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Roy A, Kulkarni AV. Ascites in patients with end-stage renal disease: Challenges and solutions from diagnosis to management. Hepatol Commun 2025; 9:e0687. [PMID: 40178483 PMCID: PMC11970822 DOI: 10.1097/hc9.0000000000000687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 02/10/2025] [Indexed: 04/05/2025] Open
Abstract
Metabolic diseases have exponentially increased in recent years, which has led to an increased prevalence of metabolic dysfunction-associated steatotic liver disease and concomitant kidney diseases. Ascites are a common presentation of cirrhosis, and renal impairment in cirrhosis is well described. However, patients with end-stage renal disease (ESRD) may also present with ascites even in the absence of cirrhosis. The literature on the management of patients with ESRD with ascites with or without concomitant cirrhosis is limited. Massive ascites in this population are often refractory to medical therapy and are associated with dismal prognosis. Pathophysiologically, increased hepatic vein hydrostatic pressure, fluid retention, increased peritoneal membrane permeability, and impaired peritoneal lymphatic drainage are proposed mechanisms for ascites in ESRD without cirrhosis. Identifying underlying cirrhosis and portal hypertension (PH) has therapeutic implications in such patients. However, diagnostic tools such as serum ascites albumin gradient and noninvasive tests to identify cirrhosis have limited utility in ESRD. Hemodialysis and continuous ambulatory peritoneal dialysis are effective but can be associated with hemodynamic compromise and peritonitis, especially in those with PH. TIPS for ascites has a limited role in the presence of ESRD due to the increased risk of HE. Kidney transplant is the treatment of choice in ESRD with ascites without PH. Simultaneous liver-kidney transplant remains the definitive treatment in the presence of PH, but is less commonly feasible, and kidney transplant alone in the presence of PH can be associated with the risk of decompensations. This review discusses the approach and management of ascites in chronic kidney disease and ESRD specifically.
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Affiliation(s)
- Akash Roy
- Department of Hepatology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, India
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Marrapu S, Kumar R. Transition from acute kidney injury to chronic kidney disease in liver cirrhosis patients: Current perspective. World J Nephrol 2025; 14:102381. [PMID: 40134649 PMCID: PMC11755238 DOI: 10.5527/wjn.v14.i1.102381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/22/2024] [Accepted: 01/11/2025] [Indexed: 01/20/2025] Open
Abstract
In liver cirrhosis patients, acute kidney injury (AKI) is a common and severe complication associated with significant morbidity and mortality, often leading to chronic kidney disease (CKD). This progression reflects a complex interplay of renal and hepatic pathophysiology, with AKI acting as an initiator through maladaptive repair mechanisms. These mechanisms-such as tubular cell cycle arrest, inflammatory cascades, and fibrotic processes-are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis. Following AKI episodes, persistent kidney dysfunction or acute kidney disease (AKD) often serves as a bridge to CKD. AKD represents a critical phase in renal deterioration, characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI. The progression from AKD to CKD is further influenced by recurrent AKI episodes, impaired renal autoregulation, and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease, which compound kidney damage. The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury, the application of novel biomarkers, and precision interventions. Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression, necessitating novel biomarkers for early detection and intervention.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Nguyen NN, Nguyen BT, Nguyen TDT, Tran TTT, Mai TNH, Le HNT, Dang HN, Nguyen VBN, Ngo NYT, Vo CT. A novel risk-predicted nomogram for acute kidney injury progression in decompensated cirrhosis: a double-center study in Vietnam. Int Urol Nephrol 2025:10.1007/s11255-025-04398-1. [PMID: 39955461 DOI: 10.1007/s11255-025-04398-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 01/26/2025] [Indexed: 02/17/2025]
Abstract
OBJECTIVES Acute kidney injury (AKI) is commonly encountered in patients hospitalized for decompensated cirrhosis and is associated with prolonged hospital stays, increased treatment burden, and even mortality. The present study aimed to determine the prevalence of and develop a predictive nomogram for AKI in patients with decompensated cirrhosis. METHODS This cross-sectional, double-center study involved 544 patients hospitalized with decompensated cirrhosis. Acute kidney injury was diagnosed using American Gastroenterological Association's guidelines with one more criterion: an increase in serum creatinine ≥ 0.3 mg/dL within 48 h or an increase in serum creatinine ≥ 50% compared to baseline serum creatinine or when the urine output is reduced below 0.5 mL/kg/h for > 6 h. We used the Bayesian model averaging method find the optimal model for predicting AKI. A predictive nomogram was also developed to enable risk prediction. RESULTS The overall AKI prevalence was 26.7% (95% Confidence interval [CI] 25.7-27.7). The optimal model for predicting AKI included diuretic therapy (odds ratio [OR]: 5.55; 95%CI 3.31-9.33), infection (OR: 2.06; 95%CI 1.31-3.22), ascites (OR: 3.20; 95%CT: 1.67-6.13), Child-Pugh group C (OR: 2.91; 95%CI 1.84-4.62), serum potassium (OR per 1 mmol/L increase: 1.62; 95%CI 1.25-2.1) and serum chloride (OR per 1 mmol/L decrease: 1.03; 95%CI 1.01-1.06). The area under the receiver operating characteristic curve was 0.8, with a 95%CI ranging from 0.75 to 0.84. CONCLUSIONS Acute kidney injury was relatively common among patients hospitalized for decompensated cirrhosis. A novel nomogram-including diuretic therapy, infection, ascites, Child-Pugh group C, serum potassium and, serum chloride, was helpful for the selective screening of AKI in patients with decompensated cirrhosis.
