Skip to main content

Advertisement

SpringerLink
Log in

Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background and Aims

Although renal dysfunction is a known complication of acute liver failure (ALF), its frequency, severity, and impact among patients with ALF on the US liver transplant list are not well defined.

Methods

Organ Procurement and Transplantation data for ALF patients listed as status 1/1A from 2002 to 2012 were analyzed. The frequency and severity of renal dysfunction at the time of listing [the latter was categorized in 5 stages using estimated GFR (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation] were determined and the association between renal dysfunction and waiting list mortality was assessed using Cox proportional hazard regression analysis.

Results

There were a total of 2280 adult patients with ALF, including 56 % with renal dysfunction (defined as eGFR < 60 ml/min/1.73 m2) at listing. The highest proportion of patients with renal dysfunction was among those with ALF caused by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, fatty liver disease of pregnancy, heat stroke/hyperthermia, hepatitis A virus, and drug-induced liver injury due to acetaminophen APAP, phenytoin, trimethoprim-sulfamethoxazole, and macrolides. Despite the fact that 69 % (468/674) of patients with APAP-induced ALF listed as status 1/1A had renal dysfunction, only 0.9 % underwent simultaneous liver-kidney transplantation. Six-week survival probabilities in patients with ALF on the liver transplant waiting list were 71, 59, 56, 59, and 42 % with renal dysfunction stages of 1, 2, 3, 4, and 5, respectively. Multivariate analysis showed that after controlling for age, etiology of ALF, INR, total bilirubin, and region, the relative risk of death increased progressively as eGFR declined (P < 0.0001).

Conclusions

Among patients with ALF on the liver transplant waiting list, renal dysfunction was common (overall prevalence of 56 %). Most importantly, severe renal dysfunction was associated with significantly increased mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ALF:

Acute liver failure

OPTN:

Organ Procurement and Transplantation Network

UNOS:

United network for organ sharing

INR:

International normalized ratio

MELD:

Model for end-stage liver disease

References

  1. Lee WM, Stravitz RT, Larson AMCP. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2011;55:965–967.

    Article  Google Scholar 

  2. Polson J, Lee WM. Disease AAftSoL. AASLD position paper: the management of acute liver failure. Hepatology. 2005;41:1179–1197.

    Article  PubMed  Google Scholar 

  3. Czaja AJ, Freese DK. Disease AAftSoL. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002;36:479–497.

    Article  PubMed  Google Scholar 

  4. Lee WC, Wu MJ, Cheng CH, et al. Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients. Am J Kidney Dis. 2001;38:1074–1081.

    Article  PubMed  CAS  Google Scholar 

  5. Peters DJ, Greene WH, Ruggiero F, et al. Herpes simplex-induced fulminant hepatitis in adults: a call for empiric therapy. Dig Dis Sci. 2000;45:2399–2404.

    Article  PubMed  CAS  Google Scholar 

  6. Smilkstein MJ, Knapp GL, Kulig KW, et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988;319:1557–1562.

    Article  PubMed  CAS  Google Scholar 

  7. Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947–954.

    Article  PubMed  Google Scholar 

  8. O’Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97:439–445.

    PubMed  Google Scholar 

  9. Belcher JM, Garcia-Tsao G, Sanyal AJ, et al. Association of AKI with mortality and complications in hospitalized patients with cirrhosis. Hepatology. 2013;57:753–762.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Mindikoglu AL, Regev A, Seliger SL, et al. Gender disparity in liver transplant waiting-list mortality: the importance of kidney function. Liver Transpl. 2010;16:1147–1157.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137–147.

    Article  PubMed  Google Scholar 

  13. SAS Activity-Based Management 6.3: User’s Guide. Cary, N.C.: SAS Institute, Inc.; 2007.

  14. Minitab 16 Statistical Software (2010). Computer Software. State College, PA: Minitab, Inc. (www.minitab.com).

  15. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assn. 1958;53:457–481.

    Article  Google Scholar 

  16. Cox DR. Regression models and life-table. J R Stat Soc B. 1972;34:187–220.

    Google Scholar 

  17. Wilkinson SP, Moodie H, Arroyo VA, et al. Frequency of renal impairment in paracetamol overdose compared with other causes of acute liver damage. J Clin Pathol. 1977;30:141–143.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Wilkinson SP, Blendis LM, Williams R. Frequency and type of renal and electrolyte disorders in fulminant hepatic failure. Br Med J. 1974;1:186–189.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Tujios SR, Hynan LS, Vazquez MA, et al. Risk factors and outcomes of acute kidney injury in patients with acute liver failure. Clin Gastroenterol Hepatol. 2015;13:352–359.

