Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone

Abstract

Background & Aims: In a recent trial, patients with severe-alcohol-associated-hepatitis (sAH) treated with anakinra-plus-zinc (A+Z) had lower survival and higher acute-kidney-injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial. Approach & Results: Data from 147-participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI-phenotypes, and kidney-injury biomarkers were compared between participants who did/did not develop AKI in the two treatment-arms. Multivariable competing-risk analyses were performed to identify baseline risk-factors for incident AKI, with death treated as a competing event. Risk-factors considered were age, sex, mean arterial pressure, white blood cell count, albumin, MELD, ascites, hepatic encephalopathy, and treatment arm. At baseline, no participants had AKI; 33% (n=49) developed AKI during follow-up. AKI incidence was higher in A+Z than PRED [45% (n=33) versus 22% (n=16), p=0.001]. AKI-phenotypes were similar between the two treatment-arms (p=0.361) but peak-AKI severity was greater in A+Z than PRED [stage-3 n=21 (63.6%) versus n=8 (50.0%), p=0.035]. At baseline, urine-neutrophil-gelatinase-associated-lipocalin (uNGAL) levels were similar between participants who developed AKI in both treatment-arms (p=0.319). However, day 7 and 14 uNGAL levels were significantly elevated in A+Z-treated participants who developed AKI versus PRED-treated participants who developed AKI (p=0.002 and p=0.032, respectively). On multivariable competing-risk analysis, only A+Z was independently associated with incident AKI (sHR 2.35, p=0.005). Conclusions: AKI occurred more frequently and was more severe in A+Z-treated participants. A+Z-treated participants with AKI had higher uNGAL, suggesting that A+Z maybe nephrotoxic in sAH patients.