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Loeffler J, Hassan M, Qaqish F, Dimachkie R, Dehghani S, Sasso R, Abou Yassine A, Deeb L. Predictors of Renal Replacement Therapy Requirement in Cirrhotic Patients with Acute Kidney Injury. Dig Dis Sci 2025; 70:1540-1546. [PMID: 39954191 DOI: 10.1007/s10620-025-08881-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 01/17/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Renal failure is a well-known and often devastating complication in patients with liver cirrhosis and contributes to significant morbidity and mortality. AIMS This study aimed to evaluate the clinical profile and factors associated with the utilization of renal replacement therapy (RRT) requirement in cirrhotic patients presenting with AKI. METHODS We conducted a retrospective cohort study of cirrhotic inpatient visits across all Northwell Health hospitals between January 1, 2019 and December 31, 2020. Patients meeting inclusion criteria were identified using the International Classification of Disease, tenth revision clinical modification (ICD-10-CM) codes. Clinical variables, including demographics, medical history, laboratory data, and outcomes, were collected. Statistical analyses were performed to compare variables between patients requiring RRT and those not requiring RRT. RESULTS Of 701 cirrhotic patient encounters, 516 met inclusion criteria. The most common etiology of AKI was pre-renal (45.3%), followed by hepatorenal syndrome (18.6%) and acute tubular necrosis (14.7%). Sixty patients (11.6%) required RRT, with worse outcomes observed in this group. Independent predictors of RRT requirement included hepatorenal syndrome, acute tubular necrosis, and pneumonia. Pre-renal AKI was associated with decreased likelihood of requiring RRT. CONCLUSION This study identified clinical and laboratory factors predicting RRT requirement in cirrhotic patients with AKI. Hepatorenal syndrome, acute tubular necrosis, and pneumonia were associated with increased likelihood of RRT. Understanding these predictors may aid in prognostication and management decisions for cirrhotic patients presenting with AKI, warranting further prospective validation studies.
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Affiliation(s)
- Jeffrey Loeffler
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA.
| | - Mohammed Hassan
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Faris Qaqish
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Reem Dimachkie
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Shabnam Dehghani
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Roula Sasso
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Ahmad Abou Yassine
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Liliane Deeb
- Department of Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
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Aguirre-Guemez AV, Groah SL. Managing Recurrent Urinary Tract Infections After Spinal Cord Injury: Practical Approaches and Emerging Concepts. Phys Med Rehabil Clin N Am 2025; 36:73-98. [PMID: 39567040 DOI: 10.1016/j.pmr.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
The majority of individuals with neurogenic lower urinary tract dysfunction will have complicated urinary tract infections (UTIs) that will qualify as recurrent. Existing inconsistencies and challenges contribute to its subjective diagnosis. Thus, there is a pressing need for a reconceptualization of our understanding of UTI, accompanied by a paradigm shift in diagnosis and treatment approaches.
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Affiliation(s)
- Ana Valeria Aguirre-Guemez
- MedStar National Rehabilitation Hospital, Washington, DC, USA; Department of Rehabilitation Medicine, Georgetown University Medical Center, Washington, DC, USA; MedStar Health Research Institute, Hyattsville, MD, USA.
| | - Suzanne L Groah
- MedStar National Rehabilitation Hospital, Washington, DC, USA; Department of Rehabilitation Medicine, Georgetown University Medical Center, Washington, DC, USA
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Seo Kwak E, Alharbi A, Bosaily A, Alsughayer A, Igbal A, Salichs O, Khuder S, Fourman M, Assaly R. Inpatient complications and mortality in cirrhotic patients undergoing bariatric surgery: a comprehensive analysis. Hosp Pract (1995) 2025; 53:2455921. [PMID: 39849896 DOI: 10.1080/21548331.2025.2455921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 01/16/2025] [Indexed: 01/25/2025]
Abstract
INTRODUCTION Liver cirrhosis, a complex and progressive disease, imposes a significant global health burden, characterized by irreversible liver tissue scarring and various life-threatening complications. Traditionally linked to factors like chronic alcohol consumption and viral hepatitis infections, the rising prevalence of obesity introduces a new dimension to its etiology. As obesity rates continue to climb worldwide, the confluence of liver cirrhosis and bariatric surgery has become an increasingly pertinent and clinically relevant topic of inquiry. METHODS In this study, we aimed to investigate the impact of liver cirrhosis on patients who underwent bariatric surgery, using data from the 2020 National Inpatient Sample (NIS) database. We compared the outcomes of 82,414 patients who had bariatric surgery, stratifying them based on the presence or absence of liver cirrhosis. We assessed baseline demographic characteristics and comorbidities, in-hospital outcomes, and complications related to the surgery. RESULTS Patients with liver cirrhosis who underwent bariatric surgery demonstrated several distinct trends. On average, they were older (mean age 63 years) and predominantly female (52%) compared to those without cirrhosis (mean age 52, 71% female). Furthermore, comorbidities such as hypertension, diabetes with chronic complications, and alcohol abuse were more prevalent in the cirrhosis group. In terms of outcomes, patients with liver cirrhosis faced significantly higher inpatient mortality rates (4%) compared to those without cirrhosis (1%) with p < 0.001. They also experienced a notably longer average length of hospital stay (2.35 days longer, 95% CI: -3.46 --1.25, p < 0.001) and incurred higher hospitalization costs (add AOR and p value here). Additionally, patients with cirrhosis had increased odds of experiencing acute heart failure (adjusted odds ratio: 1.87, 95% CI: 1.14-2.57, p = 0.01) and requiring blood transfusions (adjusted odds ratio: 1.71,95% CI: 1.13-3.09, p = 0.009). Although the adjusted odds ratio for inpatient mortality was higher in cirrhosis patients (1.58, 95% CI: 0.76-3.30, p = 0.21), it did not reach statistical significance. CONCLUSION This study highlights the substantial impact of liver cirrhosis on post-bariatric surgery outcomes. Patients with cirrhosis who undergo bariatric surgery face higher inpatient mortality rates and a greater risk of complications, particularly acute heart failure and the need for blood transfusions. The longer hospital stays and increased costs further emphasize the challenges in managing this unique patient population. These findings emphasize the need for careful patient selection, risk assessment, and a multidisciplinary approach when considering bariatric surgery for individuals with both liver cirrhosis and obesity.
