|
1
|
Pelusio C, Endres P, Neyra JA, Allegretti AS. Renal Replacement Therapy in Cirrhosis: A Contemporary Review. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:133-138. [PMID: 38649217 PMCID: PMC11103613 DOI: 10.1053/j.akdh.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 12/20/2023] [Accepted: 01/02/2024] [Indexed: 04/25/2024]
Abstract
Acute kidney injury is a common complication of decompensated cirrhosis, frequently requires hospitalization, and carries a high short-term mortality. This population experiences several characteristic types of acute kidney injury: hypovolemic-mediated (prerenal), ischemic/nephrotoxic-mediated (acute-tubular necrosis), and hepatorenal syndrome. Prerenal acute kidney injury is treated with volume resuscitation. Acute-tubular necrosis is treated by optimizing perfusion pressure and discontinuing the offending agent. Hepatorenal syndrome, a unique physiology of decreased effective arterial circulation leading to renal vasoconstriction and ultimately acute kidney injury, is treated with plasma expansion with albumin and splanchnic vasoconstrictors such as terlipressin or norepinephrine. Common acute stressors such as bleeding, infection, and volume depletion often contribute to multifactorial acute kidney injury. Even with optimal medical management, many clinicians are faced with the challenge of initiating renal replacement therapy in these patients. This article reviews the epidemiology, indications, and complex considerations of renal replacement therapy for acute kidney injury in decompensated cirrhosis.
Collapse
Affiliation(s)
- Caterina Pelusio
- Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Florence, Italy; Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Paul Endres
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
| | - Javier A Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
| |
Collapse
|
|
2
|
Allegretti AS, Patidar KR, Ma AT, Cullaro G. From past to present to future: Terlipressin and hepatorenal syndrome-acute kidney injury. Hepatology 2024:01515467-990000000-00741. [PMID: 38353565 PMCID: PMC11322426 DOI: 10.1097/hep.0000000000000790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/11/2023] [Indexed: 03/01/2024]
Abstract
Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive "cure" for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.
Collapse
Affiliation(s)
- Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Kavish R. Patidar
- Section of Gastroenterology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, USA
| | - Ann T. Ma
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Giuseppe Cullaro
- Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco CA, USA
| |
Collapse
|
|
3
|
Arnold J, Avila E, Idalsoaga F, Diaz LA, Ayala Valverde M, Ayares G, Arrese M, Roessler E, Huidobro JP, Hudson D, Khan MQ, Arab JP. Advances in the diagnosis and management of hepatorenal syndrome: insights into HRS-AKI and liver transplantation. EGASTROENTEROLOGY 2023; 1:e100009. [PMID: 39943997 PMCID: PMC11770447 DOI: 10.1136/egastro-2023-100009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/27/2023] [Indexed: 01/04/2025]
Abstract
In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI-liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.
Collapse
Affiliation(s)
- Jorge Arnold
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Avila
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Gustavo Ayares
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eric Roessler
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Huidobro
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - David Hudson
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Mohammad Qasim Khan
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| |
Collapse
|
|
4
|
Buccheri S, Da BL. Hepatorenal Syndrome: Definitions, Diagnosis, and Management. Clin Liver Dis 2022; 26:181-201. [PMID: 35487604 DOI: 10.1016/j.cld.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatorenal syndrome (HRS) is a hemodynamically driven process mediated by renal dysregulation and inflammatory response. Albumin, antibiotics, and β-blockers are among therapies that have been studied in HRS prevention. There are no Food and Drug Administration-approved treatments for HRS although multiple liver societies have recommended terlipressin as first-line pharmacotherapy. Renal replacement therapy is the primary modality used to bridge to definitive therapy with orthotopic liver transplant or simultaneous liver-kidney transplant. Advances in our understanding of HRS pathophysiology and emerging therapeutic modalities are needed to change outcomes for this vulnerable population.
Collapse
Affiliation(s)
- Sebastiano Buccheri
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA
| | - Ben L Da
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
| |
Collapse
|
|
5
|
Bruno R, Cammà C, Caraceni P, D'Amico G, Grattagliano I, La Mura V, Riggio O, Schepis F, Senzolo M, Angeli P, de Franchis R. Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF). Dig Liver Dis 2021; 53:1089-1104. [PMID: 34321192 DOI: 10.1016/j.dld.2021.06.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/30/2021] [Accepted: 06/20/2021] [Indexed: 02/06/2023]
Abstract
Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to national regulations and resources, local circumstances and settings, infrastructure, and cost/benefit strategies to avoid duplication of efforts and optimize resource utilization. The committee defined the objectives, the key issues and retrieved the relevant evidence by performing a systematic review of the literature. Finally, the committee members (chosen on the basis of their specific expertise) identified the guidelines' key questions and developed them following the PICO format (Population, Intervention, Comparison, Outcomes). For each of the PICO questions, the systematic review of the literature was made on the most important scientific databases (Pubmed, Scopus, Embase).
Collapse
|
|
6
|
Gupta K, Bhurwal A, Law C, Ventre S, Minacapelli CD, Kabaria S, Li Y, Tait C, Catalano C, Rustgi VK. Acute kidney injury and hepatorenal syndrome in cirrhosis. World J Gastroenterol 2021; 27:3984-4003. [PMID: 34326609 PMCID: PMC8311533 DOI: 10.3748/wjg.v27.i26.3984] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/19/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. AKI is separated into two categories, non-HRS AKI and HRS-AKI. The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease. The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation. The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients; novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models. The overall management of non-HRS AKI and HRS-AKI requires a systematic approach. Although pharmacological treatments have shown mortality benefit, the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. This article reviews the current guidelines and recommendations of AKI in cirrhosis.
