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

Published in the journal Hepatology. Here is a link to the article.

Regenstrief Institute authors: Wanzhu Tu, PhD.

Abstract

Background and Aims:

In a recent trial, patients with severe alcohol-associated 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.

Authors:

Kavish R Patidar ^1,2, Wanzhu Tu ³, Thomas G Cotter ⁴, Douglas A Simonetto ⁵, Amon Asgharpour ⁶, Muhammad Y Jan ⁷, Qing Tang ³, Yunpeng Yu ³, Yang Li ³, Moyinoluwa Taiwo ⁸, Prashanth Thevkar Nagesh ⁹, Srinivasan Dasarathy ⁸, Patrick S Kamath ⁵, Craig J McClain ¹⁰, Naga Chalasani ¹, Gyongyi Szabo ⁹, Ramon Bataller ^11,12, Mack Mitchell ⁴, Wajahat Z Mehal ^13,14, Laura E Nagy ¹⁵, Vijay H Shah ⁵, Samer Gawrieh ¹, Arun J Sanyal ⁶; AlcHepNet Investigators

Affiliations:

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA

²Department of Internal Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA

³Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA

⁴Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

⁵Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

⁶Division of Gastroenterology, Department of Internal Medicine, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA

⁷Division of Nephrology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA

⁸Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA

⁹Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

¹0Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Louisville, Louisville, Kentucky, USA

¹¹Division of Gastroenterology and Hepatology and Nutrition, Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

¹²School of Medicine and Health Sciences, Liver Unit, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

¹³Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA

¹⁴Department of Internal Medicine, Veterans Affairs Medical Center, West Haven, Connecticut, USA

¹⁵Department of Inflammation and Immunity, Cleveland Clinic Foundation, Cleveland, Ohio, USA