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Affiliation(s)
- Eun Seo Kwak
- Department of Internal Medicine, University of Toledo, Toledo, OH, USA
| | | | - Ahmad Bosaily
- Department of Surgery, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Anas Alsughayer
- Department of Internal Medicine, University of Toledo, Toledo, OH, USA
| | - Amna Igbal
- Department of Internal Medicine, University of Toledo, Toledo, OH, USA
| | - Oscar Salichs
- Department of Internal Medicine, University of Toledo, Toledo, OH, USA
| | - Sadik Khuder
- Department of Medicine, Department of Public Health, The University of Toledo Medical Center, Toledo, OH, USA
| | - Matthew Fourman
- Department of Surgery, ProMedica Toledo Hospital, Toledo, OH, USA
| | - Ragheb Assaly
- Pulmonary and Critical Care Medicine, University of Toledo, Toledo, OH, USA
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Glendell RM, Puxty KA, Shaw M, Sim MAB, Traynor JP, Mark PB, Andonovic M. Longitudinal trend in post-discharge estimated glomerular filtration rate in intensive care survivors. J Intensive Care Soc 2025; 26:29-37. [PMID: 39734804 PMCID: PMC11670225 DOI: 10.1177/17511437241308673] [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: 12/31/2024] Open
Abstract
Background Acute kidney injury (AKI) within the intensive care unit (ICU) is common but evidence is limited on longer-term renal outcomes. We aimed to model the trend of kidney function in ICU survivors using estimated glomerular filtration rate (eGFR), comparing those with and without AKI, and investigate potential risk factors associated with eGFR decline. Methods This observational cohort study included all patients aged 16 or older admitted to two general adult ICUs in Scotland between 1st July 2015 and 30th June 2018 who survived to 30 days following hospital discharge. Baseline serum creatinine and subsequent values were used to identify patients with AKI and calculate eGFR following hospital discharge. Mixed effects modelling was used to control for repeated measures and to allow inclusion of several exploratory variables. Results 3649 patients were included, with 1252 (34%) experiencing in-ICU AKI. Patients were followed up for up to 2000 days with a median 21 eGFR measurements. eGFR declined at a rate of -1.9 ml/min/1.73m2/year (p-value < 0.001) in the overall ICU survivor cohort. Patients with AKI experienced an accelerated rate of post-ICU eGFR decline of -2.0 ml/min/1.73m2/year compared to a rate of -1.83 ml/min/1.73m2/year in patients who did not experience AKI (p-value 0.007). Pre-existing diabetes or liver disease and in-ICU vasopressor support were associated with accelerated eGFR decline regardless of AKI experience. Conclusions ICU survivors experienced a decline in kidney function beyond that which would be expected regardless of in-ICU AKI. Long-term follow-up is warranted in ICU survivors to monitor kidney function and reduce morbidity and mortality.
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Affiliation(s)
- Rebecca M Glendell
- Undergraduate Medical School, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Kathryn A Puxty
- Department of Intensive Care Medicine, Glasgow Royal Infirmary, Glasgow, UK
- Department of Anaesthesia, Critical Care and Pain, School of Medicine, University of Glasgow, Glasgow, UK
| | - Martin Shaw
- Department of Anaesthesia, Critical Care and Pain, School of Medicine, University of Glasgow, Glasgow, UK
| | - Malcolm AB Sim
- Department of Anaesthesia, Critical Care and Pain, School of Medicine, University of Glasgow, Glasgow, UK
- Department of Intensive Care, Queen Elizabeth University Hospital, Glasgow, UK
| | - Jamie P Traynor
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
| | - Patrick B Mark
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Mark Andonovic
- Department of Anaesthesia, Critical Care and Pain, School of Medicine, University of Glasgow, Glasgow, UK
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Shimizu Y, Hanada K, Watanabe T, Sasaki Y, Yamazaki T, Komasaka E, Kadota K. The use of concomitant medications on nephrotoxicity associated with teicoplanin: A retrospective observational study. J Infect Chemother 2025; 31:102512. [PMID: 39237002 DOI: 10.1016/j.jiac.2024.08.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/21/2024] [Accepted: 08/29/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND Teicoplanin (TEIC) is a nephrotoxic agent. However, little is known about the effects of concomitant medications on nephrotoxicity. In this study, we investigated the effects of concomitant drugs on nephrotoxicity. METHODS A retrospective observational case-control study was conducted on patients (≥18 years) who started TEIC at the Tokyo Dental College, Ichikawa General Hospital, between January 2013 and April 2023. The primary outcome was nephrotoxicity, defined as an increase in serum creatinine levels of ≥50 % or ≥0.5 mg/dL from baseline. Logistic regression analysis was used to determine the risk factors for nephrotoxicity associated with TEIC. In addition, we investigated the relationship between nephrotoxicity and predicted free TEIC concentrations. RESULTS Of 305 patients, 43 (14.1 %) developed nephrotoxicity. The multivariate logistic regression analysis identified that serum albumin (odds ratio [OR] = 0.50, 95 % confidence interval [CI] 0.27-0.89, p = 0.02), concomitant use of loop diuretics (OR = 2.22, 95 % CI 1.10-4.59, p = 0.03), antivirals (OR = 3.24, 95 % CI 1.32-7.62, p < 0.01), and vasopressors (OR = 2.57, 95 % CI 1.10-5.78, p = 0.03) were the associated risk factors for nephrotoxicity in patients administered with TEIC. In 216 patients, predicted TEIC concentrations were 3.6 [interquartile range (IQR), 2.6-4.9] μg/mL in the nephrotoxicity group versus 3.6 [IQR, 2.5-4.7] μg/mL in the non-nephrotoxicity group, with no significant difference (p = 0.69). CONCLUSION Our results indicate the importance of modifying the concomitant use of loop diuretics, antivirals, and vasopressors.
