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Malakar S, Rungta S, Samanta A, Shamsul Hoda U, Mishra P, Pande G, Roy A, Giri S, Rai P, Mohindra S, Ghoshal UC. Understanding acute kidney injury in cirrhosis: Current perspective. World J Hepatol 2025; 17:104724. [DOI: 10.4254/wjh.v17.i5.104724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 03/13/2025] [Accepted: 04/15/2025] [Indexed: 05/27/2025] Open
Abstract
Acute kidney injury (AKI) is present in 30%-40% of hospitalized patients with cirrhosis. Its incidence is higher in patients with severe alcoholic hepatitis, spontaneous bacterial peritonitis, and acute-on-chronic-liver failure (ACLF). Kidney injury is an important landmark event in the natural history of cirrhosis as it is associated with higher mortality. Overwhelming systemic vasodilation, cardiac dysfunction, hypoperfusion, endotoxemia, and direct nephrotoxicity predispose patients with cirrhosis to kidney injury. Infection is present in 25% of patients with decompensated cirrhosis and 35%-40% of patients with ACLF. Advanced cirrhosis with portal hypertension leads to a sluggish portal flow, leading to increased gut congestion, altered gut permeability and bacterial translocations. They drive infection and endotoxemia in such patients. Pathogen-associated molecular patterns activate inflammatory cascades, which leads to further deterioration in hemodynamics and reduced glomerular filtration rate. Infections and pro-inflammatory cytokines like interleukin 6 (IL-6), IL-1, and tumor necrosis factor alpha may directly cause kidney parenchymal injury. The combined effect of dysfunctional albumin and systemic and splanchnic vasodilatation leads to low effective blood volume, activating the renin-angiotensin-aldosterone system. This causes renal vasoconstriction, water retention, and ascites, which progresses to hepatorenal physiology and AKI development. Vasoconstriction and volume expansion effectively improve arterial blood volume and systemic hemodynamics, thereby improving renal blood flow. It is of paramount importance to predict, detect, and treat AKI in its early state, as progressive renal dysfunction is invariably associated with higher mortality in patients with decompensated cirrhosis and ACLF. This comprehensive review will focus on the recent evolving concepts of the pathophysiology, diagnosis, and management of AKI in patients with cirrhosis.
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Affiliation(s)
- Sayan Malakar
- Department of Gastroenterology, King George's Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Sumit Rungta
- Department of Medical Gastroenterology, King George's Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Arghya Samanta
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Umair Shamsul Hoda
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Piyush Mishra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Gaurav Pande
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Akash Roy
- Department of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata 700054, West Bengal, India
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar 751024, Odisha, India
| | - Praveer Rai
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Ostermann M. Acute kidney injury in liver cirrhosis: a global challenge. Lancet Gastroenterol Hepatol 2025; 10:400-401. [PMID: 40058396 DOI: 10.1016/s2468-1253(25)00044-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/02/2025] [Accepted: 02/03/2025] [Indexed: 04/14/2025]
Affiliation(s)
- Marlies Ostermann
- Department of Intensive Care, King's College London, Guy's & St Thomas' Hospital, London SE1 7EH, UK.
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Song Y, Yang X, Yu C. Understanding and Treating Hepatorenal Syndrome: Insights from Recent Research. Semin Liver Dis 2025. [PMID: 40169136 DOI: 10.1055/a-2570-3330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/03/2025]
Abstract
Acute kidney injury (AKI) is a critical and often fatal complication in decompensated cirrhosis, significantly affecting inpatient survival rates. Hepatorenal syndrome (HRS), a distinct subtype of AKI, develops in individuals with advanced cirrhosis and portal hypertension. It is marked by progressive kidney dysfunction, poor prognosis, and frequently causes death before liver transplantation. The pathogenesis of HRS involves vasodilation of the splanchnic vessels, leading to overactivation of the endogenous vasoactive systems, circulatory dysfunction, and reduced renal perfusion, which ultimately impairs glomerular filtration. Recent studies have highlighted the role of systemic inflammation in exacerbating renal damage. Despite these changes, renal histology in HRS usually shows no significant abnormalities, and there is typically no hematuria, proteinuria, or abnormal findings on ultrasound. Common risk factors for HRS include spontaneous bacterial peritonitis, infections, and large-volume paracentesis without albumin infusion. Diagnosing HRS is challenging, particularly in distinguishing it from acute tubular necrosis, due to the absence of specific biomarkers. Treatment primarily involves vasoconstrictors such as terlipressin and albumin, with liver transplantation being the definitive therapeutic option. This review provides an updated understanding of HRS, addressing its pathophysiology, diagnosis, management, and future challenges, based on recent expert consensus.
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Affiliation(s)
- Yuli Song
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Xiaochen Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Chengbo Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
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Nadim MK, Kellum JA, Durand F. Reply to: "Inclusion of patients with active urinary sediment in treatment of hepatorenal syndrome". J Hepatol 2025:S0168-8278(25)00147-3. [PMID: 40024548 DOI: 10.1016/j.jhep.2025.02.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 02/23/2025] [Indexed: 03/04/2025]
Affiliation(s)
- Mitra K Nadim
- Division of Nephrology and Hypertension, Keck School of Medicine, University of South California, Los Angels, CA, USA
| | - John A Kellum
- Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA
| | - François Durand
- Hepatology & Liver Intensive Care, Beaujon Hospital, Clichy, France. University Paris Cité, Paris, France.
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Khemichian S, Nadim MK, Terrault NA. Update on Hepatorenal Syndrome: From Pathophysiology to Treatment. Annu Rev Med 2025; 76:373-387. [PMID: 39869432 DOI: 10.1146/annurev-med-050223-112947] [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: 01/29/2025]
Abstract
Hepatorenal syndrome-acute kidney injury (HRS-AKI) occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites. HRS-AKI is found in ∼20% of patients presenting to the hospital with AKI, but it may coexist with other causes of AKI and/or with preexisting chronic kidney disease, thereby making the diagnosis challenging. Novel biomarkers such as urinary neutrophil gelatinase-associated lipocalin may be useful. While HRS-AKI is a functional form of AKI related to circulatory and neurohormonal dysfunction, there is increasing recognition of the importance of systemic inflammation and the renal microenvironment. Early diagnosis and initiation of HRS-AKI-specific treatment can improve outcomes. The mainstay of therapy is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases. Liver transplantation is the only option for patients failing to respond to medical therapies.
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Affiliation(s)
- Saro Khemichian
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;
| | - Mitra K Nadim
- Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;
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Kronsten VT, Shawcross DL. Clinical Implications of Inflammation in Patients With Cirrhosis. Am J Gastroenterol 2025; 120:65-74. [PMID: 39194320 PMCID: PMC11676607 DOI: 10.14309/ajg.0000000000003056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024]
Abstract
Cirrhosis-associated immune dysfunction refers to the concurrent systemic inflammation and immunoparesis evident across the disease spectrum of chronic liver disease, ranging from the low-grade inflammatory plasma milieu that accompanies compensated disease to the intense high-grade inflammatory state with coexistent severe immune paralysis that defines acute decompensation and acute-on-chronic liver failure. Systemic inflammation plays a crucial role in the disease course of cirrhosis and is a key driver for acute decompensation and the progression from compensated to decompensated cirrhosis. Severe systemic inflammation is fundamental to the development of organ dysfunction and failure and, in its most extreme form, acute-on-chronic liver failure. Systemic inflammation propagates the development of hepatic encephalopathy and hepatorenal syndrome-acute kidney injury. It may also be involved in the pathogenesis of further complications such as hepatocellular carcinoma and mental illness. Those patients with the most profound systemic inflammation have the worst prognosis. Systemic inflammation exerts its negative clinical effects through a number of mechanisms including nitric oxide-mediated increased splanchnic vasodilation, immunopathology, and metabolic reallocation.
