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Sikerwar S, Yao L, Elfarra Y, Jesudian A. Optimal Management of the Inpatient With Decompensated Cirrhosis. J Clin Gastroenterol 2025; 59:420-432. [PMID: 39889207 DOI: 10.1097/mcg.0000000000002143] [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: 08/21/2024] [Accepted: 01/14/2025] [Indexed: 02/02/2025]
Abstract
Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.
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Affiliation(s)
- Sandeep Sikerwar
- NewYork-Presbyterian Hospital/Columbia University Medical Center
| | - Leah Yao
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Yasmine Elfarra
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Arun Jesudian
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
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Olayinka OT, Orelus J, Nisar MR, Kotha R, Saad-Omer SI, Singh S, Yu AK. Comparative Mortality Rates of Vasoconstrictor Agents in the Management of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e67034. [PMID: 39286706 PMCID: PMC11402629 DOI: 10.7759/cureus.67034] [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: 06/24/2024] [Accepted: 08/14/2024] [Indexed: 09/19/2024] Open
Abstract
Hepatorenal syndrome (HRS) is an acute complication of advanced liver disease, which manifests with a rapidly progressive decline in kidney function. Though pharmacological treatment has been recently advanced, there are still high mortality rates. The study compares the mortality rate in patients using different vasoconstrictor agents in the management of HRS. A complete literature search was done in the following databases: PubMed, Cochrane Library, PubMed Central (PMC), and Multidisciplinary Digital Publishing Institute (MDPI). Studies were included according to previously established criteria, in which all studies reporting on adult patients with HRS treated with vasoconstrictor agents were eligible. The data extracted were analyzed with a random-effects model to express variability between studies, and the principal measure was the risk ratio (RR) for mortality. Of the 8,137 studies identified, 29 met the inclusion criteria. In the meta-analysis, vasoconstrictors, mainly terlipressin, significantly improved renal function and decreased the need for renal replacement therapy (RRT) versus placebo. However, a significant impact on mortality was lacking (0.94 (0.84-1.06), p = 0.31). The subgroup analysis found that mortality rates were not significantly different between vasoconstrictors, whether used in combination with or without albumin (0.97 (0.77-1.23), p = 0.79, and 0.98 (0.79-1.21), p = 0.86). Global heterogeneity was low, indicating consistent results in the studies. Vasoconstrictors are helpful in managing HRS, with improvement in renal function and reduction in RRT requirements. However, the effect on mortality was small and nonsignificant. Such findings support the use of terlipressin in HRS management; concomitantly, they emphasize the need for personalized treatment strategies and future research to find alternative therapies that may be more effective for improved survival results with fewer side effects.
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Affiliation(s)
- Oluwatoba T Olayinka
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Jaslin Orelus
- Emergency Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Mah Rukh Nisar
- Neurology and Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Rudrani Kotha
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Sabaa I Saad-Omer
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Shivani Singh
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Ann Kashmer Yu
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
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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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Belcher JM. Hepatorenal Syndrome Type 1: Diagnosis and Treatment. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:100-110. [PMID: 38649214 DOI: 10.1053/j.akdh.2023.05.001] [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: 10/20/2022] [Revised: 04/16/2023] [Accepted: 05/08/2023] [Indexed: 04/25/2024]
Abstract
Hepatorenal syndrome (HRS) is a feared complication in patients with advanced cirrhosis and is associated with significant morbidity and mortality. While recognized as a distinct physiologic condition for well over one hundred years, a lack of objective diagnostic tests has made the diagnosis one of exclusion. Since 1979, multiple sets of diagnostic criteria have been proposed. Though varying in detail, the principal intent of these criteria is to identify patients with severe, functional acute kidney injury that is unresponsive to volume resuscitation and exclude those with structural injury. However, accurate differential diagnosis remains challenging. Recently, multiple urinary biomarkers of kidney injury, including neutrophil gelatinase-associated lipocalin, have been studied as a means of objectively phenotyping etiologies of acute kidney injury in patients with cirrhosis. Along with markers reflecting tubular functional integrity, including the fractional excretion of sodium, injury markers will likely be incorporated into future diagnostic criteria. Making an accurate diagnosis is critical, as therapeutic options exist for HRS but must be given in a timely manner and only to those patients likely to benefit. Terlipressin, an analog of vasopressin, is the first line of therapy for HRS in much of the world and has recently been approved for use in the United States. Significant questions remain regarding the optimal dosing strategy, metrics for titration, and the potential role of point-of-care ultrasound to help guide concurrent albumin administration.
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Affiliation(s)
- Justin M Belcher
- Yale University School of Medicine, Department of Internal Medicine, Section of Nephrology, New Haven, CT; Department of Internal Medicine, Section of Nephrology, VA Connecticut Healthcare, West Haven, CT.
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Weinberg E, Rahematpura S, Gonzalez SA, Izzy MJ, Simonetto DA, Frederick RT, Rubin RA, Ikahihifo-Bender J, Harte M, Kim-Lee G, Witkiewicz S, Tobin W, Jamil K, Fricker Z, Reddy KR. INFUSE: Rationale and design of a multi-center, open label, collaborative study to treat HRS-AKI with continuous terlipressin infusion. Contemp Clin Trials Commun 2023; 36:101211. [PMID: 37953795 PMCID: PMC10632660 DOI: 10.1016/j.conctc.2023.101211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/25/2023] [Accepted: 10/01/2023] [Indexed: 11/14/2023] Open
Abstract
Background Hepatorenal syndrome-acute kidney injury (HRS-AKI) carries significant morbidity and mortality among those with end-stage liver disease. Bolus terlipressin for treatment of HRS-AKI received FDA approval in September 2022. US implementation of terlipressin, however, is hindered by the paucity of local data on the optimal patient population and administration mode, as well as the effect on transplant priority. The INFUSE study is designed to evaluate the use of continuous terlipressin infusion among transplant candidates with advanced liver disease and HRS-AKI. Methods Fifty prospective patients with HRS-AKI will receive a single bolus of terlipressin 0.5 mg followed by continuous infusions of terlipressin from 2 to 8 mg/day for up to 14 days. The cohort will be enriched with those listed, in evaluation, or eligible for liver transplantation, while those with ACLF grade 3, MELD ≥35, and serum creatinine >5.0 mg/dL will be excluded. Fifty patients who received midodrine plus octreotide or norepinephrine for HRS-AKI will serve as a retrospective comparator cohort. Conclusion The INFUSE study aims to assess the safety and efficacy of continuous terlipressin infusion among largely transplant-eligible patients with HRS-AKI, and to provide US-based data on transplant outcomes. This novel study design simultaneously mitigates terlipressin adverse events while providing renal benefits to patients, thus addressing the unmet medical need of those with HRS-AKI who have limited treatment options and are awaiting liver transplantation in the US.
