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Patidar KR, Ma AT, Juanola A, Barone A, Incicco S, Kulkarni AV, Hernández JLP, Wentworth B, Asrani SK, Alessandria C, Abdelkader NA, Wong YJ, Xie Q, Pyrsopoulos NT, Kim SE, Fouad Y, Torre A, Cerda E, Ferrer JD, Maiwall R, Simonetto DA, Papp M, Orman ES, Perricone G, Solé C, Lange CM, Farias AQ, Pereira G, Gadano A, Caraceni P, Thevenot T, Verma N, Kim JH, Vorobioff JD, Cordova-Gallardo J, Ivashkin V, Roblero JP, Maan R, Toledo C, Gioia S, Fassio E, Marino M, Nabilou P, Vargas V, Merli M, Goncalves LL, Rabinowich L, Krag A, Balcar L, Montes P, Mattos AZ, Bruns T, Mohammed A, Laleman W, Carrera E, Cabrera MC, Girala M, Samant H, Raevens S, Madaleno J, Kim RW, Arab JP, Presa J, Ferreira CN, Galante A, Allegretti AS, Takkenberg B, Marciano S, Sarin SK, Durand F, Ginès P, Angeli P, Solà E, Piano S. Global epidemiology of acute kidney injury in hospitalised patients with decompensated cirrhosis: the International Club of Ascites GLOBAL AKI prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol 2025; 10:418-430. [PMID: 40058397 DOI: 10.1016/s2468-1253(25)00006-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 01/03/2025] [Accepted: 01/06/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a serious complication of cirrhosis. A systematic, global characterisation of AKI occurring in patients with cirrhosis is lacking. We therefore aimed to assess global differences in the characteristics, management, and outcomes of AKI in hospitalised patients with cirrhosis. METHODS In this prospective, multicentre, cohort study, we enrolled adults (≥18 years) with decompensated cirrhosis who were hospitalised for a cirrhosis-related complication, with or without AKI, at 65 centres across five continents. We captured AKI prevalence, stage, phenotype, and details on AKI management and clinical course. Universal health coverage index and gross national income per capita were also collected. The primary outcome was 28-day mortality. Multivariable models including demographic and clinical variables, cirrhosis cause, cirrhosis severity, AKI severity, AKI management variables, universal health coverage, and gross national income were used to analyse independent associations with 28-day mortality. Secondary outcomes were AKI classification, progression, and resolution. This study is complete and registered with ClinicalTrials.gov (NCT05387811). FINDINGS Between July 1, 2022, and May 31, 2023, we enrolled 3821 patients who were hospitalised for decompensated cirrhosis. Mean age was 57·7 years (SD 13·1), 2467 (64·6%) were men, and 1354 (35·4%) were women. Most patients were White (2128 [55·7%]). 1456 (38·1%, 95% CI 36·6-39·6) of 3821 patients had AKI (943 [64·8%] men and 513 [35·2%] women). Globally, patients presented with similar AKI stages, but patients from North America and Asia had the highest MELD-Na scores at presentation and the highest rates of peak AKI stage 3. Overall, hypovolaemic AKI was the most common phenotype (858 [58·9%] of 1456), followed by HRS-AKI (253 [17·4%]) and acute tubular necrosis (216 [14·8%]). The prevalences of hypovolaemic AKI and HRS-AKI were similar across regions, but acute tubular necrosis was more frequent in Asia (p<0·0001 across regions). Additionally, regional differences in the management of AKI (use of albumin, vasopressors, and diuretics) were found. 335 (28·6%) of 1171 patients with initial AKI stages 1 or 2 had progression to higher stages during hospitalisation. AKI resolved in 862 (59·2%) cases during hospitalisation. 333 (22·9%) patients with AKI had died by 28 days. Multivariable analyses showed that increased age, female sex, presence of ascites, presence of hepatic encephalopathy, increased white blood cell count, increased MELD-Na, hospital-acquired AKI, a lower universal health coverage index (<80), and not being in a high-income country were independently associated with an increased risk of 28-day mortality. Increased serum albumin was associated with a decreased risk of 28-day mortality. INTERPRETATION This study found important regional differences in AKI severity, phenotype, management, and outcomes in patients with decompensated cirrhosis. Health-care coverage remains an important driver of survival in patients with cirrhosis and AKI. FUNDING European Association Study for the Study of the Liver and the Italian Society of Internal Medicine.
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Affiliation(s)
- Kavish R Patidar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Ann T Ma
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
| | - Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Anna Barone
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | - Simone Incicco
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | | | - José Luis Pérez Hernández
- Department of Gastroenterology and Hepatology, Hospital General de México Dr Eduardo Liceaga, Mexico City, Mexico
| | - Brian Wentworth
- Division of Gastroenterology and Hepatology, University of Virginia School of Medicine, Charlottesville, VA, USA
| | | | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, University of Turin, Turin, Italy
| | | | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore; Duke-NUS Medical School, Singapore
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Nikolaos T Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Sung-Eun Kim
- Division of Gastroenterology and Hepatology, Hallym University College of Medicine, Chuncheon, South Korea
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Minia University, Minia, Egypt
| | - Aldo Torre
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Eira Cerda
- Central Military Hospital, Mexico City, Mexico
| | - Javier Diaz Ferrer
- Departamento del Aparato Digestivo, Hospital Edgardo Rebagliati-Clínica Internacional, Lima, Peru
| | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, NY, USA
| | - Maria Papp
- Division of Gastroenterology, Kalman Laki Doctoral School of Biomedical and Clinical Sciences, and Institute of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Eric S Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Giovanni Perricone
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Cristina Solé
- Gastroenterology and Hepatology Department, Parc Taulí University Hospital, Sabadell, Spain; Institut d'investigació i innovació Parc Taulí, Sabadell, Spain; CiberEHD, Madrid, Spain
| | - Christian M Lange
- Department of Medicine II, LMU University Hospital Munich, Munich, Germany
| | | | - Gustavo Pereira
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil
| | - Adrian Gadano
- Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-related diseases, IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Thierry Thevenot
- Department of Hepatology, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jeong Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea
| | - Julio D Vorobioff
- Gastroenterology Department and Liver Unit, University of Rosario Medical School, Rosario, Argentina
| | | | - Vladimir Ivashkin
- Department of Internal Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Juan Pablo Roblero
- Departamento de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Claudio Toledo
- Gastroenterology Unit, Universidad Australe de Chile, Valdivia, Chile
| | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Eduardo Fassio
- Gastroenterology Department and Liver Unit, Hospital Nacional Prof Alejandro Posadas, Buenos Aires, Argentina
| | - Monica Marino
- Liver Unit, Carlos Bonorino Udaondo Hospital, Buenos Aires, Argentina
| | - Puria Nabilou
- Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Victor Vargas
- Liver Unit, Hospital Vall d'Hebron, Universitat Autònoma, Barcelona, Spain
| | - Manuela Merli
- Department of Translational and Precision Medicine, Universita' degli Studi di Roma Sapienza, Roma, Italy
| | - Luciana Lofego Goncalves
- Serviço de Gastroenterologia, University Hospital-Federal University of Espirito Santo, Vitòria, Brazil
| | - Liane Rabinowich
- Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Gastroenterology, Tel Aviv University, Tel Aviv, Israel
| | - Aleksander Krag
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Pedro Montes
- Servicio de Gastroenterología, Hospital Nacional Daniel A Carrion, Bellavista, Peru
| | - Angelo Z Mattos
- Gastroenterology and Hepatology Unit, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Tony Bruns
- Medical Department III, University Hospital RWTH Aachen, Aachen, Germany
| | | | - Wim Laleman
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU LEUVEN, Leuven, Belgium; Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany
| | - Enrique Carrera
- Departamento de Gastroenterologia y Hepatologia, Hospital Eugenio Espejo, Universidad San Francisco de Quito, Quito, Ecuador
| | - María Cecilia Cabrera
- Gastroenterology Unit, Guillermo Almenara Hospital, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Marcos Girala
- Departamento de Gastroenterología, Universidad Nacional de Asunciòn, Asunciòn, Paraguay
| | - Hrishikesh Samant
- Department of Hepatology, Ochsner Transplant Center, New Orleans, LA, USA
| | - Sarah Raevens
- Liver Research Centre Ghent, Ghent University Hospital, Ghent, Belgium
| | - Joao Madaleno
- Internal Medicine Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal
| | - Ray W Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Juan Pablo Arab
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile; Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - José Presa
- Liver Unit, Centro Hospitalar de Trásos-Montes e Alto Douro, Vila Real, Portugal
| | - Carlos Noronha Ferreira
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Unidade Local de Saúde Santa Maria, Lisbon, Portugal
| | - Antonio Galante
- Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland
| | | | - Bart Takkenberg
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | | | - Shiv K Sarin
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - François Durand
- Hepatology and Liver Intensive Care, Beaujon Hospital, Clichy, France
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | - Elsa Solà
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy.
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Zhong HJ, Chen JY, Wu WM, He XX, Zhan YQ. Clinical significance of platelet-to-white blood cell ratio in patients with Wilson disease: a retrospective cohort study. PeerJ 2025; 13:e19379. [PMID: 40321812 PMCID: PMC12047222 DOI: 10.7717/peerj.19379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 04/07/2025] [Indexed: 05/08/2025] Open
Abstract
Objective To assess the correlation between the platelet-to-white blood cell ratio (PWR) and the severity of liver dysfunction, hepatic complications, and prognosis in Wilson disease (WD) patients. Methods A retrospective analysis was conducted on medical records from January 1, 2016, to March 30, 2022. Both univariate and multivariate analyses were performed to examine the impact of a low PWR (<26.3) on WD severity, liver complications, and disease progression. Additionally, the effect of splenectomy on PWR was evaluated. Results The study included 315 patients with WD, among whom 105 had a low PWR and 210 had a high PWR. Those with low PWR exhibited significantly elevated levels of bilirubin, international normalized ratio, prothrombin time, procollagen type-III N-terminal propeptide, type IV collagen, hyaluronic acid, and portal vein diameter. Conversely, they had lower levels of albumin, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (all P < 0.05). A low PWR correlated with a greater incidence of splenomegaly/hypersplenism, esophagogastric varices, and ascites (all P < 0.05). Furthermore, low PWR independently predicted hepatic decompensation (P < 0.05), and splenectomy led to a marked increase in PWR among WD patients (P < 0.001). Conclusion A low PWR in WD patients is linked to heightened disease severity, increased risk of liver complications, and rapid progression to decompensation. The results imply that splenectomy, by enhancing PWR, may serve as a viable strategy to slow WD progression.