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Affiliation(s)
- Victoria T. Kronsten
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London
| | - Debbie L. Shawcross
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London
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Hamadah A, Gharaibeh K. Inclusion of patients with active urinary sediment in treatment of hepatorenal syndrome. J Hepatol 2024:S0168-8278(24)02743-0. [PMID: 39617132 DOI: 10.1016/j.jhep.2024.11.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 11/15/2024] [Indexed: 04/26/2025]
Affiliation(s)
| | - Kamel Gharaibeh
- Department of Internal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Granda ML, Luitweiler E, Prince DK, Allegretti AS, Paine C, Pichler R, Sibulesky L, Biggins SW, Kestenbaum B. Proximal Tubule Secretory Clearance, Injury, and Kidney Viability in Cirrhosis. Clin Transl Gastroenterol 2024; 15:e00775. [PMID: 39374041 PMCID: PMC11596343 DOI: 10.14309/ctg.0000000000000775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 09/18/2024] [Indexed: 10/08/2024] Open
Abstract
INTRODUCTION Cirrhosis affects all structures of the kidney, in particular the tubules, which are responsible for secretion of protein-bound metabolites and electrolyte/water homeostasis. Yet, prevailing assessments of kidney function focus solely on glomerular filtration rate (GFR), which may incompletely reflect these processes. We sought to characterize markers of tubular function, injury, and viability in patients with and without cirrhosis. METHODS We recruited outpatients undergoing liver transplantation evaluation for a collection of plasma and 24-hour urine, matching by GFR to control participants without cirrhosis. We measured urinary kidney injury molecule-1, a marker of proximal tubular injury, as well as epidermal growth factor (EGF), a marker of viability necessary for tubular epithelial cell proliferation after injury. We also estimated secretory clearance by measuring several highly secreted endogenous metabolites in urine and plasma. RESULTS We recruited 39 patients with cirrhosis (mean model for end-stage liver disease 17 ± 4, Child-Pugh 8 ± 2, estimated glomerular filtration rate 66 ± 20 mL/min/1.73 m 2 ) and 58 GFR-matched controls without cirrhosis (estimated glomerular filtration rate 66 ± 21 mL/min/1.73 m 2 ). Urinary kidney injury molecule-1 was 4.4-fold higher than controls (95% confidence interval: 2.9-6.5), and EGF averaged 7.41-fold higher than controls (95% confidence interval: 2.15-25.53). We found that of 8 solutes, 5 had significantly greater kidney clearance in cirrhosis (1.3-2.1-fold higher): indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine. DISCUSSION Cirrhosis was characterized by molecular signs of tubular injury in stable outpatients without acute kidney injury, accompanied by largely preserved tubular secretory clearance and greater signs of tubular viability. Within the limitations of the study, this suggests a phenotype of chronic ischemic injury but with initial preservation of tubular function in cirrhosis.
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Affiliation(s)
- Michael L. Granda
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
| | - Eric Luitweiler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - David K. Prince
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
| | - Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Cary Paine
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Raimund Pichler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Lena Sibulesky
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, Washington, USA
| | - Scott W. Biggins
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Bryan Kestenbaum
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
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Kalo E, Read S, Baig A, Marshall K, Ma WS, Crowther H, Gofton C, Lynch KD, Sood S, Holmes J, Lubel J, Wigg A, McCaughan G, Roberts SK, Caraceni P, Ahlenstiel G, Majumdar A. Efficacy of albumin use in decompensated cirrhosis and real-world adoption in Australia. JGH Open 2024; 8:e70029. [PMID: 39301299 PMCID: PMC11410680 DOI: 10.1002/jgh3.70029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 08/26/2024] [Accepted: 09/03/2024] [Indexed: 09/22/2024]
Abstract
The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long-term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis-related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis-related complications and discuss key challenges for wide application of long-term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9-11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long-term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature.
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Affiliation(s)
- Eric Kalo
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Scott Read
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Asma Baig
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Kate Marshall
- Royal Prince Alfred Hospital Sydney New South Wales Australia
| | - Wai-See Ma
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Helen Crowther
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Cameron Gofton
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
- Department of Gastroenterology and Hepatology Royal North Shore Hospital St Leonards New South Wales Australia
| | - Kate D Lynch
- Department of Gastroenterology and Hepatology Royal Adelaide Hospital, Central Adelaide Local Health Network Adelaide South Australia Australia
- Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia
| | - Siddharth Sood
- Department of Gastroenterology Northern Health Melbourne Victoria Australia
- Department of Medicine The University of Melbourne Parkville Victoria Australia
| | - Jacinta Holmes
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Department of Gastroenterology St Vincent's Hospital Fitzroy Victoria Australia
| | - John Lubel
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Alan Wigg
- Hepatology and Liver Transplant Medicine Unit Southern Adelaide Local Health Network Adelaide South Australia Australia
- Flinders University of South Australia Adelaide South Australia Australia
| | - Geoff McCaughan
- A.W. Morrow Gastroenterology and Liver Centre Centenary Research Institute for Cancer Research and Cell Biology Camperdown New South Wales Australia
- Australian National Liver Transplant Unit Royal Prince Alfred Hospital Sydney New South Wales Australia
- Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Stuart K Roberts
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Paolo Caraceni
- Unit of Semeiotics, Liver and Alcohol-Related Diseases IRCCS Azienda-Ospedaliera Universitaria di Bologna, EMR Bologna Italy
- Department of Medical and Surgical Sciences University of Bologna, EMR Bologna Italy
| | - Golo Ahlenstiel
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Avik Majumdar
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Victorian Liver transplant Unit Austin Health Heidelberg Victoria Australia
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Nadim MK, Kellum JA, Forni L, Francoz C, Asrani SK, Ostermann M, Allegretti AS, Neyra JA, Olson JC, Piano S, VanWagner LB, Verna EC, Akcan-Arikan A, Angeli P, Belcher JM, Biggins SW, Deep A, Garcia-Tsao G, Genyk YS, Gines P, Kamath PS, Kane-Gill SL, Kaushik M, Lumlertgul N, Macedo E, Maiwall R, Marciano S, Pichler RH, Ronco C, Tandon P, Velez JCQ, Mehta RL, Durand F. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol 2024; 81:163-183. [PMID: 38527522 PMCID: PMC11193657 DOI: 10.1016/j.jhep.2024.03.031] [Citation(s) in RCA: 47] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 02/28/2024] [Accepted: 03/07/2024] [Indexed: 03/27/2024]
Abstract
Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
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Affiliation(s)
- Mitra K Nadim
- Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, USA
| | - John A Kellum
- Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Lui Forni
- School of Medicine, University of Surrey and Critical Care Unit, Royal Surrey Hospital Guildford UK
| | - Claire Francoz
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, Paris, France
| | | | - Marlies Ostermann
- King's College London, Guy's & St Thomas' Hospital, Department of Critical Care, London, UK
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Javier A Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jody C Olson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Padova, Italy
| | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Elizabeth C Verna
- Division of Digestive and Liver Diseases, Columbia University, New York, NY, USA
| | - Ayse Akcan-Arikan
- Department of Pediatrics, Divisions of Critical Care Medicine and Nephrology, Baylor College of Medicine, Houston, TX, USA
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, University and Teaching Hospital of Padua, Italy
| | - Justin M Belcher
- Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA
| | - Scott W Biggins
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Akash Deep
- Pediatric Intensive Care Unit, King's College Hospital, London, UK
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Yale University School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA
| | - Yuri S Genyk
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Division of Abdominal Organ Transplantation at Children's Hospital of Los Angeles, Los Angeles, CA, USA
| | - Pere Gines
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer and Ciber de Enfermedades Hepàticas y Digestivas, Barcelona, Catalonia, Spain
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Sandra L Kane-Gill
- Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
| | - Manish Kaushik
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Nuttha Lumlertgul
- Excellence Centre in Critical Care Nephrology and Division of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Etienne Macedo
- Division of Nephrology, Department of Medicine, University of California San Diego, CA, USA
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Raimund H Pichler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Claudio Ronco
- International Renal Research Institute of Vicenza, Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza-Italy
| | - Puneeta Tandon
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Juan-Carlos Q Velez
- Department of Nephrology, Ochsner Health, New Orleans, LA, USA; Ochsner Clinical School, The University of Queensland, Brisbane, QLD, Australia
| | - Ravindra L Mehta
- Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - François Durand
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, Paris, France; University Paris Cité, Paris, France.
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Saxena D, Yadav M, Kumar T, Sharma S, Beniwal P, Malhotra V, Agarwal D, Nijhawan S. Acute Kidney Injury in Chronic Liver Disease in Northwest India: Still a Battle to Conquer. Indian J Nephrol 2024; 34:317-322. [PMID: 39156834 PMCID: PMC11328058 DOI: 10.25259/ijn_286_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 10/19/2023] [Indexed: 08/20/2024] Open
Abstract
Background Patients with cirrhosis are susceptible to development of acute kidney injury (AKI), which leads to poor outcome. We conducted a study to evaluate the spectrum of AKI in patients with cirrhosis. Materials and Methods This study was conducted in consecutive cirrhotic patients with AKI admitted in a tertiary care center of India from April 2020 to December 2022. Details including history, examination findings, and results of laboratory investigations were recorded. Results A total of 243 patients were enrolled in this study. The majority (91.3%) of the patients were males. The most common etiology of cirrhosis was alcohol in 58.4% (n = 142) followed by hepatitis B in 10.3% (n = 25) of patients. Pre-renal form of AKI was present in 54.4% (n = 132) of patients and hepatorenal syndrome (HRS) in 21.8% (n = 53) of patients. IgA nephropathy was the commonest (n = 6) glomerular pathology in nonresponders with intrinsic renal disease. Majority of the patients belonged to stage II (46.9%) and stage I AKI (37%), while only 16.1% had stage III AKI. Various stages of AKI showed a significant correlation (P < 0.05) with Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD)-Na score. The overall in-hospital mortality rate was found to be 18.5% (n = 45). Conclusion Renal dysfunction is a frequent complication among cirrhotic patients. Pre-renal factors were the most common cause of AKI in cirrhotics. Stages of AKI showed significant correlation with liver prognostic scores. Renal biopsy should be considered in patients not responding to treatment, to guide further management.
