Dynamic AARC-AKI score determines Extrarenal Organ Failures and Bacterial Infection in patients with Acute on Chronic Liver Failure

Abstract

Background and Aim: AKI is a dynamic event in patients with Acute‐on‐chronic liver failure (ACLF) and is associated with poor prognosis. AKI can predispose to infections and in animal models has been shown to cause remote organ dysfunction. The course of AKI in progressive liver failure in a cirrhotic is not well understood. We studied the association between the dynamic course of AKI in ACLF patients and occurrence of infections, extrarenal organ failures(E‐OFs) and 30‐day mortality and developed a dynamic score (AARC‐AKI Score) using a derivative (Gr. A, n=1060) and validation cohort(Gr. B, n=1579). Methods: Prospectively collected data from AARC data base was analysed The AKI‐score was constructed by the beta‐coefficients of the course (resolution vs. persistent vs progression) and stage of AKI (0:1:2:3) from 12 different combinations of clinical course patterns at each time point (Day0‐3,4‐7,8‐15) using repeated measures; Generalised Estimating Equations (GEE) for prediction of 30‐day mortality. Results: Of the 2639 patients with ACLF; mean age 45±12 yr, 86% male, 45% alcoholic, 1461 with AKI, of which 63% had AKI at admission [Stage1:2:3(%); 31:58:11] while 37% developed new AKI [58%:32%:10%] respectively The peak AKI stage in majority was 2 or 3 i. e. 62%; peak stage[1:2:3(%) 38:41:21]. At last follow‐up, AKI resolved in 37.3%, remained stable in 46.3% and progressed in 16 4% The AARC‐AKI Score developed from the GEE model showed a progressive increase in mortality (HR, 95%CI) (1. 31, 1.29‐1.34), E‐OFs (1.23, 1,21‐1. 25) and infections (1.16, 1.14‐1. 17) at 30‐day with increasing risk scores from 1‐9 in both groups and showed a good discrimination and calibration (Harrell's C‐0.76). A score of >7 at day 15 was associated with 99% mortality. A significant increase in 30‐day mortality (HR,95% CI) (1 vs 3.5, 3.2‐3.8 vs 7.4, 6.7‐8.1), E‐OFs (1 vs 2.2,1. 9‐2.3 vs 4.1, 3 7‐4 6) and development of bacterial infections (1 vs 1 8, 1 6‐2 vs 2 7, 2 5‐3 1) was noted on stratification of patients into 3 classes derived from AKI score (Class 1‐1‐3, Class 2‐4‐6 and Class 3‐7‐9) in both group A and B respectively Conclusions: Almost 50% of patients with ACLF manifest with AKI which, in majority is severe, resolves in a third and follows a stable or progressive course in the rest The stage and course of AKI impacts function of other organs, predisposes to bacterial infections and is an independent predictor of 30‐day mortality. Sequential use of AARC‐AKI score for stratifying patients and intervening in the first two weeks may be the therapeutic golden‐window for preventing AKI related mortality in ACLF.