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Affiliation(s)
- Ethan Weinberg
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Suditi Rahematpura
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Stevan A. Gonzalez
- Division of Hepatology, Simmons Transplant Institute, Baylor Scott and White All Saints Medical Center, Fort Worth, TX, USA
| | - Manhal J. Izzy
- Department of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - R. Todd Frederick
- Department of Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco, CA, USA
| | - Raymond A. Rubin
- Department of Transplantation, Piedmont Transplant Institute, Atlanta, GA, USA
| | - Jade Ikahihifo-Bender
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Maggie Harte
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Grace Kim-Lee
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | | | | | - Khurram Jamil
- Mallinckrodt Ltd, Scientific Affairs, Hampton, NJ, USA
| | - Zachary Fricker
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Sohal A, Chaudhry H, Dukovic D, Kowdley KV. Outcomes among patients with hepatorenal syndrome based on hospital teaching and transplant status: Analysis of 159 845 hospitalizations. JGH Open 2023; 7:848-854. [PMID: 38162842 PMCID: PMC10757492 DOI: 10.1002/jgh3.12985] [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: 06/01/2023] [Revised: 09/05/2023] [Accepted: 10/13/2023] [Indexed: 01/03/2024]
Abstract
Background and Aim Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver disease. This study aimed to examine the impact of hospital teaching/transplant status and availability of liver transplantation on survival among hospitalized patients with HRS in the United States. Methods Patients with HRS were identified from the national inpatient sample 2016-2019. Information was collected regarding patient demographics, hospital characteristics, liver disease etiology, presence of liver disease decompensations, Elixhauser comorbidities, and interventions. Patients were classified as being treated at three hospital groups: non-teaching hospitals (NTHs), teaching non-transplant centers (TNTCs), and teaching transplant centers (TTCs). The relationship between hospital teaching/transplant status and in-hospital mortality and transplant-free mortality was examined using multivariable linear and logistic regression analysis. Results A total of 159,845 patients met the criteria for HRS. Of these, 24% were admitted to NTHs, 50.8% to TNTCs, and 25.2% to TTCs. Admission to a TTC was independently associated with a lower mortality risk compared to admission to non-TTCs (aOR = 0.75, 95% CI: 0.68-0.83, P <0.001). Patients at TTCs had a lower transplant-free mortality risk than those at NTHs (aOR = 0.75, 95% CI: 0.67-0.83, P < 0.001). There was no significant difference in all-cause or transplant-free mortality between TNTCs and NTHs. Conclusion Patients with HRS admitted to TTCs have higher disease severity, but significantly improved outcomes compared to those admitted to NTHs. These data suggest opportunities for increased disease awareness and education among NTHs and support early referral for liver transplant evaluation among hospitalized patients with HRS.
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Affiliation(s)
- Aalam Sohal
- Department of HepatologyLiver Institute NorthwestSeattleWashingtonUSA
| | - Hunza Chaudhry
- Department of Internal MedicineUniversity of CaliforniaFresnoCaliforniaUSA
| | - Dino Dukovic
- Department of MedicineRoss University School of MedicineMiramarFloridaUSA
| | - Kris V. Kowdley
- Department of HepatologyLiver Institute NorthwestSeattleWashingtonUSA
- Department of Medicine, Elson S. Floyd College of MedicineWashington State UniversityPullmanWashingtonUSA
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Ayyad A, Al-Horani RA. Terlipressin for the Prevention and Treatment of Renal Decline in Hepatorenal Syndrome: A Drug Profile. GASTROENTEROLOGY INSIGHTS 2023; 14:420-430. [PMID: 37873544 PMCID: PMC10587779 DOI: 10.3390/gastroent14040031] [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] [Indexed: 10/25/2023] Open
Abstract
Hepatorenal syndrome stands as one of several potential triggers of acute kidney injury in individuals grappling with either acute or persistent liver ailments. The nature of the decline in kidney function has led to the identification of two variants of hepatorenal syndrome. In cases where terlipressin therapy is accessible, the initial approach involves administering terlipressin alongside albumin. Terlipressin, a synthetic analog of vasopressin, boasts double the preference for vasopressin V1 receptors compared to V2 receptors. The FDA granted approval to terlipressin in September 2022, demonstrating its intrinsic activity, although a significant portion of its function arises from its transformation into lysine vasopressin. This article provides a comprehensive examination of terlipressin's various pharmacodynamic and pharmacokinetic facets, as well as its clinical utility, aiming to keep the scientific community well informed about its safe and efficient utilization.
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Affiliation(s)
- Ahlam Ayyad
- Division of Clinical and Administrative Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
| | - Rami A. Al-Horani
- Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
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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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Duong N, Kakadiya P, Bajaj JS. Current Pharmacologic Therapies for Hepatorenal Syndrome-Acute Kidney Injury. Clin Gastroenterol Hepatol 2023; 21:S27-S34. [PMID: 37625864 DOI: 10.1016/j.cgh.2023.06.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 05/30/2023] [Accepted: 06/03/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND & AIMS Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment. This review will highlight randomized controlled trials for HRS pharmacotherapy. METHODS A PubMed review of randomized controlled trials conducted over the past 25 years was undertaken; 18 studies were included. RESULTS Initial studies showed that norepinephrine is as effective as terlipressin for HRS reversal. Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality. Recently, terlipressin with albumin led to significantly higher rates of HRS reversal compared to albumin alone. Non-response to terlipressin can predict 90-day mortality in acute-on-chronic-liver failure. CONCLUSIONS Our current understanding of HRS treatment is improved by recent randomized clinical trials. Previous studies using varying medication doses along with the "old" definition of hepatorenal syndrome (HRS type 1) rather than HRS-AKI means that there is still a need for future multicenter prospective studies further refining the risk-benefit ratio of vasoconstrictors for HRS-AKI patients. The Food and Drug Administration has approved terlipressin for use in September 2022. Because it will take time to adapt into clinical practice, less cost-prohibitive vasoconstrictors should still be considered. Opportunities also exist to clarify the safety, timing of initiation, as well as possible discontinuation of terlipressin.
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Affiliation(s)
- Nikki Duong
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia
| | - Payal Kakadiya
- Division of Pharmacy, Virginia Commonwealth University Health, Richmond, Virginia
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia.
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Arnold J, Avila E, Idalsoaga F, Diaz LA, Ayala Valverde M, Ayares G, Arrese M, Roessler E, Huidobro JP, Hudson D, Khan MQ, Arab JP. Advances in the diagnosis and management of hepatorenal syndrome: insights into HRS-AKI and liver transplantation. EGASTROENTEROLOGY 2023; 1:e100009. [PMID: 39943997 PMCID: PMC11770447 DOI: 10.1136/egastro-2023-100009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/27/2023] [Indexed: 01/04/2025]
Abstract
In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI-liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.
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Affiliation(s)
- Jorge Arnold
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Avila
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Gustavo Ayares
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eric Roessler
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Huidobro
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - David Hudson
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Mohammad Qasim Khan
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
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Roy P, Minhaz N, Shah-Riar P, Simona SY, Tasha T, Binte Hasan T, Abbasi FK, Alam F, Nila SA, Akter J, Akter S, Biswas S, Sultana N. A Comprehensive Systematic Review of the Latest Management Strategies for Hepatorenal Syndrome: A Complicated Syndrome to Tackle. Cureus 2023; 15:e43073. [PMID: 37680416 PMCID: PMC10481992 DOI: 10.7759/cureus.43073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2023] [Indexed: 09/09/2023] Open
Abstract
Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.