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Affiliation(s)
- Yuki Shimizu
- Department of Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
| | - Kazuhiko Hanada
- Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan
| | - Takeaki Watanabe
- Department of Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Yuka Sasaki
- Department of Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Tomoka Yamazaki
- Department of Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Emi Komasaka
- Department of Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Keiko Kadota
- Department of Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan; Department of Clinical Pharmacy, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
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Aziz AA, Aziz MA, Amir M, Shah R, Ali IA. Outcomes of Acute Pancreatitis in Patients With and Without Liver Cirrhosis: A Retrospective Analysis. Cureus 2025; 17:e78933. [PMID: 40092023 PMCID: PMC11909785 DOI: 10.7759/cureus.78933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
Background Acute pancreatitis (AP) is a common cause of hospitalization in the United States. Our study aimed to investigate the impact of liver cirrhosis (LC) on the outcomes of AP in adult patients hospitalized with AP. Methods We performed a retrospective study of adult patients with AP utilizing the Nationwide Inpatient Sample (NIS) database from 2020 to 2022. We compared AP outcomes in patients with and without LC. The primary outcome was all-cause inpatient mortality. Secondary outcomes were the length of stay (LOS), healthcare cost utilization adjusted to 2022, the incidence of acute renal failure (ARF), sepsis, shock, venous thromboembolism (VTE), and the need for intensive care unit (ICU) admission. Statistical analyses were performed using STATA, version 16.1 (StataCorp., College Station, Texas, USA). A multivariate logistic regression analysis was conducted to assess if gender was an independent predictor for these outcomes and to adjust for any confounders. Results From 2020 to 2022, 738,139 adult patients underwent AP admissions. Among the patients, 723,959 had AP without LC, and 14,180 had AP with LC. The mean age for patients with and without LC was the same, 50.9 years. Patients without LC had a higher prevalence of cerebrovascular accident (CVA) and obesity. Patients with LC had a higher prevalence of congestive heart failure (CHF), diabetes mellitus type 2 (DM2), diabetes mellitus type 1 (DM1), chronic kidney disease (CKD), and smoking/tobacco use. We found that AP patients with LC had a significantly higher likelihood of in-hospital mortality (aOR: 1.74, 95% CI: 1.22-2.42, P < 0.01), longer LOS (+ 0.46 days, 95% CI: 0.26-0.67, P < 0.01), higher healthcare utilization cost (+ $4163, 95% CI: $1530.9-$6796.0, P < 0.01), shock (aOR: 1.87, 95% CI: 1.42-2.46, P < 0.01), ARF (aOR: 1.44, 95% CI: 1.30-1.59, P < 0.01), ICU admission (aOR: 1.67, 95% CI: 1.38-1.91, P < 0.01), and acute VTE (aOR: 1.65, 95% CI: 1.30-2.11, P < 0.01). Conclusions We found that patients with AP who concomitantly had LC had significantly poor clinical outcomes, including higher mortality, ARF, shock, ICU admission, VTE, LOS, and total hospitalization charges as compared to AP patients who did not have LC. Our study highlights that cirrhotic patients with AP have poor inpatient hospital outcomes and need aggressive treatment to prevent morbidity and mortality.
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Affiliation(s)
- Ahmed Ali Aziz
- Internal Medicine, INTEGRIS Health Baptist Medical Center, Oklahoma City, USA
| | - Muhammad Ali Aziz
- Internal Medicine, University of Kentucky College of Medicine, Lexington, USA
| | - Muhammad Amir
- Transplant Hepatology, INTEGRIS Health Baptist Medical Center, Oklahoma City, USA
| | - Rehan Shah
- Internal Medicine, Bayonne Medical Center, Bayonne, USA
| | - Ijlal Akbar Ali
- Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, USA
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Cama-Olivares A, Ouyang T, Takeuchi T, St. Hillien SA, Robinson JE, Chung RT, Cullaro G, Karvellas CJ, Levitsky J, Orman ES, Patidar KR, Regner KR, Saly DL, Sawinski D, Sharma P, Teixeira JP, Ufere NN, Velez JCQ, Wadei HM, Wahid N, Allegretti AS, Neyra JA, Belcher JM. Association of Hepatorenal Syndrome-Acute Kidney Injury with Mortality in Patients with Cirrhosis Requiring Renal Replacement Therapy: Results from the HRS-HARMONY Consortium. KIDNEY360 2025; 6:247-256. [PMID: 39348201 PMCID: PMC11882256 DOI: 10.34067/kid.0000000589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 09/18/2024] [Indexed: 10/02/2024]
Abstract
Key Points In patients with cirrhosis and AKI requiring renal replacement therapy (RRT), hepatorenal syndrome-AKI was not associated with an increased 90-day mortality when compared with other AKI etiologies. Etiology of AKI may not be a critical factor regarding decisions to trial RRT in acutely ill patients with cirrhosis and AKI. Although elevated, mortality rates in this study are comparable with those reported in general hospitalized patients with AKI requiring RRT. Background While AKI requiring renal replacement therapy (AKI-RRT) is associated with increased mortality in heterogeneous inpatient populations, the epidemiology of AKI-RRT in hospitalized patients with cirrhosis is not fully known. Herein, we evaluated the association of etiology of AKI with mortality in hospitalized patients with cirrhosis and AKI-RRT in a multicentric contemporary cohort. Methods This is a multicenter retrospective cohort study using data from the HRS-HARMONY consortium, which included 11 US hospital network systems. Consecutive adult patients admitted in 2019 with cirrhosis and AKI-RRT were included. The primary outcome was 90-day mortality, and the main independent variable was AKI etiology, classified as hepatorenal syndrome (HRS-AKI) versus other (non–HRS-AKI). AKI etiology was determined by at least two independent adjudicators. We performed Fine and Gray subdistribution hazard analyses adjusting for relevant clinical variables. Results Of 2063 hospitalized patients with cirrhosis and AKI, 374 (18.1%) had AKI-RRT. Among them, 65 (17.4%) had HRS-AKI and 309 (82.6%) had non–HRS-AKI, which included acute tubular necrosis in most cases (62.6%). Continuous renal replacement therapy was used as the initial modality in 264 (71%) of patients, while intermittent hemodialysis was used in 108 (29%). The HRS-AKI (versus non–HRS-AKI) group received more vasoconstrictors for HRS management (81.5% versus 67.9%), whereas the non–HRS-AKI group received more mechanical ventilation (64.3% versus 50.8%) and more continuous renal replacement therapy (versus intermittent hemodialysis) as the initial RRT modality (73.9% versus 56.9%). In the adjusted model, HRS-AKI (versus non–HRS-AKI) was not independently associated with increased 90-day mortality (subdistribution hazard ratio, 1.36; 95% confidence interval, 0.95 to 1.94). Conclusions In this multicenter contemporary cohort of hospitalized adult patients with cirrhosis and AKI-RRT, HRS-AKI was not independently associated with an increased risk of 90-day mortality when compared with other AKI etiologies. The etiology of AKI appears less relevant than previously considered when evaluating the prognosis of hospitalized adult patients with cirrhosis and AKI requiring RRT.