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Affiliation(s)
- Disha Saxena
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Manoj Yadav
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Tarun Kumar
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sanjeev Sharma
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Pankaj Beniwal
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Vinay Malhotra
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Dhananjai Agarwal
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sandeep Nijhawan
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
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12
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Peluso L, Savi M, Coppalini G, Veliaj D, Villari N, Albano G, Petrou S, Pace MC, Fiore M. Management of hepatorenal syndrome and treatment-related adverse events. Curr Med Res Opin 2024; 40:1155-1162. [PMID: 38773739 DOI: 10.1080/03007995.2024.2358242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 05/05/2024] [Accepted: 05/17/2024] [Indexed: 05/24/2024]
Abstract
Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome-acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment.
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Affiliation(s)
- Lorenzo Peluso
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Marzia Savi
- Department of Anesthesia and Intensive Care, Humanitas Gavazzeni, Bergamo, Italy
| | - Giacomo Coppalini
- Department of Anesthesia and Intensive Care, Humanitas Gavazzeni, Bergamo, Italy
| | - Deliana Veliaj
- Department of Anesthesia and Intensive Care, Humanitas Gavazzeni, Bergamo, Italy
| | - Nicola Villari
- Department of Anesthesia and Intensive Care, Humanitas Gavazzeni, Bergamo, Italy
| | - Giovanni Albano
- Department of Anesthesia and Intensive Care, Humanitas Gavazzeni, Bergamo, Italy
| | - Stephen Petrou
- Department of Emergency Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Maria C Pace
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Marco Fiore
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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13
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Sharan K, Sharma A, Rana S, Patnaik I, Gupta R. Neutrophil Gelatinase-associated Lipocalin Predicts Short-term Outcomes in Decompensated Cirrhosis With Acute Kidney Injury. J Clin Exp Hepatol 2024; 14:101274. [PMID: 38076377 PMCID: PMC10709204 DOI: 10.1016/j.jceh.2023.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 08/24/2023] [Indexed: 01/05/2025] Open
Abstract
Background and aims Acute kidney injury (AKI) increases mortality in cirrhosis. Early identification of the cause of AKI helps in planning appropriate management. We aimed to find whether neutrophil gelatinase-associated lipocalin (NGAL) can be used to differentiate between different types of AKI in cirrhosis and predict short-term outcomes in patients with decompensated cirrhosis and AKI. Method This was a time-bound study in which consecutive hospitalized patients with cirrhosis and AKI were prospectively recruited and managed as per standard care. Acute on chronic liver failure (ACLF) was diagnosed as per the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) criteria. Urine NGAL was measured by enzyme-linked immunosorbent assay (ELISA) by Epitope Diagnostics Inc. kit (San Diego, USA.) in all patients on admission, and patients were followed up until hospital discharge or death. Results A total of 110 consecutive patients (median [range] age: 44 [28-81] years;87.3%were male; ACLF: 71.8%; acute decompensation 28.2%; Model for end-stage liver disease (MELD) 27 [13-46]; Child-Turcotte-Pugh (CTP) 11 [7-15]) with cirrhosis and AKI were recruited. Alcohol was the most common etiology of cirrhosis(64.5%)). Pre-renal azotemia (PRA) was the most common cause of AKI (n = 56). Urine NGAL was significantly elevated in acute tubular necrosis (ATN) (1747 [6-6141] ng/ml than in hepatorenal syndrome (HRS) (379 [33.5-2320] ng/ml; P < 0.0001) and PRA (167 ng/ml [3.34-660]; P < 0.0001). Sixty-four percent patients with ATN, 27.6% patients with HRS, and none with PRA required dialysis. A total of 79.31% patients with HRS and 76% with ATN died. Urine NGAL was significantly higher in patients who required hemodialysis than in those who did not (1733 [243-6141] ng/ml vs 235 [3.34-2320] ng/ml; P < 0.0001). Both urine NGAL (n = 110) and plasma NGAL (n = 90) were significantly higher in patients who died (urine NGAL: -475 [6-6141] ng/ml vs 247 [3.34-2320] ng/ml; P = 0.002;plasma NGAL-950 [94-4859] ng/ml vs 608 [18-3300)]g/ml; P < 0.001). On multivariate analysis, urine NGAL and INR could predict mortality. Conclusion NGAL can differentiate between different types of AKI in cirrhosis and predict the need for hemodialysis and mortality in decompensated cirrhosis with AKI.
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Affiliation(s)
- Kshitiz Sharan
- Department of Medical Gastroenterology, All India Institute of Medical Sciences (AIIMS), Rishikesh, India
| | - Anand Sharma
- Department of Medical Gastroenterology, All India Institute of Medical Sciences (AIIMS), Rishikesh, India
| | - Satyavati Rana
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Rishikesh, India
| | - Itish Patnaik
- Department of Medical Gastroenterology, All India Institute of Medical Sciences (AIIMS), Rishikesh, India
| | - Rohit Gupta
- Department of Medical Gastroenterology, All India Institute of Medical Sciences (AIIMS), Rishikesh, India
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14
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [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] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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15
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Chouik Y, Lebossé F, Plissonnier ML, Lega JC, Pradat P, Antonini T, Subic M, Hartig-Lavie K, Erard D, Villeret F, Guichon C, Payancé A, Radenne S, Rautou PE, Zoulim F, Levrero M. Circulating microRNAs improve bacterial infection diagnosis and overall survival prediction in acute decompensation of liver cirrhosis. iScience 2023; 26:107427. [PMID: 37575179 PMCID: PMC10415934 DOI: 10.1016/j.isci.2023.107427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 05/23/2023] [Accepted: 07/17/2023] [Indexed: 08/15/2023] Open
Abstract
Bacterial infections are the most frequent precipitating event in patients with acute decompensation of cirrhosis (AD) and are associated with high mortality. Early diagnosis is challenging due to cirrhosis-related systemic inflammation. Here we investigated the potential of circulating microRNAs to diagnose bacterial infections and predict survival in cirrhotic patients with AD. High throughput profiling of circulating microRNAs was performed using the Nanostring technology in 57 AD patients and 24 patients with compensated cirrhosis (CC). Circulating miRs profiling showed that: (a) miRs differentially detected in AD vs. CC were mostly down-regulated; (b) a composite score including absolute neutrophil count, C reactive protein and miR-362-3p could diagnose bacterial infection with an excellent performance (AUC of 0.825 [95% CI = 0.671-0.980; p < 0.001]); (c) a composite score including miR-382-5p, miR-592 and MELD-Na improved 6-month survival prediction. Circulating miRs are strongly dysregulated in patients with AD and may help to improve bacterial infection diagnosis and survival prediction.
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Affiliation(s)
- Yasmina Chouik
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS UMR5286, Lyon, France
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- University of Lyon Claude Bernard 1 (UCLB1), Lyon, France
| | - Fanny Lebossé
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS UMR5286, Lyon, France
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- University of Lyon Claude Bernard 1 (UCLB1), Lyon, France
| | | | - Jean-Christophe Lega
- Department of Internal Medicine, Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - Pierre Pradat
- Clinical Research Center, GHN, Hospices Civils de Lyon, Lyon, France
| | - Teresa Antonini
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | | | - Kerstin Hartig-Lavie
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Domitille Erard
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - François Villeret
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- University of Lyon Claude Bernard 1 (UCLB1), Lyon, France
| | - Céline Guichon
- Department of Anesthesiology and Intensive Care, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Audrey Payancé
- Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France
| | - Sylvie Radenne
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Pierre-Emmanuel Rautou
- Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France
- Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS UMR5286, Lyon, France
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- University of Lyon Claude Bernard 1 (UCLB1), Lyon, France
| | - Massimo Levrero
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS UMR5286, Lyon, France
- Department of Hepatology, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- University of Lyon Claude Bernard 1 (UCLB1), Lyon, France
- Department of Medicine SCIAC and the Italian Institute of Technology (IIT) Center for Life Nanosciences (CLNS), University of Rome La Sapienza, Rome, Italy
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16
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Calleri A, Alessandria C. Renal damage in Hepatorenal Syndrome: A still unsolved issue. Clin Res Hepatol Gastroenterol 2023; 47:102178. [PMID: 37453679 DOI: 10.1016/j.clinre.2023.102178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 07/02/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023]
Abstract
Acute kidney injury (AKI) is a common complication of cirrhosis, burdened by high morbidity and mortality rates and progression to chronic kidney disease. Hepatorenal syndrome (HRS) is a peculiar type of functional AKI observed in cirrhotic patients with ascites. HRS diagnosis is still clinical, once pre-renal azotemia and intrinsic kidney damage have been excluded by applying well-established and internationally adopted criteria. HRS is considered reversible because of the absence of intrinsic renal damage. However, HRS reversibility has been questioned, due to the lack of response to treatment with vasoconstrictors plus albumin in a relevant percentage of patients and to the persistence of renal dysfunction in HRS patients who underwent liver transplantation (LT). Indeed, LT is the only ultimate treatment, as it solves both liver failure and portal hypertension. Thus, the presence of renal damage in HRS can be hypothesized. In this scenario, neutrophil gelatinase-associated lipocalin (NGAL), one of the most promising biomarkers, may help in characterizing the type of renal injury, distinguishing between HRS and acute tubular necrosis. This review gathers the available evidence in favor and against the presence of structural lesions in HRS in terms of either renal histology and urinary biomarkers with a particular focus on NGAL. The ability to properly characterize which component of renal dysfunction prevails - functional rather than structural - entails a relevant clinical impact for the treatment of these patients, both in terms of medical therapy and liver vs. combined liver-kidney transplantation.