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Affiliation(s)
- Hao-Jie Zhong
- Shenzhen Second People’s Hospital, Shenzhen, China
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Jun-Yi Chen
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Wei-Ming Wu
- Shenzhen Second People’s Hospital, Shenzhen, China
| | - Xing-Xiang He
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
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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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Fu L, Yokus B, Gao B, Pacher P. An Update on IL-22 Therapies in Alcohol-Associated Liver Disease and Beyond. THE AMERICAN JOURNAL OF PATHOLOGY 2025:S0002-9440(25)00117-8. [PMID: 40254130 DOI: 10.1016/j.ajpath.2025.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 04/22/2025]
Abstract
Excessive alcohol consumption drives the development of alcohol-associated liver disease (ALD), including steatohepatitis, cirrhosis, and hepatocellular carcinoma, and its associated complications, such as hepatorenal syndrome. Hepatocyte death, inflammation, and impaired liver regeneration are key processes implicated in the pathogenesis and progression of ALD. Despite extensive research, therapeutic options for ALD remain limited. IL-22 has emerged as a promising therapeutic target because of its hepatoprotective properties mediated through the activation of the STAT3 signaling pathway. IL-22 enhances hepatocyte survival by mitigating apoptosis, oxidative stress, and inflammation while simultaneously promoting liver regeneration through the proliferation of hepatocytes and hepatic progenitor cells and the up-regulation of growth factors. Additionally, IL-22 exerts protective effects on epithelial cells in various organs affected by ALD and its associated complications. Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration. However, the heterogeneity and multifactorial nature of ALD present ongoing challenges. Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits, and limitations.
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Affiliation(s)
- Lihong Fu
- Laboratory of Cardiovascular Physiology and Tissue Injury, NIH/National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
| | - Burhan Yokus
- Laboratory of Cardiovascular Physiology and Tissue Injury, NIH/National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
| | - Bin Gao
- Laboratory of Liver Diseases, NIH/National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
| | - Pal Pacher
- Laboratory of Cardiovascular Physiology and Tissue Injury, NIH/National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
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Schleicher EM, Karbannek H, Weinmann-Menke J, Galle PR, Stallmach A, Gairing SJ, Zipprich A, Ripoll C, Labenz C. Effect of albumin treatment duration on response rates and outcomes in patients with cirrhosis and acute kidney injury. J Hepatol 2025:S0168-8278(25)00164-3. [PMID: 40118117 DOI: 10.1016/j.jhep.2025.03.008] [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: 12/06/2024] [Revised: 03/05/2025] [Accepted: 03/11/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND & AIMS Guidelines recommended volume expansion with albumin for 48 hours for patients with cirrhosis and acute kidney injury (AKI) to correct hypovolemia and rule out prerenal AKI. A recent update in the ADQI-ICA consensus guidelines suggested shortening this duration to 24 hours, primarily based on expert opinion. This study aimed to evaluate the response rates to albumin treatment after 24 and 48 hours and to compare and assess the prognostic significance of three different definitions of response to albumin therapy. METHODS Data from 127 prospectively recruited patients with cirrhosis and AKI from two German centers were analyzed. We examined three response definitions after 24 and 48 hours: (1) serum creatinine (SCr) decrease >0.3 mg/dl, (2) SCr decrease >25%, and (3) SCr decrease in at least one AKI stage. Follow-up was prolonged until liver transplantation, death or hemodialysis. RESULTS Overall, 30-54% of the patients responded to albumin treatment depending on the definition, and response rates were balanced across AKI stages. Notably, a relevant number of patients who responded at 48 hours did not respond within the first 24 hours. Additional responses to albumin during the second 24 hours according to definitions 1, 2, and 3 were 28%, 22%, and 18%, respectively. Response according to definition 3 was associated with higher hemodialysis- and transplantation-free survival rates. CONCLUSION A substantial proportion of patients require 48 hours to respond to albumin treatment. Shortening the duration of albumin therapy may lead to overtreatment with terlipressin. IMPACT AND IMPLICATIONS This study provides valuable insights into the optimal duration of albumin treatment for patients with cirrhosis and acute kidney injury, challenging the recent recommendation to shorten the duration of albumin treatment. Furthermore, the optimal definition for response to albumin (reduction of at least one acute kidney injury stage) has been assessed. The results of this study are highly clinically relevant since shortening albumin therapy may lead to overtreatment with terlipressin, and evidence to support a specific definition of response to albumin was lacking. Clinicians can use these findings to predict treatment outcomes better, avoid fluid overload, and improve patient prognosis, while also considering the potential risks of early intervention with terlipressin.
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Affiliation(s)
- Eva Maria Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Henrik Karbannek
- Clinic for Internal Medicine IV, Jena University Hospital, Friedrich-Schiller University Jena, Germany
| | - Julia Weinmann-Menke
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Research Center of Immunotherapy, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Andreas Stallmach
- Clinic for Internal Medicine IV, Jena University Hospital, Friedrich-Schiller University Jena, Germany
| | - Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Alexander Zipprich
- Clinic for Internal Medicine IV, Jena University Hospital, Friedrich-Schiller University Jena, Germany
| | - Cristina Ripoll
- Clinic for Internal Medicine IV, Jena University Hospital, Friedrich-Schiller University Jena, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
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Mattos ÂZ, Dornelles CMR, Schiavon LDL, Mendes LSC, de Carvalho Filho RJ, Codes L, Farias AQ, Álvares-da-Silva MR, Terra C, Pereira G, Manica M, Bischoff HM, Narciso-Schiavon JL, Romeres SGB, Garcia JB, Bittencourt PL, Ximenes RO, Arrojo RS, Mattos AA. Acute kidney injury stage 1a increases mortality of patients with cirrhosis: a prospective multicenter cohort study. Hepatol Int 2025:10.1007/s12072-025-10790-x. [PMID: 40014296 DOI: 10.1007/s12072-025-10790-x] [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: 10/17/2024] [Accepted: 02/04/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND AND AIMS Acute kidney injury is a severe complication of cirrhosis. However, the impact of mild decreases in renal function is controversial. This study aims to evaluate the prognosis of the different stages of acute kidney injury in cirrhosis. METHODS This is a multicenter prospective cohort study of patients hospitalized for acute decompensation of cirrhosis, with serum creatinine values measured at least twice. Primary outcome was mortality (in-hospital, 30 days, 90 days and 12 months). RESULTS Nine hundred twenty-eight patients were included in the study. Acute kidney injury was diagnosed in 505 patients (stages 1a-21.6%, 1b-27.5%, 2-28.1%, 3-22.8%). Mortality rates of patients with acute kidney injury stage 1a were significantly higher than those of individuals without acute kidney injury (in-hospital-19.3% vs 4.7%; 30-day-21.8% vs 6.7%; 90-day-35.2% vs 17.5%; 12-month-54.1% vs 37.1%; p < 0.05 for all comparisons). Mortality rates were even higher for acute kidney injury stages 1b, 2 and 3. Survival analysis demonstrated that patients without acute kidney injury performed significantly better than those with any stage of acute kidney injury (p < 0.01). Acute kidney injury stages 1a, 1b, 2 and 3 were independently associated with survival in the multivariate analysis (p < 0.01). CONCLUSIONS Patients hospitalized for acute decompensation of cirrhosis who develop acute kidney injury have significantly higher mortality rates than those who do not develop this complication. This is true even for the mildest stages of acute kidney injury (stage 1a) and remains so at different time-points, supporting recommendations for earlier treatments.
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Affiliation(s)
- Ângelo Z Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, 245 Sarmento Leite Street, Porto Alegre, RS, Brazil.
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, 295 Professor Annes Dias Street, Porto Alegre, RS, Brazil.
- , 154, Professor Annes Dias Street, Office 1103, PO-Box 90020-090, Porto Alegre, Brazil.
| | - Caroline Machado Rotta Dornelles
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, 245 Sarmento Leite Street, Porto Alegre, RS, Brazil
| | - Leonardo de Lucca Schiavon
- Division of Gastroenterology, Federal University of Santa Catarina, Professora Maria Flora Pausewang Street, Florianópolis, SC, Brazil
| | - Liliana Sampaio Costa Mendes
- Gastroenterology and Hepatology Unit, Hospital de Base do Distrito Federal, SMHS - Special Area Block 101 - South Wing, Brasília, DF, Brazil
| | | | - Liana Codes
- Gastroenterology and Hepatology Unit, Hospital Português, 914 Princesa Isabel Avenue, Salvador, BA, Brazil
| | - Alberto Queiroz Farias
- Department of Gastroenterology, University of São Paulo, 455 Doutor Arnaldo Avenue, São Paulo, SP, Brazil
| | - Mário Reis Álvares-da-Silva
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, Porto Alegre, RS, Brazil
- School of Medicine, Federal University of Rio Grande do Sul, CNPq Researcher, 2400 Ramiro Barcelos Street, Porto Alegre, RS, Brazil
| | - Carlos Terra
- Gastroenterology and Hepatology Unit, State University of Rio de Janeiro, 381 Marechal Rondon Avenue, Rio de Janeiro, RJ, Brazil
- Liver Unit, Hospital da Lagoa, 501 Jardim Botânico Street, Rio de Janeiro, RJ, Brazil
| | - Gustavo Pereira
- Gastroenterology and Hepatology Unit, Hospital Federal de Bonsucesso, 616 Londres Avenue, Rio de Janeiro, RJ, Brazil
- Liver Transplant Program, Complexo Hospitalar Américas, 550 Jorge Cure Avenue, Rio de Janeiro, RJ, Brazil
| | - Muriel Manica
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, 245 Sarmento Leite Street, Porto Alegre, RS, Brazil
| | - Helena Marcon Bischoff
- Division of Internal Medicine, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, Porto Alegre, RS, Brazil
| | - Janaína Luz Narciso-Schiavon
- Division of Gastroenterology, Federal University of Santa Catarina, Professora Maria Flora Pausewang Street, Florianópolis, SC, Brazil
| | - Silas Gustavo Barboza Romeres
- Gastroenterology and Hepatology Unit, Hospital de Base do Distrito Federal, SMHS - Special Area Block 101 - South Wing, Brasília, DF, Brazil
| | - Jéssica Bastos Garcia
- Division of Gastroenterology, Federal University of São Paulo, 740 Botucatu Street, São Paulo, SP, Brazil
| | - Paulo Lisboa Bittencourt
- Gastroenterology and Hepatology Unit, Hospital Português, 914 Princesa Isabel Avenue, Salvador, BA, Brazil
| | - Rafael Oliveira Ximenes
- Department of Gastroenterology, University of São Paulo, 455 Doutor Arnaldo Avenue, São Paulo, SP, Brazil
| | - Raul Salinas Arrojo
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, Porto Alegre, RS, Brazil
| | - Angelo A Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, 245 Sarmento Leite Street, Porto Alegre, RS, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, 295 Professor Annes Dias Street, Porto Alegre, RS, Brazil
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Lekakis V, Wong F, Gkoufa A, Papatheodoridis GV, Cholongitas E. Mortality of Acute Kidney Injury in Cirrhosis: A Systematic Review and Meta-Analysis of Over 5 Million Patients Across Different Clinical Settings. Aliment Pharmacol Ther 2025; 61:420-432. [PMID: 39641300 PMCID: PMC11707646 DOI: 10.1111/apt.18426] [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: 07/19/2024] [Revised: 08/01/2024] [Accepted: 11/23/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) represents a commonly seen condition in the natural course of cirrhosis associated with unfavourable outcomes. AIMS To evaluate and compare the pooled mortality rates of patients with cirrhosis, with versus without AKI, across different clinical settings and diagnostic criteria. METHODS A systematic search of several databases was performed up to Oct 2023. Meta-analysis was performed using a generalised linear mixed model with a random effects model for all calculations. RESULTS A total of 59 studies comparing patients with cirrhosis, with and without AKI, were included in the meta-analysis, encompassing 1,153,193 individuals with AKI and 4,630,814 without AKI. AKI development predisposed to significantly higher short (in-hospital and 30-days)-, intermediate (90-days)- and long (1-year)-term mortality rates in both inpatients and outpatients. Remarkably, patients with AKI admitted to intensive care unit (ICU) or diagnosed with acute-on-chronic liver failure (ACLF) experienced the higher short-term mortality rates, reaching 76% [95% confidence interval (CI): 73%-79%] and 54% (95%CI: 33%-73%), respectively. AKI staging correlated with mortality risk, with higher stages indicating higher mortality rates, while the timing of AKI development, whether community-acquired or hospital-acquired, plays a crucial role in patient prognosis, with distinct mortality patterns observed in each group. The selection of diagnostic criteria for AKI may also impact its association with the short-term mortality risk. CONCLUSIONS AKI substantially affects the prognosis of patients with cirrhosis, especially those in ICU and/or with ACLF. Prognosis is also greatly influenced by the AKI stage, timing of onset and diagnostic criteria.