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Affiliation(s)
- Nghia N Nguyen
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Bao T Nguyen
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam.
| | - Thuy D T Nguyen
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Tam T T Tran
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Tan N H Mai
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Huyen N T Le
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Hoang N Dang
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Vy B N Nguyen
- Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
| | - Nhi Y T Ngo
- Hoan My Cuu Long Hospital, 20 Vo Nguyen Giap Street, Phu Thu Ward, Cai Rang District, Can Tho City, 902510, Vietnam
| | - Cuong T Vo
- Can Tho University of Medicine and Pharmacy Hospital, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho City, 902510, Vietnam
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Lekakis V, Wong F, Gkoufa A, Papatheodoridis GV, Cholongitas E. Mortality of Acute Kidney Injury in Cirrhosis: A Systematic Review and Meta-Analysis of Over 5 Million Patients Across Different Clinical Settings. Aliment Pharmacol Ther 2025; 61:420-432. [PMID: 39641300 PMCID: PMC11707646 DOI: 10.1111/apt.18426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/01/2024] [Accepted: 11/23/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) represents a commonly seen condition in the natural course of cirrhosis associated with unfavourable outcomes. AIMS To evaluate and compare the pooled mortality rates of patients with cirrhosis, with versus without AKI, across different clinical settings and diagnostic criteria. METHODS A systematic search of several databases was performed up to Oct 2023. Meta-analysis was performed using a generalised linear mixed model with a random effects model for all calculations. RESULTS A total of 59 studies comparing patients with cirrhosis, with and without AKI, were included in the meta-analysis, encompassing 1,153,193 individuals with AKI and 4,630,814 without AKI. AKI development predisposed to significantly higher short (in-hospital and 30-days)-, intermediate (90-days)- and long (1-year)-term mortality rates in both inpatients and outpatients. Remarkably, patients with AKI admitted to intensive care unit (ICU) or diagnosed with acute-on-chronic liver failure (ACLF) experienced the higher short-term mortality rates, reaching 76% [95% confidence interval (CI): 73%-79%] and 54% (95%CI: 33%-73%), respectively. AKI staging correlated with mortality risk, with higher stages indicating higher mortality rates, while the timing of AKI development, whether community-acquired or hospital-acquired, plays a crucial role in patient prognosis, with distinct mortality patterns observed in each group. The selection of diagnostic criteria for AKI may also impact its association with the short-term mortality risk. CONCLUSIONS AKI substantially affects the prognosis of patients with cirrhosis, especially those in ICU and/or with ACLF. Prognosis is also greatly influenced by the AKI stage, timing of onset and diagnostic criteria.