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Affiliation(s)
- Pooja Roy
- Internal Medicine, Harlem Hospital Center, New York, USA
| | - Naofel Minhaz
- Internal Medicine, Dhaka Medical College, Dhaka, BGD
| | | | | | - Tasniem Tasha
- Internal Medicine, Rajshahi Medical College, Rajshahi, BGD
| | | | | | - Farhana Alam
- Internal Medicine, Chittagong Medical College, Chittagong, BGD
| | - Shamima A Nila
- Internal Medicine, Cumilla Medical College and Hospital, Cumilla, BGD
| | - Janifa Akter
- Internal Medicine, Gonoshasthaya Samaj Vittik Medical College, Dhaka, BGD
- Internal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, BGD
| | - Sharmin Akter
- Internal Medicine, Shaheed Ziaur Rahman Medical College, Bogura, BGD
| | - Shammo Biswas
- Internal Medicine, Sir Salimullah Medical College Mitford Hospital, Dhaka, BGD
| | - Nigar Sultana
- Internal Medicine, Sir Salimullah Medical College Mitford Hospital, Dhaka, BGD
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Scheinberg AR, Martin P, Bhamidimarri KR. The Clinical Spectrum and Manifestations of Acute-on-Chronic Liver Failure. Clin Liver Dis 2023; 27:671-680. [PMID: 37380290 DOI: 10.1016/j.cld.2023.03.010] [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: 06/30/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is characterized by abrupt decompensation in a patient with chronic liver disease with extrahepatic organ dysfunction and is implicated in an increased risk of mortality. ACLF may be present in approximately 20% to 40% of hospitalized cirrhosis. There are several diagnostic scoring systems for ACLF; one defined by the North American Consortium for Study of End-stage Liver Disease is the presence of acutely decompensated cirrhosis complicated by failure of two or more organ systems: circulatory, renal, neurological, coagulopathy, and/or pulmonary.
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Affiliation(s)
- Andrew R Scheinberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA.
| | - Kalyan Ram Bhamidimarri
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA
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13
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Attieh RM, Wadei HM. Acute Kidney Injury in Liver Cirrhosis. Diagnostics (Basel) 2023; 13:2361. [PMID: 37510105 PMCID: PMC10377915 DOI: 10.3390/diagnostics13142361] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/01/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.
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Affiliation(s)
- Rose Mary Attieh
- Department of Transplant, Division of Kidney and Pancreas Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Hani M Wadei
- Department of Transplant, Division of Kidney and Pancreas Transplant, Mayo Clinic, Jacksonville, FL 32224, USA
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14
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Abstract
Hepatorenal syndrome (HRS) is a primarily functional form of acute kidney injury (AKI) that develops in patients with decompensated cirrhosis. The pathophysiologic cascade that leads to HRS begins with pooling of blood in the splanchnic system, resulting in a decrease in effective circulating arterial volume. The definitive treatment of HRS is liver transplantation. When this is not possible, HRS is treated with a combination of vasoconstrictor agents and intravenous albumin. Although the combination of midodrine and octreotide is used in the United States, the recently approved terlipressin, an analog of vasopressin, is likely to become the first-line standard of care.
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Affiliation(s)
- Justin M Belcher
- Section of Nephrology, Yale University School of Medicine, VA Connecticut Healthcare System, VA Connecticut Healthcare, Room G126B, 950 Campbell Avenue, West Haven, CT 06516, USA.
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15
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Rao S, Peterson CJ, Elmassry M, Songtanin B, Benjanuwattra J, Nugent K. Spontaneous peritoneal drainage following paracentesis in a hospitalized patient with resolution of type 1 hepatorenal syndrome. Am J Med Sci 2022; 364:789-795. [PMID: 35793730 DOI: 10.1016/j.amjms.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/21/2022] [Accepted: 06/28/2022] [Indexed: 01/25/2023]
Abstract
The hepatorenal syndrome develops in a small percentage of patients with advanced liver disease. The pathogenesis involves intravascular volume contraction secondary to pooling of blood in the splanchnic vessels, stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone pathway, and increased intra-abdominal pressure secondary to the formation of large volumes of ascitic fluid. The treatment options are limited, and liver transplant is the only definitive form of management. Here we suggest an alternative approach to treating hepatorenal syndrome based on the unexpected continuous peritoneal drainage in a 36-year-old man hospitalized with hepatic encephalopathy and hepatorenal syndrome. A total of 11.2 L ascitic fluid drained over 5 days from a paracentesis puncture site with marked improvement in renal function; the creatinine decreased from 3.3 mg/dL to 0.7 mg/dL and the BUN decreased from 42 mg/dL to 10 mg/dL. The discussion with this case report summarizes the pathogenesis, including the effect of intra-abdominal pressure, of the hepatorenal syndrome, outlines medical management, and makes a proposal for clinical study based on this case.
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Affiliation(s)
- Sanjana Rao
- School of Medicine, Texas Tech University Health Sciences CenterLubbock, TX, USA
| | | | - Marawan Elmassry
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Juthipong Benjanuwattra
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
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16
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Wu HHL, Athwal VS, Kalra PA, Chinnadurai R. COVID-19 and hepatorenal syndrome. World J Gastroenterol 2022; 28:5666-5678. [PMID: 36338894 PMCID: PMC9627428 DOI: 10.3748/wjg.v28.i39.5666] [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: 09/04/2022] [Revised: 09/21/2022] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - Varinder S Athwal
- Faculty of Biology, Medicine & Health (Division of Diabetes, Metabolism & Gastroenterology), The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Philip A Kalra
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
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17
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Lankarani KB, Safa H, Ghahramani S, Sayari M, Malekhosseini SA. Impact of Octreotide on Early Complications After Liver Transplant: A Randomized, Double-Blind Placebo-Controlled Trial. EXP CLIN TRANSPLANT 2022; 20:835-841. [DOI: 10.6002/ect.2022.0080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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18
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Buccheri S, Da BL. Hepatorenal Syndrome: Definitions, Diagnosis, and Management. Clin Liver Dis 2022; 26:181-201. [PMID: 35487604 DOI: 10.1016/j.cld.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatorenal syndrome (HRS) is a hemodynamically driven process mediated by renal dysregulation and inflammatory response. Albumin, antibiotics, and β-blockers are among therapies that have been studied in HRS prevention. There are no Food and Drug Administration-approved treatments for HRS although multiple liver societies have recommended terlipressin as first-line pharmacotherapy. Renal replacement therapy is the primary modality used to bridge to definitive therapy with orthotopic liver transplant or simultaneous liver-kidney transplant. Advances in our understanding of HRS pathophysiology and emerging therapeutic modalities are needed to change outcomes for this vulnerable population.
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Affiliation(s)
- Sebastiano Buccheri
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA
| | - Ben L Da
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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19
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Velez JCQ. Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic Therapy. KIDNEY360 2022; 3:382-395. [PMID: 35373127 PMCID: PMC8967638 DOI: 10.34067/kid.0006722021] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 12/02/2021] [Indexed: 05/05/2023]
Abstract
Hepatorenal syndrome type 1 (HRS-1) is a serious form of AKI that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. Although the diagnostic criteria dictated by the International Club of Ascites provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of acute tubular injury, distinguishing these two causes of AKI has direct implications in management. Therefore, the use of the International Club of Ascites criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1, but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacologic therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible, and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors, and their use should be determined by availability, ease of administration, and attention to optimal risk-benefit balance for each clinical scenario.
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Affiliation(s)
- Juan Carlos Q. Velez
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, University of Queensland, Brisbane, Australia
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20
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Gupta MM, Deng X. Hepatorenal Syndrome. APPROACHES TO CHRONIC KIDNEY DISEASE 2022:151-168. [DOI: 10.1007/978-3-030-83082-3_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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21
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Nassar M, Nso N, Medina L, Ghernautan V, Novikov A, El-Ijla A, Soliman KM, Kim Y, Alfishawy M, Rizzo V, Daoud A. Liver Kidney Crosstalk: Hepatorenal Syndrome. World J Hepatol 2021; 13:1058-1068. [PMID: 34630874 PMCID: PMC8473490 DOI: 10.4254/wjh.v13.i9.1058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
The dying liver causes the suffocation of the kidneys, which is a simplified way of describing the pathophysiology of hepatorenal syndrome (HRS). HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate, secondary to increased vasodilators. Over the years, HRS has gained much attention and focus among hepatologists and nephrologists. HRS is a diagnosis of exclusion, and in some cases, it carries a poor prognosis. Different classifications have emerged to better understand, diagnose, and promptly treat this condition. This targeted review aims to provide substantial insight into the epidemiology, pathophysiology, diagnosis, and management of HRS, shed light on the various milestones of this condition, and add to our current understanding.