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Affiliation(s)
- Alberto Calleri
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Italy.
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17
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Amer K, Flikshteyn B, Lingiah V, Tafesh Z, Pyrsopoulos NT. Mechanisms of Disease and Multisystemic Involvement. Clin Liver Dis 2023; 27:563-579. [PMID: 37380283 DOI: 10.1016/j.cld.2023.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Affiliation(s)
- Kamal Amer
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 538, Newark, NJ 07101-1709, USA
| | - Ben Flikshteyn
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 538, Newark, NJ 07101-1709, USA
| | - Vivek Lingiah
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 538, Newark, NJ 07101-1709, USA
| | - Zaid Tafesh
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 53, Newark, NJ 07101-1709, USA
| | - Nikolaos T Pyrsopoulos
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 536, Newark, NJ 07101-1709, USA.
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18
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Attieh RM, Wadei HM. Acute Kidney Injury in Liver Cirrhosis. Diagnostics (Basel) 2023; 13:2361. [PMID: 37510105 PMCID: PMC10377915 DOI: 10.3390/diagnostics13142361] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/01/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.
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Affiliation(s)
- Rose Mary Attieh
- Department of Transplant, Division of Kidney and Pancreas Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Hani M Wadei
- Department of Transplant, Division of Kidney and Pancreas Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
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19
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Abraldes JG, Caraceni P, Ghabril M, Garcia-Tsao G. Update in the Treatment of the Complications of Cirrhosis. Clin Gastroenterol Hepatol 2023; 21:2100-2109. [PMID: 36972759 PMCID: PMC11097249 DOI: 10.1016/j.cgh.2023.03.019] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 02/17/2023] [Accepted: 03/07/2023] [Indexed: 03/29/2023]
Abstract
Cirrhosis consists of 2 main stages: compensated and decompensated, the latter defined by the development/presence of ascites, variceal hemorrhage, and hepatic encephalopathy. The survival rate is entirely different, depending on the stage. Treatment with nonselective β-blockers prevents decompensation in patients with clinically significant portal hypertension, changing the previous paradigm based on the presence of varices. In patients with acute variceal hemorrhage at high risk of failure with standard treatment (defined as those with a Child-Pugh score of 10-13 or those with a Child-Pugh score of 8-9 with active bleeding at endoscopy), a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) improves the mortality rate and has become the standard of care in many centers. In patients with bleeding from gastrofundal varices, retrograde transvenous obliteration (in those with a gastrorenal shunt) and/or variceal cyanoacrylate injection have emerged as alternatives to TIPS. In patients with ascites, emerging evidence suggests that TIPS might be used earlier, before strict criteria for refractory ascites are met. Long-term albumin use is under assessment for improving the prognosis of patients with uncomplicated ascites and confirmatory studies are ongoing. Hepatorenal syndrome is the least common cause of acute kidney injury in cirrhosis, and first-line treatment is the combination of terlipressin and albumin. Hepatic encephalopathy has a profound impact on the quality of life of patients with cirrhosis. Lactulose and rifaximin are first- and second-line treatments for hepatic encephalopathy, respectively. Newer therapies such as L-ornithine L-aspartate and albumin require further assessment.
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Affiliation(s)
- Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Paolo Caraceni
- Istituto di Ricerca e Cura a Carattere Scientifico Azienda Ospedaliera-Universitaria di Bologna, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Guadalupe Garcia-Tsao
- Yale University School of Medicine, Veterans Administration - Connecticut Healthcare System, West Haven, Connecticut.
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20
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Kiani C, Zori AG. Recent advances in pathophysiology, diagnosis and management of hepatorenal syndrome: A review. World J Hepatol 2023; 15:741-754. [PMID: 37397940 PMCID: PMC10308288 DOI: 10.4254/wjh.v15.i6.741] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/18/2023] [Accepted: 05/06/2023] [Indexed: 06/25/2023] Open
Abstract
Hepatorenal syndrome with acute kidney injury (HRS-AKI) is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure. Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation, leading to reduction of effective arterial blood volume and glomerular filtration rate. Thus, volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy. However, a significant proportion of patients do not respond to medical management. These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation. Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications, better-calibrated studies, more widely available biomarkers, and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.
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Affiliation(s)
- Calvin Kiani
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Florida, Gainesville, FL 32610, United States
| | - Andreas G Zori
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Florida, Gainesville, FL 32610, United States
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21
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Ibáñez-Samaniego L, Baines A, Bañares R. Afectación renal en la enfermedad hepática crónica avanzada. Síndrome hepatorrenal. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2023; 13:4841-4849. [DOI: 10.1016/j.med.2023.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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23
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Wang S, Zhou Z, Xu C, Chen H, Ren W, Yang X, Yin Q, Zheng W, Pan H. Establishment and evaluation of an early prediction model of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis. BMC Gastroenterol 2023; 23:1. [PMID: 36593456 PMCID: PMC9809024 DOI: 10.1186/s12876-022-02618-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 12/12/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND AND AIM In China, hepatorenal syndrome is a serious complication in the decompensated stage of hepatitis B cirrhosis, which requires early clinical intervention, so the early diagnosis of hepatorenal syndrome is crucial. This study establishes a new predictive model based on serum biomarkers for the early diagnosis of hepatorenal syndrome. METHODS Patients with decompensated hepatitis B cirrhosis who met the inclusion and exclusion criteria were retrospectively enrolled. Patients were randomly assigned to the training dataset and validation dataset at a 7:3 ratio. Univariate and multivariate logistic regression analyses were used to screen the risk factors for hepatorenal syndrome. The identified risk factors were used to establish and verify a model. RESULTS This study included 255 patients with decompensated hepatitis B cirrhosis, including 184 in the training group and 71 in the validation group. The multivariate logistic regression model was established in the training group and verified in the validation group. Logistic regression showed that hemoglobin (OR 0.938, 95% CI 0.908-0.969), total bilirubin (OR 1.014, 95% CI 1.008-1.021) and creatinine (OR 1.079, 95% CI 1.043-1.117) were independent risk factors for hepatorenal syndrome (P < 0.05). These were used to establish the model. In the training group and the validation group, the area under the ROC curve of the nomogram for the diagnosis of hepatorenal syndrome was 0.968 and 0.980, respectively. CONCLUSION The three serum biomarkers, including hemoglobin, total bilirubin and creatinine, can be used as independent early predictors of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis.