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Affiliation(s)
- Vasileios Lekakis
- Department of GastroenterologyGeneral Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of AthensAthensGreece
| | - Florence Wong
- Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health NetworkUniversity of TorontoTorontoCanada
| | - Aikaterini Gkoufa
- First Department of Internal Medicine“Laiko”, General Hospital, Medical School of National and Kapodistrian University of AthensAthensGreece
| | - George V. Papatheodoridis
- Department of GastroenterologyGeneral Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of AthensAthensGreece
| | - Evangelos Cholongitas
- Department of GastroenterologyGeneral Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of AthensAthensGreece
- First Department of Internal Medicine“Laiko”, General Hospital, Medical School of National and Kapodistrian University of AthensAthensGreece
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8
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Cama-Olivares A, Ouyang T, Takeuchi T, St. Hillien SA, Robinson JE, Chung RT, Cullaro G, Karvellas CJ, Levitsky J, Orman ES, Patidar KR, Regner KR, Saly DL, Sawinski D, Sharma P, Teixeira JP, Ufere NN, Velez JCQ, Wadei HM, Wahid N, Allegretti AS, Neyra JA, Belcher JM. Association of Hepatorenal Syndrome-Acute Kidney Injury with Mortality in Patients with Cirrhosis Requiring Renal Replacement Therapy: Results from the HRS-HARMONY Consortium. KIDNEY360 2025; 6:247-256. [PMID: 39348201 PMCID: PMC11882256 DOI: 10.34067/kid.0000000589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 09/18/2024] [Indexed: 10/02/2024]
Abstract
Key Points In patients with cirrhosis and AKI requiring renal replacement therapy (RRT), hepatorenal syndrome-AKI was not associated with an increased 90-day mortality when compared with other AKI etiologies. Etiology of AKI may not be a critical factor regarding decisions to trial RRT in acutely ill patients with cirrhosis and AKI. Although elevated, mortality rates in this study are comparable with those reported in general hospitalized patients with AKI requiring RRT. Background While AKI requiring renal replacement therapy (AKI-RRT) is associated with increased mortality in heterogeneous inpatient populations, the epidemiology of AKI-RRT in hospitalized patients with cirrhosis is not fully known. Herein, we evaluated the association of etiology of AKI with mortality in hospitalized patients with cirrhosis and AKI-RRT in a multicentric contemporary cohort. Methods This is a multicenter retrospective cohort study using data from the HRS-HARMONY consortium, which included 11 US hospital network systems. Consecutive adult patients admitted in 2019 with cirrhosis and AKI-RRT were included. The primary outcome was 90-day mortality, and the main independent variable was AKI etiology, classified as hepatorenal syndrome (HRS-AKI) versus other (non–HRS-AKI). AKI etiology was determined by at least two independent adjudicators. We performed Fine and Gray subdistribution hazard analyses adjusting for relevant clinical variables. Results Of 2063 hospitalized patients with cirrhosis and AKI, 374 (18.1%) had AKI-RRT. Among them, 65 (17.4%) had HRS-AKI and 309 (82.6%) had non–HRS-AKI, which included acute tubular necrosis in most cases (62.6%). Continuous renal replacement therapy was used as the initial modality in 264 (71%) of patients, while intermittent hemodialysis was used in 108 (29%). The HRS-AKI (versus non–HRS-AKI) group received more vasoconstrictors for HRS management (81.5% versus 67.9%), whereas the non–HRS-AKI group received more mechanical ventilation (64.3% versus 50.8%) and more continuous renal replacement therapy (versus intermittent hemodialysis) as the initial RRT modality (73.9% versus 56.9%). In the adjusted model, HRS-AKI (versus non–HRS-AKI) was not independently associated with increased 90-day mortality (subdistribution hazard ratio, 1.36; 95% confidence interval, 0.95 to 1.94). Conclusions In this multicenter contemporary cohort of hospitalized adult patients with cirrhosis and AKI-RRT, HRS-AKI was not independently associated with an increased risk of 90-day mortality when compared with other AKI etiologies. The etiology of AKI appears less relevant than previously considered when evaluating the prognosis of hospitalized adult patients with cirrhosis and AKI requiring RRT.
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Affiliation(s)
- Augusto Cama-Olivares
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Tianqi Ouyang
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Tomonori Takeuchi
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shelsea A. St. Hillien
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Jevon E. Robinson
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Raymond T. Chung
- Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, California
| | - Constantine J. Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Eric S. Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Kavish R. Patidar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Kevin R. Regner
- Division of Nephrology at the Medical College of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Danielle L. Saly
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Deirdre Sawinski
- Division of Nephrology and Hypertension, Weill Cornell College of Medicine, New York, New York
| | - Pratima Sharma
- Department of Gastroenterology and Transplant Hepatology at University of Michigan Health, University of Michigan Health, Ann Arbor, Michigan
| | - J. Pedro Teixeira
- Divisions of Nephrology and Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico
| | - Nneka N. Ufere
- Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Juan Carlos Q. Velez
- Department of Nephrology at the Ochsner Medical Center, Ochsner Medical Center, New Orleans, Louisiana
| | - Hani M. Wadei
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida
| | - Nabeel Wahid
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Javier A. Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Justin M. Belcher
- Section of Nephrology, Department of Internal Medicine, Yale University and VA Connecticut Healthcare, New Haven, Connecticut
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Mohan PB, Nagaraju SP, Musunuri B, Rajpurohit S, Bhat G, Shetty S. Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients. Ir J Med Sci 2024; 193:1817-1825. [PMID: 38517600 PMCID: PMC11294372 DOI: 10.1007/s11845-024-03663-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 02/29/2024] [Indexed: 03/24/2024]
Abstract
INTRODUCTION Acute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients. METHODOLOGY In the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis. RESULTS Of 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001). CONCLUSION AKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.
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Affiliation(s)
- Pooja Basthi Mohan
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
| | - Shankar Prasad Nagaraju
- Department of Nephrology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
| | - Balaji Musunuri
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
| | - Siddheesh Rajpurohit
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
| | - Ganesh Bhat
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India.
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Juanola A, Ma AT, Gratacós-Ginès J, Soria A, Solé C, Pose E, Ginès P. Renal Complications in Portal Hypertension. Clin Liver Dis 2024; 28:503-523. [PMID: 38945640 DOI: 10.1016/j.cld.2024.03.011] [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: 07/02/2024]
Abstract
Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Ann Thu Ma
- Toronto Centre for Liver Disease Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada
| | - Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Anna Soria
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Cristina Solé
- Department of Gastroenterology and Hepatology, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain.
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Lekakis V, Gkoufa A, Vlachogiannakos J, Papatheodoridis GV, Cholongitas E. Incidence and risk factors of acute kidney injury in cirrhosis: a systematic review and meta-analysis of 5,202,232 outpatients, inpatients, and ICU-admitted patients. Expert Rev Gastroenterol Hepatol 2024; 18:377-388. [PMID: 39001566 DOI: 10.1080/17474124.2024.2380299] [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: 03/01/2024] [Accepted: 07/11/2024] [Indexed: 07/18/2024]
Abstract
INTRODUCTION Acute kidney injury (AKI) is a commonly seen condition in the natural course of cirrhosis. The aim of this study was to evaluate the pooled incidence and risk factors of AKI in different clinical stages and situations in patients with cirrhosis. METHODS Search was conducted on 13 December 2023 across MEDLINE (PubMed), Embase, and Cochrane databases. Meta-analysis was performed using a generalized linear mixed model. RESULTS In total, 73 studies with 5,202,232 patients were finally enrolled in the meta-analysis. AKI commonly occurs among hospitalized cirrhotics experiencing any decompensation event (29%) as well as among stable outpatients (28%) throughout a 1-year follow-up period. On admission, patients with infection or sepsis/septic shock had the highest AKI rate (47%), followed by those with hepatic encephalopathy (41%). Furthermore, the severity of liver disease proved to be a substantial driver for AKI development, while patients at intensive care unit had the greatest AKI incidence (61%). CONCLUSIONS Both hospitalized patients and stable outpatients with cirrhosis exhibited an elevated susceptibility to AKI. Patients at intensive care unit and those with severe liver disease, infection, sepsis/septic shock, hepatic encephalopathy, or acute on chronic liver failure upon admission are at higher risk for AKI. TRIAL REGISTRATION PROSPERO, registered 09/12/23, CRD42023487736.
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Affiliation(s)
- Vasileios Lekakis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Aikaterini Gkoufa
- First Department of Internal Medicine, "Laiko", General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, "Laiko", General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Puthumana J, Lugon NC, Xu Y, Deng Y, Mistry PK, Parikh CR. Systematic Review and Meta-Analysis of Urine Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury in Cirrhosis. Kidney Int Rep 2024; 9:2278-2281. [PMID: 39081737 PMCID: PMC11284356 DOI: 10.1016/j.ekir.2024.04.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 03/27/2024] [Accepted: 04/23/2024] [Indexed: 08/02/2024] Open
Affiliation(s)
- Jeremy Puthumana
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
| | - Nicolas Chong Lugon
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
| | - Yunshan Xu
- Yale Center for Analytical Sciences, Yale University, New Haven, Connecticut, USA
| | - Yanhong Deng
- Yale Center for Analytical Sciences, Yale University, New Haven, Connecticut, USA
| | - Pramod K. Mistry
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
| | - Chirag R. Parikh
- Division of Nephrology, Johns Hopkins University, Baltimore, Maryland, USA
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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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Wejnaruemarn S, Prasoppokakorn T, Srisawat N, Teerasarntipan T, Thanapirom K, Phathong C, Chaiteerakij R, Komolmit P, Tangkijvanich P, Treeprasertsuk S. Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients. SIRIRAJ MEDICAL JOURNAL 2024; 76:198-208. [DOI: 10.33192/smj.v76i4.268004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025] Open
Abstract
Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients.
Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality.
Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02).
Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality.