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Affiliation(s)
- Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Luis Medina
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Victoria Ghernautan
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Anastasia Novikov
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Alli El-Ijla
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Yungmin Kim
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Mostafa Alfishawy
- Department of Infectious Diseases, Infectious Diseases Consultants and Academic Researchers of Egypt IDCARE, Cairo 11562, Egypt
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai / NYC Health + Hospitals / Queens, New York, NY 11432, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11211, Egypt.
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22
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Hepatorenal syndrome: pathophysiology and evidence-based management update. ROMANIAN JOURNAL OF INTERNAL MEDICINE 2021; 59:227-261. [DOI: 10.2478/rjim-2021-0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 11/20/2022] Open
Abstract
Abstract
Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.
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23
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Bruno R, Cammà C, Caraceni P, D'Amico G, Grattagliano I, La Mura V, Riggio O, Schepis F, Senzolo M, Angeli P, de Franchis R. Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF). Dig Liver Dis 2021; 53:1089-1104. [PMID: 34321192 DOI: 10.1016/j.dld.2021.06.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/30/2021] [Accepted: 06/20/2021] [Indexed: 02/06/2023]
Abstract
Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to national regulations and resources, local circumstances and settings, infrastructure, and cost/benefit strategies to avoid duplication of efforts and optimize resource utilization. The committee defined the objectives, the key issues and retrieved the relevant evidence by performing a systematic review of the literature. Finally, the committee members (chosen on the basis of their specific expertise) identified the guidelines' key questions and developed them following the PICO format (Population, Intervention, Comparison, Outcomes). For each of the PICO questions, the systematic review of the literature was made on the most important scientific databases (Pubmed, Scopus, Embase).
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24
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Paine CH, Pichler RH, Evans L, Biggins SW. Toward Norepinephrine as a First-Line Treatment for All Hospitalized Patients With Hepatorenal Syndrome. Liver Transpl 2021; 27:1087-1088. [PMID: 34028156 DOI: 10.1002/lt.26106] [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: 05/18/2021] [Accepted: 05/18/2021] [Indexed: 01/13/2023]
Affiliation(s)
- Cary H Paine
- Division of Nephrology, University of Washington, Seattle, WA.,Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, WA
| | - Raimund H Pichler
- Division of Nephrology, University of Washington, Seattle, WA.,Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, WA
| | - Laura Evans
- Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA
| | - Scott W Biggins
- Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, WA.,Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA
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25
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El-Desoki Mahmoud EI, Abdelaziz DH, Abd-Elsalam S, Mansour NO. Norepinephrine is More Effective Than Midodrine/Octreotide in Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Randomized Controlled Trial. Front Pharmacol 2021; 12:675948. [PMID: 34276366 PMCID: PMC8283260 DOI: 10.3389/fphar.2021.675948] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/07/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Terlipressin is the first-line pharmacological treatment for hepatorenal syndrome. When terlipressin is unavailable, midodrine/octreotide or norepinephrine, with albumin, represent the alternative treatments. The comparative efficacy of these alternative regimens remains unclear. Objective: To compare the efficacy of midodrine/octreotide to that of norepinephrine for the treatment of patients with hepatorenal syndrome. Methods: In the intensive care setting, sixty patients with hepatorenal syndrome were randomized to initially receive either 0.5 mg/h of norepinephrine (maximum 3 mg/h) or 5 mg of oral midodrine three times/day (maximum 12.5 mg three times/day) plus octreotide (100 μg/6 h) as subcutaneous injection (maximum 200 μg/6 h), together with albumin (20-40 g/day). Treatment was allowed for a maximum of 10 days. Survival was analyzed for up to 30 days. The primary efficacy outcome was the proportion of patients who achieved full response, defined as the return of serum creatinine to a value within 0.3 mg/dl of the baseline at the end of treatment. Results: There was a significantly higher rate of full response in the norepinephrine group (15/26, 57.60%) than the midodrine/octreotide group (5/25, 20%) (p = 0.006). Eleven (42.30%) patients in the norepinephrine group and 6 (24%) in the midodrine/octreotide group survived (p = 0.166). Conclusion: Norepinephrine plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with hepatorenal syndrome. (ClinicalTrials.gov, identifier: NCT03455322). https://clinicaltrials.gov/ct2/show/NCT03455322?cond = Hepatorenal+Syndrome&cntry = EG&draw = 2&rank = 1.
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Affiliation(s)
| | - Doaa H Abdelaziz
- Department of Clinical Pharmacy, The National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Pharmacy Practice and Clinical Pharmacy Department, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt
| | - Sherief Abd-Elsalam
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Noha O. Mansour
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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26
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Perez I, Bolte FJ, Bigelow W, Dickson Z, Shah NL. Step by Step: Managing the Complications of Cirrhosis. Hepat Med 2021; 13:45-57. [PMID: 34079394 PMCID: PMC8164676 DOI: 10.2147/hmer.s278032] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/24/2021] [Indexed: 12/12/2022] Open
Abstract
According to the Centers for Disease Control and Prevention, chronic liver disease and cirrhosis is the 11th leading cause of death in the United States. Common causes of chronic liver disease include alcohol, viral hepatitis, and non-alcoholic steatohepatitis (NASH). Inflammation is a critical driver in the progression of liver disease to liver fibrosis and ultimately cirrhosis. While the severity of chronic liver disease extends over a continuum, the management is more easily differentiated between compensated and decompensated cirrhosis. In this review, we discuss pathophysiology, clinical features and management of common complications of liver cirrhosis based on literature review and the current clinical practice guidelines of the American Association for the Study of Liver Diseases (AASLD).
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Affiliation(s)
- Irene Perez
- Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA
| | - Fabian J Bolte
- Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA
| | - William Bigelow
- Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA
| | - Zachary Dickson
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
| | - Neeral L Shah
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
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27
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Standardized approach of albumin, midodrine and octreotide on hepatorenal syndrome treatment response rate. Eur J Gastroenterol Hepatol 2021; 33:102-106. [PMID: 32243349 DOI: 10.1097/meg.0000000000001700] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) remains a serious complication of cirrhosis with a high mortality rate. There is little information on the effect of standardizing albumin, midodrine and octreotide combination on treatment response in patients with HRS. OBJECTIVE The aim of the study was to determine the impact of a standardized HRS treatment regimen on renal function recovery. The primary outcome was full response rate. Secondary outcomes included partial and no response rates, 30-day all-cause mortality, ICU length of stay (LOS), hospital LOS, liver transplantation and total dose of albumin. METHODS This retrospective study evaluated the impact of using a standardized approach with albumin, midodrine and octreotide on treatment response rates compared to a historical group. RESULTS Of the patients with HRS, 28 received a standardized approach with albumin, midodrine and octreotide while 60 received a nonstandardized approach. Ten percent of patients achieved full response in the prestandardization group compared with 25% in the poststandardization group (P = 0.07). Renal replacement therapy was significantly more prevalent in the prestandardization group vs. poststandardization group (45% vs. 21.4%, P = 0.03). Liver transplantation was performed significantly more often in the prestandardization group compared the poststandardization group (23% vs. 3.6%, P = 0.02). Amount of albumin used was statistically lower in the poststandardization group (425 vs. 332 g, P = 0.05). No significant differences in days of HRS treatment, mortality rate, hospital and ICU LOS were observed. CONCLUSION A trend towards improved treatment response rate was observed after standardizing the HRS treatment regimen. Standardized therapy led to significantly lower rates of renal replacement therapy and liver transplantation, suggesting patients in poststandardization were effectively managed medically without requiring further intervention.