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Affiliation(s)
- Shouhao Wang
- grid.410645.20000 0001 0455 0905Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Qingdao University, 310014 Hangzhou, Zhejiang China ,grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Zhewen Zhou
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Chengan Xu
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Hanzhu Chen
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Wenya Ren
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Xingdi Yang
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Qiaoqiao Yin
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Wei Zheng
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
| | - Hongying Pan
- grid.417401.70000 0004 1798 6507Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014 Zhejiang China
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Duan Z, Jiang M, Huang X, Liu H, Yu H, Meng Q. Urinary Neutrophil Gelatinase-Associated Lipocalin Can Predict the Efficacy of Volume Expansion Therapy in Patients With Hepatitis B Cirrhosis and AKI. Front Pharmacol 2022; 13:839250. [PMID: 35784735 PMCID: PMC9240615 DOI: 10.3389/fphar.2022.839250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 05/11/2022] [Indexed: 11/19/2022] Open
Abstract
Backgrounds: Kidney biomarkers in urine appear to be useful in differential diagnosis between acute tubular necrosis and other types of acute kidney injury (AKI) in cirrhosis. In clinical practice, prerenal azotemia (PRA) is often distinguished from other types of AKI by volume expansion therapy. The aim of the current study was to investigate the accuracy of urinary biomarkers in the differential diagnosis between PRA and other types of AKI. Methods: A total of 65 patients with hepatitis B cirrhosis were prospectively included and divided into AKI and non-AKI groups. Patients with hepatitis B cirrhosis and AKI discontinue diuretics, vasodilators, and nephrotoxic drugs and give volume expansion therapy. The efficacy was judged after 48 h of treatment. Urinary biomarkers were measured at the time of diagnosis of AKI and 48 h after volume expansion therapy. Univariate and multivariate analyses were used to identify independent risk factors for nonresponse to volume expansion therapy. Results: Of the 65 patients, 49 patients with newly diagnosed AKI were screened in the study, and 16 hospitalized patients with hepatitis B cirrhosis without AKI at the same period were screened as the control group. In patients with cirrhosis and AKI, 29 (59.18%) patients were in the response group and 20 (40.81%) patients were in the nonresponse group. The mortality rate in the nonresponse group was significantly higher than that in the response group (75% vs. 13.8% p < 0.001). After logistic regression analysis, urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr) at diagnosis of AKI showed significant association with nonresponse to volume expansion therapy. The cutoff values for SCr and urinary NGAL were 128.50 µmol/L and 90.75 ng/ml, respectively. The area under the receiver operating curve (AUC) for SCr and urinary NGAL was 0.815 and 0.831. Conclusion: Elevated urinary NGAL can reflect the degree of kidney injury and is an independent risk factor for nonresponse to volume expansion therapy in patients with hepatitis B cirrhosis and AKI.
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Affiliation(s)
- Zhonghui Duan
- Department of Emergency, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Minjie Jiang
- Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaojie Huang
- Department of Infectious Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Haixia Liu
- Department of Intensive Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hongwei Yu
- Department of Outpatient, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Li F, Wang T, Zhan L, Jia Z, Luo T, Chen S, Zhao Q, Guo Z, He X, Wang D. Clinical Outcomes of Liver Transplantation in Patients With Hepatorenal Syndrome: A Single Center Study in China. Front Surg 2022; 8:781648. [PMID: 35155548 PMCID: PMC8831834 DOI: 10.3389/fsurg.2021.781648] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 12/22/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Liver transplantation (LT) is an optimal treatment for hepatorenal syndrome (HRS) patients but renal function recovery is not universal after operation. The aim of this study is to explore the association between stages of hepatorenal syndrome—acute kidney injury (HRS-AKI) and incidence of post-operation chronic kidney disease (CKD). Methods Data of HRS-AKI patients who received LT were collected from the First Affiliated Hospital of Sun Yat-sen University from 2016 to 2020. A survival and incidence curve and multivariable model were established to analyze the impacts of HRS-AKI stages and variables on 90-day survival and CKD within 12 months. Results A total of 62 HRS-AKI patients were enrolled in this study. Overall, 35 (57%), 17 (27%), and 10 (16%) patients were diagnosed as stages 1, 2, and 3, respectively. The patients at stage 3 had the poorest outcomes with the lowest rate of 90-day survival and the highest incidence of CKD in 12 months. Stage 3 (SHR = 7.186, 95% CI, 1.661–32.043) and postoperative renal replacement therapy (RRT) (SHR = 3.228, 95% CI, 1.115–9.345) were found as useful indicators for poor prognosis. Conclusions In our study, the classification of HRS-AKI stages can be used to predict the prognosis of HRS patients after LT. The peak serum creatinine level is a risky predictor in high HRS-AKI stage patients.
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Gupta MM, Deng X. Hepatorenal Syndrome. APPROACHES TO CHRONIC KIDNEY DISEASE 2022:151-168. [DOI: 10.1007/978-3-030-83082-3_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ojeda-Yuren AS, Cerda-Reyes E, Herrero-Maceda MR, Castro-Narro G, Piano S. An Integrated Review of the Hepatorenal Syndrome. Ann Hepatol 2021; 22:100236. [PMID: 32846202 DOI: 10.1016/j.aohep.2020.07.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 07/24/2020] [Accepted: 07/26/2020] [Indexed: 02/04/2023]
Abstract
Among the complications of cirrhosis, hepatorenal syndrome (HRS) is characterized by having the worst survival rate. HRS is a disorder that involves the deterioration of kidney function caused primarily by a systemic circulatory dysfunction, but in recent years, systemic inflammation and cirrhotic cardiomyopathy have been discovered to also play an important role. The diagnosis of HRS requires to meet the new International Club of Ascites-Acute Kidney Injury (ICA-AKI) and Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) criteria after ruling out other causes of kidney injury. At the time of diagnosis, it is important to start the medical treatment as soon as possible where three types of vasoconstrictors have been recognized: vasopressin analogs (ornipressin and terlipressin), alpha-adrenergic agonists (norepinephrine and midodrine) and somatostatin analogues (octreotide); all should be combined with albumin infusion. Among them, terlipressin and albumin are the first lines of treatment in most cases, although terlipressin should be monitor closely due to its adverse events. The best treatment of choice is a liver transplant, because it is the only definitive treatment for this disease.
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Affiliation(s)
- Alicia S Ojeda-Yuren
- Gastroenterology Section, Central Military Hospital, Ring Road, Blvrd. Manuel Avila Camacho, Militar, Miguel Hidalgo, 11200 Mexico City, Mexico.
| | - Eira Cerda-Reyes
- Gastroenterology Section, Central Military Hospital, Ring Road, Blvrd. Manuel Avila Camacho, Militar, Miguel Hidalgo, 11200 Mexico City, Mexico; Army and Air Force University of Mexico, Gastroenterology Specialization Course of the Military School of Health Graduates, Batalla de Celaya 202, Lomas of Sotelo, Militar, Miguel Hidalgo, 11200 Mexico City, Mexico.
| | - Maria R Herrero-Maceda
- Gastroenterology Section, Central Military Hospital, Ring Road, Blvrd. Manuel Avila Camacho, Militar, Miguel Hidalgo, 11200 Mexico City, Mexico; Army and Air Force University of Mexico, Gastroenterology Specialization Course of the Military School of Health Graduates, Batalla de Celaya 202, Lomas of Sotelo, Militar, Miguel Hidalgo, 11200 Mexico City, Mexico.
| | - Graciela Castro-Narro
- Gastroenterology Department, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", Vasco of Quiroga 15, Belisario Domínguez Secc 16, Tlalpan, 14080 Mexico City, Mexico.
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padua, Via 8 Febbraio 1848, 2, 35122 Padova, PD, Italy.
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Chaney A. A Review for the Practicing Clinician: Hepatorenal Syndrome, a Form of Acute Kidney Injury, in Patients with Cirrhosis. Clin Exp Gastroenterol 2021; 14:385-396. [PMID: 34675586 PMCID: PMC8502008 DOI: 10.2147/ceg.s323778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022] Open
Abstract
The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.
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Affiliation(s)
- Amanda Chaney
- Department of Transplant, College of Medicine, Mayo Clinic, Jacksonville, FL, USA
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Hepatorenal syndrome: pathophysiology and evidence-based management update. ROMANIAN JOURNAL OF INTERNAL MEDICINE 2021; 59:227-261. [DOI: 10.2478/rjim-2021-0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 11/20/2022] Open
Abstract
Abstract
Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.
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Maurel P, Prémaud A, Carrier P, Essig M, Barbier L, Rousseau A, Silvain C, Causse X, Debette-Gratien M, Jacques J, Marquet P, Salamé E, Loustaud-Ratti V. Evaluation of Longitudinal Exposure to Tacrolimus as a Risk Factor of Chronic Kidney Disease Occurrence Within the First-year Post-Liver Transplantation. Transplantation 2021; 105:1585-1594. [PMID: 32639405 DOI: 10.1097/tp.0000000000003384] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Renal failure is predictive of mortality in the early postliver-transplantation period and calcineurin inhibitors toxicity is a main challenge. Our aim is to assess the impact of longitudinal tacrolimus exposure (TLE) and other variables on chronic kidney disease (CKD)-free 1-year-survival. METHODS Retrospective data of consecutive patients transplanted between 2011 and 2016 and treated with tacrolimus were collected. TLE and all relevant pre- and post-liver transplantation (LT) predictive factors of CKD were tested and included in a time-to-event model. CKD was defined by repeated estimated glomerular filtration rate (eGFR) values below 60 mL/min/1.73m2 at least for the last 3 months before M12 post-LT. RESULTS Data from 180 patients were analyzed. CKD-free survival was 74.5% and was not associated with TLE. Pre-LT acute kidney injury (AKI) and eGFR at 1-month post-LT (eGFRM1) <60 mL/min/1.73m2 were significant predictors of CKD. By distinguishing 2 situations within AKI (ie, with or without hepatorenal syndrome [HRS]), only HRS-AKI remained associated to CKD. HRS-AKI and eGFRM1 <60 mL/min/1.73m2 increased the risk of CKD (hazard ratio, 2.5; 95% confidence interval, 1.2-4.9; hazard ratio, 4.8; 95% confidence interval, 2.6-8.8, respectively). CONCLUSIONS In our study, TLE, unlike HRS-AKI and eGFRM1, was not predictive of CKD-free survival at 1-year post-LT. Our results once again question the reversibility of HRS-AKI.