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Affiliation(s)
- Augusto Cama-Olivares
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Tianqi Ouyang
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Tomonori Takeuchi
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shelsea A. St. Hillien
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Jevon E. Robinson
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Raymond T. Chung
- Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, California
| | - Constantine J. Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Eric S. Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Kavish R. Patidar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Kevin R. Regner
- Division of Nephrology at the Medical College of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Danielle L. Saly
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Deirdre Sawinski
- Division of Nephrology and Hypertension, Weill Cornell College of Medicine, New York, New York
| | - Pratima Sharma
- Department of Gastroenterology and Transplant Hepatology at University of Michigan Health, University of Michigan Health, Ann Arbor, Michigan
| | - J. Pedro Teixeira
- Divisions of Nephrology and Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico
| | - Nneka N. Ufere
- Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Juan Carlos Q. Velez
- Department of Nephrology at the Ochsner Medical Center, Ochsner Medical Center, New Orleans, Louisiana
| | - Hani M. Wadei
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida
| | - Nabeel Wahid
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Javier A. Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Justin M. Belcher
- Section of Nephrology, Department of Internal Medicine, Yale University and VA Connecticut Healthcare, New Haven, Connecticut
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Cirovic A, Satarug S, Jevtic J, Ivanovski A, Orisakwe OE, Jankovic S, Cirovic A. The overlooked impact of cadmium on the progression of chronic hepatitis and the onset of renal failure in advanced cirrhosis. J Trace Elem Med Biol 2024; 86:127542. [PMID: 39395285 DOI: 10.1016/j.jtemb.2024.127542] [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: 08/25/2024] [Revised: 09/30/2024] [Accepted: 10/05/2024] [Indexed: 10/14/2024]
Abstract
The mechanism of hepatocyte destruction in chronic hepatitis is not completely understood, while renal failure in individuals with advanced cirrhosis is a significant concern. It is well known that smokers who are chronically infected with hepatitis B and C viruses (HBV, HCV) have a poor prognosis. In the present review, we propose a novel hypothesis that environmental exposure to a nephrotoxic metal pollutant, cadmium (Cd) may contribute to hepatocyte destruction and, subsequently, affect the duration of chronic hepatitis. The metal binding protein, metallothionein (MT) sequesters cadmium as CdMT complexes, and effectively neutralize its adverse effects. Cadmium can cause the damage to hepatocytes, only when it is in an unbound form. In addition to its ability to bind cadmium, MT can act as a scavenger of reactive oxygen species (ROS). However, the cellular MT levels may decrease, when ROS is excessively produced under the pathologic chronic viral hepatitis conditions, especially while the cellular levels of zinc may also be low. Zinc is an endogenous inducer of MT, and is required for maximal MT expression. High ROS levels in the hepatocytes diminishes MT binding to metals. Consequently, the proportion of unbound Cd is increased and thus there is more hepatic damage. Hepatic damage leads to a copious release of CdMT into the circulation. This significant cadmium load, which occurs after hepatic damage, and in some cases, muscle atrophy, induces kidney damage with resultant renal failure in advanced cirrhosis.
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Affiliation(s)
- Ana Cirovic
- Faculty of Medicine, Institute of Anatomy, University of Belgrade, Dr Subotica 4/2, Belgrade 11000, Serbia
| | - Soisungwan Satarug
- Kidney Disease Research Collaborative, Translational Research Institute, Woolloongabba, Brisbane, QLD 4102, Australia.
| | - Jovan Jevtic
- Faculty of Medicine, Institute of Pathology, University of Belgrade, Dr Subotica 1, Belgrade 11000, Serbia
| | - Ana Ivanovski
- Faculty of Medicine, University of Belgrade, Dr Subotica 4/2, Belgrade 11000, Serbia
| | - Orish E Orisakwe
- African Centre of Excellence for Public Health and Toxicological Research (ACE-PUTOR), University of Port Harcourt, PMB, Choba, Port Harcourt 5323, Nigeria; Advanced Research Centre, European University of Lefke, Lefke, Northern Cyprus, TR-10, Mersin, Turkey
| | - Sasa Jankovic
- Institute of Meat Hygiene and Technology, Kacanskog 13, Belgrade 11040, Serbia
| | - Aleksandar Cirovic
- Faculty of Medicine, Institute of Anatomy, University of Belgrade, Dr Subotica 4/2, Belgrade 11000, Serbia.
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Lin S, Wang X, Xu Z, Li L, Kang R, Li S, Wu X, Zhu Y, Gao H. Construction of a prediction model for hepatic encephalopathy in acute-on-chronic liver failure patients. Ann Med 2024; 56:2410403. [PMID: 39387525 PMCID: PMC11469415 DOI: 10.1080/07853890.2024.2410403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 03/14/2024] [Accepted: 09/08/2024] [Indexed: 10/15/2024] Open
Abstract
OBJECTIVE Hepatic encephalopathy (HE) is a serious complication of acute-on-chronic liver failure (ACLF) that requires early detection and intervention to positively impact patient prognosis. This study aimed to develop a reliable model to predict HE in ACLF patients during hospitalization. METHODS Retrospectively recruiting 255 hepatitis B-related ACLF patients, including 67 who developed HE during hospitalization, the study analysed clinical data and biochemical indices collected during the first week of admission. The least absolute shrinkage and selection operator (LASSO) was used to identify characteristic predictors for hospitalization HE events, and a logistic regression model was subsequently developed. Receiver operating characteristic (ROC) curves, calibration curves, and bootstrap resampling were used to evaluate the model's discrimination, consistency, and accuracy, and a nomogram was created to visualize the model. An external validation cohort of 236 liver failure patients collected from the same medical centre between 2007 and 2010 was used to validate the model. RESULTS The study found that blood urea nitrogen (BUN), alpha-fetoprotein (AFP), international normalized ratio (INR), serum ammonia, and infection complications during hospitalization were risk factors for HE in ACLF patients. The new model predicted the development of HE in ACLF patients with an area under the receiver operating characteristic curve (AUROC) of 85.2%, which was superior to other models. The best threshold for the new model was 0.28, resulting in a specificity of 81.4% and a sensitivity of 80.6%. In the validation group, the new model showed similar results, with an AUROC of 79% and a specificity of 83.6% and a sensitivity of 56.6%. CONCLUSION This study developed and validated a new prediction model for HE in ACLF patients offering a useful tool for early identification of patients with a high risk of HE in clinical settings. However, to ascertain the model's general effectiveness, future prospective multicentre studies are warranted.
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Affiliation(s)
- Shenglong Lin
- Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- Department of Hepatology, Hepatology Research Institute, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
| | - Xiangmei Wang
- Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
| | - Zixin Xu
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Lu Li
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Rui Kang
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Songtao Li
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Xiaoyong Wu
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Yueyong Zhu
- Department of Hepatology, Hepatology Research Institute, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Haibing Gao
- Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
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Duailibe JBB, Viau CM, Saffi J, Fernandes SA, Porawski M. Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats. World J Nephrol 2024; 13:95627. [PMID: 39351184 PMCID: PMC11439093 DOI: 10.5527/wjn.v13.i3.95627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 06/07/2024] [Accepted: 07/25/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS. AIM To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats. METHODS Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with P ≤ 0.05. RESULTS Omega-3 significantly decreased the production of reactive oxygen species (P < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 (P < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group (P < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential (P < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group (P > 0.05) were observed. CONCLUSION The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.
