Anakinra Plus Zinc May Cause More Kidney Damage in Severe Alcohol Hepatitis, Study Reveals

"Those receiving A+Z who developed AKI exhibited elevated levels of urine-neutrophil-gelatinase-associated lipocalin, indicating that A+Z may have nephrotoxic effects in patients with severe alcohol-associated hepatitis," the researchers wrote in the journal Hepatology.

A recent trial had shown lower survival and higher acute kidney injury rates versus prednisone (PRED) in patients with severe alcohol-associated hepatitis treated with anakinra plus zinc. Kavish R. Patidar, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA, and colleagues characterized the clinical factors and potential mechanisms associated with AKI development in that trial.

For this purpose, the researchers analyzed data from 147 participants in a multicenter randomized clinical trial, with 74 receiving A+Z and 73 receiving PRED. They compared the incidence of acute kidney injury, AKI phenotypes, and kidney injury biomarkers between participants who developed AKI and those who did not in both treatment groups.

Multivariable competing risk analyses were conducted to identify baseline risk factors for incident AKI, treating death as a competing event. The factors considered included age, sex, mean arterial pressure (MAP), white blood cell count, albumin, MELD score, ascites, hepatic encephalopathy (HE), and treatment arm.

The following were the key findings of the study:

• 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% versus 22%).
• 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 63.6% versus 50.0%).
• At baseline, urine-neutrophil-gelatinase–associated lipocalin levels were similar among participants who developed AKI in both treatment arms.
• Day 7 and 14 urine-neutrophil-gelatinase–associated lipocalin levels increased significantly in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI.
• On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35).

Study limitations include a lack of data necessary to fully understand the mechanism behind AKI.

The authors concluded that "the use of A+Z might have led to a decrease in MAP, which could have triggered acute tubular injury and contributed to higher mortality rates observed in the clinical trial comparing A+Z to prednisone for severe alcohol-associated hepatitis."

Reference:

Patidar, Kavish R.1,2; Tu, Wanzhu3; Cotter, Thomas G.4; Simonetto, Douglas A.5; Asgharpour, Amon6; Jan, Muhammad Y.7; Tang, Qing3; Yu, Yunpeng3; Li, Yang3; Taiwo, Moyinoluwa8; Thevkar Nagesh, Prashanth9; Dasarathy, Srinivasan8; Kamath, Patrick S.5; McClain, Craig J.10; Chalasani, Naga1; Szabo, Gyongyi9; Bataller, Ramon11,12; Mitchell, Mack4; Mehal, Wajahat Z.13,14; Nagy, Laura E.15; Shah, Vijay H.5; Gawrieh, Samer1; Sanyal, Arun J.6; for The AlcHepNet Investigators. Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone. Hepatology ():10.1097/HEP.0000000000001019, July 19, 2024. | DOI: 10.1097/HEP.0000000000001019