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Affiliation(s)
- Pauline Maurel
- Hepatology and Gastroenterology Unit, University Hospital of Limoges, Limoges, France
| | - Aurélie Prémaud
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
| | - Paul Carrier
- Hepatology and Gastroenterology Unit, University Hospital of Limoges, Limoges, France
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
| | - Marie Essig
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
| | - Louise Barbier
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
- Department of Digestive Surgery and Liver Transplantation, Trousseau University Hospital, Chambray-lès-Tours, France
| | - Annick Rousseau
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
| | - Christine Silvain
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
- Hepatology and Gastroenterology Unit, University Hospital of Poitiers, Poitiers, France
| | - Xavier Causse
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
- Hepatology and Gastroenterology Unit, Regional Hospital Center of Orléans, Orléans La Source, France
| | - Marilyne Debette-Gratien
- Hepatology and Gastroenterology Unit, University Hospital of Limoges, Limoges, France
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
| | - Jérémie Jacques
- Hepatology and Gastroenterology Unit, University Hospital of Limoges, Limoges, France
| | - Pierre Marquet
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
| | - Ephrem Salamé
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
- Department of Digestive Surgery and Liver Transplantation, Trousseau University Hospital, Chambray-lès-Tours, France
| | - Véronique Loustaud-Ratti
- Hepatology and Gastroenterology Unit, University Hospital of Limoges, Limoges, France
- INSERM U1248, University of Limoges, F-87000, Limoges, France
- FHU SUPORT: University Hospital Federation SUrvival oPtimization in ORgan Transplantation, Limoges, F-87000, Tours, F-30000, Poitiers F-86000, Orléans F-45000, France
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Jalan R, D'Amico G, Trebicka J, Moreau R, Angeli P, Arroyo V. New clinical and pathophysiological perspectives defining the trajectory of cirrhosis. J Hepatol 2021; 75 Suppl 1:S14-S26. [PMID: 34039485 DOI: 10.1016/j.jhep.2021.01.018] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 02/06/2023]
Abstract
Traditionally, the complications of cirrhosis, namely variceal bleeding, ascites and hepatic encephalopathy, were thought to result predominantly from circulatory dysfunction and altered organ perfusion arising as a result of portal hypertension. Over the past 20 years, large, international prospective studies have indicated the importance of systemic inflammation and organ immunopathology as additional determinants of organ dysfunction in cirrhosis, which not only manifests in the liver, brain, circulation and the kidneys, but also the immune system, gut, muscles, adrenal glands, reproductive organs, heart and lungs. This review provides an overview of the traditional and emerging concepts around the initiation and maintenance of organ dysfunction in cirrhosis and proposes a new paradigm based upon a better understanding of acute decompensation of cirrhosis. The interaction between the traditional concepts and the emerging perspectives remains a matter of great interest and the basis for future research.
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Affiliation(s)
- Rajiv Jalan
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Liver Failure Group, Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
| | - Gennaro D'Amico
- Gastroenterology Unit, Ospedale Cervello and University of Palermo, Italy
| | - Jonel Trebicka
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; JW Goethe University Hospital, Frankfurt, Germany
| | - Richard Moreau
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L'Inflammation, Paris, France
| | - Paolo Angeli
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; University of Padova, Padova, Italy
| | - Vicente Arroyo
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
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Engelmann C, Clària J, Szabo G, Bosch J, Bernardi M. Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction. J Hepatol 2021; 75 Suppl 1:S49-S66. [PMID: 34039492 PMCID: PMC9272511 DOI: 10.1016/j.jhep.2021.01.002] [Citation(s) in RCA: 203] [Impact Index Per Article: 50.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/31/2020] [Accepted: 01/04/2021] [Indexed: 02/07/2023]
Abstract
Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes.
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Affiliation(s)
- Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany; Institute for Liver and Digestive Health, University College London, London, United Kingdom; Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
| | - Joan Clària
- European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain,Biochemistry and Molecular Genetics Service, Hospital ClínicIDIBAPS and CIBERehd, Spain,Department of Biomedical Sciences, University of Barcelona, Barcelona, Spain
| | - Gyongyi Szabo
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Jaume Bosch
- IDIBAPS and CIBERehd, University of Barcelona, Barcelona, Spain,Department for Biomedical Research (DBMR), Bern University, Bern, Switzerland
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences; Alma Mater Studiorum – University of Bologna; Italy
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Morelli MC, Rendina M, La Manna G, Alessandria C, Pasulo L, Lenci I, Bhoori S, Messa P, Biancone L, Gesualdo L, Russo FP, Petta S, Burra P. Position paper on liver and kidney diseases from the Italian Association for the Study of Liver (AISF), in collaboration with the Italian Society of Nephrology (SIN). Dig Liver Dis 2021; 53 Suppl 2:S49-S86. [PMID: 34074490 DOI: 10.1016/j.dld.2021.03.035] [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: 02/16/2021] [Revised: 03/31/2021] [Accepted: 03/31/2021] [Indexed: 02/07/2023]
Abstract
Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.
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Affiliation(s)
- Maria Cristina Morelli
- Internal Medicine Unit for the treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di S.Orsola, Bologna, Italy, Via Albertoni 15, 40138, Bologna, Italy
| | - Maria Rendina
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Policlinic Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Gaetano La Manna
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St. Orsola Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Torino, Corso Bramante 88, 10126, Torino, Italy
| | - Luisa Pasulo
- Gastroenterology and Transplant Hepatology, "Papa Giovanni XXIII" Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | - Ilaria Lenci
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome Viale Oxford 81, 00133, Rome, Italy
| | - Sherrie Bhoori
- Hepatology and Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS, Istituto Nazionale Tumori, Via Giacomo Venezian, 1, 20133, Milan, Italy
| | - Piergiorgio Messa
- Unit of Nephrology, Università degli Studi di Milano, Via Commenda 15, 20122, Milano, Italy; Nephrology, Dialysis and Renal Transplant Unit-Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Via Commenda 15, 20122 Milano, Italy
| | - Luigi Biancone
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, Città Della Salute e della Scienza Hospital, University of Turin, Corso Bramante, 88-10126, Turin, Italy
| | - Loreto Gesualdo
- Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, Università degli Studi di Bari "Aldo Moro", Piazza G. Cesare 11, 70124, Bari, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Piazza delle Cliniche, 2 90127, Palermo, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy.
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Kumar R, Priyadarshi RN, Anand U. Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol 2021; 27:990-1005. [PMID: 33776368 PMCID: PMC7985728 DOI: 10.3748/wjg.v27.i11.990] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/17/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) in patients with liver cirrhosis has become a new frontier in hepatology. In recent years, a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis. The rising prevalence of risk factors, such as diabetes, hypertension and nonalcoholic fatty liver disease, appears to have contributed significantly to the high prevalence of CKD. Moreover, the diagnosis of CKD in cirrhosis is now based on a reduction in the estimated glomerular filtration rate of < 60 mL/min over more than 3 mo. This definition has resulted in a better differentiation of CKD from acute kidney injury (AKI), leading to its greater recognition. It has also been noted that a significant proportion of AKI transforms into CKD in patients with decompensated cirrhosis. CKD in cirrhosis can be structural CKD due to kidney injury or functional CKD secondary to circulatory and neurohormonal imbalances. The available literature on combined cirrhosis-CKD is extremely limited, as most attempts to assess renal dysfunction in cirrhosis have so far concentrated on AKI. Due to problems related to glomerular filtration rate estimation in cirrhosis, the absence of reliable biomarkers of CKD and technical difficulties in performing renal biopsy in advanced cirrhosis, CKD in cirrhosis can present many challenges for clinicians. With combined hepatorenal dysfunctions, fluid mobilization becomes problematic, and there may be difficulties with drug tolerance, hemodialysis and decision-making regarding the need for liver vs simultaneous liver and kidney transplantation. This paper offers a thorough overview of the increasingly known CKD in patients with cirrhosis, with clinical consequences and difficulties occurring in the diagnosis and treatment of such patients.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Rajeev Nayan Priyadarshi
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Scurt FG, Bose K, Canbay A, Mertens PR, Chatzikyrkou C. [Acute kidney injury following acute pancreatitis (AP-AKI): Definition, Pathophysiology, Diagnosis and Therapy]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:1241-1266. [PMID: 33291178 DOI: 10.1055/a-1255-3413] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis (AP) is the most frequent gastrointestinal cause for hospitalization and one of the leading causes of in-hospital deaths. Severe acute pancreatitis is often associated with multiorgan failure and especially with acute kidney injury (AKI). AKI can develop early or late in the course of the disease and is a strong determinator of outcome. The mortality in the case of dialysis-dependent AKI and acute pancreatitis raises exponentially in the affected patients. AP-induced AKI (AP-AKI) shows many similarities but also distinct differences to other causes of AKI occurring in the intensive care unit setting. The knowledge of the exact pathophysiology can help to adjust, control and improve therapeutic approaches to the disease. Unfortunately, there are only a few studies dealing with AP and AKI.In this review, we discuss recent data about pathogenesis, causes and management of AP-AKI in patients with severe acute pancreatitis and exploit in this regard the diagnostic and prognostic potential of respective newer serum and urine markers.
