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

Background and Aims: In a recent trial, patients with severe alcoholassociated hepatitis 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 and 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 2 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, HE, 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 in PRED (45% [n =33] versus 22% [n= 16], p= 0.001). AKI phenotypes were similar between the 2 treatment arms (p = 0.361), but peak AKI severity was greater in A+Z than PRED (stage 3 n= 21 [63.6%] vs. n= 8 [50.0%], p = 0.035). At baseline, urine-neutrophil-gelatinase-associated lipocalin levels were similar between participants who developed AKI in both treatment arms (p =0.319). However, day 7 and 14 urine-neutrophil-gelatinase- associated lipocalin levels were significantly elevated in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI (p =0.002 and 0.032, respectively). On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35, p =0.005). Conclusions: AKI occurred more frequently and was more severe in participants treated with A+Z. A+Z-treated participants with AKI had higher urine-neutrophil-gelatinase-associated lipocalin, suggesting that A+Z maybe nephrotoxic in patients with severe alcohol-associated hepatitis.