Collapse
Affiliation(s)
- Kapil Gupta
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Abhishek Bhurwal
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Cindy Law
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Scott Ventre
- Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Carlos D Minacapelli
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Savan Kabaria
- Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - You Li
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Christopher Tait
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Carolyn Catalano
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Vinod K Rustgi
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| |
Collapse
|
|
7
|
McAllister S, Lai JC, Copeland TP, Johansen KL, McCulloch CE, Kwong YD, Seth D, Grimes B, Ku E. Renal Recovery and Mortality Risk among Patients with Hepatorenal Syndrome Receiving Chronic Maintenance Dialysis. KIDNEY360 2021; 2:819-827. [PMID: 35373067 PMCID: PMC8791353 DOI: 10.34067/kid.0005182020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 02/26/2021] [Indexed: 02/04/2023]
Abstract
Background Kidney replacement therapy is controversial for patients with hepatorenal syndrome who may not be liver transplant candidates. Data surrounding the likelihood of recovery of kidney function and mortality after outpatient dialysis initiation in patients with dialysis-requiring hepatorenal syndrome could inform discussions between patients and providers. Methods We performed a retrospective cohort study of patients with hepatorenal syndrome who were registered in the United States Renal Data System between 1996 and 2015 (n=7830) as receiving maintenance dialysis. We characterized patients with hepatorenal syndrome by recovery of kidney function using Fine and Gray models. We also examined hazard of recovery of kidney function and death among those with hepatorenal syndrome versus those with acute tubular necrosis (n=48,861) using adjusted Fine-Gray and Cox models, respectively. Results Of the patients with hepatorenal syndrome, 11% recovered kidney function. Those with higher likelihood of recovery were younger, non-Hispanic White, and had a history of alcohol use. Compared with patients with acute tubular necrosis, patients with hepatorenal syndrome as the attributed cause of kidney disease had a lower hazard of recovery (HR, 0.22; 95% CI, 0.21 to 0.24) and higher hazard of death within 1 year (HR, 3.10; 95% CI, 2.99 to 3.23) in fully adjusted models. Conclusions Patients with hepatorenal syndrome receiving chronic maintenance dialysis had a lower likelihood of recovery of kidney function and higher mortality risk compared with patients with acute tubular necrosis. Among patients with hepatorenal syndrome, those most likely to recover kidney function were younger, had a history of alcohol use, and lacked comorbid conditions. These data may inform prognosis and discussions surrounding treatment options when patients with hepatorenal syndrome need chronic maintenance dialysis therapy.
Collapse
Affiliation(s)
- Sophie McAllister
- School of Medicine, University of California San Francisco, San Francisco, California
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California
| | - Timothy P. Copeland
- Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California
| | - Kirsten L. Johansen
- Division of Nephrology, Department of Medicine, Hennepin Healthcare and University of Minnesota, Minneapolis, Minnesota
| | - Charles E. McCulloch
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California
| | - Yuenting D. Kwong
- Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California
| | - Divya Seth
- Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California
- Division of Pediatric Nephrology, Department of Pediatrics, University of California San Francisco, San Francisco, California
| | - Barbara Grimes
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California
| | - Elaine Ku
- Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California
- Division of Pediatric Nephrology, Department of Pediatrics, University of California San Francisco, San Francisco, California
| |
Collapse
|
|
8
|
Luedemann C, Plota J, Nattermann J, Strassburg CP, Lutz P, Goeser F. Renal replacement therapy as bridging-to-recovery in refractory hepatorenal syndrome. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:331-335. [PMID: 33634437 DOI: 10.1055/a-1369-9859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
A 50-year-old female patient with cirrhosis due to alcoholic steatohepatitis was referred to our department because of recurrent hepatorenal syndrome (HRS) and hepatic hydrothorax. Clinically, severe anasarca was the leading problem. In contrast to previous episodes, HRS did not respond to standard treatment including terlipressin.Given the severe, refractory hyperhydration, we finally initiated renal replacement therapy (RRT). Subsequently, RRT was performed without severe side effects for more than 100 days. In the meantime, liver function remarkably improved, most probably due to the prolonged abstinence from alcohol. Finally, RRT could be stopped. Since then, our patient has remained in good clinical condition for more than 6 months, with well-compensated Child-Pugh stage A cirrhosis and only mild chronic kidney disease stage III.In conclusion, this case highlights that RRT may be considered in individual cases as bridging therapy in refractory HRS until the liver regenerates due to the absence of damaging mechanisms.
Collapse
Affiliation(s)
- Christoph Luedemann
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany
| | - Jessica Plota
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany
| | - Philipp Lutz
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany
| | - Felix Goeser
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany
| |
Collapse
|
|
9
|
Allegretti AS. Acute Kidney Injury Treatment in Decompensated Cirrhosis: A Focus on Kidney Replacement Therapy. Kidney Med 2021; 3:12-14. [PMID: 33604536 PMCID: PMC7873819 DOI: 10.1016/j.xkme.2020.09.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| |
Collapse
|
|
10
|
Velez JCQ. Patients with Hepatorenal Syndrome Should Be Dialyzed? PRO. KIDNEY360 2020; 2:406-409. [PMID: 35369012 PMCID: PMC8785999 DOI: 10.34067/kid.0006952020] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 12/07/2020] [Indexed: 02/04/2023]
|
|
11
|
Tariq R, Singal AK. Management of Hepatorenal Syndrome: A Review. J Clin Transl Hepatol 2020; 8:192-199. [PMID: 32832400 PMCID: PMC7438356 DOI: 10.14218/jcth.2020.00011] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 04/23/2020] [Accepted: 05/08/2020] [Indexed: 12/11/2022] Open
Abstract
Acute kidney injury (AKI) occurs frequently in patients with cirrhosis, and hepatorenal syndrome (HRS) is second most common etiology of AKI after volume responsible pre-renal etiology. AKI in these patients negatively impacts pre- and post-transplant patient survival and healthcare burden. Reduced effective blood volume with consequent reduced renal blood flow, along with systemic inflammation in patients with decompensated cirrhosis, result in susceptibility to HRS. In this article, we will review updates over the last 5 years on the changing definition with diagnostic criteria and nomenclature of AKI and HRS, data on medical treatment with vasoconstrictors, and urinary biomarkers in diagnosis of etiology of AKI. We will also discuss the significance of liver transplantation evaluation once the diagnosis of HRS is established and the post-transplant immunosuppression management. We will also review one of the challenging issues that remains among transplant-eligible patients, that of allocation of simultaneous liver kidney transplant. Finally, we will review the new implemented policy from the Organ Procurement Transplant Network on simultaneous liver kidney allocation.