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Affiliation(s)
- Vasileios Lekakis
- Department of GastroenterologyGeneral Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of AthensAthensGreece
| | - Florence Wong
- Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health NetworkUniversity of TorontoTorontoCanada
| | - Aikaterini Gkoufa
- First Department of Internal Medicine“Laiko”, General Hospital, Medical School of National and Kapodistrian University of AthensAthensGreece
| | - George V. Papatheodoridis
- Department of GastroenterologyGeneral Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of AthensAthensGreece
| | - Evangelos Cholongitas
- Department of GastroenterologyGeneral Hospital of Athens “Laiko”, Medical School of National and Kapodistrian University of AthensAthensGreece
- First Department of Internal Medicine“Laiko”, General Hospital, Medical School of National and Kapodistrian University of AthensAthensGreece
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Maiwall R, Sharma F. AKI in ACLF: navigating the complex therapeutic puzzle. Expert Rev Gastroenterol Hepatol 2025; 19:165-180. [PMID: 39825627 DOI: 10.1080/17474124.2025.2456121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 01/16/2025] [Indexed: 01/20/2025]
Abstract
INTRODUCTION Acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF) is driven by the severity of systemic inflammation, acute portal hypertension driving circulatory dysfunction, hyperbilirubinemia, and toxicity of bile acids. The spectrum is mostly structural, associated with reduced response to vasoconstrictors. The progression is rapid, and need of renal replacement therapy and extracorporeal therapies may be required for the management. The development of renal failure is usually considered when defining the syndrome of ACLF. AREAS COVERED In the current review we discuss the pathophysiological basis, natural course, and response to the current therapeutic modalities and challenges in assessing and managing AKI in patients with ACLF. We conducted a comprehensive search of electronic databases such as PubMed, Web of Science, and Scopus using keywords like lactate, NGAL, and PHTN, as well as CRRT, PLEX, ACLF, and AKI phases for our review. Peer-reviewed English papers that addressed our issue were considered. EXPERT OPINION The difficulties and specific management strategies for AKI in ACLF patients are discussed emphasizing the importance of customized protocols, risk assessment guided by biomarkers, and investigation of extracorporeal therapies that target bile acids.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Fagun Sharma
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
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Li X, Ouyang T, Belcher JM, Patidar KR, Cullaro G, Asrani SK, Wadei HM, Simonetto DA, Regner KR, Dageforde LA, Przybyszewski EM, Wilechansky RM, Sharma P, Ufere NN, Duarte-Rojo A, Wahid NA, Orman ES, St Hillien SA, Robinson JE, Chung RT, Allegretti AS. Impact of acute kidney injury response on survival and liver transplant rates in hospitalized patients with cirrhosis awaiting liver transplantation: Results from the HRS-HARMONY consortium. Liver Transpl 2024; 30:1106-1115. [PMID: 39073567 DOI: 10.1097/lvt.0000000000000445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 06/06/2024] [Indexed: 07/30/2024]
Abstract
Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in patients with cirrhosis awaiting LT. This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score. Among the 317 patients in this study, 170 had an AKI response (53.6%), and 147 had no response (46.4%). Compared to nonresponders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted subhazard ratio for mortality 0.34, p =0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p <0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted subhazard ratio 0.55, p =0.005); 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in nonresponders occurred during hospitalization, with the remainder occurring postdischarge at a median of 58 days. In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.
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Affiliation(s)
- Xing Li
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Tianqi Ouyang
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Justin M Belcher
- Section of Nephrology, Department of Internal Medicine, Yale University and VA Connecticut Healthcare, New Haven, Connecticut, USA
| | - 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, USA
| | - Giuseppe Cullaro
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York City, New York, USA
| | | | - Hani M Wadei
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Transplant Hepatology, Mayo Clinic, Rochester, Rochester, Minnesota, USA
| | - Kevin R Regner
- Division of Nephrology at the Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Leigh A Dageforde
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Eric M Przybyszewski
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Robert M Wilechansky
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Pratima Sharma
- Department of Gastroenterology and Transplant Hepatology, University of Michigan Health, Ann Arbor, Michigan, USA
| | - Nneka N Ufere
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Nabeel A Wahid
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Eric S Orman
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA
| | - Shelsea A St Hillien
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jevon E Robinson
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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Granda ML, Luitweiler E, Prince DK, Allegretti AS, Paine C, Pichler R, Sibulesky L, Biggins SW, Kestenbaum B. Proximal Tubule Secretory Clearance, Injury, and Kidney Viability in Cirrhosis. Clin Transl Gastroenterol 2024; 15:e00775. [PMID: 39374041 PMCID: PMC11596343 DOI: 10.14309/ctg.0000000000000775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 09/18/2024] [Indexed: 10/08/2024] Open
Abstract
INTRODUCTION Cirrhosis affects all structures of the kidney, in particular the tubules, which are responsible for secretion of protein-bound metabolites and electrolyte/water homeostasis. Yet, prevailing assessments of kidney function focus solely on glomerular filtration rate (GFR), which may incompletely reflect these processes. We sought to characterize markers of tubular function, injury, and viability in patients with and without cirrhosis. METHODS We recruited outpatients undergoing liver transplantation evaluation for a collection of plasma and 24-hour urine, matching by GFR to control participants without cirrhosis. We measured urinary kidney injury molecule-1, a marker of proximal tubular injury, as well as epidermal growth factor (EGF), a marker of viability necessary for tubular epithelial cell proliferation after injury. We also estimated secretory clearance by measuring several highly secreted endogenous metabolites in urine and plasma. RESULTS We recruited 39 patients with cirrhosis (mean model for end-stage liver disease 17 ± 4, Child-Pugh 8 ± 2, estimated glomerular filtration rate 66 ± 20 mL/min/1.73 m 2 ) and 58 GFR-matched controls without cirrhosis (estimated glomerular filtration rate 66 ± 21 mL/min/1.73 m 2 ). Urinary kidney injury molecule-1 was 4.4-fold higher than controls (95% confidence interval: 2.9-6.5), and EGF averaged 7.41-fold higher than controls (95% confidence interval: 2.15-25.53). We found that of 8 solutes, 5 had significantly greater kidney clearance in cirrhosis (1.3-2.1-fold higher): indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine. DISCUSSION Cirrhosis was characterized by molecular signs of tubular injury in stable outpatients without acute kidney injury, accompanied by largely preserved tubular secretory clearance and greater signs of tubular viability. Within the limitations of the study, this suggests a phenotype of chronic ischemic injury but with initial preservation of tubular function in cirrhosis.