    Article  PubMed  Google Scholar 

  20. Leithead JA, Ferguson JW, Bates CM, et al. The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut. 2009;58:443–449.

    Article  PubMed  CAS  Google Scholar 

  21. Ring-Larsen H, Palazzo U. Renal failure in fulminant hepatic failure and terminal cirrhosis: a comparison between incidence, types, and prognosis. Gut. 1981;22:585–591.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Garcin JM, Bronstein JA, Cremades S, et al. Acute liver failure is frequent during heat stroke. World J Gastroenterol. 2008;14:158–159.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Jin Q, Chen E, Jiang J, et al. Acute hepatic failure as a leading manifestation in exertional heat stroke. Case Rep Crit Care. 2012;2012:295867.

  24. Yeo TP. Heat stroke: a comprehensive review. AACN Clin Issues. 2004;15:280–293.

    PubMed  Google Scholar 

  25. Sibai BM, Ramadan MK, Usta I, et al. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol. 1993;169:1000–1006.

    Article  PubMed  CAS  Google Scholar 

  26. Castro MA, Fassett MJ, Reynolds TB, et al. Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases. Am J Obstet Gynecol. 1999;181:389–395.

    Article  PubMed  CAS  Google Scholar 

  27. Fesenmeier MF, Coppage KH, Lambers DS, et al. Acute fatty liver of pregnancy in 3 tertiary care centers. Am J Obstet Gynecol. 2005;192:1416–1419.

    Article  PubMed  Google Scholar 

  28. Rosenfeld J, Gura V, Boner G, et al. Interstitial nephritis with acute renal failure after erythromycin. Br Med J (Clin Res Ed). 1983;286:938–939.

    Article  CAS  Google Scholar 

  29. Soni N, Harrington JW, Weiss R, et al. Recurrent acute interstitial nephritis induced by azithromycin. Pediatr Infect Dis J. 2004;23:965–966.

    Article  PubMed  Google Scholar 

  30. Tintillier M, Kirch L, Almpanis C, et al. Telithromycin-induced acute interstitial nephritis: a first case report. Am J Kidney Dis. 2004;44:e25–e27.

    Article  PubMed  Google Scholar 

  31. Mansoor GA, Panner BJ, Ornt DB. Azithromycin-induced acute interstitial nephritis. Ann Intern Med. 1993;119:636–637.

    Article  PubMed  CAS  Google Scholar 

  32. Mindikoglu AL, Magder LS, Regev A. Outcome of liver transplantation for drug-induced acute liver failure in the United States: analysis of the United Network for Organ Sharing database. Liver Transpl. 2009;15:719–729.

    Article  PubMed  Google Scholar 

  33. Polman AJ, van der Werf TS, Tiebosch AT, et al. Early-onset phenytoin toxicity mimicking a renopulmonary syndrome. Eur Respir J. 1998;11:501–503.

    Article  PubMed  CAS  Google Scholar 

  34. Hyman LR, Ballow M, Knieser MR. Diphenylhydantoin interstitial nephritis. Roles of cellular and humoral immunologic injury. J Pediatr. 1978;92:915–920.

    Article  PubMed  CAS  Google Scholar 

  35. Parry RG, Gordon P, Mason JC, et al. Phenytoin-associated vasculitis and ANCA positivity: a case report. Nephrol Dial Transpl. 1996;11:357–359.

    Article  CAS  Google Scholar 

  36. Michael JR, Mitch WE. Reversible renal failure and myositis caused by phenytoin hypersensitivity. JAMA. 1976;236:2773–2775.

    Article  PubMed  CAS  Google Scholar 

  37. Blakely P, McDonald BR. Acute renal failure due to acetaminophen ingestion: a case report and review of the literature. J Am Soc Nephrol. 1995;6:48–53.

    PubMed  CAS  Google Scholar 

  38. Leithead JA, Ferguson JW, Bates CM, et al. The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut. 2009;58:443–449.

    Article  PubMed  CAS  Google Scholar 

  39. O’Riordan A, Brummell Z, Sizer E, et al. Acute kidney injury in patients admitted to a liver intensive therapy unit with paracetamol-induced hepatotoxicity. Nephrol Dial Transplant. 2011;26:3501–3508.

