TY - JOUR
T1 - Acute Kidney Injury in Severe Alcohol-Associated Hepatitis Treated with Anakinra plus Zinc or Prednisone
AU - The AlcHepNet Investigators
AU - Patidar, Kavish R.
AU - Tu, Wanzhu
AU - Cotter, Thomas G.
AU - Simonetto, Douglas A.
AU - Asgharpour, Amon
AU - Jan, Muhammad Y.
AU - Tang, Qing
AU - Yu, Yunpeng
AU - Li, Yang
AU - Taiwo, Moyinoluwa
AU - Nagesh, Prashanth Thevkar
AU - Dasarathy, Srinivasan
AU - Kamath, Patrick S.
AU - McClain, Craig J.
AU - Chalasani, Naga
AU - Szabo, Gyongyi
AU - Bataller, Ramon
AU - Mitchell, Mack
AU - Mehal, Wajahat Z.
AU - Nagy, Laura E.
AU - Shah, Vijay H.
AU - Gawrieh, Samer
AU - Sanyal, Arun J.
N1 - Publisher Copyright:
Copyright © 2024 American Association for the Study of Liver Diseases.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - MELD
KW - acute tubular necrosis
KW - alcohol-associated liver disease
KW - hepatorenal syndrome
KW - renal failure
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UR - http://www.scopus.com/inward/citedby.url?scp=85199567062&partnerID=8YFLogxK
U2 - 10.1097/HEP.0000000000001019
DO - 10.1097/HEP.0000000000001019
M3 - Article
C2 - 39028887
AN - SCOPUS:85199567062
SN - 0270-9139
JO - Hepatology
JF - Hepatology
ER -