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28
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Gallo A, Dedionigi C, Civitelli C, Panzeri A, Corradi C, Squizzato A. Optimal Management of Cirrhotic Ascites: A Review for Internal Medicine Physicians. J Transl Int Med 2020; 8:220-236. [PMID: 33511049 PMCID: PMC7805288 DOI: 10.2478/jtim-2020-0035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Clinical history of liver cirrhosis is characterised by two phases: the asymptomatic phase, also termed 'compensated cirrhosis', and the phase of complications due to the development of portal hypertension and liver dysfunction, also termed 'decompensated cirrhosis', in which patients may develop ascites, the most frequent and clinically relevant complication of liver cirrhosis. Ascites can be classified into uncomplicated and complicated according to the development of refractoriness, spontaneous bacterial peritonitis (SBP) or the association with hepatorenal syndrome (HRS). In this narrative review, we will extensively discuss the optimal pharmacological and non-pharmacological management of cirrhotic ascites with the aim to offer an updated practical guide to Internal Medicine physicians. According to the amount of fluid in the abdominal cavity, uncomplicated ascites is graded from 1 to 3, and the cornerstone of its management consists of restriction of salt intake, diuretics and large-volume paracentesis (LVP); in recent years, long-term administration of human albumin has acquired a new interesting role. Refractory ascites is primarily managed with LVP and transjugular intrahepatic portosystemic shunt (TIPS) placement in selected patients. The occurrence of renal impairment, especially HRS, worsens the prognosis of patients with cirrhotic ascites and deserves a specific treatment. Also, the management of SBP faces the rising and alarming spread of antibiotic resistance. Hepatic hydrothorax may even complicate the course of the disease and its management is a challenge. Last but not least, liver transplantation (LT) is the ultimate and more effective measure to offer to patients with cirrhotic ascites, particularly when complications occur.
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Affiliation(s)
- Andrea Gallo
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Cristina Dedionigi
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Chiara Civitelli
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
| | - Anna Panzeri
- Department of Medicine and Surgery, University of Insubria, Como/Varese, Italy
- Hepatology Center, Ospedale Sant’Anna, Como, Italy
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Bodh V, Sharma B, Sharma R. Hepatorenal syndrome: A review into changing definition, diagnostic criteria, pathophysiology, and management. CHRISMED JOURNAL OF HEALTH AND RESEARCH 2020. [DOI: 10.4103/cjhr.cjhr_117_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Velez JCQ, Therapondos G, Juncos LA. Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis. Nat Rev Nephrol 2019; 16:137-155. [PMID: 31723234 DOI: 10.1038/s41581-019-0218-4] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/25/2019] [Indexed: 12/12/2022]
Abstract
The occurrence of acute kidney injury (AKI) in patients with end-stage liver disease constitutes one of the most challenging clinical scenarios in in-hospital and critical care medicine. Hepatorenal syndrome type 1 (HRS-1), which is a specific type of AKI that occurs in the context of advanced cirrhosis and portal hypertension, is associated with particularly high mortality. The pathogenesis of HRS-1 is largely viewed as a functional derangement that ultimately affects renal vasculature tone. However, new insights suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms, including those traditionally associated with HRS-1 and non-traditional factors, might contribute to the development of AKI in patients with cirrhosis. Moreover, histological evidence of morphological abnormalities in the kidneys of patients with cirrhosis and renal dysfunction has prompted the functional nature of HRS-1 to be re-examined. From a clinical perspective, a diagnosis of HRS-1 guides utilization of vasoconstrictive therapy and decisions regarding renal replacement therapy. Patients with cirrhosis are at risk of AKI owing to a wide range of factors. However, the tools currently available to ascertain the diagnosis of HRS-1 and guide therapy are suboptimal. Short of liver transplantation, goal-directed haemodynamically targeted pharmacotherapy remains the cornerstone of treatment for this condition; improved understanding of the underlying pathogenic mechanisms might lead to better clinical outcomes. Here, we examine our current understanding of the pathophysiology of HRS-1 and existing challenges in its diagnosis and treatment.
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Affiliation(s)
- Juan Carlos Q Velez
- Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA, USA. .,Ochsner Clinical School, The University of Queensland, Brisbane, Australia.
| | - George Therapondos
- Department of Gastroenterology and Hepatology, Ochsner Clinic Foundation, New Orleans, LA, USA
| | - Luis A Juncos
- Division of Nephrology, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.,Renal Section, Department of Medicine, Central Arkansas Veterans Affairs Medical Center, Little Rock, AR, USA
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News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document. J Hepatol 2019; 71:811-822. [PMID: 31302175 DOI: 10.1016/j.jhep.2019.07.002] [Citation(s) in RCA: 272] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 06/13/2019] [Accepted: 07/04/2019] [Indexed: 12/12/2022]
Abstract
Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease. Hepatorenal syndrome (HRS) has been defined as a purely "functional" type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems.4,5 In 2007, the International Club of Ascites (ICA) classified HRS into types 1 and 2 (HRS-1 and HRS-2).5 HRS-1 is characterised by a rapid deterioration of renal function that often occurs because of a precipitating event, while HRS-2 is a moderate and stable or slowly progressive renal dysfunction that often occurs without an obvious precipitant. Clinically, HRS-1 is characterised by acute renal failure while HRS-2 is mainly characterised by refractory ascites. Nevertheless, after these two entities were first described, new concepts, definitions, and diagnostic criteria have been developed by nephrologists for renal dysfunction in the general population and hospitalised patients. In particular, the definitions and characterisation of acute kidney injury (AKI), acute kidney disease and chronic kidney disease have been introduced/refined.6 Accordingly, a debate among hepatologists of the ICA led to a complete revision of the nomenclature and diagnosistic criteria for HRS-1, which was renamed HRS-AKI.7 Additionally, over recent years, greater granularity has been gained regarding the pathogenesis of HRS; it is now increasingly recognised that it is not a purely "functional" entity with haemodynamic derangements, but that systemic inflammation, oxidative stress and bile salt-related tubular damage may contribute significantly to its development. That is, HRS has an additional structural component that would not only make traditional diagnostic criteria less reliable, but would explain the lack of response to pharmacological treatment with vasoconstrictors plus albumin that correlates with a progressive increase in inflammation. Because classification, nomenclature, diagnostic criteria and pathogenic theories have evolved over the years since the traditional classification of HRS-1 and HRS-2 was first described, it was considered that all these novel aspects be reviewed and summarised in a position paper. The aim of this position paper authored by two hepatologists (members of ICA) and two nephrologists involved in the study of renal dysfunction in cirrhosis, is to complete the re-classification of HRS initiated by the ICA in 2012 and to provide an update on the definition, classification, diagnosis, pathophysiology and treatment of HRS.
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Ahmed M, Ahmed S. Functional, Diagnostic and Therapeutic Aspects of Gastrointestinal Hormones. Gastroenterology Res 2019; 12:233-244. [PMID: 31636773 PMCID: PMC6785288 DOI: 10.14740/gr1219] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 09/23/2019] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) hormones are essential to many physiologic functions in our body. They have many GI and extra-GI functions. Some of the functions of these hormones, which have GI and extra-GI sources, are still unknown. Specific GI hormones can affect the brain to control food intake, while others can proliferate normal and neoplastic tissue when their receptors are expressed in certain neoplasms. GI hormones also have many diagnostic and therapeutic roles. Physiologic and pathophysiologic aspects as well as the diagnostic and therapeutic values of GI hormones are elaborated in this review.
