Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone-Reference-Cited by-同舟云学术

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

Published:2024-07-19 Issue: Volume: Page:
ISSN:0270-9139
Container-title:Hepatology
language:en
Short-container-title:

Author:

Patidar Kavish R.¹²^ORCID,Tu Wanzhu³^ORCID,Cotter Thomas G.⁴^ORCID,Simonetto Douglas A.⁵^ORCID,Asgharpour Amon⁶,Jan Muhammad Y.⁷,Tang Qing³,Yu Yunpeng³,Li Yang³,Taiwo Moyinoluwa⁸,Thevkar Nagesh Prashanth⁹^ORCID,Dasarathy Srinivasan⁸^ORCID,Kamath Patrick S.⁵^ORCID,McClain Craig J.¹⁰,Chalasani Naga¹,Szabo Gyongyi⁹^ORCID,Bataller Ramon¹¹¹²,Mitchell Mack⁴^ORCID,Mehal Wajahat Z.¹³¹⁴^ORCID,Nagy Laura E.¹⁵,Shah Vijay H.⁵,Gawrieh Samer¹^ORCID,Sanyal Arun J.⁶^ORCID,

Affiliation:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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