Collapse
Affiliation(s)
- Raseen Tariq
- Department of Medicine, Rochester General Hospital, Rochester, NY, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Sanford School of Medicine, Sioux Falls, SD, USA
- Correspondence to: Ashwani K. Singal, Division of Gastroenterology and Hepatology, University of South Dakota, Sanford School of Medicine, Transplant Hepatologist and Chief Clinical Research Program, Avera Transplant and Research Institutes, Sioux Falls, SD 57105, USA. Tel: +1-605-322-8545, Fax: +1-605-322-8536, E-mail:
| |
Collapse
|
|
12
|
Abstract
PURPOSE OF REVIEW Acute kidney injury (AKI) in cirrhosis consists of varying phenotypes, with hepatorenal syndrome (HRS) representing a single entity. Prompt recognition and diagnosis of AKI cause identifies appropriate therapeutic measures. This review provides an overview of AKI definitions, highlights challenges in quantifying renal impairment in cirrhosis, lists novel diagnostic AKI biomarkers, and summarizes transplantation implications. RECENT FINDINGS Biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, and liver-type fatty acid-binding protein) may assist in the identification of underlying acute tubular necrosis. Of these, neutrophil gelatinase-associated lipocalin is the most promising; however, significant overlap occurs among AKI phenotypes, with diagnostic values yet to be defined. Mainstay treatment of HRS consists of albumin and vasopressors. Acute-on-chronic liver failure grade independently predicts response to terlipressin treatment. Many end-stage liver disease patients with AKI have underlying chronic kidney disease with important implications on pre and postliver transplantation mortality. Simultaneous liver-kidney transplant candidacy is based on low likelihood of renal recovery. SUMMARY Novel biomarkers may assist in identification of acute tubular necrosis and persistent/severe AKI. Norepinephrine has been suggested to be inferior to terlipressin, with additional research required. Increasing acute-on-chronic liver failure grade correlates with lower likelihood of vasopressor response in HRS. Severe preliver transplantation AKI confers significantly worse postliver transplantation renal outcomes.
Collapse
|
|
13
|
MacDonald AJ, Karvellas CJ. Acute kidney injury: A critical care perspective for orthotopic liver transplantation. Best Pract Res Clin Anaesthesiol 2019; 34:69-78. [PMID: 32334788 DOI: 10.1016/j.bpa.2019.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 12/11/2019] [Indexed: 02/06/2023]
Abstract
Acute kidney injury (AKI) is associated with high perioperative mortality in patients undergoing liver transplantation (LT). In the era of Model of End-stage Liver Disease score-based allocation, more patients with impaired renal function are receiving LT. The majority of preoperative AKI is secondary to azotemia, including hepatorenal syndrome - a progressive form of renal impairment unique to liver failure. Prompt recognition and initiation of cause-directed therapies are central to improving post-transplant survival. Given that, the healthcare providers must develop an expertise in liver failure-related renal complications, specifically their management and perioperative implications. Notably, AKI may complicate intraoperative course, exacerbating hemodynamic instability, metabolic acidosis, and electrolyte and coagulation abnormalities. Adjunctive intraoperative continuous renal replacement therapy has been employed; however, prospective studies remain necessary to validate potential benefits.
Collapse
Affiliation(s)
| | - Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada; Department of Critical Care Medicine, University of Alberta, Edmonton, Canada.
| |
Collapse
|
|
14
|
Facciorusso A. Hepatorenal Syndrome Type 1: Current Challenges And Future Prospects. Ther Clin Risk Manag 2019; 15:1383-1391. [PMID: 31819465 PMCID: PMC6886557 DOI: 10.2147/tcrm.s205328] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 11/05/2019] [Indexed: 12/13/2022] Open
Abstract
Renal dysfunction represents a dreadful complication of advanced liver cirrhosis. In addition to the traditional types of acute kidney injury (AKI) that can occur in the general population, cirrhotics might experience a different kind of renal dysfunction, called hepatorenal syndrome (HRS). The exact definition of HRS is a functional renal dysfunction caused by overactivity of the endogenous vasoactive systems (in particular intrarenal circulation) which lead to reduced renal perfusion. Type I HRS (HRS-1) is characterized by an abrupt deterioration in renal function (in less than 2 weeks), defined by a doubling of baseline sCr to >2.5 mg/dL or a 50% reduction in the initial 24 hrs creatinine clearance to <20 mL/min. Frequent precipitating events leading to HRS-1 are bacterial infections, gastrointestinal hemorrhage, or large-volume paracentesis without adequate albumin administration as well as massive diuretic use. In 2015, the international club of ascites (ICA) revised the definitions and recommendations concerning HRS. The revised definition allows to adopt effective pharmacological therapy based on albumin and vasoconstrictors in an earlier stage thus not influenced anymore by a rigid sCr cut-off value as by the previous definition of HRS-1. The aim of this article was to provide an updated overview of the latest advancements in the field of hepatorenal syndrome and of the recent amendments of the previous definitions of kidney injury in cirrhotic patients.
Collapse
|
|
15
|
Velez JCQ, Therapondos G, Juncos LA. Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis. Nat Rev Nephrol 2019; 16:137-155. [PMID: 31723234 DOI: 10.1038/s41581-019-0218-4] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/25/2019] [Indexed: 12/12/2022]
Abstract
The occurrence of acute kidney injury (AKI) in patients with end-stage liver disease constitutes one of the most challenging clinical scenarios in in-hospital and critical care medicine. Hepatorenal syndrome type 1 (HRS-1), which is a specific type of AKI that occurs in the context of advanced cirrhosis and portal hypertension, is associated with particularly high mortality. The pathogenesis of HRS-1 is largely viewed as a functional derangement that ultimately affects renal vasculature tone. However, new insights suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms, including those traditionally associated with HRS-1 and non-traditional factors, might contribute to the development of AKI in patients with cirrhosis. Moreover, histological evidence of morphological abnormalities in the kidneys of patients with cirrhosis and renal dysfunction has prompted the functional nature of HRS-1 to be re-examined. From a clinical perspective, a diagnosis of HRS-1 guides utilization of vasoconstrictive therapy and decisions regarding renal replacement therapy. Patients with cirrhosis are at risk of AKI owing to a wide range of factors. However, the tools currently available to ascertain the diagnosis of HRS-1 and guide therapy are suboptimal. Short of liver transplantation, goal-directed haemodynamically targeted pharmacotherapy remains the cornerstone of treatment for this condition; improved understanding of the underlying pathogenic mechanisms might lead to better clinical outcomes. Here, we examine our current understanding of the pathophysiology of HRS-1 and existing challenges in its diagnosis and treatment.