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Affiliation(s)
- João Bruno Beretta Duailibe
- Department of Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Cassiana Macagnan Viau
- Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Jenifer Saffi
- Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Sabrina Alves Fernandes
- Department of Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Marilene Porawski
- Department of Hepatology and Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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Tu H, Su J, Gong K, Li Z, Yu X, Xu X, Shi Y, Sheng J. A dynamic model to predict early occurrence of acute kidney injury in ICU hospitalized cirrhotic patients: a MIMIC database analysis. BMC Gastroenterol 2024; 24:290. [PMID: 39192202 DOI: 10.1186/s12876-024-03369-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 08/13/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND This study aimed to develop a tool for predicting the early occurrence of acute kidney injury (AKI) in ICU hospitalized cirrhotic patients. METHODS Eligible patients with cirrhosis were identified from the Medical Information Mart for Intensive Care database. Demographic data, laboratory examinations, and interventions were obtained. After splitting the population into training and validation cohorts, the least absolute shrinkage and selection operator regression model was used to select factors and construct the dynamic online nomogram. Calibration and discrimination were used to assess nomogram performance, and clinical utility was evaluated by decision curve analysis (DCA). RESULTS A total of 1254 patients were included in the analysis, and 745 developed AKI. The mean arterial pressure, white blood cell count, total bilirubin level, Glasgow Coma Score, creatinine, heart rate, platelet count and albumin level were identified as predictors of AKI. The developed model had a good ability to differentiate AKI from non-AKI, with AUCs of 0.797 and 0.750 in the training and validation cohorts, respectively. Moreover, the nomogram model showed good calibration. DCA showed that the nomogram had a superior overall net benefit within wide and practical ranges of threshold probabilities. CONCLUSIONS The dynamic online nomogram can be an easy-to-use tool for predicting the early occurrence of AKI in critically ill patients with cirrhosis.
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Affiliation(s)
- Huilan Tu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Junwei Su
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Kai Gong
- Department of Infectious Diseases, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xia Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xianbin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, 310003, China.
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Singh J, Ebaid M, Saab S. Advances in the management of complications from cirrhosis. Gastroenterol Rep (Oxf) 2024; 12:goae072. [PMID: 39104730 PMCID: PMC11299547 DOI: 10.1093/gastro/goae072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/29/2024] [Accepted: 06/15/2024] [Indexed: 08/07/2024] Open
Abstract
Cirrhosis with complications of liver decompensation and hepatocellular carcinoma (HCC) constitute a leading cause of morbidity and mortality worldwide. Portal hypertension is central to the progression of liver disease and decompensation. The most recent Baveno VII guidance included revision of the nomenclature for chronic liver disease, termed compensated advanced chronic liver disease, and leveraged the use of liver stiffness measurement to categorize the degree of portal hypertension. Additionally, non-selective beta blockers, especially carvedilol, can improve portal hypertension and may even have a survival benefit. Procedural techniques with interventional radiology have become more advanced in the management of refractory ascites and variceal bleeding, leading to improved prognosis in patients with decompensated liver disease. While lactulose and rifaximin are the preferred treatments for hepatic encephalopathy, many alternative treatment options may be used in refractory cases and even procedural interventions such as shunt embolization may be of benefit. The approval of terlipressin for the treatment of hepatorenal syndrome (HRS) in the USA has improved the way in which HRS is managed and will be discussed in detail. Malnutrition, frailty, and sarcopenia lead to poorer outcomes in patients with decompensated liver disease and should be addressed in this patient population. Palliative care interventions can lead to improved quality of life and clinical outcomes. Lastly, the investigation of systemic therapies, in particular immunotherapy, has revolutionized the management of HCC. These topics will be discussed in detail in this review.
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Affiliation(s)
- Jasleen Singh
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Mark Ebaid
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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13
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Zhang M, Han Z, Lin Y, Jin Z, Zhou S, Wang S, Tang Y, Li J, Li X, Chen H. Understanding the relationship between HCV infection and progression of kidney disease. Front Microbiol 2024; 15:1418301. [PMID: 39006752 PMCID: PMC11239345 DOI: 10.3389/fmicb.2024.1418301] [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: 04/16/2024] [Accepted: 06/18/2024] [Indexed: 07/16/2024] Open
Abstract
Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.
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Affiliation(s)
- Meiqi Zhang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhongyu Han
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Naniing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yumeng Lin
- Naniing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zi Jin
- Department of Anesthesiology and Pain Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China
| | - Shuwei Zhou
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Siyu Wang
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yuping Tang
- Hepatobiliary Department of the Third Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi, China
| | - Jiaxuan Li
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Xueping Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haoran Chen
- Department of General Surgery, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, Chengdu, China
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14
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Li X, Li X, Zhao W, Wang D. Development and validation of a nomogram for predicting in-hospital death in cirrhotic patients with acute kidney injury. BMC Nephrol 2024; 25:175. [PMID: 38773418 PMCID: PMC11110328 DOI: 10.1186/s12882-024-03609-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 05/13/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUND The purpose of this study was to develop a nomogram for predicting in-hospital mortality in cirrhotic patients with acute kidney injury (AKI) in order to identify patients with a high risk of in-hospital death early. METHODS This study collected data on cirrhotic patients with AKI from 2008 to 2019 using the Medical Information Mart for Intensive Care IV. Multivariate logistic regression was used to identify confounding factors related to in-hospital mortality, which were then integrated into the nomogram. The concordance index (C-Index) was used to evaluate the accuracy of the model predictions. The area under the curve (AUC) and decision curve analysis (DCA) was used to assess the predictive performance and clinical utility of the nomogram. RESULTS The final study population included 886 cirrhotic patients with AKI, and 264 (29.8%) died in the hospital. After multivariate logistic regression, age, gender, cerebrovascular disease, heart rate, respiration rate, temperature, oxygen saturation, hemoglobin, blood urea nitrogen, serum creatinine, international normalized ratio, bilirubin, urine volume, and sequential organ failure assessment score were predictive factors of in-hospital mortality. In addition, the nomogram showed good accuracy in estimating the in-hospital mortality of patients. The calibration plots showed the best agreement with the actual presence of in-hospital mortality in patients. In addition, the AUC and DCA curves showed that the nomogram has good prediction accuracy and clinical value. CONCLUSIONS We have created a prognostic nomogram for predicting in-hospital death in cirrhotic patients with AKI, which may facilitate timely intervention to improve prognosis in these patients.
