Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2025; 17(4): 105120
Published online Apr 27, 2025. doi: 10.4254/wjh.v17.i4.105120
Bile cast nephropathy: A systematic review of case reports and case series
Iyiad Alabdul Razzak, Hind El Naamani, Dimo Dimitrov, Rebecca Morin, Bertrand L Jaber
Iyiad Alabdul Razzak, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States
Hind El Naamani, Dimo Dimitrov, Bertrand L Jaber, Department of Medicine, St. Elizabeth’s Medical Center, Boston, MA 02135, United States
Rebecca Morin, Department of Research and Instruction, Tufts University, Boston, MA 02111, United States
Author contributions: Alabdul Razzak I and Jaber BL designed the study and search protocol; Morin R conducted the literature search; Alabdul Razzak I, El Naamani H, and Dimitrov D performed reference screening and data extraction; Jaber BL performed the statistical analysis; Alabdul Razzak I, El Naamani H, and Dimitrov D drafted the manuscript; Jaber BL critically revised and edited the manuscript for important intellectual content; and all authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Iyiad Alabdul Razzak, MD, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, United States. ialabdul@bidmc.harvard.edu
Received: January 13, 2025
Revised: February 27, 2025
Accepted: March 25, 2025
Published online: April 27, 2025
Processing time: 103 Days and 17.8 Hours
Abstract
BACKGROUND

Bile cast nephropathy (BCN) is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury. While postmortem studies reveal a high prevalence of BCN, little is known about this orphan acute kidney injury syndrome.

AIM

To address this knowledge gap, we performed a systematic review of case reports and case series of BCN, focusing on risk factors, diagnostic criteria, clinical presentation, kidney biopsy findings, severity, treatment approaches, and outcomes.

METHODS

Electronic databases were searched to identify eligible studies of patients with possible, probable, or definite BCN, using pre-established criteria. Relevant variables were extracted and analyzed. We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease. Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.

RESULTS

Sixty-seven case reports and six case series (involving 2 patients each) met the inclusion criteria, totaling 79 cases of BCN. The mean age was 48.3 years, and 83.5% were men. The most common cause of liver disease was drug-induced injury (30.4%), followed by infection (18.9%) and alcoholism (12.7%). BCN diagnosis was deemed definite, probable, and possible in 65.8%, 32.9%, and 1.3% of cases, respectively. Levels of serum creatinine, dialysis requirement, and renal recovery did not differ among the total bilirubin tertile groups. However, both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group (P = 0.011 and P = 0.012, respectively). There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group (80% vs 52%, P = 0.098). Finally, higher initial serum creatinine (per 1 mg/dL increase) was independently associated with dialysis requirement or death (adjusted odds ratio 1.291, 95% confidence interval: 1.032-1.615, P = 0.025).

CONCLUSION

BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease. The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes. However, in alcoholic liver disease, BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease. Serum creatinine may be a valuable predictor of BCN prognosis. Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.

Keywords: Cholemic nephropathy; Acute kidney injury; Liver disease; Bile acids; Oxidative stress; Kidney biopsy; Prognostic factors; Outcomes

Core Tip: This systematic review highlights bile cast nephropathy (BCN) as a serious yet underrecognized cause of acute kidney injury in patients with liver disease. Despite its clinical significance, universally accepted diagnostic criteria and therapeutic approaches are currently lacking. Among the various liver disease etiologies implicated in BCN, alcohol-related liver disease appears to be associated with more severe acute kidney injury. Additionally, higher initial serum creatinine was identified as a predictor of dialysis requirement or death. These findings underscore the need for further research into non-invasive diagnostic tools and viable therapeutic strategies for BCN.