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Pose E, Piano S, Juanola A, Ginès P. Hepatorenal Syndrome in Cirrhosis. Gastroenterology 2024; 166:588-604.e1. [PMID: 38246506 DOI: 10.1053/j.gastro.2023.11.306] [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: 06/16/2023] [Revised: 11/10/2023] [Accepted: 11/19/2023] [Indexed: 01/23/2024]
Abstract
Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
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16
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Patidar KR, Cullaro G, Naved MA, Kabir S, Grama A, Orman ES, Piano S, Allegretti AS. Prognostic significance of acute kidney injury stage 1B in hospitalized patients with cirrhosis: A US nationwide study. Liver Transpl 2024; 30:244-253. [PMID: 37556190 PMCID: PMC10853477 DOI: 10.1097/lvt.0000000000000241] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 07/31/2023] [Indexed: 08/10/2023]
Abstract
Understanding the prognostic significance of acute kidney injury (AKI) stage 1B [serum creatinine (sCr) ≥1.5 mg/dL] compared with stage 1A (sCr < 1.5 mg/dL) in a US population is important as it can impact initial management decisions for AKI in hospitalized cirrhosis patients. Therefore, we aimed to define outcomes associated with stage 1B in a nationwide US cohort of hospitalized cirrhosis patients with AKI. Hospitalized cirrhosis patients with AKI in the Cerner-Health-Facts database from January 2009 to September 2017 (n = 6250) were assessed for AKI stage 1 (≥1.5-2-fold increase in sCr from baseline) and were followed for 90 days for outcomes. The primary outcome was 90-day mortality; secondary outcomes were in-hospital AKI progression and AKI recovery. Competing-risk multivariable analysis was performed to determine the independent association between stage 1B, 90-day mortality (liver transplant as a competing risk), and AKI recovery (death/liver transplant as a competing risk). Multivariable logistic regression analysis was performed to determine the independent association between stage 1B and AKI progression. In all, 4654 patients with stage 1 were analyzed: 1A (44.3%) and 1B (55.7%). Stage 1B patients had a significantly higher cumulative incidence of 90-day mortality compared with stage 1A patients, 27.2% versus 19.7% ( p < 0.001). In multivariable competing-risk analysis, patients with stage 1B (vs. 1A) had a higher risk for mortality at 90 days [sHR 1.52 (95% CI 1.20-1.92), p = 0.001] and decreased probability for AKI recovery [sHR 0.76 (95% CI 0.69-0.83), p < 0.001]. Furthermore, in multivariable logistic regression analysis, AKI stage 1B (vs. 1A) was independently associated with AKI progression, OR 1.42 (95% CI 1.14-1.72) ( p < 0.001). AKI stage 1B patients have a significantly higher risk for 90-day mortality, AKI progression, and reduced probability of AKI recovery compared with AKI stage 1A patients. These results could guide initial management decisions for AKI in hospitalized patients with cirrhosis.
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Affiliation(s)
- Kavish R. Patidar
- Department of Medicine, Section of Gastroenterology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Giuseppe Cullaro
- Department of Medicine, Division of Gastroenterology, University of California-San Francisco, San Francisco, California, USA
| | - Mobasshir A. Naved
- Department of Computer Science, Purdue University, West Lafayette, Indiana, USA
| | - Shaowli Kabir
- College of Public Health, University of Kentucky, Lexington, Kentucky, USA
| | - Ananth Grama
- Department of Computer Science, Purdue University, West Lafayette, Indiana, USA
| | - Eric S. Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Salvatore Piano
- Department of Medicine, Unit of Internal Medicine and Hepatology, University of Padova, Padova, Italy
| | - Andrew S. Allegretti
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
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17
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Winters AC, Belcher J. The prognostic implications of early-stage AKI: Defining the threshold for concern. Liver Transpl 2024; 30:235-236. [PMID: 37903066 DOI: 10.1097/lvt.0000000000000292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 10/17/2023] [Indexed: 11/01/2023]
Affiliation(s)
- Adam C Winters
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Justin Belcher
- Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, VA Connecticut Healthcare, West Haven, Connecticut, USA
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18
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Allegretti AS, Patidar KR, Ma AT, Cullaro G. From past to present to future: Terlipressin and hepatorenal syndrome-acute kidney injury. Hepatology 2024:01515467-990000000-00741. [PMID: 38353565 PMCID: PMC11322426 DOI: 10.1097/hep.0000000000000790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/11/2023] [Indexed: 03/01/2024]
Abstract
Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive "cure" for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.
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Affiliation(s)
- Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Kavish R. Patidar
- Section of Gastroenterology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, USA
| | - Ann T. Ma
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Giuseppe Cullaro
- Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco CA, USA
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19
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Thuluvath PJ. Hepatorenal Syndrome-Acute Kidney Injury Definition Needs a Minimum Threshold for Serum Creatinine. Clin Gastroenterol Hepatol 2024; 22:435-436. [PMID: 37211268 DOI: 10.1016/j.cgh.2023.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/23/2023]
Affiliation(s)
- Paul J Thuluvath
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
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20
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Fickert P. Detour of bile acid routes as therapeutic roadmap for cholemic nephropathy. J Hepatol 2024; 80:188-190. [PMID: 38013144 DOI: 10.1016/j.jhep.2023.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 11/21/2023] [Indexed: 11/29/2023]
Affiliation(s)
- Peter Fickert
- Department of Medicine, Division of Gastroenterology and Hepatology, Medical University Graz, Austria.
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21
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Giammarino A, Kalia H. A hospitalist's approach to managing acute kidney injury (hepatorenal syndrome) in cirrhosis. Clin Liver Dis (Hoboken) 2024; 23:e0159. [PMID: 38681513 PMCID: PMC11049700 DOI: 10.1097/cld.0000000000000159] [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: 10/18/2023] [Accepted: 02/17/2024] [Indexed: 05/01/2024] Open
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22
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Tyson LD, Atkinson S, Hunter RW, Allison M, Austin A, Dear JW, Forrest E, Liu T, Lord E, Masson S, Nunes J, Richardson P, Ryder SD, Wright M, Thursz M, Vergis N. In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs. Aliment Pharmacol Ther 2023; 58:1217-1229. [PMID: 37781965 PMCID: PMC10946848 DOI: 10.1111/apt.17733] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/01/2023] [Accepted: 09/18/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain. AIMS We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date. METHODS Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses. RESULTS D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01). CONCLUSIONS Incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.
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Affiliation(s)
- Luke D. Tyson
- Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
- The Liver UnitSt Mary's HospitalLondonUK
| | - Stephen Atkinson
- Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
- The Liver UnitSt Mary's HospitalLondonUK
| | - Robert W. Hunter
- Centre for Cardiovascular ScienceUniversity of EdinburghEdinburghUK
| | - Michael Allison
- Cambridge NIHR Biomedical Research CentreAddenbrooke's HospitalCambridgeUK
| | | | - James W. Dear
- Centre for Cardiovascular ScienceUniversity of EdinburghEdinburghUK
| | - Ewan Forrest
- Department of HepatologyGlasgow Royal InfirmaryGlasgowUK
- University of GlasgowGlasgowUK
| | - Tong Liu
- Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
| | - Emma Lord
- Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
| | - Steven Masson
- Department of HepatologyNewcastle Freeman HospitalNewcastle upon TyneUK
| | | | - Paul Richardson
- Department of HepatologyThe Royal Liverpool University HospitalLiverpoolUK
| | - Stephen D. Ryder
- NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of NottinghamQueens Medical CentreNottinghamUK
| | - Mark Wright
- Department of HepatologyUniversity Hospital Southampton NHS Foundation TrustSouthamptonUK
| | - Mark Thursz
- Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
- The Liver UnitSt Mary's HospitalLondonUK
| | - Nikhil Vergis
- Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
- The Liver UnitSt Mary's HospitalLondonUK
- GSKBrentfordUK
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23
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Mohanty A, Cárdenas A. Securing the diagnosis of HRS-AKI: implications for current therapies. Expert Rev Gastroenterol Hepatol 2023; 17:1233-1239. [PMID: 37982156 DOI: 10.1080/17474124.2023.2284189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/13/2023] [Indexed: 11/21/2023]
Abstract
INTRODUCTION Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high mortality and morbidity. It is characterized by rapid deterioration of renal function due to reduced renal blood flow secondary to portal hypertensive splanchnic and systemic vasodilation. Early diagnosis and treatment of HRS-AKI are associated with greater likelihood of improvement in renal function, lower need for dialysis, and better post-transplant outcomes. AREAS COVERED This review discusses the diagnostic criteria for HRS-AKI, which has undergone several key changes over the last decade, with an aim to secure an early diagnosis and aid swift treatment initiation. Additionally, this review outlines the current treatment paradigms for HRS-AKI. EXPERT OPINION In the last 20 years, there have been several advances in understanding the pathophysiology and natural course of HRS-AKI. These have led to critical changes in its definition and diagnostic algorithm. However, prognosis of HRS-AKI remains dismal with no significant improvement in HRS-AKI reversal or HRS-related mortality over this time. We discuss several gaps in the current understanding and management of HRS-AKI that will benefit from further research.
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Affiliation(s)
- Arpan Mohanty
- Boston University Chobanian and Avedisian School of Medicine and Boston Medical Center, United States
| | - Andrés Cárdenas
- GI and Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Barcelona and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
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24
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Harden Waibel B, Kamien AJ. Resuscitation and Preparation of the Emergency General Surgery Patient. Surg Clin North Am 2023; 103:1061-1084. [PMID: 37838456 DOI: 10.1016/j.suc.2023.05.011] [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: 10/16/2023]
Abstract
Traditionally, the workflow surrounding a general surgery patient allows for a period of evaluation and optimization of underlying medical issues to allow for risk modification; however, in the emergency, this optimization period is largely condensed because of its time-dependent nature. Because the lack of optimization can lead to complications, the ability to rapidly resuscitate the patient, proceed to procedural intervention to control the situation, and manage common medical comorbidities is paramount. This article provides an overview on these subjects.
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Affiliation(s)
- Brett Harden Waibel
- Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198-3280, USA.
| | - Andrew James Kamien
- Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198-3280, USA
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25
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Choi JC, Yoo JJ. [Hepatorenal Syndrome]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:224-232. [PMID: 37997218 DOI: 10.4166/kjg.2023.108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/16/2023] [Accepted: 09/19/2023] [Indexed: 11/25/2023]
Abstract
Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology. The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances. Understanding these mechanisms is crucial for the timely identification and management of HRS. The diagnosis of HRS is primarily clinical and relies on specific criteria that consider the exclusion of other causes of renal dysfunction. The management of HRS comprises two main approaches: vasoconstrictor therapy and albumin infusion, which aim to improve renal perfusion and mitigate the hyperdynamic circulation often seen in advanced liver disease. Additionally, strategies such as liver transplantation and renal replacement therapy are essential considerations based on individual patient characteristics and disease severity. This review article provides a comprehensive overview of hepatorenal syndrome, focusing on its pathophysiology, diagnostic criteria, and current management strategies.
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Affiliation(s)
- Jun Cheol Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
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26
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Jung CY, Chang JW. Hepatorenal syndrome: Current concepts and future perspectives. Clin Mol Hepatol 2023; 29:891-908. [PMID: 37050843 PMCID: PMC10577351 DOI: 10.3350/cmh.2023.0024] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/10/2023] [Accepted: 04/10/2023] [Indexed: 04/14/2023] Open
Abstract
Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.