Collapse
Affiliation(s)
- Juan Carlos Q Velez
- Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA, USA. .,Ochsner Clinical School, The University of Queensland, Brisbane, Australia.
| | - George Therapondos
- Department of Gastroenterology and Hepatology, Ochsner Clinic Foundation, New Orleans, LA, USA
| | - Luis A Juncos
- Division of Nephrology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.,Renal Section, Department of Medicine, Central Arkansas Veterans Affairs Medical Center, Little Rock, AR, USA
| |
Collapse
|
|
16
|
Niewinski G, Raszeja-Wyszomirska J, Hrenczuk M, Rozga A, Malkowski P, Rozga J. Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury. Artif Organs 2019; 44:91-99. [PMID: 31267563 DOI: 10.1111/aor.13532] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/13/2019] [Accepted: 06/25/2019] [Indexed: 12/14/2022]
Abstract
Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3 ± 1.4]. The baseline MELD-Na score was 37.6 ± 6.6 and decreased to 33.4 ± 8.7 after SPAD/CVVHD (P < 0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P = 0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n = 11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.
Collapse
Affiliation(s)
- Grzegorz Niewinski
- 2nd Department of Anesthesiology and Intensive Medical Care, Central Independent Public Clinical Hospital, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marta Hrenczuk
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Agata Rozga
- School of Interactive Computing, Georgia Institute of Technology, Atlanta, Georgia
| | - Piotr Malkowski
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Jacek Rozga
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| |
Collapse
|
|
17
|
Chmielewski J, Lewandowski RJ, Maddur H. Hepatorenal Syndrome: Physiology, Diagnosis and Management. Semin Intervent Radiol 2018; 35:194-197. [PMID: 30087522 DOI: 10.1055/s-0038-1660797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Individuals with end-stage liver disease are susceptible to a myriad of highly morbid complications, including hepatorenal syndrome (HRS). This specific type of renal dysfunction in patients with underlying liver disease occurs in pathophysiologically normal kidneys and is a result of renal vasoconstriction secondary to diminished renal blood flow in the setting of worsening hepatic dysfunction. Liver transplantation is curative; shortage of available organs limits access to this beneficial therapy. Medical management of HRS has demonstrated increasing promise. Transjugular intrahepatic portosystemic shunt creation has also been shown to be efficacious in enhancing transplant-free survival, although further study is advisable before widespread implementation of this strategy.
Collapse
Affiliation(s)
| | - Robert J Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois.,Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.,Department of Surgery, Northwestern University, Chicago, Illinois
| | - Haripriya Maddur
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, Illinois
| |
Collapse
|
|
18
|
Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1780] [Impact Index Per Article: 254.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
|
|
19
|
Mindikoglu AL, Pappas SC. New Developments in Hepatorenal Syndrome. Clin Gastroenterol Hepatol 2018; 16:162-177.e1. [PMID: 28602971 PMCID: PMC5831376 DOI: 10.1016/j.cgh.2017.05.041] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/26/2017] [Accepted: 05/28/2017] [Indexed: 02/07/2023]
Abstract
Hepatorenal syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis, leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain because of the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal dysfunction. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to estimate measured GFR more accurately. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr that regard HRS type 1 as a special form of acute kidney injury promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from prerenal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction, although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown, but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is rooted firmly in the setting of progressive reduction in renal blood flow as a result of portal hypertension and splanchnic vasodilation. Progressive marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide production, both increased and decreased, may play a major role in the pathophysiology of this evolution. The inflammatory cascade, triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestation of acute-on-chronic liver failure, also may play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve renal blood flow. Several meta-analyses have confirmed the value of vasopressors, chiefly terlipressin and noradrenaline, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation has increased dramatically in the Model for End-stage Liver Disease era, with changes in organ allocation policies. This has resulted in a more urgent need to predict native kidney recovery from HRS after liver transplantation alone, to avoid unnecessary simultaneous liver-kidney transplantation.
Collapse
Affiliation(s)
- Ayse L. Mindikoglu
- Baylor College of Medicine, Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation,Baylor College of Medicine, Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology
| | - Stephen C. Pappas
- Baylor College of Medicine, Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology
| |
Collapse
|
|
20
|
Allegretti AS, Parada XV, Eneanya ND, Gilligan H, Xu D, Zhao S, Dienstag JL, Chung RT, Thadhani RI. Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT. Clin J Am Soc Nephrol 2018; 13:16-25. [PMID: 29122911 PMCID: PMC5753306 DOI: 10.2215/cjn.03610417] [Citation(s) in RCA: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 10/04/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES Literature on the prognosis of patients with cirrhosis who require RRT for AKI is sparse and is confounded by liver transplant eligibility. An update on outcomes in the nonlisted subgroup is needed. Our objective was to compare outcomes in this group between those diagnosed with hepatorenal syndrome and acute tubular necrosis, stratifying by liver transplant listing status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Retrospective cohort study of patients with cirrhosis acutely initiated on hemodialysis or continuous RRT at five hospitals, including one liver transplant center. Multivariable regression and survival analysis were performed. RESULTS Four hundred seventy-two subjects were analyzed (341 not listed and 131 listed for liver transplant). Among nonlisted subjects, 15% (51 of 341) were alive at 6 months after initiating RRT. Median survival was 21 (interquartile range [IQR], 8, 70) days for those diagnosed with hepatorenal syndrome and 12 (IQR, 3, 43) days for those diagnosed with acute tubular necrosis (P=0.25). Among listed subjects, 48% (63 of 131) received a liver transplant. Median transplant-free survival was 15 (IQR, 5, 37) days for those diagnosed with hepatorenal syndrome and 14 (IQR, 4, 31) days for those diagnosed with acute tubular necrosis (P=0.60). When stratified by transplant listing, with adjusted Cox models we did not detect a difference in the risk of death between hepatorenal syndrome and acute tubular necrosis (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.59 to 1.11, among those not listed; HR, 0.73; 95% CI, 0.44 to 1.19, among those listed). CONCLUSIONS Cause of AKI was not significantly associated with mortality in patients with cirrhosis who required RRT. Among those not listed for liver transplant, mortality rates were extremely high in patients both with hepatorenal syndrome and acute tubular necrosis. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_09_CJASNPodcast_18_1_A.mp3.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Jules L. Dienstag
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Raymond T. Chung
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | | |
Collapse
|
|
21
|
Olson JC, Karvellas CJ. Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit. Liver Transpl 2017; 23:1465-1476. [PMID: 28688155 DOI: 10.1002/lt.24815] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 06/28/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023]
Abstract
Patients with cirrhosis who are awaiting liver transplantation (LT) are at high risk for developing critical illnesses. Current liver allocation policies that dictate a "sickest first" approach coupled with a mismatch between need and availability of organs result in longer wait times, and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well-compensated cirrhosis may suffer acute deterioration; the syndrome of acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction and a marked increase in associated short-term morbidity and mortality. For patients on transplant waiting lists, the development of multisystem organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (eg, infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo LT. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and to describe our approach management in critically ill patients awaiting LT in our centers. Liver Transplantation 23 1465-1476 2017 AASLD.
