevated in the Acute Kidney Stress and can predict the probability of developing Acute Kidney Injury (AKI). Approximately 25% of those patients with AKI deteriorate clinically and are unable to maintain adequate homeostasis, eventually requiring continuous renal replacement therapy. However, when clinical improvement occurs, the ideal mode of weaning patients from CRRT is an unmet medical need. Methods We performed a prospective single-center study of AKI patients treated with CRRT between October 2017 to April 2019 in a multidisciplinary ICU of an Italian hospital. All patients admitted to ICU requiring CRRT were enrolled. Urine samples for measuring urinary TIMP-2*IGFBP7 levels were collected immediately upon enrollment and at the moment when CRRT was discontinued. The primary endpoint was independence from RRT for at least 7 days after CRRT discontinuation. Renal recovery, which was defined as serum creatinine (SCr) level 2(ng/ml) 2 /1000 at enrollment were longer CRRT-dependent. The ROC-AUC values for the prediction of successful discontinuation with TIMP-2*IGFBP7 concentrations at enrollment, at discontinuation of CRRT and with the final model were 0.828, 0.814 and 0.882, respectively. The risk for CRRT discontinuation failure was nearly 5 times higher patients with a positive biomarker at CRRT discontinuation (OR 4.879, P=0.043), and 3.5 times higher in patients with a TIMP-2*IGFBP7 concentration >2(ng/ml) 2 /1000 at patient enrollment (OR 3.515, P=0.016). Multivariate Cox regression analysis showed a significant association between successful discontinuation of CRRT and TIMP-2*IGFBP7-negative patients at CRRT discontinuation (RR 0.436, 95% CI 0.202-0.939, P=0.034). Kaplan-Meier curves revealed that TIMP-2*IGFBP7 concentration