    Article  PubMed  Google Scholar 

  40. Lines SW, Wood A, Bellamy MC, et al. The outcomes of critically ill patients with combined severe acute liver and kidney injury secondary to paracetamol toxicity requiring renal replacement therapy. Ren Fail. 2011;33:785–788.

    Article  PubMed  CAS  Google Scholar 

  41. Fan PC, Chen YC, Tian YC, et al. Acute renal failure associated with acute non-fulminant hepatitis A: a case report and review of literature. Ren Fail. 2009;31:756–764.

    Article  PubMed  CAS  Google Scholar 

  42. Kim HW, Yu MH, Lee JH, et al. Experiences with acute kidney injury complicating non-fulminant hepatitis A. Nephrology (Carlton). 2008;13:451–458.

    Article  CAS  Google Scholar 

  43. Pal RB, Saha P, Das I, et al. Fulminant hepatitis and glomerulonephritis—a rare presentation of hepatitis A virus infection. Acta Paediatr. 2011;100:e132–e134.

    Article  PubMed  Google Scholar 

  44. McCann UG 2nd, Rabito F, Shah M, et al. Acute renal failure complicating nonfulminant hepatitis A. West J Med. 1996;165:308–310.

    PubMed  PubMed Central  Google Scholar 

  45. Jung YJ, Kim W, Jeong JB, et al. Clinical features of acute renal failure associated with hepatitis A virus infection. J Viral Hepat. 2010;17:611–617.

    PubMed  CAS  Google Scholar 

  46. Watanabe S, Nomoto H, Matsuda M, et al. A case of acute renal failure associated with type A acute hepatitis responds dramatically to plasmapheresis. Tokai J Exp Clin Med. 1986;11:1–4.

    PubMed  CAS  Google Scholar 

  47. Zikos D, Grewal KS, Craig K, et al. Nephrotic syndrome and acute renal failure associated with hepatitis A virus infection. Am J Gastroenterol. 1995;90:295–298.

    PubMed  CAS  Google Scholar 

  48. Evans JT, Shepard MM, Oates JC, et al. Rituximab-responsive cryoglobulinemic glomerulonephritis in a patient with autoimmune hepatitis. J Clin Gastroenterol. 2008;42:862–863.

    Article  PubMed  Google Scholar 

  49. Section 2: AKI definition. Kidney Int Suppl. 2012;2:19–36.

Download references

Acknowledgments

This work was supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. We thank Jean-Pierre Raufman, M.D. (Professor of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine) for reviewing our manuscript.

Authorship

Nathalie H. Urrunaga M.D., M.S., designed and performed the study, analyzed the data, and wrote the paper. Laurence S. Magder Ph.D., M.P.H., analyzed the data and contributed with important suggestions. Matthew R. Weir, M.D., contributed with important suggestions. Don C. Rockey, M.D., wrote the paper and contributed with important suggestions. Ayse L. Mindikoglu M.D., M.P.H., designed and performed the study, analyzed the data, and wrote the paper.

Funding

The project described was supported by Grant Number 5 K23 DK089008-05 from the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (to Ayse L. Mindikoglu, M.D., M.P.H.), and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the NIH.” “Nathalie H. Urrunaga, M.D., M.S., was supported by Grant Number 5 T32 DK067872-10 from the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 22 S. Greene Street, N3W50, Baltimore, MD, 21201, USA

    Nathalie H. Urrunaga & Ayse L. Mindikoglu

  2. Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA

    Laurence S. Magder

  3. Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Matthew R. Weir

  4. Department of Medicine, Medical University of South Carolina, Charleston, SC, USA

    Don C. Rockey

Authors
  1. Nathalie H. Urrunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laurence S. Magder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew R. Weir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Don C. Rockey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ayse L. Mindikoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ayse L. Mindikoglu.

Ethics declarations

Conflict of interest

None to declare.

Meeting material

Urrunaga N, Mindikoglu AL. Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List. Gastroenterology 2014, 146, Issue 5, S-915. Abstract was presented on May 4, 2014, at Digestive Disease Week (DDW), Chicago, IL.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Urrunaga, N.H., Magder, L.S., Weir, M.R. et al. Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List. Dig Dis Sci 61, 309–316 (2016). https://doi.org/10.1007/s10620-015-3870-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3870-y

Keywords

Search

Navigation