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Affiliation(s)
- Chan-Young Jung
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jai Won Chang
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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27
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Lizaola-Mayo B, Vargas HE. Hepatorenal Syndrome-Acute Kidney Injury in Liver Transplantation. Clin Gastroenterol Hepatol 2023; 21:S20-S26. [PMID: 37625863 DOI: 10.1016/j.cgh.2023.06.010] [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: 02/06/2023] [Revised: 05/18/2023] [Accepted: 06/07/2023] [Indexed: 08/27/2023]
Abstract
Hepatorenal syndrome (HRS) is a serious complication of cirrhosis. HRS nomenclature has recently changed to HRS-AKI (acute kidney injury). HRS is a complex response to chronic vasodilatory changes brought about by portal hypertension and exacerbated by inflammatory responses that portends poor prognosis to patients with cirrhosis. This syndrome is commonly seen in the setting of infections, particularly spontaneous bacterial peritonitis. Because of the frequency of renal injury in the patient with cirrhosis, HRS-AKI has to be considered high in the differential diagnosis of AKI. Discontinuation of potential triggering agents and elimination of pre-renal AKI, intrinsic renal disease, and structural uropathy as causes of injury are imperative on presentation. Volume expansion with albumin and vasoconstrictive drugs to counteract the underlying splanchnic vasodilation constitutes the most effective medical modality to manage this process. Although the most effective therapy is generally considered to be liver transplantation (LT), the logistic barriers of offering this life-saving therapy on time to all needing it is a major limitation. Terlipressin has been shown to reverse HRS-AKI in a significant proportion of those treated and consequently can lead to increased LT patient survival and freedom from renal replacement therapy. We will review the impact of HRS on the management of patients awaiting LT, present strategies to prevent this significant complication, and discuss major implications of recent therapeutic advances in the setting of LT.
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Affiliation(s)
| | - Hugo E Vargas
- Mayo Clinic Arizona, Liver Transplantation Center, Phoenix, Arizona.
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28
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Surace M, Andria I, Valentini G. Renal dysfunctions and liver disease: a brief update on management with particular attention to hepatorenal syndrome. Minerva Gastroenterol (Torino) 2023; 69:412-422. [PMID: 33829727 DOI: 10.23736/s2724-5985.21.02816-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In 2015 the International Club of Ascites gave an accurate, exact and new definition of acute renal injury in cirrhotic patient, identifying objective criteria of severity and recoding hepatorenal syndrome as a particular form of renal dysfunction for which excessive renal vasoconstriction is one of the main, but not the only, pathophysiological mechanisms. In this review we tried to outline new pathophysiological and therapeutic insights, and to summarize the most recent recommendations. Vasopressor such as terlipressin and norepinephrine, in combination with albumin, still represent the first line therapy. However, the new discoveries in the pathophysiology of the disease have led the search for new pharmacological approaches, although, to date, the only definitive remedy is represented by liver (or simultaneous liver-kidney) transplantation.
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Affiliation(s)
- Monica Surace
- Unit of Gastroenterology, Hospital of Rivoli, Rivoli, Turin, Italy -
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29
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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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30
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Griffin C, Asrani SK, Regner KR. Update on Assessment of Estimated Glomerular Filtration Rate in Patients With Cirrhosis. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:307-314. [PMID: 37389536 DOI: 10.1053/j.akdh.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 06/01/2023] [Accepted: 06/06/2023] [Indexed: 07/01/2023]
Abstract
Kidney disease is associated with adverse outcomes in patients with cirrhosis including increased post-liver transplantation (LT) mortality. Therefore, diagnosis and staging of kidney disease are critical to timely implementation of treatment and have important implications for transplant eligibility. Serum creatinine (sCr) is a key component of the Model for End-Stage Liver Disease score in LT candidates, and sCr-based estimated glomerular filtration rate (eGFR) values play an important role in determining medical urgency for LT. However, the use of sCr to assess kidney function may be limited in the cirrhotic milieu due to decreased creatinine production, interference of bilirubin with some laboratory assays for sCr, and expansion of the volume of distribution of creatinine. Therefore, conventional eGFR equations perform poorly in patients with cirrhosis and may overestimate kidney function leading to delayed diagnosis of acute kidney injury or lower priority for LT in patients with a truly low glomerular filtration rate. In this review, we will provide an update on the use of sCr for diagnosis and staging of kidney disease in patients with cirrhosis, discuss the limitations of sCr-based eGFR equations, and discuss novel eGFR equations that have been developed in patients with cirrhosis.
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Affiliation(s)
- Connor Griffin
- Division of Hepatology, Baylor University Medical Center, Dallas, TX
| | - Sumeet K Asrani
- Division of Hepatology, Baylor University Medical Center, Dallas, TX
| | - Kevin R Regner
- Division of Nephrology, Medical College of Wisconsin, Milwaukee, WI.
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Gonzalez SA, Farfan Ruiz AC, Ibrahim RM, Wadei HM. Essentials of Liver Transplantation in the Setting of Acute Kidney Injury and Chronic Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:356-367. [PMID: 37657882 DOI: 10.1053/j.akdh.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 06/06/2023] [Accepted: 06/26/2023] [Indexed: 09/03/2023]
Abstract
Kidney dysfunction is common among liver transplant candidates with decompensated cirrhosis and has a major impact on pre- and post-liver transplant survival. Updated definitions of acute kidney injury and criteria for the diagnosis of hepatorenal syndrome allow for early recognition and intervention, including early initiation of vasoconstrictor therapy for hepatorenal syndrome. The rise of the metabolic syndrome and nonalcoholic fatty liver disease as a cause of cirrhosis has coincided with an increase in intrinsic chronic kidney disease recognized in transplant candidates and recipients. Ultimately, the ability to accurately assess kidney function and associated risk is essential to decision-making in the context of transplantation, including selection of candidates for simultaneous liver and kidney transplantation.
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Affiliation(s)
- Stevan A Gonzalez
- Division of Hepatology, Annette C. and Harold C. Simmons Transplant Institute, Baylor Scott & White All Saints Medical Center Fort Worth and Baylor University Medical Center Dallas, TX; Department of Medicine, Burnett School of Medicine at TCU, Fort Worth, TX.
| | - Ana Cecilia Farfan Ruiz
- Division of Transplant Nephrology, Department of Transplant, Mayo Clinic College of Medicine and Science, Jacksonville, FL
| | - Ramez M Ibrahim
- Division of Transplant Nephrology, Department of Transplant, Mayo Clinic College of Medicine and Science, Jacksonville, FL
| | - Hani M Wadei
- Division of Transplant Nephrology, Department of Transplant, Mayo Clinic College of Medicine and Science, Jacksonville, FL
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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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Claudel SE, Jaganathan J, Patel A, Tapper EB, Verma A. Review article: Practical considerations for fluid resuscitation in cirrhosis. Aliment Pharmacol Ther 2023; 57:1066-1082. [PMID: 36998204 PMCID: PMC11839201 DOI: 10.1111/apt.17458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/25/2022] [Accepted: 02/26/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND Standard clinical methods of assessing volume and providing resuscitation are not always applicable to patients with advanced or decompensated cirrhosis. Despite this being well known from a clinical perspective, there remains relatively little evidence to guide clinicians though fluid management in patients with cirrhosis and, often, multi-organ system dysfunction. AIMS This review summarises the current understanding of the circulatory dysfunction in cirrhosis, modalities for assessing volume status, and considerations for fluid selection. It additionally provides a practical approach to fluid resuscitation. METHODS We review current literature on cirrhosis pathophysiology in steady-state and shock, clinical implications of fluid resuscitation, and strategies to assess intravascular volume. Literature reviewed here was identified by the authors through PubMed search and review of selected papers' references. RESULTS Clinical management of resuscitation in advanced cirrhosis remains relatively stagnant. Although several trials have attempted to establish the superior resuscitative fluid, the lack of improvement in hard clinical outcomes leaves clinicians without clear guidance. CONCLUSIONS The absence of consistent evidence for fluid resuscitation in patients with cirrhosis limits our ability to produce a clearly evidence-based protocol for fluid resuscitation in cirrhosis. However, we propose a preliminary practical guide to managing fluid resuscitation in patients with decompensated cirrhosis. Further studies are needed to develop and validate volume assessment tools in the specific context of cirrhosis, while randomised clinical trials of protocolized resuscitation may improve care of this patient population.
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Affiliation(s)
- Sophie E. Claudel
- Department of Internal Medicine, Boston Medical Center, Boston, Massachusetts, USA
| | - Jeeva Jaganathan
- Digestive Sciences and Nutrition, University of Kentucky College of Medicine, Lexington, Kentucky, USA
| | - Ankit Patel
- Department of Medicine, Renal Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | - Elliot B. Tapper
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ashish Verma
- Department of Internal Medicine, Section on Nephrology, Boston Medical Center, Boston, Massachusetts, USA
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Gambino C, Piano S, Stenico M, Tonon M, Brocca A, Calvino V, Incicco S, Zeni N, Gagliardi R, Cosma C, Zaninotto M, Burra P, Cillo U, Basso D, Angeli P. Diagnostic and prognostic performance of urinary neutrophil gelatinase-associated lipocalin in patients with cirrhosis and acute kidney injury. Hepatology 2023; 77:1630-1638. [PMID: 36125403 PMCID: PMC10113003 DOI: 10.1002/hep.32799] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 08/18/2022] [Accepted: 09/12/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS Acute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) could help discriminate between different etiologies of AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI. APPROACH AND RESULTS One hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml [95% CI 423-2105 ng/ml] vs. 109 ng/ml [95% CI 52-192 ng/ml]; p < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR [aOR], 6.17; 95% CI 1.41-27.03; p = 0.016). In multivariable analysis (adjusted for age, Model for End-Stage Liver Disease, acute-on-chronic liver failure, leukocytes, and type of AKI), uNGAL was an independent predictor of in-hospital mortality (aOR, 1.74; 95% CI 1.26-2.38; p = 0.001). CONCLUSIONS uNGAL is an adequate biomarker for making a differential diagnosis of AKI in cirrhosis and predicting the response to terlipressin and albumin in patients with HRS-AKI. In addition, it is an independent predictor of in-hospital mortality.