Collapse
Affiliation(s)
- Jody C Olson
- Divisions of Critical Care Medicine and Hepatology, University of Kansas Medical Center, Kansas City, KS
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.,Division of Division of Gastroenterology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
22
|
Abstract
Acute kidney injury (AKI) is common in patients with cirrhosis and ascites on the waiting list for liver transplant. Hepatorenal syndrome (HRS) is an important cause of AKI among cirrhotics. A dynamic definition of AKI in patients with cirrhosis has been introduced and changed the diagnosis criteria. Liver transplantation remains the better option but the medical management of HRS has changed. Terlipressin plus albumin is currently the gold standard. Surgery and liver or kidney support systems have been recommended. Clinical trials will assess the most appropriate approach for the treatment of HRS in light of the revised diagnostic criteria.
Collapse
Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy.
| | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| |
Collapse
|
|
23
|
Hung TH, Lay CJ, Tseng CW, Tsai CC, Tsai CC. The Effect of Renal Function Impairment on the Mortality of Cirrhotic Patients: A Nationwide Population-Based 3-Year Follow-up Study. PLoS One 2016; 11:e0162987. [PMID: 27631098 PMCID: PMC5025109 DOI: 10.1371/journal.pone.0162987] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 08/03/2016] [Indexed: 12/21/2022] Open
Abstract
Renal function impairment (RFI) contributes to poor prognosis in cirrhotic patients. However, there have been no studies that seek to identify the effect of different types of RFI on the mortality of cirrhotic patients. We used the National Health Insurance Database, derived from the Taiwan National Health Insurance Program, to identify 44365 cirrhotic patients between January 1, 2007 and December 31, 2007. RFI was identified in 2832 cirrhotic patients, including 1075 with acute renal failure (ARF) (169 with hepatorenal syndrome, HRS; 906 with non-hepatorenal syndrome, NHRS), 705 with chronic kidney disease (CKD), and 1052 with end stage renal disease (ESRD). After Cox proportional hazard regression analysis adjusted by gender, age, and comorbid disorders, the 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortality hazard ratios (HR) compared to the non-RFI group were: (ARF) 5.19 (4.70-5.74), 3.23 (2.76-3.77), 1.51 (1.26-1.81), and 1.35 (1.13-1.61), respectively; (CKD) 2.70 (2.30-3.18), 2.03 (1.66-2.49), 1.60 (1.34-1.90), and 1.26 (1.06-1.49), respectively; and (ESRD) 1.42 (1.17-1.72), 1.62 (1.35-1.94), 1.90 (1.68-2.15), and 1.67 (1.48-1.89), respectively. Compared to NHRS, the 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortality HRs of HRS were 1.03 (0.80-1.32), 2.13 (1.46-3.11), 1.58 (0.90-2.75), and 2.51 (1.41-4.48), respectively, in cirrhotic patients with ARF. These results indicate the effects of CKD and ESRD on the mortality of cirrhotic patients are distributed equally in every survival stage, whereas the effect of ARF appears only in the early stage. Compared to NHRS, HRS contributes to a higher mortality risk at the late survival stage.
Collapse
Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chorng-Jang Lay
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Infectious diseases, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chih-Wei Tseng
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Chun Tsai
- Department of Mathematics, Tamkang University, Tamsui, Taiwan
| | - Chen-Chi Tsai
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Infectious diseases, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- * E-mail:
| |
Collapse
|
|
24
|
Arab JP, Claro JC, Arancibia JP, Contreras J, Gómez F, Muñoz C, Nazal L, Roessler E, Wolff R, Arrese M, Benítez C. Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus. World J Hepatol 2016; 8:1075-1086. [PMID: 27660674 PMCID: PMC5026999 DOI: 10.4254/wjh.v8.i25.1075] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 07/07/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.
METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded.
RESULTS Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described.
CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.
Collapse
|
|
25
|
Erly B, Carey WD, Kapoor B, McKinney JM, Tam M, Wang W. Hepatorenal Syndrome: A Review of Pathophysiology and Current Treatment Options. Semin Intervent Radiol 2015; 32:445-54. [PMID: 26622108 PMCID: PMC4640915 DOI: 10.1055/s-0035-1564794] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Brian Erly
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - William D. Carey
- Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio
| | - Baljendra Kapoor
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic, Cleveland, Ohio
| | | | - Mathew Tam
- Department of Radiology, Southend University Hospital, Essex, United Kingdom
| | - Weiping Wang
- Department of Radiology, Mayo Clinic, Jacksonville, Florida
| |
Collapse
|
|
26
|
Baraldi O, Valentini C, Donati G, Comai G, Cuna V, Capelli I, Angelini ML, Moretti MI, Angeletti A, Piscaglia F, Manna GL. Hepatorenal syndrome: Update on diagnosis and treatment. World J Nephrol 2015; 4:511-520. [PMID: 26558188 PMCID: PMC4635371 DOI: 10.5527/wjn.v4.i5.511] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 08/13/2015] [Accepted: 09/18/2015] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome (HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.
Collapse
|
|
27
|
|
|
28
|
|
|
29
|
Abstract
PURPOSE OF REVIEW Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. RECENT FINDINGS New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver-kidney transplantation is advised. SUMMARY Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes.