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Affiliation(s)
- Xiang Li
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, China
| | - Xunliang Li
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wenman Zhao
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Deguang Wang
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
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Arenas DV, Aldehuelo RS, Varela CÁ, Gandía MR. Ascitis y síndrome hepatorrenal en la cirrosis hepática. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2024; 14:557-567. [DOI: 10.1016/j.med.2024.05.012] [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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Chen T, Chang C, Hou B, Qiu L, Sun H, Zhu X. Research progress in the role of gut microbiota in acute kidney injury. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2024; 49:385-391. [PMID: 38970512 PMCID: PMC11208396 DOI: 10.11817/j.issn.1672-7347.2024.230526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Indexed: 07/08/2024]
Abstract
Acute kidney injury (AKI) remains a global public health problem with high incidence, high mortality rates, expensive medical costs, and limited treatment options. AKI can further progress to chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). Previous studies have shown that trauma, adverse drug reactions, surgery, and other factors are closely associated with AKI. With further in-depth exploration, the role of gut microbiota in AKI is gradually revealed. After AKI occurs, there are changes in the composition of gut microbiota, leading to disruption of the intestinal barrier, intestinal immune response, and bacterial translocation. Meanwhile, metabolites of gut microbiota can exacerbate the progression of AKI. Therefore, elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.
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Affiliation(s)
- Tianxiao Chen
- Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China.
| | - Chang Chang
- Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China
| | - Bao Hou
- Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China
| | - Liying Qiu
- Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China
| | - Haijian Sun
- Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China
| | - Xuexue Zhu
- Department of Basic Medicine, Wuxi Medical College, Jiangnan University, Wuxi Jiangsu 214122, China.
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Fu Y, Sun D, Qin Y, Zheng T, Zhou Z, Zhou X, Zhao X, Xu Y, Huang B. Development and application of an amplified luminescent proximity homogeneous assay-linked immunosorbent assay for the accurate quantification of kidney injury molecule-1. Front Mol Biosci 2024; 10:1280681. [PMID: 38304229 PMCID: PMC10832993 DOI: 10.3389/fmolb.2023.1280681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 12/06/2023] [Indexed: 02/03/2024] Open
Abstract
Background: Kidney injury molecule-1 (Kim-1), a specific marker of kidney injury, is usually not expressed in normal kidneys or at very low levels but is highly expressed in injured renal tubular epithelial cells until the damaged cells recover completely. Therefore, we aimed to develop an efficient and highly sensitive assay to accurately quantify Kim-1 levels in human serum and urine. Methods: In this study, a novel immunoassay was developed and named amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). Anti-Kim-1 antibodies can be directly coupled to carboxyl-modified donor and acceptor beads for the rapid detection of Kim-1 by double-antibody sandwich method. Serum and urine samples for Kim-1 measurements were obtained from 129 patients with nephropathy and 17 healthy individuals. Results: The linear range of Kim-1 detected by AlphaLISA was 3.83-5000 pg/mL, the coefficients of variation of intra-assay and inter-assay batches were 3.36%-4.71% and 5.61%-11.84%, respectively, and the recovery rate was 92.31%-99.58%. No cross reactions with neutrophil gelatinase-associated lipocalin, liver-type fatty acid binding protein, and matrix metalloproteinase-3 were observed. A good correlation (R 2 = 0.9086) was found between the findings of Kim-1-TRFIA and Kim-AlphaLISA for the same set of samples. In clinical trials, both serum and urine Kim-1 levels were significantly higher in patients with nephropathy than in healthy individuals, especially in patients with acute kidney injury. Furthermore, serum Kim-1 was superior to urinary Kim-1 in distinguishing between patients with nephropathy and healthy individuals. Conclusion: The developed Kim-1-AlphaLISA is highly efficient, precise, and sensitive, and it is suitable for the rapid detection of patients with acute kidney injury.
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Affiliation(s)
- Yulin Fu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Danqin Sun
- Department of Nephrology, Jiangnan University Medicine Center, Wuxi, China
| | - Yuan Qin
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Tianyu Zheng
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Zixuan Zhou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Xiumei Zhou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Xueqin Zhao
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yan Xu
- Department of Nephrology, Suzhou Ninth People’s Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China
| | - Biao Huang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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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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20
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Zhang Y, Fang XM. The pan-liver network theory: From traditional chinese medicine to western medicine. CHINESE J PHYSIOL 2023; 66:401-436. [PMID: 38149555 DOI: 10.4103/cjop.cjop-d-22-00131] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2023] Open
Abstract
In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang-xiang theory, yin-yang theory, meridians and collaterals theory, and the five-viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother-child relationships between the liver and the heart, and the yin-yang and exterior-interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex "pan-hepatic network" model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.
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Affiliation(s)
- Yaxing Zhang
- Department of Physiology; Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong; Issue 12th of Guangxi Apprenticeship Education of Traditional Chinese Medicine (Shi-Cheng Class of Guangxi University of Chinese Medicine), College of Continuing Education, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Xian-Ming Fang
- Department of Cardiology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine (Guangxi Hospital of Integrated Chinese Medicine and Western Medicine, Ruikang Clinical Faculty of Guangxi University of Chinese Medicine), Guangxi University of Chinese Medicine, Nanning, Guangxi, China
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21
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Scheinberg AR, Martin P, Turkeltaub JA. Terlipressin in the management of liver disease. Expert Opin Pharmacother 2023; 24:1665-1671. [PMID: 37535437 DOI: 10.1080/14656566.2023.2244427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 07/26/2023] [Accepted: 08/01/2023] [Indexed: 08/05/2023]
Abstract
INTRODUCTION Terlipressin is a synthetic vasopressin analog which has been recently approved in the United States by the Food and Drug Administration for the treatment of hepatorenal syndrome. Terlipressin stimulates vasopressin receptors located on the smooth muscle vasculature of the splanchnic circulation and renal tubules which results in splanchnic vasoconstriction with improved renal perfusion and antidiuretic activity, respectively. AREAS COVERED In this review, we discuss available data regarding the FDA approved use of terlipressin, safety, and tolerability, as well as highlight alternative uses in chronic liver disease currently still under investigation. EXPERT OPINION Terlipressin is more efficacious compared to other vasoactive agents including midodrine octreotide and norepinephrine in reversal of hepatorenal syndrome and improves short-term survival. Other potential applications of terlipressin's vasoconstrictor actions reported in the literature include management of variceal hemorrhage and other complications of portal hypertension.