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Affiliation(s)
- Carmine Gambino
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Matteo Stenico
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Alessandra Brocca
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Valeria Calvino
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Simone Incicco
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Nicola Zeni
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Roberta Gagliardi
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Chiara Cosma
- Laboratory Medicine Unit, Department of Medicine, University of Padova, Padova, Italy
| | - Martina Zaninotto
- Laboratory Medicine Unit, Department of Medicine, University of Padova, Padova, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Daniela Basso
- Laboratory Medicine Unit, Department of Medicine, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
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Yewale RV, Ramakrishna BS, Venugopal G, Doraiswami BV, Rajini K. Urine neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury and prognosis in decompensated chronic liver disease: A prospective study. Indian J Gastroenterol 2023; 42:106-117. [PMID: 36763249 PMCID: PMC9913035 DOI: 10.1007/s12664-022-01312-w] [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: 01/31/2022] [Accepted: 11/08/2022] [Indexed: 02/11/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) heralds deterioration in patients with decompensated chronic liver disease (DCLD). Serum creatinine (sCr), a component of the model for end-stage liver disease-sodium (MELD-Na) prognostic score, has limitations in patients with DCLD. We evaluated the prognostic role of urine neutrophil gelatinase-associated lipocalin (NGAL) in DCLD and its ability to sub-type AKI. METHODS Total 147 consecutive patients hospitalized between June 2018 and June 2020 for complications of DCLD were evaluated. Urine NGAL was estimated and demographic, clinical and biochemical parameters recorded at baseline. Participants were followed up till the end of study period or mortality, whichever came earlier. Primary outcomes included all-cause mortality and time to death after index hospitalization. Secondary outcomes included the presence and type of AKI, need for intensive care unit (ICU) stay, length of ICU/hospital stay, in-hospital mortality, development of new-onset/recurrent AKI and recurrent hospitalization after index admission. RESULTS Urine NGAL was highest in acute tubular necrosis (ATN), lowest in pre-renal azotemia (PRA) and intermediate in hepatorenal syndrome (HRS-AKI). Urine NGAL (p = 0.0208) was superior to sCr (p = 0.0388) and inferior to fractionated excretion of sodium (FENa) (p = 0.0013) in stratifying AKI. A cut-off of 203.9 ng/mL discriminated between HRS and PRA with sensitivity 77.8% and specificity 68.7%. Urine NGAL correlated with MELD-Na score, need for ICU stay, in-hospital mortality and mortality at three and six months. Two-year survival was significantly lower in patients with urine NGAL > 205 ng/mL. Addition of log-urine-NGAL score did not improve predictive performance of MELD-Na. CONCLUSION Urine NGAL could identify AKI sub-types and correlated with short-term clinical outcomes, including mortality.
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Affiliation(s)
- Rohan Vijay Yewale
- SIMS Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institutes for Medical Science, 1 Jawaharlal Nehru Road, Chennai, 600 026, India.
| | - Balakrishnan Siddartha Ramakrishna
- SIMS Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institutes for Medical Science, 1 Jawaharlal Nehru Road, Chennai, 600 026, India
| | - Giriprasad Venugopal
- SIMS Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institutes for Medical Science, 1 Jawaharlal Nehru Road, Chennai, 600 026, India
| | - Babu Vinish Doraiswami
- SIMS Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institutes for Medical Science, 1 Jawaharlal Nehru Road, Chennai, 600 026, India
| | - Kayalvizhi Rajini
- SIMS Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institutes for Medical Science, 1 Jawaharlal Nehru Road, Chennai, 600 026, India
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Matchett CL, Simonetto DA, Kamath PS. Renal Insufficiency in Patients with Cirrhosis. Clin Liver Dis 2023; 27:57-70. [PMID: 36400467 DOI: 10.1016/j.cld.2022.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Renal failure is one of the most prevalent complications in patients with cirrhosis and is of the utmost prognostic relevance. Acute kidney injury (AKI) in cirrhosis results from a spectrum of etiologies, of which hepatorenal syndrome (HRS) carries the worst prognosis. Correct differentiation of the etiology of AKI in cirrhosis is imperative, as treatment defers substantially. This review summarizes the current diagnostic criteria, pathophysiology, diagnosis, and therapeutic concepts for AKI and HRS-AKI in cirrhosis.
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Affiliation(s)
- Caroline L Matchett
- Internal Medicine Residency Program, Department of Medicine, Mayo Clinic, 200 1st Street Southwest, Rochester, 55902 MN, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 1st Street Southwest, Rochester, 55902 MN, USA
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 1st Street Southwest, Rochester, 55902 MN, USA.
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Tangpanithandee S, Thongprayoon C, Krisanapan P, Mao MA, Kaewput W, Pattharanitima P, Boonpheng B, Cheungpasitporn W. Distinct Subtypes of Hepatorenal Syndrome and Associated Outcomes as Identified by Machine Learning Consensus Clustering. Diseases 2023; 11:18. [PMID: 36810532 PMCID: PMC9944494 DOI: 10.3390/diseases11010018] [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: 12/04/2022] [Revised: 01/15/2023] [Accepted: 01/20/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND The utilization of multi-dimensional patient data to subtype hepatorenal syndrome (HRS) can individualize patient care. Machine learning (ML) consensus clustering may identify HRS subgroups with unique clinical profiles. In this study, we aim to identify clinically meaningful clusters of hospitalized patients for HRS using an unsupervised ML clustering approach. METHODS Consensus clustering analysis was performed based on patient characteristics in 5564 patients primarily admitted for HRS in the National Inpatient Sample from 2003-2014 to identify clinically distinct HRS subgroups. We applied standardized mean difference to evaluate key subgroup features, and compared in-hospital mortality between assigned clusters. RESULTS The algorithm revealed four best distinct HRS subgroups based on patient characteristics. Cluster 1 patients (n = 1617) were older, and more likely to have non-alcoholic fatty liver disease, cardiovascular comorbidities, hypertension, and diabetes. Cluster 2 patients (n = 1577) were younger and more likely to have hepatitis C, and less likely to have acute liver failure. Cluster 3 patients (n = 642) were younger, and more likely to have non-elective admission, acetaminophen overdose, acute liver failure, to develop in-hospital medical complications and organ system failure, and to require supporting therapies, including renal replacement therapy, and mechanical ventilation. Cluster 4 patients (n = 1728) were younger, and more likely to have alcoholic cirrhosis and to smoke. Thirty-three percent of patients died in hospital. In-hospital mortality was higher in cluster 1 (OR 1.53; 95% CI 1.31-1.79) and cluster 3 (OR 7.03; 95% CI 5.73-8.62), compared to cluster 2, while cluster 4 had comparable in-hospital mortality (OR 1.13; 95% CI 0.97-1.32). CONCLUSIONS Consensus clustering analysis provides the pattern of clinical characteristics and clinically distinct HRS phenotypes with different outcomes.
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Affiliation(s)
- Supawit Tangpanithandee
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10540, Thailand
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
| | - Pajaree Krisanapan
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine Thammasat University, Pathum Thani 12120, Thailand
- Division of Nephrology, Department of Internal Medicine, Thammasat University Hospital, Pathum Thani 12120, Thailand
| | - Michael A. Mao
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
| | - Pattharawin Pattharanitima
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine Thammasat University, Pathum Thani 12120, Thailand
| | - Boonphiphop Boonpheng
- Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA 98195, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Yewale RV, Ramakrishna BS. Novel biomarkers of acute kidney injury in chronic liver disease: Where do we stand after a decade of research? Hepatol Res 2023; 53:3-17. [PMID: 36262036 DOI: 10.1111/hepr.13847] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/06/2022] [Accepted: 10/14/2022] [Indexed: 01/03/2023]
Abstract
Acute kidney injury (AKI) is a frequently encountered complication in decompensated chronic liver disease (CLD) with an estimated prevalence of 20%-50% among hospitalized patients. AKI often heralds the onset of a downhill course in the natural history of CLD. Serum creatinine has several limitations as a stand-alone marker of AKI in patients with decompensated CLD. The concept of hepatorenal syndrome, the prototype of AKI in decompensated CLD, has evolved tremendously over recent years. There is emerging evidence of an additional "structural" component in the pathophysiology of hepatorenal syndrome-AKI, which was previously identified as a purely "functional" form of renal impairment. Lacunae in the existent biochemical arsenal for diagnosis and prognosis of AKI have fueled enthusiastic research in the field of novel biomarkers of kidney injury in patients with cirrhosis. The advent of these biomarkers provides a crucial window of opportunity to improve the diagnosis and clinical outcomes of this vulnerable cohort of patients. This review summarizes the dynamic concept of renal dysfunction in CLD and the available literature on the role of novel biomarkers of AKI in assessing renal function, identifying AKI subtypes, and predicting prognosis. There is special emphasis on the renal tubular injury marker, neutrophil gelatinase-associated lipocalin, the most exhaustively studied biomarker of AKI in the CLD population.
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Affiliation(s)
- Rohan Vijay Yewale
- Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institutes for Medical Science, Chennai, India
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Ning Y, Zou X, Xu J, Wang X, Ding M, Lu H. Impact of acute kidney injury on the risk of mortality in patients with cirrhosis: a systematic review and meta-analysis. Ren Fail 2022; 44:1-14. [PMID: 36380739 PMCID: PMC9673785 DOI: 10.1080/0886022x.2022.2142137] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective To compare the risk of mortality in patients with cirrhosis with and without the associated acute kidney injury (AKI). Methods We performed a systematic search in the PubMed, Embase, and Scopus databases for observational studies that were done on patients with cirrhosis. Eligible studies reported AKI in patients with cirrhosis and compared mortality among patients with and without AKI. We used a random-effects model, using STATA version 16.0, for deriving pooled effect sizes that were reported as odds ratio (OR) with 95% confidence intervals (CIs). Results Thirty-two studies were included. In patients with cirrhosis, AKI was significantly associated with higher in-hospital mortality (OR 5.92), and mortality at 30 days (OR 4.78), 90 days (OR 4.34), and at 1 year follow-up (OR 4.82) compared to patients without AKI. Conclusions AKI is associated with an increased risk of mortality in patients with cirrhosis. Careful monitoring to identify the development of AKI and early prompt management is necessary.
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Affiliation(s)
- Yunfeng Ning
- Department of Nephropathy, First Affiliated Hospital, Huzhou Teachers College, the First People’s Hospital of Huzhou, Huzhou, China
| | - Xiaoyue Zou
- Department of Emergency ICU, First Affiliated Hospital, Huzhou Teachers College, the First People’s Hospital of Huzhou, Huzhou, China
| | - Jing Xu
- Department of Nephropathy, First Affiliated Hospital, Huzhou Teachers College, the First People’s Hospital of Huzhou, Huzhou, China
| | - Xiao Wang
- Department of Nephropathy, First Affiliated Hospital, Huzhou Teachers College, the First People’s Hospital of Huzhou, Huzhou, China
| | - Min Ding
- Department of Nephropathy, First Affiliated Hospital, Huzhou Teachers College, the First People’s Hospital of Huzhou, Huzhou, China
| | - Hulin Lu
- Department of Nephropathy, First Affiliated Hospital, Huzhou Teachers College, the First People’s Hospital of Huzhou, Huzhou, China
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40
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Intensive care management of liver transplant recipients. Curr Opin Crit Care 2022; 28:709-714. [PMID: 36226713 DOI: 10.1097/mcc.0000000000001002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
PURPOSE OF REVIEW Liver transplantation remains the only definitive treatment for advanced liver disease and liver failure. Current allocation schemes utilized for liver transplantation mandate a 'sickest first' approach, thus most liver transplants occur in patients with severe systemic illness. For intensive care providers who care for liver transplant recipients, a foundation of knowledge of technical considerations of orthotopic liver transplantation, basic management considerations, and common complications is essential. This review highlights the authors' approach to intensive care management of the postoperative liver transplant recipient with a review of common issues, which arise in this patient population. RECENT FINDINGS The number of centers offering liver transplantation continues to increase globally and the number of patients receiving liver transplantation also continues to increase. The number of patients with advanced liver disease far outpaces organ availability and, therefore, patients undergoing liver transplant are sicker at the time of transplant. Outcomes for liver transplant patients continue to improve owing to advancements in surgical technique, immunosuppression management, and intensive care management of liver disease both pretransplant and posttransplant. SUMMARY Given a global increase in liver transplantation, an increasing number of intensive care professionals are likely to care for this patient population. For these providers, a foundational knowledge of the common complications and key management considerations is essential.