Collapse
Affiliation(s)
- Nathalie H. Urrunaga
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Ayse L. Mindikoglu
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Don C. Rockey
- Department of Internal Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| |
Collapse
|
|
30
|
Affiliation(s)
- Nadia K Bozanich
- Medicine, Indiana University School of Medicine, 975 West Walnut, IB 327, Indianapolis, IN 46202, USA
| | - Paul Y Kwo
- Medicine, Indiana University School of Medicine, 975 West Walnut, IB 327, Indianapolis, IN 46202, USA.
| |
Collapse
|
|
31
|
Belcher JM. Is There a Role for Dialysis in Patients with Hepatorenal Syndrome Who Are Not Liver Transplant Candidates? Semin Dial 2014; 27:288-91. [DOI: 10.1111/sdi.12224] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Justin M. Belcher
- Section of Nephrology; Yale University School of Medicine; New Haven Connecticut
| |
Collapse
|
|
32
|
Abstract
Hepatorenal syndrome is a severe complication of end-stage liver disease. The pathophysiological hallmark is severe renal vasoconstriction, resulting from peripheral and splanchnic vasodilation as well as activation of renal vasoconstrictor molecules, which induce the effective arterial volume reduction and the functional renal failure. The diagnosis of hepatorenal syndrome is currently based on the exclusion of other causes of renal failure (especially prerenal). Spontaneous bacterial peritonitis is one of the triggering factors and should be sought in all patients with severe liver disease and acute renal failure. Quickly treating patients with parental antibiotics and albumin infusion significantly decreases the risk. The combined use of intravenous albumin, splanchnic and peripheral vasoconstrictor and/or renal replacement therapy sometimes enables a delay until liver transplantation (or combined liver-kidney in selected patients). Transplantation is in fact the only way to improve the long-term prognosis.
Collapse
Affiliation(s)
- Evangéline Pillebout
- Service de néphrologie, hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France.
| |
Collapse
|
|
33
|
Fabrizi F, Aghemo A, Messa P. Hepatorenal syndrome and novel advances in its management. Kidney Blood Press Res 2013; 37:588-601. [PMID: 24356549 DOI: 10.1159/000355739] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/30/2013] [Indexed: 12/30/2022] Open
Abstract
Hepatorenal syndrome is a complication of end stage liver disease. It is a unique form of functional renal failure related to kidney vasoconstriction in the absence of underlying kidney pathology. Hepatorenal syndrome is classified into 2 types: type-1 HRS shows a rapid and progressive decline in renal function with a very poor prognosis (median survival of about 2 weeks); type-2 HRS has a more stable kidney failure, with a median survival of 6 months; its main clinical manifestation is refractory ascites. The most appropriate therapy for HRS is liver transplantation but only a minority of HRS patients undergo the procedure due to the high mortality; survival among liver transplant recipients is lower in HRS than among their counterparts without HRS. A large body of evidence, based on observational studies and randomized controlled trials, has been accumulated in the last decade showing that terlipressin represents a milestone in the management of HRS. According to our meta-analysis of randomized trials comparing terlipressin vs. placebo (five trials, n=243 patients), the pooled rate of patients who reversed HRS by terlipressin was 8.09 (95% CI, 3.52; 18.59) (P<0.001). Among vasoconstrictors, terlipressin (a V1 vasopressin agonist) is the most widely used; however, noradrenaline is another good choice. Vasoconstrictor drugs alone or with albumin reduce mortality compared with no intervention or albumin (RR of mortality, 0.82; 95% Confidence Intervals, 0.70; 0.96) (P<0.01). Two series of patients with HRS recurrence after the first treatment have recently shown that long-term therapy with terlipressin and albumin is beneficial as a bridge to liver transplant. Nevertheless, recovery of renal function can be achieved in less than 50% of patients with HRS after terlipressin use and the recovery of renal function may also be partial in patients who are defined full responders. Renal replacement therapy should not be considered a first-line therapy for HRS Clinical trials are under way in order to assess efficacy and safety of novel therapeutic agents for the treatment of type-1 and type-2 HRS.
Collapse
Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | | | | |
Collapse
|
|
34
|
Collins P, Ayres L, Valliani T. Drug therapies in liver disease. Clin Med (Lond) 2013; 13:585-91. [PMID: 24298107 PMCID: PMC5873662 DOI: 10.7861/clinmedicine.13-6-585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The likelihood of a general physician encountering a patient with compensated and decompensated liver disease is increasing. This article provides an overview of pharmaceutical agents currently used in the management of cirrhosis and is designed to allow a better understanding of the rationale for using certain drugs in patients with often complex pathology.
Collapse
Affiliation(s)
- Peter Collins
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | |
Collapse
|
|
35
|
Nayak SL, Maiwall R, Nandwani A, Ramanarayanan S, Mathur RP, Kumar R, Sarin SK, Vashishtha C. Management of acute kidney injury in cirrhosis. Hepatol Int 2013; 7:813-819. [PMID: 26201918 DOI: 10.1007/s12072-013-9456-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Accepted: 06/29/2013] [Indexed: 01/15/2023]
Abstract
Acute kidney injury (AKI) is a relatively frequent problem, occurring in approximately 20 % of hospitalized patients with cirrhosis. Although serum creatinine (S Cr) is the most commonly used method to determine AKI because of easy availability and low cost, practically it underestimates the extent of kidney injury in patients with chronic liver disease. AKI is defined as an abrupt rise in S Cr of 0.3 mg/dl or more (>26.4 mmol/l) or an increase of 150 % or more (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can be subdivided into either functional or structural. The functional group includes volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome). Volume responsive is the most common type of AKI due to frequent use of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding in patients with liver disease. The structural causes include acute tubular necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated cirrhosis are in a vasodilatory state leading to a decrease in effective arterial blood volume, predisposing to AKI. Therefore, management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause. The outcome in cirrhosis when patients are on dialysis is very dismal. Every effort should be made to prevent AKI.
Collapse
Affiliation(s)
- Suman Lata Nayak
- Department of Nephrology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi, 110070, India.