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Affiliation(s)
- Andrew R Scheinberg
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
| | - Paul Martin
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
| | - Joshua A Turkeltaub
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
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22
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Abstract
Clinical trials have been a central driver of change and have provided the evidence base necessary to advance new therapies for liver diseases. This review provides a perspective on the status of trials in hepatology and a vantage point into the emerging capabilities and external forces that will shape the conduct of clinical trials in the future. The adaptations to clinical trial operations in response to the disruptions by the COVID-19 pandemic and opportunities for innovation in hepatology trials are emphasized. Future trials in hepatology will be driven by unmet therapeutic needs and fueled by technological advances incorporating digital capabilities with expanded participant-derived data collection, computing, and analytics. Their design will embrace innovative trial designs adapted to these advances and that emphasize broader and more inclusive participant engagement. Their conduct will be further shaped by evolving regulatory needs and the emergence of new stakeholders in the clinical trials ecosystem. The evolution of clinical trials will offer unique opportunities to advance new therapeutics that will ultimately improve the lives of patients with liver diseases.
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Affiliation(s)
- Paul Y Kwo
- Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA
| | - Tushar Patel
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida, USA
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23
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Mazumder NR, Junna S, Sharma P. The Diagnosis and Non-pharmacological Management of Acute Kidney Injury in Patients with Cirrhosis. Clin Gastroenterol Hepatol 2023; 21:S11-S19. [PMID: 37625862 DOI: 10.1016/j.cgh.2023.04.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/01/2023] [Accepted: 04/06/2023] [Indexed: 08/27/2023]
Abstract
Acute kidney injury in patients with cirrhosis is quite common, and is seen in up to 50% of patients hospitalized for decompensated cirrhosis. Causes of acute kidney injury include prerenal, renal, or postrenal etiologies. The diagnosis and early institution of nonpharmacologic and pharmacologic management are key to the recovery of renal function. The objective of this review is to provide a practical approach to the use of diagnostic biomarkers and highlight the nonpharmacologic management and prevention of acute kidney injury.
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Affiliation(s)
- Nikhilesh R Mazumder
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan; Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan
| | - Shilpa Junna
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Pratima Sharma
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan; Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan.
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24
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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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25
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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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26
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Zhao X, Yang T, Zhou J, Chen Y, Shen Q, Zhang J, Qiu Q. Fucoidan alleviates the hepatorenal syndrome through inhibition organic solute transporter α/β to reduce bile acids reabsorption. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2023; 5:100159. [PMID: 37416532 PMCID: PMC10320405 DOI: 10.1016/j.crphar.2023.100159] [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] [Received: 10/16/2022] [Revised: 03/03/2023] [Accepted: 06/22/2023] [Indexed: 07/08/2023] Open
Abstract
The high levels of bile acids are a critical factor in hepatorenal syndrome. Organic solute transporter α/β (Ostα/β) participate in bile acids reabsorption in the kidney. Fucoidan has the great potential in protecting against liver and kidney injury. However, whether Ostα/β increase bile acids reabsorption in bile duct ligature (BDL)-induced hepatorenal syndrome and the blockade of fucoidan are still not clear. Male mice that received BDL were given to fucoidan (at 12.5, 25 and 50 mg/kg) through intraperitoneal injection once daily for three weeks. The serum, liver and kidney samples of these experimental mice were collected to carry out biochemical, pathological and Western blot analysis. In this study, fucoidan significantly lowered serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased serum levels of uric acid, creatinine and uric nitrogen, restored the deregulation of the renal urate transporter 1 (URAT1), organic anion transporter 1 (OAT1), and organic cation/carnitine transporter 1/2 (OCTN1/2), consistence with alleviation BDL-induced liver and kidney dysfunction, inflammation and fibrosis in mice. Furthermore, fucoidan significantly hampered Ostα/β and reduced bile acids reabsorption in BDL-induced mice, protected against AML12 and HK-2 cells injury in vitro. These results demonstrate that fucoidan alleviates BDL-induced hepatorenal syndrome through inhibition Ostα/β to reduce bile acids reabsorption in mice. Therefore, suppression of Ostα/β by fucoidan may be a novel strategy for attenuating hepatorenal syndrome.
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27
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Canillas L, Pelegrina A, Álvarez J, Colominas-González E, Salar A, Aguilera L, Burdio F, Montes A, Grau S, Grande L, Carrión JA. Clinical Guideline on Perioperative Management of Patients with Advanced Chronic Liver Disease. LIFE (BASEL, SWITZERLAND) 2023; 13:life13010132. [PMID: 36676081 PMCID: PMC9860873 DOI: 10.3390/life13010132] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/27/2022] [Accepted: 12/28/2022] [Indexed: 01/06/2023]
Abstract
(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of the literature to support a narrative clinical guideline about the assessment of mortality risk and management of perioperative morbidity in patients with ACLD undergoing surgical procedures; (3) Results: Slight data exist to guide the perioperative management of patients with ACLD, and most recommendations are based on case series and expert opinion. The severity of liver dysfunction, portal hypertension, cardiopulmonary and renal comorbidities, and complexity of surgery and type (elective versus emergent) are predictors of perioperative morbidity and mortality. Expert multidisciplinary teams are necessary to evaluate and manage ACLD before, during, and after surgical procedures; (4) Conclusions: This clinical practice document updates the available data and recommendations to optimize the management of patients with advanced chronic liver disease who undergo surgical procedures.