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Affiliation(s)
- Monjur Ahmed
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
- Both authors contributed equally to write the manuscript
| | - Sarah Ahmed
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
- Both authors contributed equally to write the manuscript
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KASL clinical practice guidelines for liver cirrhosis: Ascites and related complications. Clin Mol Hepatol 2018; 24:230-277. [PMID: 29991196 PMCID: PMC6166105 DOI: 10.3350/cmh.2018.1005] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 04/06/2018] [Indexed: 02/07/2023] Open
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Kim MY, Seo YS. [Acute Kidney Injury and Hepatorenal Syndrome]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 72:64-73. [PMID: 30145858 DOI: 10.4166/kjg.2018.72.2.64] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Acute kidney injury (AKI) is common in patients with liver cirrhosis, occurring in 13-20% of patients hospitalized with decompensated cirrhosis, and is significantly associated with the prognosis. The development and progression of AKI is an independent predictive factor for mortality in these patients. If AKI develops, the renal function declines progressively even if AKI is improved later, the patients have a poorer prognosis compared to those who have not developed AKI. In addition, in patients without appropriate treatment or no improvement with the initial treatment, AKI often progress to hepatorenal syndrome (HRS), which is associated with significant morbidity and mortality. Therefore, early detection and appropriate management for the development of AKI is very important in these patients. Recently, there have been significant revisions in the diagnostic criteria and treatment of AKI and HRS; this manuscript reviews these changes.
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Affiliation(s)
- Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1773] [Impact Index Per Article: 253.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
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Abstract
BACKGROUND Hepatorenal syndrome (HRS) is a serious complication of advanced chronic liver disease. Different pharmacological therapies have variable efficacy. We performed a systematic review and meta-analysis to compare the efficacy of various drugs in the treatment of HRS. STUDY Randomized controlled trials comparing active drug with placebo or comparing 2 different drugs were included in this analysis. Primary study outcome was reversal of HRS. Secondary outcomes were HRS relapse and patient survival. Subgroup analysis was performed on patients with type 1 HRS. RESULTS Thirteen randomized controlled trial were eligible for analysis. Terlipressin plus albumin was more efficacious than placebo plus albumin (odds ratio=4.72; 95% confidence interval, 1.72-12.93; P=0.003) or midodrine plus albumin and octreotide (odds ratio=5.94; 95% confidence interval, 1.69-20.85; P=0.005), for HRS reversal. However, no significant difference was noted comparing terlipressin plus albumin versus noradrenaline plus albumin, octreotide plus albumin versus placebo plus albumin or noradrenaline plus albumin versus midodrine plus albumin and octreotide. None of the comparisons showed difference on HRS relapse or patient survival. Subgroup analysis revealed that terlipressin was more effective than placebo for type 1 HRS reversal, but no significant differences were noted between any other comparisons, and none of the comparisons showed difference on HRS relapse or patient survival. CONCLUSIONS Intravenous infusion of terlipressin is the most effective medical therapy for reversing HRS. Intravenous infusion of noradrenaline is an acceptable alternative. Studies are needed as basis for developing pharmacological strategies to reduce relapse of HRS and improve patient survival.
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The emergency medicine evaluation and management of the patient with cirrhosis. Am J Emerg Med 2018; 36:689-698. [PMID: 29290508 DOI: 10.1016/j.ajem.2017.12.047] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/21/2017] [Accepted: 12/22/2017] [Indexed: 12/12/2022] Open
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Fabrizi F, Dixit V, Messa P, Martin P. Terlipressin for Hepatorenal Syndrome: A Meta-Analysis of Randomized Trials. Int J Artif Organs 2018. [DOI: 10.1177/039139880903200303] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Hepatorenal syndrome (HRS) is a severe complication of end-stage renal disease whose management still constitutes a big challenge. Various approaches have been used for hepatorenal syndrome treatment, including vasoconstrictor therapy. Terlipressin, a vasopressin analogue, has frequently been used. Aim To evaluate the efficacy and safety of terlipressin in patients with HRS by performing a systematic review with a meta-analysis of controlled, clinical trials. Methods Only prospective, placebo-controlled, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird, with heterogeneity and subgroups analyses. The primary end-point of interest was the HRS reversal after terlipressin (or placebo) therapy in study patients vs. control patients (as a measure of efficacy). The secondary outcome was the rate of ischemic side-effects in study patients vs. placebo patients (as a measure of tolerability). The additional end-point was the impact of terlipressin on survival in the HRS population. Results We identified five studies involving 243 unique patients with HRS. Pooling of study results showed a significant increase in HRS reversal among study (terlipressin) versus control (placebo) patients; the pooled odd ratio (OR) of HRS reversal was 8.09; 95% CI, 3.521; 18.59; p=0.0001. The p-value was 0.5 for our test of study heterogeneity. In a subgroup analysis excluding case-control trials these results did not change. The rate of severe ischemic events was higher in study than control patients, pooled OR=2.907; 95% CI, 1.094; 7.723 (p=0.032). The test for heterogeneity was not significant. Terlipressin use had no significant impact upon survival (pooled OR for survival rate, 2.064; 95% CI, 0.939; 4.538; p=0.07). No significant heterogeneity (NS) was found. Conclusions Our meta-analysis shows that terlipressin has higher efficacy than placebo in reversing renal function in the HRS population. There was no apparent impact of terlipressin therapy on survival in HRS patients but further large-size trials are needed. Terlipressin use in the HRS population requires careful selection of patients and close clinical surveillance. These results support the use of terlipressin for reversal of renal function in the HRS population.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milan - Italy
- Center for Liver Diseases, School of Medicine, University of Miami, Miami, FL - USA
| | - Vivek Dixit
- Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, CA - USA
| | - Piergiorgio Messa
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milan - Italy
| | - Paul Martin
- Center for Liver Diseases, School of Medicine, University of Miami, Miami, FL - USA
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Abstract
Acute kidney injury (AKI) is common in patients with cirrhosis and ascites on the waiting list for liver transplant. Hepatorenal syndrome (HRS) is an important cause of AKI among cirrhotics. A dynamic definition of AKI in patients with cirrhosis has been introduced and changed the diagnosis criteria. Liver transplantation remains the better option but the medical management of HRS has changed. Terlipressin plus albumin is currently the gold standard. Surgery and liver or kidney support systems have been recommended. Clinical trials will assess the most appropriate approach for the treatment of HRS in light of the revised diagnostic criteria.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy.
| | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
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40
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Patel S, Nguyen DS, Rastogi A, Nguyen MK, Nguyen MK. Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide. Front Med (Lausanne) 2017; 4:17. [PMID: 28352627 PMCID: PMC5348528 DOI: 10.3389/fmed.2017.00017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 02/09/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Hyponatremia in the setting of cirrhosis is a common electrolyte disorder with few therapeutic options. The free water retention is due to non-osmotic vasopressin secretion resulting from the cirrhosis-associated splanchnic vasodilatation. Therefore, vasoconstrictive therapy may correct this electrolyte abnormality. The aim of this study was to assess the efficacy of midodrine and octreotide as a therapeutic approach to increasing urinary electrolyte-free water clearance (EFWC) in the correction of cirrhosis-associated hyponatremia. METHODS This observational study consisted of 10 patients with cirrhosis-associated hyponatremia. Hypovolemia was ruled out as the cause of the hyponatremia with a 48-h albumin challenge (25 g IV q6 h). Patients whose hyponatremia failed to improve with albumin challenge were started on midodrine and octreotide at 10 mg po tid and 100 μg sq tid, respectively, with rapid up-titration as tolerated to respective maximal doses of 15 mg tid and 200 μg tid within the first 24 h. We assessed urinary EFWC and serum sodium concentration before and 72 h after treatment. RESULTS Pretreatment serum sodium levels ranged from 119 to 133 mmol/L. The mean pretreatment serum sodium concentration ± SEM was 124 mmol/L ± 1.6 vs 130 mmol/L ± 1.5 posttreatment (p = 0.00001). The mean pretreatment urinary EFWC ± SEM was 0.33 L ± 0.07 vs 0.82 L ± 0.11 posttreatment (p = 0.0003). CONCLUSION Our data show a statistically significant increase in serum sodium concentration and urinary EFWC with the use of midodrine and octreotide in the treatment of cirrhosis-associated hyponatremia.