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Affiliation(s)
- Florian Gunnar Scurt
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg, Germany
| | - Katrin Bose
- Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg, Germany.,Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Otto-von-Guericke-Universität, Magdeburg, Deutschland
| | - Ali Canbay
- Ruhr-Universität Bochum, Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland
| | - Peter R Mertens
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg, Germany
| | - Christos Chatzikyrkou
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg, Germany
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36
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Gallo A, Dedionigi C, Civitelli C, Panzeri A, Corradi C, Squizzato A. Optimal Management of Cirrhotic Ascites: A Review for Internal Medicine Physicians. J Transl Int Med 2020; 8:220-236. [PMID: 33511049 PMCID: PMC7805288 DOI: 10.2478/jtim-2020-0035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Clinical history of liver cirrhosis is characterised by two phases: the asymptomatic phase, also termed 'compensated cirrhosis', and the phase of complications due to the development of portal hypertension and liver dysfunction, also termed 'decompensated cirrhosis', in which patients may develop ascites, the most frequent and clinically relevant complication of liver cirrhosis. Ascites can be classified into uncomplicated and complicated according to the development of refractoriness, spontaneous bacterial peritonitis (SBP) or the association with hepatorenal syndrome (HRS). In this narrative review, we will extensively discuss the optimal pharmacological and non-pharmacological management of cirrhotic ascites with the aim to offer an updated practical guide to Internal Medicine physicians. According to the amount of fluid in the abdominal cavity, uncomplicated ascites is graded from 1 to 3, and the cornerstone of its management consists of restriction of salt intake, diuretics and large-volume paracentesis (LVP); in recent years, long-term administration of human albumin has acquired a new interesting role. Refractory ascites is primarily managed with LVP and transjugular intrahepatic portosystemic shunt (TIPS) placement in selected patients. The occurrence of renal impairment, especially HRS, worsens the prognosis of patients with cirrhotic ascites and deserves a specific treatment. Also, the management of SBP faces the rising and alarming spread of antibiotic resistance. Hepatic hydrothorax may even complicate the course of the disease and its management is a challenge. Last but not least, liver transplantation (LT) is the ultimate and more effective measure to offer to patients with cirrhotic ascites, particularly when complications occur.
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Affiliation(s)
- Andrea Gallo
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Cristina Dedionigi
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Chiara Civitelli
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Anna Panzeri
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
- Hepatology Center, Ospedale Sant’Anna, Como, Italy
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Renal disease in the allograft recipient. Best Pract Res Clin Gastroenterol 2020; 46-47:101690. [PMID: 33158468 DOI: 10.1016/j.bpg.2020.101690] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]
Abstract
Chronic renal failure after liver transplantation (LT) is significantly more frequent than after lung or heart transplantation and it results in an increased short and long-term mortality. Renal impairment may occur before LT (functional or due to preexisting parenchymal kidney disease), in the peri-operative period or later after LT. The number of patients with renal failure after LT has increased due to the liver allocation based on MELD and to the more liberal use of higher risk grafts. Calcineurin inhibitor (CNI) nephrotoxicity is the most important cause of renal dysfunction but is a modifiable factor. Strategy to prevent CNI-associated nephrotoxicity is post-op CNI minimization by induction therapy and reduced dose and/or delayed introduction of CNI in combination with mycophenolate mofetil (MMF) or everolimus with no penalty in term of rejection. With everolimus, usually started one month after LT, a drastic minimization of CNI is possible and this results in superior kidney function until at least 3 years follow up. At the moment of renal impairment a drastic reduction of CNI dose together with the introduction of MMF results in an improvement in GFR at 6 to 2 years with a low rate of acute rejection. However, secondary prevention fails to normalize renal function in most of the patients once e GFR <60 ml/min/1.73m2ml.
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Francoz C. Acute kidney injury in cirrhosis: An immediate threat but also a ticking time bomb. J Hepatol 2020; 72:1043-1045. [PMID: 32197803 DOI: 10.1016/j.jhep.2020.02.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 02/16/2020] [Indexed: 02/08/2023]
Affiliation(s)
- Claire Francoz
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, France, INSERM U1149, Centre de Recherche sur l'Inflammation, Paris, France.
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Trojnar E, Erdelyi K, Matyas C, Zhao S, Paloczi J, Mukhopadhyay P, Varga ZV, Hasko G, Pacher P. Cannabinoid-2 receptor activation ameliorates hepatorenal syndrome. Free Radic Biol Med 2020; 152:540-550. [PMID: 31770583 DOI: 10.1016/j.freeradbiomed.2019.11.027] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 11/21/2019] [Indexed: 02/07/2023]
Abstract
STUDY RATIONALE Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease characterized by the rapid decline of kidney function. Herein, we explored the therapeutic potential of targeting the cannabinoid-2 receptor (CB2-R) utilizing a commonly used mouse model of liver fibrosis and hepatorenal syndrome (HRS), induced by bile duct ligation (BDL). METHODS Gene expression analysis, histological evaluation, determination of serum levels of renal injury-biomarkers were used to characterize the BDL-induced organ injury; laser speckle analysis to measure microcirculation in the kidneys. KEY RESULTS We found that liver injury triggered marked inflammation and oxidative stress in the kidneys of BDL-operated mice. We detected pronounced histopathological alterations with tubular injury paralleled with increased inflammation, oxidative/nitrative stress and fibrotic remodeling both in hepatic and renal tissues as well as endothelial activation and markedly impaired renal microcirculation. This was accompanied by increased CB2-R expression in both the liver and the kidney tissues of diseased animals. A selective CB2-R agonist, HU-910, markedly decreased numerous markers of inflammation, oxidative stress and fibrosis both in the liver and in the kidneys. HU-910 also attenuated markers of kidney injury and improved the impaired renal microcirculation in BDL-operated mice. CONCLUSIONS Our results suggest that oxidative stress, inflammation and microvascular dysfunction are key events in the pathogenesis of BDL-associated renal failure. Furthermore, we demonstrate that targeting the CB2-R by selective agonists may represent a promising new avenue to treat HRS by attenuating tissue and vascular inflammation, oxidative stress, fibrosis and consequent microcirculatory dysfunction in the kidneys.
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Affiliation(s)
- Eszter Trojnar
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Katalin Erdelyi
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Csaba Matyas
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Suxian Zhao
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Janos Paloczi
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Partha Mukhopadhyay
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Zoltan V Varga
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
| | - Gyorgy Hasko
- Department of Anesthesiology, Columbia University, New York, NY, 10032, USA.
| | - Pal Pacher
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism (NIAAA), 5625 Fishers Lane, 20852, Rockville, MD, USA.
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Siavashpour A, Khalvati B, Azarpira N, Mohammadi H, Niknahad H, Heidari R. Poly (ADP-Ribose) polymerase-1 (PARP-1) overactivity plays a pathogenic role in bile acids-induced nephrotoxicity in cholestatic rats. Toxicol Lett 2020; 330:144-158. [PMID: 32422328 DOI: 10.1016/j.toxlet.2020.05.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 05/05/2020] [Accepted: 05/11/2020] [Indexed: 02/07/2023]
Abstract
Cholestatic liver disease is a clinical complication with a wide range of etiologies. The liver is the primary organ influenced by cholestasis. Other organs, rather than the liver (e.g., kidneys), could also be affected by cholestatic liver disease. Cholestasis-induced renal injury is known as cholemic nephropathy (CN). Although the structural and functional alterations of the kidney in cholestasis have been well described, the cellular and molecular mechanisms of CN are not well understood. Some studies mentioned the role of oxidative stress and mitochondrial impairment in CN. Several cellular targets, including proteins, lipids, and DNA, could be affected by oxidative stress. Poly (ADP-Ribose) polymerase-1 (PARP-1) is an enzyme that its physiological activity plays a fundamental role in DNA repair. However, PARP-1 overexpression is associated with enhanced oxidative stress and cell death. The current study was designed to evaluate the role of PARP-1 activity in the pathogenesis of CN. Bile duct ligated (BDL) rats were treated with nicotinamide (NA) as a PARP-1 inhibitor. Kidney, urine, and plasma samples were collected at scheduled time intervals (3, 7, 14, and 28 days after BDL surgery). Serum and urine biomarkers of kidney injury, markers of oxidative stress and DNA damage, PARP-1 expression and activity in the kidney tissue, inflammatory response, renal fibrosis markers, and kidney histopathological alterations were assessed. Significant changes in the serum and urine biomarkers of kidney injury were evident in the BDL rats. Markers of oxidative stress were increased, and tissue ATP levels and antioxidant capacity were decreased in the kidney of cholestatic animals. A significant increase in PARP-1 expression and activity was evident in BDL rats (3, 7, 14, and 28 days after BDL). Moreover, inflammatory response (IL-1β and TNF-α expression; and myeloperoxidase activity), renal tissue histopathological alterations, and kidney fibrosis (α-SMA and TGF-β expression, as well as collagen deposition) were detected in cholestatic animals. It was found that the PARP-1 inhibitor, NA (50 and 100 mg/kg, i.p), significantly mitigated cholestasis-induced renal injury. The positive effects of NA were more significant at a lower dose and the early stage of CN. These data indicate a pathogenic role for PARP-1 overexpression in CN.