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Ashish Nandwani
- Department of Nephrology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi, 110070, India
| | | | - R P Mathur
- Department of Nephrology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi, 110070, India
| | - Ramesh Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - S K Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | | |
Collapse
|
|
36
|
Hepatorenal syndrome: are we missing some prognostic factors? Dig Dis Sci 2012; 57:210-4. [PMID: 21850494 DOI: 10.1007/s10620-011-1861-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Accepted: 08/03/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is the functional renal failure associated with advanced cirrhosis and has also been described in fulminant hepatic failure. Without liver transplantation its prognosis is dismal. Our study included patients with type 1 HRS associated with cirrhosis, who were not liver transplant candidates. AIM To identify variables associated with improved survival. METHODS Sixty-eight patients fulfilled the revised Ascites Club Criteria for type 1 HRS. None of them was suitable for liver transplantation. All the patients were treated with combinations of: albumin, midodrine and octreotide, pressors, and hemodialysis. RESULTS Median survival was 13 days for the whole group. Survival varied with the end-stage liver disease (ESLD) etiology: autoimmune, 49 days, cardiac cirrhosis, 22 days, idiopathic, 15.5 days, viral, 15 days, hepatitis C and alcohol, 14.5 days, alcohol 8 days, and neoplasia 4 days (p = 0.048). Survival of HRS associated with alcoholic liver disease versus other etiologies was not statistically significant (p = 0.1). Increased serum creatinine (p = 0.02) and urinary sodium 6-10 mEq/l (p = 0.027) at the initiation of therapy were prognostic factors for mortality. HRS treatment modalities (p = 0.73), use of dialysis (p = 0.56), dialysis modality (p = 0.35), use of vasopressors (p = 0.26), pre-existing renal disease (p = 0.49), gender (p = 0.90), and age (p = 0.57) were not associated with survival. CONCLUSIONS We report for the first time ESLD etiology as a prognostic factor for survival. The renal function (expressed as serum creatinine) and urinary Na (<5 mEq/l) at the time of diagnosis were found to be associated with survival, suggesting that early treatment might increase survival.
Collapse
|
|
37
|
El-Shabrawi MHF, Kamal NM. Medical management of chronic liver diseases (CLD) in children (part II): focus on the complications of CLD, and CLD that require special considerations. Paediatr Drugs 2011; 13:371-383. [PMID: 21999650 DOI: 10.2165/11591620-000000000-00000] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Treatment of the causes of many chronic liver diseases (CLDs) may not be possible. In this case, complications must be anticipated, prevented or at least controlled by the best available therapeutic modalities. There are three main goals for the management of portal hypertension: (i) prevention of the first episode of variceal bleeding largely by non-selective β-adrenoceptor antagonists, which is not generally recommended in children; (ii) control of bleeding by using a stepwise approach from the least to most invasive strategies; (iii) and prevention of re-bleeding using bypass operations, with particular enthusiasm for the use of meso-Rex bypass in the pediatric population. Hepatic encephalopathy management also consists of three main aspects: (i) ruling out other causes of encephalopathy; (ii) identifying and treating precipitating factors; and (iii) starting empiric treatment with drugs such as lactulose, rifaximin, sodium benzoate, and flumazenil. Treatment of mild ascites and peripheral edema should begin with the restriction of sodium and water, followed by careful diuresis, then large-volume paracentesis associated with colloid volume expansion in severe cases. Empiric broad spectrum antimicrobial therapy should be used for the treatment of spontaneous bacterial peritonitis, bacterial and fungal sepsis, and cholangitis, after taking appropriate cultures, with appropriate changes in therapy after sensitivity testing. Empirical therapies continue to be the standard practice for pruritus; these consist of bile acid binding agents, phenobarbital (phenobarbitone), ursodeoxycholic acid, antihistamines, rifampin (rifampicin), and carbamazepine. Partial external biliary diversion can be used in refractory cases. Once hepatorenal syndrome is suspected, treatment should be initiated early in order to prevent the progression of renal failure; approaches consist of general supportive measures, management of concomitant complications, screening for sepsis, treatment with antibiotics, use of vasopressin analogs (terlipressin), and renal replacement therapy if needed. Hepatopulmonary syndrome and portopulmonary hypertension are best managed by liver transplantation. Provision of an adequate caloric supply, nutrition, and vitamin/mineral supplements for the management of growth failure, required vaccinations, and special care for ensuring psychologic well-being should be ensured. Anticoagulation might be attempted in acute portal vein thrombosis. Some CLDs, such as extrahepatic biliary atresia (EHBA), Crigler-Najjar syndrome, and Indian childhood cirrhosis, require special considerations. For EHBA, Kasai hepatoportoenterostomy is the current standard surgical approach in combination with nutritional therapy and supplemental fat and water soluble vitamins, minerals, and trace elements. In type 1 Crigler-Najjar syndrome, extensive phototherapy is the mainstay of treatment, in association with adjuvant therapy to bind photobilirubin such as calcium phosphate, cholestyramine, or agar, until liver transplantation can be carried out. Treating Indian childhood cirrhosis with penicillamine early in the course of the disease and at doses similar to those used to treat Wilson disease decreases the mortality rate by half. New hopes for the future include extracorporeal liver support devices (the molecular adsorbent recirculating system [MARS®] and Prometheus®), hepatocyte transplantation, liver-directed gene therapy, genetically engineered enzymes, and therapeutic modalities targeting fibrogenesis. Hepapoietin, a naturally occurring cytokine that promotes hepatocyte growth, is under extensive research.
Collapse
|
|
38
|
Abstract
Care of the liver transplant candidate is one of the most challenging, yet rewarding aspects of hepatology. Anticipation and intervention for the major complications of advanced liver disease increase the likelihood of survival until transplant.
Collapse
Affiliation(s)
- Hui-Hui Tan
- Department of Gastroenterology & Hepatology, Singapore General Hospital.
| | | |
Collapse
|
|
39
|
Abstract
Hepatorenal syndrome (HRS) is a functional form of acute kidney injury (AKI) associated with advanced liver cirrhosis or fulminant hepatic failure. Various new concepts have emerged since the initial diagnostic criteria and definition of HRS was initially published. These include better understanding of the pathophysiological mechanisms involved in HRS, identification of bacterial infection (especially spontaneous bacterial peritonitis) as the most important HRS-precipitating event, recognition that insufficient cardiac output plays a role in the occurrence of HRS, and evidence that renal failure reverses with pharmacotherapy. Patients with HRS are often critically ill and, by definition, have multiorgan failure. The purpose of this review is to provide an update on novel advances in HRS, with emphasis on the different aspects of management of these patients in the intensive care unit.