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Maiwall R, Rastogi A, Pasupuleti SSR, Hidam AK, Singh M, Kadyan S, Jain P, Kumar G, Sarin SK. Natural history, spectrum and outcome of stage 3 AKI in patients with acute-on-chronic liver failure. Liver Int 2022; 42:2800-2814. [PMID: 36017749 DOI: 10.1111/liv.15413] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 07/30/2022] [Accepted: 08/24/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM There is limited data on natural course and interventions in stage-3 acute kidney injury (AKI-3) in patients with acute-on-chronic liver failure (ACLF). We studied the factors of AKI-3 reversal and outcomes of dialysis in ACLF patients. METHODS Consecutive patients with ACLF were prospectively enrolled (n = 1022) and variables determining AKI and its outcomes were analysed. RESULTS At 1 month, 337 (33%) patients had AKI-3, of which, 131 had AKI-3 at enrolment and 206 developed AKI-3 during hospital stay. Of patients with AKI-3 at enrolment, 18% showed terlipressin response, 21% had AKI resolution and 59% required dialysis. High MELD (≥35) (model 1), serum bilirubin (≥23 mg/dL) (model 2) and AARC score (≥11) (model 3) were independent risk factors for dialysis. Dialysis was associated with worse survival in all AKI patients but improved outcomes in patients with AKI-3 (p = .022, HR 0.69 [0.50-0.95]). Post-mortem kidney biopsies (n = 61) revealed cholemic nephropathy (CN) in 54%, acute tubular necrosis (ATN) in 31%, and a combination (CN and ATN) in 15%. Serum bilirubin was significantly higher in patients with CN, CN and ATN compared with ATN respectively ([30.8 ± 12.2] vs. [26.7 ± 12.0] vs. [18.5 ± 9.8]; p = .002). CONCLUSION AKI-3 rapidly increases from 13% to 33% within 30 days in ACLF patients. Histopathological data suggested cholemic nephropathy as the predominant cause which correlated with high bilirubin levels. AKI-3 resolves in only one in five patients. Patients with AARC grade 3 and MELD >35 demand need for early dialysis in AKI-3 for improved outcomes.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Samba Siva R Pasupuleti
- Department of Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India
| | - Ashini K Hidam
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Mansi Singh
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sonia Kadyan
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Priyanka Jain
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Abstract
Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic de Barcelona, 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), Barcelona, Catalonia, Spain
| | - Ann T Ma
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic de Barcelona, 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), Barcelona, Catalonia, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, 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), Barcelona, Catalonia, Spain.,Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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Kim RW, Raghunathan K, Martin GS, Davis EA, Sindhwani NS, Telang S, Lodaya K. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. GASTRO HEP ADVANCES 2022; 2:252-260. [PMID: 39132612 PMCID: PMC11307587 DOI: 10.1016/j.gastha.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 10/19/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Patients admitted with decompensated cirrhosis who develop acute kidney injury (AKI) tend to experience poor outcomes, even if provided with increased organ support such as renal replacement therapies. We assessed the association of albumin administered ≤24 hours of admission with hospital length of stay (LOS) and in-hospital mortality. Methods The Cerner Health Facts Database was queried for hospitalized patients with cirrhosis who had >0.3 mg/dL increase in serum creatinine within 48 hours and received diuretics following admission between January 2009 and April 2018. This study received institutional review board exemption through federal regulation 45CFR46. Albumin infusion was "timely" if administered ≤24 hours after admission and "nontimely" if administered >24 hours after admission or not at all. Two subgroups were assessed: the AKILOS subgroup (patients who survived to discharge) and the AKIMORTALITY RISK subgroup (patients with the highest risk of mortality, ie, AKI stage 3). Results A total of 4135 hospitalizations with cirrhosis and AKI were grouped into AKILOS (n = 3321) and AKIMORTALITY RISK (n = 609) subgroups. Albumin administration occurred in 59.7% of the AKILOS subgroup and 77.8% of the AKIMORTALITY RISK subgroup, but timely treatment only occurred in 25.9% and 35.8% of encounters within these subgroups, respectively. Risk-adjusted analysis showed timely albumin administration to be associated with a 15.5% reduction (P < .01) in LOS in the AKILOS subgroup and a 49% reduction in the odds of death (adjusted odds ratio: 0.51; P < .01) in the AKIMORTALITY RISK subgroup, when compared to the nontimely group. Conclusion Among patients with cirrhosis and AKI, treatment with albumin ≤24 hours after admission was associated with a shorter LOS and lower risk of death in patients with stage 3 AKI.
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Affiliation(s)
- Ray W. Kim
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, California
| | | | - Greg S. Martin
- Department of Medicine, Emory University, Atlanta, Georgia
| | - E. Anne Davis
- Grifols Shared Services North America (SSNA), Research Triangle Park, North Carolina
| | - Navreet S. Sindhwani
- Grifols Shared Services North America (SSNA), Research Triangle Park, North Carolina
| | | | - Kunal Lodaya
- Boston Strategic Partners, Inc, Boston, Massachusetts
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de Mattos ÂZ, Simonetto DA, Terra C, Farias AQ, Bittencourt PL, Pase THS, Toazza MR, de Mattos AA, Alliance of Brazilian Centers for Cirrhosis Care – the ABC Group. Albumin administration in patients with cirrhosis: Current role and novel perspectives. World J Gastroenterol 2022; 28:4773-4786. [PMID: 36156923 PMCID: PMC9476855 DOI: 10.3748/wjg.v28.i33.4773] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/05/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.
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Affiliation(s)
- Ângelo Zambam de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Douglas Alano Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, United States
| | - Carlos Terra
- Department of Gastroenterology, State University of Rio de Janeiro, Rio de Janeiro 20550-170, Brazil
| | | | | | - Tales Henrique Soares Pase
- Internal Medicine Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Marlon Rubini Toazza
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Angelo Alves de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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45
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Ayares G, Idalsoaga F, Díaz LA, Arnold J, Arab JP. Current Medical Treatment for Alcohol-Associated Liver Disease. J Clin Exp Hepatol 2022; 12:1333-1348. [PMID: 36157148 PMCID: PMC9499849 DOI: 10.1016/j.jceh.2022.02.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 02/06/2022] [Indexed: 12/12/2022] Open
Abstract
Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.
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Key Words
- AC, Amoxicillin/clavulanate
- ACLF, Acute-on-Chronic Liver Failure
- ADLs, Activities of Daily Living
- AH, Alcohol-Associated Hepatitis
- AKI-HRS, Acute Kidney Injury - Hepatorenal Syndrome
- ALD
- ALD, Alcohol-Associated Liver Disease
- ASH, Alcoholic Steatohepatitis
- AUD, Alcohol Use Disorder
- AWS, Alcohol Withdrawal Syndrome
- BCAAs, Branched-Chain Amino Acids
- CDC, Center for Disease Control
- CI, Confidence Interval
- COVID-19, Coronavirus Disease 2019
- CT, Computerized Tomography
- GABA, gamma-aminobutyric acid agonist
- HBV, Hepatitis B Virus
- HCC, Hepatocellular Carcinoma
- HCV, Hepatitis C Virus
- HE, Hepatic Encephalopathy
- HIV, Human Immunodeficiency Virus
- HR, Hazard Ratio
- IBW, Ideal Body Weight
- ICA, International Club of Ascites
- IL-1β, Interleukin-1β
- IL-22, Interleukin-22
- KPS, Karnofsky Performance Status
- LB, Liver Biopsy
- LPS, Lipopolysaccharide
- LSM, Liver Stiffness Measurement
- LT, Liver Transplantation
- MDF, Maddrey’s Discriminant Function
- MELD, Model of End-Stage Liver Disease
- MRI, Magnetic Resonance Imaging
- MUST, Malnutrition Universal Screening Tool
- NIAAA, National Institute on Alcohol Abuse and Alcoholism
- NRS-2002, Nutritional Risk Screening-2002
- OR, Odds Ratio
- PAMPs, Pathogen-Activated Molecular Patterns
- PMI, Psoas Muscle Index
- PTX, Pentoxifylline
- RAI, Relative Adrenal Insufficiency
- RCT, Randomized Clinical Trials
- RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool
- ROS, Reactive Oxygen Species
- RR, Relative Risk
- SIRS, Systemic Inflammatory Response Syndrome
- TNF, Tumor Necrosis Factor
- WKS, Wernicke-Korsakoff Syndrome
- alcohol
- alcohol use disorders
- alcohol-associated hepatitis
- cirrhosis
- fatty liver disease
- steatosis
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Affiliation(s)
- Gustavo Ayares
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis A. Díaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jorge Arnold
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan P. Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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46
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Wan YP, Wang AJ, Zhang W, Zhang H, Peng GH, Zhu X. Development and validation of a nomogram for predicting overall survival in cirrhotic patients with acute kidney injury. World J Gastroenterol 2022; 28:4133-4151. [PMID: 36157113 PMCID: PMC9403434 DOI: 10.3748/wjg.v28.i30.4133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/29/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis, and is associated with poor prognosis. Therefore, identifying cirrhotic patients with AKI who are at high risk of mortality is very important and may be helpful for providing timely medical interventions to improve the prognosis of these patients. However, studies focused on investigating the risk factors for the mortality of cirrhotic patients with AKI were scarce.
AIM To identify risk factors for mortality and establish a nomogram for predicting the prognosis of these patients.
METHODS Two hundred fifty consecutive patients with cirrhosis and AKI were recruited and randomly divided into training cohort (n = 173) and validation cohort (n = 77). In the training cohort, potential risk factors for death were identified by performing a Cox regression analysis, and a nomogram was established. The predictive performance of the nomogram was internally and externally validated by calculating the area under the receiver operating characteristic curve (AUROC), constructing a calibration curve and performing decision curve analysis.
RESULTS The serum sodium level, international normalized ratio, peak serum creatinine level > 1.5 mg/dL, the presence of hepatic encephalopathy and diabetes were potential risk factors for mortality of cirrhotic patients with AKI in the training dataset. A prognostic nomogram incorporating these variables was established for predicting the overall survival of these patients. Compared with Child-Turcotte-Pugh, the model for end-stage liver disease (MELD) and the MELD-Na scores, the nomogram in predicting 90- and 180-d mortality exhibited better discriminatory power with AUROCs of 0.792 and 0.801 for the training dataset and 0.817 and 0.862 for the validation dataset, respectively. With a nomogram score of 98, patients were divided into low- and high-risk groups, and high-risk patients had a higher mortality rate.
CONCLUSION A prognostic nomogram displayed good performance for predicting the overall survival of cirrhotic patients with AKI, and will assist clinicians in evaluating the prognosis of these patients.