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Affiliation(s)
- Sharad Patel
- David Geffen School of Medicine at UCLA , Los Angeles, CA , USA
| | | | - Anjay Rastogi
- David Geffen School of Medicine at UCLA , Los Angeles, CA , USA
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41
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Bucsics T, Schwabl P, Mandorfer M, Bota S, Sieghart W, Ferlitsch A, Trauner M, Reiberger T, Peck-Radosavljevic M. The trigger matters - outcome of hepatorenal syndrome vs. specifically triggered acute kidney injury in cirrhotic patients with ascites. Liver Int 2016; 36:1649-1656. [PMID: 27169985 DOI: 10.1111/liv.13160] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 05/02/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatorenal syndrome (HRS) represents a severe form of renal injury in cirrhotic patients with ascites in the absence of certain triggers. METHODS Patients with cirrhosis and ascites were longitudinally screened for renal dysfunction. HRS was diagnosed by an increase in serum creatinine (SCr) by ≥100% to ≥1.5 mg/dl. If specific triggers (i.e. nephrotoxins, parenchymal kidney damage, hypovolaemia, infections) were found, these cases were defined as specifically triggered acute kidney injury (sAKI). RESULTS Four hundred ninety-seven cirrhotic patients were screened for AKI and we identified 71 patients with HRS and 84 with sAKI. The most common triggers of sAKI were parenchymal damage in 33%, nephrotoxins in 30% and hypovolaemia in 29%. sAKI patients showed significantly more often complete remission than HRS patients (51% vs. 13%, P < 0.001), whereas persisting impairment of renal function was more common in HRS than in sAKI (56% vs. 37%, P = 0.006). Short-term (30 days) mortality was significantly higher in HRS than in sAKI (62% vs. 45%, P = 0.038). Remission rates and mortality varied between sAKI triggers. Transplant-free survival (TFS) was not significantly, but numerically lower in HRS than in sAKI [14 (IQR: 2-99) vs. 36 (IQR: 5-371) days; P = 0.102]. CONCLUSION Patients with HRS show worse outcome and higher 30-day mortality than patients with severe triggered AKI. Different triggers of sAKI seem to influence prognosis. Prospective data are needed to implement effective screening and treatment algorithms for kidney injury in patients with cirrhosis and ascites.
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Affiliation(s)
- Theresa Bucsics
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Simona Bota
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. .,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
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Arab JP, Claro JC, Arancibia JP, Contreras J, Gómez F, Muñoz C, Nazal L, Roessler E, Wolff R, Arrese M, Benítez C. Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus. World J Hepatol 2016; 8:1075-1086. [PMID: 27660674 PMCID: PMC5026999 DOI: 10.4254/wjh.v8.i25.1075] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 07/07/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.
METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded.
RESULTS Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described.
CONCLUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.
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O'Leary JG, Levitsky J, Wong F, Nadim MK, Charlton M, Kim WR. Protecting the Kidney in Liver Transplant Candidates: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice. Am J Transplant 2016; 16:2516-31. [PMID: 26990924 DOI: 10.1111/ajt.13790] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 02/18/2016] [Accepted: 03/08/2016] [Indexed: 01/25/2023]
Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are common in patients awaiting liver transplantation, and both have a marked impact on the perioperative and long-term morbidity and mortality of liver transplant recipients. Consequently, we reviewed the epidemiology of AKI and CKD in patients with end-stage liver disease, highlighted strategies to prevent and manage AKI, evaluated the changing liver transplant waiting list's impact on kidney function, delineated important considerations in simultaneous liver-kidney transplant selection, and projected possible future transplant policy changes and outcomes. This review was assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice and Board of Directors and provides practice-based recommendations for preservation of kidney function in patients with end-stage liver disease.
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Affiliation(s)
- J G O'Leary
- Division of Hepatology, Baylor University Medical Center, Dallas, TX
| | - J Levitsky
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - F Wong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada
| | - M K Nadim
- Division of Nephology and Hypertension, Department of Medicine, University of Southern California, Los Angeles, CA
| | - M Charlton
- Intermountain Transplant Center, Murray, UT
| | - W R Kim
- Division of Gastroenterology, Department of Medicine, Stanford University, Stanford, CA
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44
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Tapper EB, Bonder A, Cardenas A. Preventing and Treating Acute Kidney Injury Among Hospitalized Patients with Cirrhosis and Ascites: A Narrative Review. Am J Med 2016; 129:461-7. [PMID: 26724589 DOI: 10.1016/j.amjmed.2015.12.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 12/15/2015] [Accepted: 12/15/2015] [Indexed: 02/07/2023]
Abstract
Acute kidney injury in the setting of ascites and cirrhosis is a medical emergency characterized by significant morbidity and mortality. Clinicians other than gastroenterologists are often the front line against acute kidney injury for patients with ascites. Owing to the specifics of cirrhotic physiology, the treatment and prevention of acute kidney injury in the setting of ascites has unique features, widespread knowledge of which will benefit our patients with cirrhosis. Early detection and treatment of infection, maximization of cardiac output, and avoidance of medications that limit cardiorenal adaptations to arterial underfilling are part of a multipronged strategy to protect the renal function of our patients with cirrhosis and ascites.
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
| | - Alan Bonder
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
| | - Andres Cardenas
- GI/Liver Unit, Hospital Clinic, Institut de Malalties Digestives i Metaboliques, University of Barcelona, Spain
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45
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Poveromo LB, Michalets EL, Sutherland SE. Midodrine for the weaning of vasopressor infusions. J Clin Pharm Ther 2016; 41:260-5. [PMID: 26945564 DOI: 10.1111/jcpt.12375] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 02/10/2016] [Indexed: 11/29/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Midodrine, an orally available α1-agonist indicated for the treatment of orthostatic hypotension, has been used at our institution as an adjunctive treatment to provide haemodynamic support to facilitate intravenous (IV) vasopressor weaning. Limited published data exist for this off-label use; thus, the objective of this study was to evaluate outcomes in patients who received midodrine for IV vasopressor weaning compared to control patients. METHODS This retrospective comparison included adult ICU patients admitted to our institution from January 2007 to March 2012. The primary outcome was the time to IV vasopressor discontinuation after midodrine initiation. Secondary outcomes included a comparison between midodrine and control patients of the time from IV vasopressor discontinuation to ICU discharge, hospital and ICU length of stay (LOS), and the number of ICU readmissions. RESULTS AND DISCUSSION The analysis included 188 patients (94 midodrine and 94 control). Patients discontinued IV vasopressors a median of 1·2 days (IQR 0·5-2·8) after midodrine initiation. ICU discharge occurred sooner after IV vasopressor discontinuation (0·8 vs. 1·5 days, P = 0·01), and 96% of patients remained off IV vasopressors after midodrine treatment. Hospital LOS was longer in midodrine patients (P < 0·01), but there were no differences in ICU LOS or readmissions. Adverse event rates after midodrine use were consistent with those observed in other studies. WHAT IS NEW AND CONCLUSION Midodrine may serve as a useful adjunct to wean IV vasopressors in difficult-to-wean patients. Further studies are needed to assess the efficacy and safety of midodrine for this indication.