Collapse
Affiliation(s)
- Hani M Wadei
- Department of Transplantation, College of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
| | | |
Collapse
|
|
40
|
Arroyo V, Fernández J. Management of hepatorenal syndrome in patients with cirrhosis. Nat Rev Nephrol 2011; 7:517-26. [DOI: 10.1038/nrneph.2011.96] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
|
|
41
|
Abstract
INTRODUCTION Renal failure in cirrhosis is a common complication that is associated with poor survival. A rapid diagnosis of the cause of renal failure is mandatory because it is associated with prognosis. AREAS COVERED This review covers the differential diagnosis between hepatorenal syndrome (HRS) and other causes of renal failure, as well as the difficulty in making a correct diagnosis, caused by the differentiation between hepatorenal syndrome and acute tubular necrosis. This review also discusses the multifactorial mechanisms involved in the pathogenesis of HRS. The paper provides diagnostic algorithms to use in clinical practice, emphasized by the fact that some patients may have HRS superimposed on pre-existent renal failure. EXPERT OPINION The correct diagnosis of renal failure is essential to initiate the correct treatment of this complication. In patients with HRS type 1, treatment with vasopressin and albumin is the treatment of choice; however, 50% of patients do not respond to this treatment.
Collapse
Affiliation(s)
- Mónica Guevara
- Hospital Clinic Barcelona, Liver Unit, IDIBAPS, CIBERHED, Barcelona, Spain.
| | | |
Collapse
|
|
42
|
Biecker E. Diagnosis and therapy of ascites in liver cirrhosis. World J Gastroenterol 2011; 17:1237-48. [PMID: 21455322 PMCID: PMC3068258 DOI: 10.3748/wjg.v17.i10.1237] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2010] [Revised: 12/22/2010] [Accepted: 12/29/2010] [Indexed: 02/06/2023] Open
Abstract
Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm3 and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.
Collapse
|
|
43
|
EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010; 53:397-417. [PMID: 20633946 DOI: 10.1016/j.jhep.2010.05.004] [Citation(s) in RCA: 1126] [Impact Index Per Article: 75.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2010] [Accepted: 05/25/2010] [Indexed: 02/07/2023]
|
|
44
|
Abstract
Hepatorenal syndrome (HRS) is a type of renal failure that occurs in patients with advanced cirrhosis. It is a result of splanchnic arterial vasodilation, renal vasoconstriction, reduced effective arterial volume, and potentially reduced cardiac output. Often, HRS is a fatal complication, and the only definitive treatment currently available is liver or liver-kidney transplantation. A number of other treatment modalities have been tested for the management of HRS, but most evidence is derived from small noncontrolled studies. The primary role of these treatment options is to provide a bridge to liver transplantation. Treatment may also provide acute reversal of renal failure and some symptomatic relief, but relapse is a common occurrence. The best therapeutic options appear to be those that reverse portal hypertension, splanchnic vasodilation, and/or renal vasoconstriction. Vasopressin analogs, particularly terlipressin, have emerged as the preferred pharmacologic therapies for management of HRS. Albumin is an appropriate adjunctive therapy to terlipressin and can be used to prevent HRS in patients with spontaneous bacterial peritonitis. Transjugular intrahepatic portosystemic shunt may provide a surgical option for qualified patients with HRS. Octreotide is ineffective as monotherapy but may be used as adjunctive therapy to other vasoactive agents. Dopamine agonists, endothelin antagonists, natriuretic peptides, and nitric oxide synthase inhibitors have not been effective for reversing HRS. Artificial hepatic support therapies have demonstrated the ability to improve laboratory abnormalities in patients with HRS, but their effect on clinical outcomes has not been determined. The role of renal replacement therapies or the newer artificial hepatic support therapies need further evaluation before they can be routinely recommended.
Collapse
Affiliation(s)
- Tyree H Kiser
- Department of Clinical Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80045, USA.
| | | | | |
Collapse
|
|
45
|
Degree of hepatic dysfunction and improvement of renal function predict survival in patients with HRS type I: a retrospective analysis. Eur J Gastroenterol Hepatol 2009; 21:1428-32. [PMID: 19794309 DOI: 10.1097/meg.0b013e32832ec16a] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is a frequent complication of end-stage liver cirrhosis. HRS type I has a very poor prognosis. From which of the more or less established therapies, such as use of vasoconstrictors together with albumin or placement of a Transjugular Intrahepatic Portosystemic Shunt patients might profit remains elusive. Therefore, it is important to define parameters that predict an improved outcome in respect to kidney function and survival. METHODS The clinical charts of 91 patients with cirrhosis and HRS type I were studied. The parameters associated with response to therapy, defined as a decrease in serum creatinine of more than 1.5 mg/dl on day 14 after diagnosis of HRS, and those associated with survival were assessed by multivariate analysis. RESULTS The median survival was 2.7 (1.5-3.8) months. Three independent predictive factors for survival were identified: Child-Pugh score (P = 0.05), Model of End-Stage Liver Disease (MELD) score less than 20 (P = 0.01), and response to therapy (P = 0.02). The Child-Pugh score (P = 0.00) and MELD score less than 20 (P = 0.02) were the parameters independently associated with the response to therapy, which occurred in 26% of the patients. CONCLUSION Our data of this large monocentric series with HRS type I confirm the poor prognosis in these patients, especially in those with high Child-Pugh and MELD scores, and in those in whom kidney function does not improve within 2 weeks.
Collapse
|
|
46
|
|
|
47
|
Affiliation(s)
- Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain
| | | |
Collapse
|
|
48
|
Wadei HM, Davis CL. Renal replacement therapy in the liver transplant candidate. Adv Chronic Kidney Dis 2009; 16:250-5. [PMID: 19576555 DOI: 10.1053/j.ackd.2009.05.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Since the implementation of the model of end-stage liver disease score to prioritize patients for orthotopic liver transplantation (OLT), the number of liver transplant candidates with renal failure and on renal replacement therapy (RRT) has dramatically increased. This review is intended to discuss the indications and implications of RRT initiation, the different RRT modalities, and special problems encountered with RRT in OLT candidates.
Collapse
|
|
49
|
|
|
50
|
Abstract
Hepatorenal syndrome (HRS) is a “functional” and reversible form of renal failure that occurs in patients with advanced chronic liver disease. The distinctive hallmark feature of HRS is the intense renal vasoconstriction caused by interactions between systemic and portal hemodynamics. This results in activation of vasoconstrictors and suppression of vasodilators in the renal circulation. Epidemiology, pathophysiology, as well as current and emerging therapies of HRS are discussed in this review.
Collapse
Affiliation(s)
- Sharon Turban
- Division of Nephrology, Johns Hopkins University, 1830 East Monument Street, Suite 416, Baltimore, Maryland 21205, USA
| | | | | |
Collapse
|