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Affiliation(s)
- Yi-Peng Wan
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - An-Jiang Wang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Wang Zhang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Hang Zhang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Gen-Hua Peng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Xuan Zhu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
- Biomolecular Research Laboratory, Jiangxi Clinical Research Center for Gastroenterology, Nanchang 331706, Jiangxi Province, China
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47
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Napoleone L, Solé C, Juanola A, Ma AT, Carol M, Pérez-Guasch M, Rubio AB, Cervera M, Avitabile E, Bassegoda O, Gratacós-Ginès J, Morales-Ruiz M, Fabrellas N, Graupera I, Pose E, Crespo G, Solà E, Ginès P. Patterns of kidney dysfunction in acute-on-chronic liver failure: Relationship with kidney and patients' outcome. Hepatol Commun 2022; 6:2121-2131. [PMID: 35535681 PMCID: PMC9315130 DOI: 10.1002/hep4.1963] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/17/2022] [Accepted: 03/20/2022] [Indexed: 11/22/2022] Open
Abstract
Impairment of kidney function is common in acute-on-chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill-defined. Aims of the current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. This prospective study includes 639 admissions for AD (232 with ACLF; 407 without) in 518 patients. Data were collected at admission and during hospitalization, and patients were followed up for 3 months. Urine samples were analyzed for kidney biomarkers. Most patients with ACLF (92%) had associated acute kidney injury (AKI), in most cases without previous chronic kidney disease (CKD), whereas some had AKI-on-CKD (70% and 22%, respectively). Prevalence of AKI in patients without ACLF was 35% (p < 0.001 vs. ACLF). Frequency of CKD alone was low and similar in both groups (4% and 3%, respectively); only a few patients with ACLF (4%) had no kidney dysfunction. AKI in ACLF was associated with poor kidney and patient outcomes compared with no ACLF (AKI resolution: 54% vs. 89%; 3-month survival: 51% vs. 86%, respectively; p < 0.001 for both). Independent predictive factors of 3-month survival were Model for End-Stage Liver Disease-Sodium score, ACLF status, and urine neutrophil gelatinase-associated lipocalin (NGAL). AKI is almost universal in patients with ACLF, sometimes associated with CKD, whereas CKD alone is uncommon. Prognosis of AKI depends on ACLF status. AKI without ACLF has good prognosis. Best predictors of 3-month survival are MELD-Na, ACLF status, and urine NGAL.
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Affiliation(s)
- Laura Napoleone
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Cristina Solé
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Adrià Juanola
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Ann T Ma
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Marta Carol
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain
| | - Martina Pérez-Guasch
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain
| | - Ana-Belén Rubio
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Marta Cervera
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain
| | - Emma Avitabile
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Octavi Bassegoda
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Manuel Morales-Ruiz
- Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain.,Biochemistry and Molecular Genetics DepartmentHospital Clínic de BarcelonaBarcelonaSpain
| | - Núria Fabrellas
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain
| | - Isabel Graupera
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain
| | - Elisa Pose
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Elsa Solà
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain
| | - Pere Ginès
- Liver Unit, Hospital Clínic de BarcelonaUniversity of BarcelonaBarcelonaSpain.,Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelonaSpain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain.,School of Medicine and Health SciencesUniversity of BarcelonaBarcelonaSpain
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48
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Patidar KR, Naved MA, Grama A, Adibuzzaman M, Aziz Ali A, Slaven JE, Desai AP, Ghabril MS, Nephew L, Chalasani N, Orman ES. Acute kidney disease is common and associated with poor outcomes in patients with cirrhosis and acute kidney injury. J Hepatol 2022; 77:108-115. [PMID: 35217065 DOI: 10.1016/j.jhep.2022.02.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS Acute kidney disease (AKD) is the persistence of acute kidney injury (AKI) for up to 3 months, which is proposed to be the time-window where critical interventions can be initiated to alter downstream outcomes of AKI. In cirrhosis, AKD and its impact on outcomes have been scantly investigated. We aimed to define the incidence and outcomes associated with AKD in a nationwide US cohort of hospitalized patients with cirrhosis and AKI. METHODS Hospitalized patients with cirrhosis and AKI in the Cerner-Health-Facts database from 1/2009-09/2017 (n = 6,250) were assessed for AKD and were followed-up for 180 days. AKI and AKD were defined based on KDIGO and ADQI AKD and renal recovery consensus criteria, respectively. The primary outcome measure was mortality, and the secondary outcome measure was de novo chronic kidney disease (CKD). Competing-risk multivariable models were used to determine the independent association of AKD with primary and secondary outcomes. RESULTS AKD developed in 32% of our cohort. On multivariable competing-risk analysis adjusting for significant confounders, patients with AKD had higher risk of mortality at 90 (subdistribution hazard ratio [sHR] 1.37; 95% CI 1.14-1.66; p = 0.001) and 180 (sHR 1.37; 95% CI 1.14-1.64; p = 0.001) days. The incidence of de novo CKD was 37.5%: patients with AKD had higher rates of de novo CKD (64.0%) compared to patients without AKD (30.7%; p <0.001). After adjusting for confounders, AKD was independently associated with de novo CKD (sHR 2.52; 95% CI 2.01-3.15; p <0.001) on multivariable competing-risk analysis. CONCLUSIONS AKD develops in 1 in 3 hospitalized patients with cirrhosis and AKI and it is associated with worse survival and de novo CKD. Interventions that target AKD may improve outcomes of patients with cirrhosis and AKI. LAY SUMMARY In a nationwide US cohort of hospitalized patients with cirrhosis and acute kidney injury, acute kidney disease developed in 1 in 3 patients and was associated with worse survival and chronic kidney disease. Interventions that target acute kidney disease may improve outcomes of patients with cirrhosis and acute kidney injury.
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Affiliation(s)
- Kavish R Patidar
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA.
| | - Mobasshir A Naved
- Department of Computer Science, Purdue University, West Lafayette, IN USA
| | - Ananth Grama
- Department of Computer Science, Purdue University, West Lafayette, IN USA
| | - Mohammad Adibuzzaman
- Department of Medical Informatics and Clinical Epidemiology, Oregon Health Sciences University, OR USA
| | - Arzina Aziz Ali
- Division of Internal Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - James E Slaven
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis IN, USA
| | - Archita P Desai
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Marwan S Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Lauren Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Eric S Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
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49
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Schleicher EM, Kremer WM, Kalampoka V, Gairing SJ, Kaps L, Schattenberg JM, Galle PR, Wörns MA, Nagel M, Weinmann-Menke J, Labenz C. Frailty as Tested by the Clinical Frailty Scale Is a Risk Factor for Hepatorenal Syndrome in Patients With Liver Cirrhosis. Clin Transl Gastroenterol 2022; 13:e00512. [PMID: 35905416 PMCID: PMC10476772 DOI: 10.14309/ctg.0000000000000512] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Frailty is common in patients with cirrhosis and increases the vulnerability to internal and external stressors. This study aimed to investigate the impact of frailty, as defined by the Clinical Frailty Scale (CFS), on the risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS-AKI) in hospitalized patients with liver cirrhosis. METHODS We analyzed data of 201 nonelectively hospitalized patients with cirrhosis and without higher-grade chronic kidney disease. Patient characteristics were captured within the first 24 hours of hospital admission, and frailty was assessed using the CFS. Patients were followed for the development of AKI and/or HRS-AKI during the hospital stay. RESULTS In the total cohort, median CFS was 3 (interquartile range 3-4), and 34 (16.9%) patients were frail (CFS >4). During the hospital stay, 110 (54.7%) and 49 (24.3%) patients developed AKI or HRS-AKI, respectively. Patients with AKI or HRS-AKI had a significantly higher CFS than patients without kidney injury (P < 0.001 each). In multivariable analyses, a higher CFS was independently associated with the development of AKI (odds ratio [OR] 1.467, 95% confidence interval (CI) 1.065-2.021) in the total cohort and HRS-AKI (OR 1.809, 95% CI 1.263-2.591) in the subcohort of patients with a history of ascites. In addition, there was a strong association between frailty (OR 3.717, 95% CI 1.456-9.491) and HRS-AKI. DISCUSSION Frailty in patients with cirrhosis is associated with AKI and HRS-AKI. In this context, CFS appears to be a reliable tool to identify patients at high risk for developing AKI or HRS-AKI on hospital admission.
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Affiliation(s)
- Eva Maria Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Wolfgang Maximilian Kremer
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Vasiliki Kalampoka
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Leonard Kaps
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Jörn M. Schattenberg
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Metabolic Liver Research Program, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Marcus-Alexander Wörns
- Department of Gastroenterology, Hematology, Oncology and Endocrinology, Klinikum Dortmund, Germany;
| | - Michael Nagel
- Department of Gastroenterology, Hematology, Oncology and Endocrinology, Klinikum Dortmund, Germany;
| | - Julia Weinmann-Menke
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
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Song Y, Wang Y, Zang C, Yang X, Li Z, Wu L, Li K. Prognostic Nomograms for Hospital Survival and Transplant-Free Survival of Patients with Hepatorenal Syndrome: A Retrospective Cohort Study. Diagnostics (Basel) 2022; 12:diagnostics12061417. [PMID: 35741226 PMCID: PMC9221587 DOI: 10.3390/diagnostics12061417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/01/2022] [Accepted: 06/04/2022] [Indexed: 12/04/2022] Open
Abstract
Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise method based on the smallest Akaike information criterion value was applied to select the covariates to be included in the Cox proportional hazards models. The Harrell C-index, area under the receiver operating characteristic curve (AUC), Brier score, and Kaplan–Meier curves with the log-rank test were used to assess nomograms. The bootstrapping method with 1000 resamples was performed for internal validation. The nomogram predicting hospital survival included prothrombin activity, HRS clinical pattern, Child–Pugh class, and baseline serum creatinine. The C-index was 0.72 (95% confidence interval (CI), 0.65–0.78), and the adjusted C-index was 0.72 (95% CI, 0.66–0.79). The nomogram predicting transplant-free survival included sex, prothrombin activity, HRS clinical pattern, model for end-stage liver disease–Na score, and peak serum creatinine. The C-index of the nomogram was 0.74 (95% CI, 0.69–0.79), and the adjusted C-index was 0.74 (95% CI, 0.68–0.79). The AUC and Brier score at 15, 30, and 45 days calculated from the hospital survival nomogram and those at 6, 12, and 18 months calculated from the transplant-free survival nomogram revealed good predictive ability. The two models can be used to identify patients at high risk of HRS and promote early intervention treatment.
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Affiliation(s)
- Yi Song
- Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; (Y.S.); (X.Y.); (Z.L.)
| | - Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
| | - Chaoran Zang
- Hepatobiliary Pancreatic Center Department, Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University, Beijing 102218, China;
| | - Xiaoxi Yang
- Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; (Y.S.); (X.Y.); (Z.L.)
| | - Zhenkun Li
- Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; (Y.S.); (X.Y.); (Z.L.)
| | - Lina Wu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
- Correspondence: (L.W.); (K.L.)
| | - Kang Li
- Biomedical Information Center, Beijing You’ An Hospital, Capital Medical University, Beijing 100069, China
- Correspondence: (L.W.); (K.L.)
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