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Affiliation(s)
- Lidia Canillas
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- Liver Section, Gastroenterology Department, Hospital del Mar, 08003 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
| | - Amalia Pelegrina
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Department of Surgery, Hospital del Mar, 08003 Barcelona, Spain
| | - Juan Álvarez
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Anesthesia Department, Hospital del Mar, 08003 Barcelona, Spain
| | - Elena Colominas-González
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- Pharmacy Department, Hospital del Mar, 08003 Barcelona, Spain
| | - Antonio Salar
- Haematology Department, Hospital del Mar, 08003 Barcelona, Spain
| | - Lluís Aguilera
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Anesthesia Department, Hospital del Mar, 08003 Barcelona, Spain
| | - Fernando Burdio
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Department of Surgery, Hospital del Mar, 08003 Barcelona, Spain
| | - Antonio Montes
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Anesthesia Department, Hospital del Mar, 08003 Barcelona, Spain
| | - Santiago Grau
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- Pharmacy Department, Hospital del Mar, 08003 Barcelona, Spain
| | - Luis Grande
- Department of Surgery, Hospital del Mar, 08003 Barcelona, Spain
- Department de Medicina, Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
| | - José A. Carrión
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- Liver Section, Gastroenterology Department, Hospital del Mar, 08003 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
- Correspondence: ; Tel.: +93-248-3220; Fax: +93-221-8644
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28
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Střídová KM, Fraňková S, Šperl J. Acute kidney injury in patients with cirrhosis - practical summary. VNITRNI LEKARSTVI 2023; 69:299-304. [PMID: 37827824 DOI: 10.36290/vnl.2023.059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Acute kidney injury (AKI) is a relatively common condition in patients with advanced liver disease and which is associated with increased mortality. It mainly affects patients with decompensated cirrhosis, particularly those with advanced portal hypertension and ascites. The dual organ involvement may have different forms. The contributing pathogenetic mechanisms are common and predict a dismal prognosis. Early diagnosis and interventions involving specialists (in particular, hepatologists and nephrologists) are essential to improve outcomes.
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29
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Critical Overview of Hepatic Factors That Link Non-Alcoholic Fatty Liver Disease and Acute Kidney Injury: Physiology and Therapeutic Implications. Int J Mol Sci 2022; 23:ijms232012464. [PMID: 36293317 PMCID: PMC9604121 DOI: 10.3390/ijms232012464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/13/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is defined as a combination of a group of progressive diseases, presenting different structural features of the liver at different stages of the disease. According to epidemiological surveys, as living standards improve, the global prevalence of NAFLD increases. Acute kidney injury (AKI) is a class of clinical conditions characterized by a rapid decline in kidney function. NAFLD and AKI, as major public health diseases with high prevalence and mortality, respectively, worldwide, place a heavy burden on societal healthcare systems. Clinical observations of patients with NAFLD with AKI suggest a possible association between the two diseases. However, little is known about the pathogenic mechanisms linking NAFLD and AKI, and the combination of the diseases is poorly treated. Previous studies have revealed that liver-derived factors are transported to distal organs via circulation, such as the kidney, where they elicit specific effects. Of note, while NAFLD affects the expression of many hepatic factors, studies on the mechanisms whereby NAFLD mediates the generation of hepatic factors that lead to AKI are lacking. Considering the unique positioning of hepatic factors in coordinating systemic energy metabolism and maintaining energy homeostasis, we hypothesize that the effects of NAFLD are not only limited to the structural and functional changes in the liver but may also involve the entire body via the hepatic factors, e.g., playing an important role in the development of AKI. This raises the question of whether analogs of beneficial hepatic factors or inhibitors of detrimental hepatic factors could be used as a treatment for NAFLD-mediated and hepatic factor-driven AKI or other metabolic disorders. Accordingly, in this review, we describe the systemic effects of several types of hepatic factors, with a particular focus on the possible link between hepatic factors whose expression is altered under NAFLD and AKI. We also summarize the role of some key hepatic factors in metabolic control mechanisms and discuss their possible use as a preventive treatment for the progression of metabolic diseases.
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30
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Wan YP, Wang AJ, Zhang W, Zhang H, Peng GH, Zhu X. Development and validation of a nomogram for predicting overall survival in cirrhotic patients with acute kidney injury. World J Gastroenterol 2022; 28:4133-4151. [PMID: 36157113 PMCID: PMC9403434 DOI: 10.3748/wjg.v28.i30.4133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/29/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis, and is associated with poor prognosis. Therefore, identifying cirrhotic patients with AKI who are at high risk of mortality is very important and may be helpful for providing timely medical interventions to improve the prognosis of these patients. However, studies focused on investigating the risk factors for the mortality of cirrhotic patients with AKI were scarce.
AIM To identify risk factors for mortality and establish a nomogram for predicting the prognosis of these patients.
METHODS Two hundred fifty consecutive patients with cirrhosis and AKI were recruited and randomly divided into training cohort (n = 173) and validation cohort (n = 77). In the training cohort, potential risk factors for death were identified by performing a Cox regression analysis, and a nomogram was established. The predictive performance of the nomogram was internally and externally validated by calculating the area under the receiver operating characteristic curve (AUROC), constructing a calibration curve and performing decision curve analysis.
RESULTS The serum sodium level, international normalized ratio, peak serum creatinine level > 1.5 mg/dL, the presence of hepatic encephalopathy and diabetes were potential risk factors for mortality of cirrhotic patients with AKI in the training dataset. A prognostic nomogram incorporating these variables was established for predicting the overall survival of these patients. Compared with Child-Turcotte-Pugh, the model for end-stage liver disease (MELD) and the MELD-Na scores, the nomogram in predicting 90- and 180-d mortality exhibited better discriminatory power with AUROCs of 0.792 and 0.801 for the training dataset and 0.817 and 0.862 for the validation dataset, respectively. With a nomogram score of 98, patients were divided into low- and high-risk groups, and high-risk patients had a higher mortality rate.
CONCLUSION A prognostic nomogram displayed good performance for predicting the overall survival of cirrhotic patients with AKI, and will assist clinicians in evaluating the prognosis of these patients.
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Affiliation(s)
- Yi-Peng Wan
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - An-Jiang Wang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Wang Zhang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Hang Zhang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Gen-Hua Peng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
| | - Xuan Zhu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang 331706, Jiangxi Province, China
- Biomolecular Research Laboratory, Jiangxi Clinical Research Center for Gastroenterology, Nanchang 331706, Jiangxi Province, China
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31
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Minjares RO, Martin P, Carrion AF. Chronic Kidney Disease After Liver Transplantation. Clin Liver Dis 2022; 26:323-340. [PMID: 35487614 DOI: 10.1016/j.cld.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Improved survival after liver transplantation has led to an aging cohort of recipients at risk of renal dysfunction. The etiology of renal dysfunction is typically multifactorial; calcineurin inhibitors nephrotoxicity, pretransplant renal dysfunction, and perioperative acute kidney injury are important risk factors. Metabolic complications such as hypertension, diabetes mellitus, and metabolic-associated fatty liver disease also contribute to the development of renal disease. Most LT recipients will eventually develop some degree of renal dysfunction. Criteria to select candidates for simultaneous liver and kidney transplantation have been established. Both delayed introduction of CNIs and renal-sparing immunosuppressive regimens may reduce progression of renal dysfunction.
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Affiliation(s)
- Ramon O Minjares
- Department of Internal Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA.
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA
| | - Andres F Carrion
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA
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