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Affiliation(s)
- Asma Siavashpour
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bahman Khalvati
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamidreza Mohammadi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Niknahad
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Reza Heidari
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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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.
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Garcia-Tsao G, Angeli P, Nadim MK, Parikh CR. Reply to: "Lack of evidence for a continuum between hepatorenal syndrome and acute tubular necrosis". J Hepatol 2020; 72:582-583. [PMID: 31810532 DOI: 10.1016/j.jhep.2019.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 11/06/2019] [Indexed: 01/17/2023]
Affiliation(s)
- Guadalupe Garcia-Tsao
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA; Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Italy.
| | - Mitra K Nadim
- Division of Nephrology & Hypertension, Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Chirag R Parikh
- Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
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Solé C, Solà E, Kamath PS, Ginès P. Lack of evidence for a continuum between hepatorenal syndrome and acute tubular necrosis. J Hepatol 2020; 72:581-582. [PMID: 31836264 DOI: 10.1016/j.jhep.2019.09.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 09/22/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Cristina Solé
- Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain
| | - Elsa Solà
- Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain.
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Pere Ginès
- Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain
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Maiwall R, Pasupuleti SSR, Bihari C, Rastogi A, Singh PK, Naik V, Singh A, Jain P, Kumar A, Mukund A, Mathur RP, Kumar G, Sarin SK. Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study. Hepatology 2020; 71:1009-1022. [PMID: 31313333 DOI: 10.1002/hep.30859] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 07/07/2019] [Indexed: 02/06/2023]
Abstract
Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07-2.33), episodes of previous AKI (SHR, 1.26; 1.02-1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30-8.25] vs. stage 2 [SHR, 4.33; 1.76-10.66] vs. stage 3 [SHR, 4.5; 1.59-12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR, 1.01; 1.00-1.03), number of AKI episodes (SHR, 1.25; 1.15-1.37), and CysC (SHR, 1.38; 1.01-1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one-third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Vini Naik
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akanksha Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Priyanka Jain
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Awinash Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - R P Mathur
- Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Bodh V, Sharma B, Sharma R. Hepatorenal syndrome: A review into changing definition, diagnostic criteria, pathophysiology, and management. CHRISMED JOURNAL OF HEALTH AND RESEARCH 2020. [DOI: 10.4103/cjhr.cjhr_117_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Wadei HM, Abader P, Alsaad AA, Croome K, Cortese C, Geiger XJ, Khouzam S, Mai ML, Taner CB, Keaveny AP. Arterial Blood Pressure at Liver Transplant Evaluation Predicts Renal Histology in Candidates With Renal Dysfunction. Liver Transpl 2019; 25:1756-1767. [PMID: 31597218 DOI: 10.1002/lt.25651] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Accepted: 09/16/2019] [Indexed: 12/14/2022]
Abstract
Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre-LT predictors of potentially reversible renal injury using histological information obtained on pre-LT renal biopsy. Data on 128 LT candidates who underwent pre-LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End-Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision-making process to list patients with renal dysfunction for LT alone versus simultaneous liver-kidney transplantation.
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Affiliation(s)
- Hani M Wadei
- Department of Transplant, Mayo Clinic, Jacksonville, FL
| | - Peter Abader
- Department of Transplant, Mayo Clinic, Jacksonville, FL
| | - Ali A Alsaad
- Department of Internal Medicine, Mayo Clinic, Jacksonville, FL
| | | | - Cherise Cortese
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL
| | | | - Samir Khouzam
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL
| | - Martin L Mai
- Department of Transplant, Mayo Clinic, Jacksonville, FL
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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.
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News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document. J Hepatol 2019; 71:811-822. [PMID: 31302175 DOI: 10.1016/j.jhep.2019.07.002] [Citation(s) in RCA: 272] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 06/13/2019] [Accepted: 07/04/2019] [Indexed: 12/12/2022]
Abstract
Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease. Hepatorenal syndrome (HRS) has been defined as a purely "functional" type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems.4,5 In 2007, the International Club of Ascites (ICA) classified HRS into types 1 and 2 (HRS-1 and HRS-2).5 HRS-1 is characterised by a rapid deterioration of renal function that often occurs because of a precipitating event, while HRS-2 is a moderate and stable or slowly progressive renal dysfunction that often occurs without an obvious precipitant. Clinically, HRS-1 is characterised by acute renal failure while HRS-2 is mainly characterised by refractory ascites. Nevertheless, after these two entities were first described, new concepts, definitions, and diagnostic criteria have been developed by nephrologists for renal dysfunction in the general population and hospitalised patients. In particular, the definitions and characterisation of acute kidney injury (AKI), acute kidney disease and chronic kidney disease have been introduced/refined.6 Accordingly, a debate among hepatologists of the ICA led to a complete revision of the nomenclature and diagnosistic criteria for HRS-1, which was renamed HRS-AKI.7 Additionally, over recent years, greater granularity has been gained regarding the pathogenesis of HRS; it is now increasingly recognised that it is not a purely "functional" entity with haemodynamic derangements, but that systemic inflammation, oxidative stress and bile salt-related tubular damage may contribute significantly to its development. That is, HRS has an additional structural component that would not only make traditional diagnostic criteria less reliable, but would explain the lack of response to pharmacological treatment with vasoconstrictors plus albumin that correlates with a progressive increase in inflammation. Because classification, nomenclature, diagnostic criteria and pathogenic theories have evolved over the years since the traditional classification of HRS-1 and HRS-2 was first described, it was considered that all these novel aspects be reviewed and summarised in a position paper. The aim of this position paper authored by two hepatologists (members of ICA) and two nephrologists involved in the study of renal dysfunction in cirrhosis, is to complete the re-classification of HRS initiated by the ICA in 2012 and to provide an update on the definition, classification, diagnosis, pathophysiology and treatment of HRS.
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Zhang J, Rössle M, Zhou X, Deng J, Liu L, Qi X. Terlipressin for the treatment of hepatorenal syndrome: an overview of current evidence. Curr Med Res Opin 2019; 35:859-868. [PMID: 30474439 DOI: 10.1080/03007995.2018.1552575] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Revised: 11/16/2018] [Accepted: 11/22/2018] [Indexed: 02/07/2023]
Abstract
Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis, which is of pre-renal origin due to central volume depletion together with cardiac dysfunction and characterized by oliguria with severe urinary sodium retention and elevated serum creatinine levels. HRS is divided into HRS I, which is rapidly progressive and mostly seen in patients with decompensated liver cirrhosis, and HRS II, which progresses more slowly and is always accompanied by gross ascites. Liver transplantation is the best choice of treatment for HRS but rarely available. Current mainstay pharmacological therapies are vasoconstrictors, such as terlipressin, noradrenaline and dopamine, in combination with albumin. This paper aims to overview the current evidence regarding outcomes of terlipressin for the treatment of HRS.
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Affiliation(s)
- Jingqiao Zhang
- a Department of Gastroenterology , General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area) , Shenyang , China
- b Department of Pharmacology , General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Millitary Area) , Shenyang , China
- c Postgraduate College, Shenyang Pharmaceutical University , Shenyang , China
| | - Martin Rössle
- d Department of Internal Medicine II , University of Freiburg , Freiburg , Germany
| | - Xinmiao Zhou
- e Postgraduate College, Jinzhou Medical University , Jinzhou , China
| | - Jiao Deng
- b Department of Pharmacology , General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Millitary Area) , Shenyang , China
| | - Lu Liu
- f Section of Medical Service, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area) , Shenyang , China
| | - Xingshun Qi
- a Department of Gastroenterology , General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area) , Shenyang , China
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Piano S, Tonon M, Angeli P. Ascites, Hyponatremia, Spontaneous Bacterial Peritonitis, and Hepatorenal Syndrome. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:662-675. [DOI: 10.1002/9781119211419.ch43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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