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Affiliation(s)
- L B Poveromo
- Department of Pharmacy, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - E L Michalets
- Department of Pharmacy, Mission Health System, Eshelman School of Pharmacy, University of North Carolina, Asheville, NC, USA
| | - S E Sutherland
- Greenville Health System Care Coordination Institute, Greenville, SC, USA
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Baraldi O, Valentini C, Donati G, Comai G, Cuna V, Capelli I, Angelini ML, Moretti MI, Angeletti A, Piscaglia F, Manna GL. Hepatorenal syndrome: Update on diagnosis and treatment. World J Nephrol 2015; 4:511-520. [PMID: 26558188 PMCID: PMC4635371 DOI: 10.5527/wjn.v4.i5.511] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 08/13/2015] [Accepted: 09/18/2015] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome (HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.
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O'Leary JG, Orloff SL, Levitsky J, Martin P, Foley DP. Keeping high model for end-stage liver disease score liver transplantation candidates alive. Liver Transpl 2015; 21:1428-37. [PMID: 26335696 DOI: 10.1002/lt.24329] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Revised: 07/14/2015] [Accepted: 08/11/2015] [Indexed: 02/07/2023]
Abstract
As the mean Model for End-Stage Liver Disease (MELD) score at time of liver transplantation continues to increase, it is crucial to implement preemptive strategies to reduce wait-list mortality. We review the most common complications that arise in patients with a high MELD score in an effort to highlight strategies that can maximize survival and successful transplantation.
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Affiliation(s)
- Jacqueline G O'Leary
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.,Liver Intestine Community of Practice, American Society of Transplantation, Mount Laurel, NJ
| | - Susan L Orloff
- Liver Intestine Community of Practice, American Society of Transplantation, Mount Laurel, NJ.,Department of Surgery, Oregon Health and Sciences University, Portland, OR
| | - Josh Levitsky
- Liver Intestine Community of Practice, American Society of Transplantation, Mount Laurel, NJ.,Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Paul Martin
- Liver Intestine Community of Practice, American Society of Transplantation, Mount Laurel, NJ.,Department of Medicine, University of Miami School of Medicine, Miami, FL
| | - David P Foley
- Liver Intestine Community of Practice, American Society of Transplantation, Mount Laurel, NJ.,Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI.,Veterans Administration Surgical Services, William S. Middleton Memorial Hospital, Madison, WI
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Velez JCQ, Kadian M, Taburyanskaya M, Bohm NM, Delay TA, Karakala N, Rockey DC, Nietert PJ, Goodwin AJ, Whelan TP. Hepatorenal Acute Kidney Injury and the Importance of Raising Mean Arterial Pressure. Nephron Clin Pract 2015; 131:191-201. [PMID: 26485256 DOI: 10.1159/000441151] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 09/15/2015] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The efficacy of vasoconstrictors in hepatorenal syndrome (HRS) is variable. We hypothesized that the effectiveness of vasoconstrictor therapy in improving kidney function ultimately relates to the magnitude of the achieved mean arterial pressure (MAP) increase. METHODS A retrospective study was conducted to identify cirrhotic individuals treated with vasoconstrictors for acute kidney injury (AKI) presumably caused by HRS to examine the relationship between change in MAP and change in serum creatinine (sCr) using multivariate mixed linear regression. RESULTS Among 73 patients treated with midodrine/octreotide, change in MAP inversely correlated with change in sCr (p = 0.0005). The quartile with the greatest increase in MAP (+15.9 to +29.4 mm Hg) was associated with a subsequent absolute decrease in sCr. The strength of the correlation increased when the analysis was restricted to those who met the HRS criteria (n = 27, p = 0.002), where the third (+5.3 to +15.6 mm Hg) and fourth (+15.9 to +20.9 mm Hg) quartiles of MAP change were associated with a decrease in sCr. A similar but stronger correlation was found among 14 patients treated with norepinephrine either after failing midodrine/octreotide (n = 10) or de novo (n = 4; p = 0.002), where a rise in MAP of +19.2 to 25 mm Hg was associated with a larger reduction in sCr. Associations remained significant after adjustment for baseline parameters. CONCLUSIONS The magnitude of MAP rise during HRS therapy with midodrine/octreotide or norepinephrine correlated with a reduction in sCr concentration. Our results suggest that achieving a pre-specified target of MAP increase might improve renal outcomes in hepatorenal AKI.
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Affiliation(s)
- Juan Carlos Q Velez
- Division of Nephrology, Medical University of South Carolina, Charleston, S.C., USA
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Russ KB, Stevens TM, Singal AK. Acute Kidney Injury in Patients with Cirrhosis. J Clin Transl Hepatol 2015; 3:195-204. [PMID: 26623266 PMCID: PMC4663201 DOI: 10.14218/jcth.2015.00015] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 06/11/2015] [Accepted: 06/12/2015] [Indexed: 12/12/2022] Open
Abstract
Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK.
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Affiliation(s)
- Kirk B. Russ
- Department of Internal Medicine, UAB, Birmingham, AL, USA
| | - Todd M Stevens
- Department of Anatomic Pathology, UAB, Birmingham, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, UAB, Birmingham, AL, USA
- Correspondence to: Ashwani K. Singal, Division of Gastroenterology and Hepatology, University of Alabama Birmingham, Birmingham, AL 35294-0012, USA. Tel: +1-205-975-9698, Fax: +1-205-975-0961, E-mail:
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Creatinine Change on Vasoconstrictors as Mortality Surrogate in Hepatorenal Syndrome: Systematic Review & Meta-Analysis. PLoS One 2015; 10:e0135625. [PMID: 26295585 PMCID: PMC4546623 DOI: 10.1371/journal.pone.0135625] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 07/24/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND AIMS Hepatorenal syndrome is a severe complication of cirrhosis and associates with significant mortality. Vasoconstrictor medications improve renal function in patients with hepatorenal syndrome. However, it is unclear to what extent changes in serum creatinine during treatment may act as a surrogate for changes in mortality. We have performed a meta-analysis of randomized trials of vasoconstrictors assessing the association between changes in serum creatinine, taken as a continuous variable, and mortality, both while on treatment and during the follow-up period for survivors. METHODS The electronic databases of PubMed, Web of Science and Embase were searched for randomized trials evaluating the efficacy of vasoconstrictor therapy for treatment of HRS type 1 or 2. The relative risk (RR) for mortality was calculated against delta creatinine. The proportion of treatment effect explained (PTE) was calculated for delta creatinine. RESULTS Seven trials enrolling 345 patients were included. The correlation between delta creatinine and ln (RR) was moderately good (R2 = 0.61). The intercept and parameter estimate indicated a fall in creatinine while on treatment of 1 mg/dL resulted in a 27% reduction in RR for mortality compared to the control arm. In patients surviving the treatment period, a fall in creatinine while on treatment of 1 mg/dL resulted in a 16% reduction in RR for post-treatment mortality during follow-up. The PTE of delta creatinine for overall mortality was 0.91 and 0.26 for post-treatment mortality. CONCLUSIONS Changes in serum creatinine in response to vasoconstrictor therapy appear to be a valid surrogate for mortality, even in the period following the completion of treatment.
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