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Affiliation(s)
- Michael L. Granda
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
| | - Eric Luitweiler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - David K. Prince
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
| | - Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Cary Paine
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Raimund Pichler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Lena Sibulesky
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, Washington, USA
| | - Scott W. Biggins
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Bryan Kestenbaum
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
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Kim JH, Kim KS, Kwon HM, Kim SH, Jun IG, Song JG, Hwang GS. Impact of Chronic Hepatitis C Virus on Acute Kidney Injury After Living Donor Liver Transplantation. Anesth Analg 2024:00000539-990000000-00987. [PMID: 39413032 DOI: 10.1213/ane.0000000000007253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) is one of the most common complications after liver transplantation (LT) and can significantly impact outcomes. The presence of hepatitis C virus (HCV) infection increases the risk of AKI development. However, the impact of HCV on AKI after LT has not been evaluated. The aim of this study was to assess the effect of HCV on AKI development in patients who underwent LT. METHODS Between January 2008 and April 2023, 2183 patients who underwent living donor LT (LDLT) were included. Patients were divided into 2 groups based on the presence of chronic HCV infection. We compared LT recipients using the propensity score matching (PSM) method. Factors associated with AKI development were evaluated using multiple logistic regression analysis. In addition, 1-year mortality and graft failure were assessed using a Cox proportional regression model. RESULTS Among 2183 patients, the incidence of AKI was 59.2%. After PSM, the patients with HCV showed a more frequent development of AKI (71.9% vs 63.9%, P = .026). In multivariate analysis after PSM, HCV was associated with AKI development (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.06-2.20, P = .022), 1-year mortality (Hazard ratio [HR], 1.98; 95% CI, 1.12-3.52, P = .019), and graft failure (HR, 2.12; 95% CI, 1.22-3.69, P = .008). CONCLUSIONS The presence of HCV was associated with increased risk for the development of AKI, 1-year mortality, and graft failure after LT.
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Affiliation(s)
- Jae Hwan Kim
- From the Department of Anesthesiology and Pain Medicine, Inje University Haeundae Paik Hospital, Busan, Republic of Korea
| | - Kyoung-Sun Kim
- Depatment of Anesthesiology and Painmedicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hye-Mee Kwon
- Depatment of Anesthesiology and Painmedicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Hoon Kim
- Depatment of Anesthesiology and Painmedicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - In-Gu Jun
- Depatment of Anesthesiology and Painmedicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jun-Gol Song
- Depatment of Anesthesiology and Painmedicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gyu-Sam Hwang
- Depatment of Anesthesiology and Painmedicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Girish V, Maiwall R. Editorial: Solving the acute kidney injury puzzle in alcohol-associated hepatitis-Challenges and insights. Aliment Pharmacol Ther 2024; 60:963-964. [PMID: 39225450 DOI: 10.1111/apt.18206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
LINKED CONTENTThis article is linked to Ma et al paper. To view this article, visit https://doi.org/10.1111/apt.18158
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Affiliation(s)
- Vishnu Girish
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
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Guo R, Wang L, Liu T, Li S, Liu Y, Yang H, Chen L, Ji C, Xia Y. Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study. Prev Med 2024; 185:108030. [PMID: 38849058 DOI: 10.1016/j.ypmed.2024.108030] [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: 02/28/2024] [Revised: 04/30/2024] [Accepted: 06/04/2024] [Indexed: 06/09/2024]
Abstract
OBJECTIVE Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. METHODS Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. RESULTS During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). CONCLUSIONS Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis.
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Affiliation(s)
- Rongchang Guo
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shenyang, China
| | - Lanbo Wang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tiancong Liu
- Department of Otorhinolaryngology-Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shiwen Li
- Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yashu Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Honghao Yang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shenyang, China
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chao Ji
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shenyang, China.
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shenyang, China.
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Juanola A, Ma AT, Gratacós-Ginès J, Soria A, Solé C, Pose E, Ginès P. Renal Complications in Portal Hypertension. Clin Liver Dis 2024; 28:503-523. [PMID: 38945640 DOI: 10.1016/j.cld.2024.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Ann Thu Ma
- Toronto Centre for Liver Disease Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada
| | - Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Anna Soria
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Cristina Solé
- Department of Gastroenterology and Hepatology, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain.
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12
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Nadim MK, Kellum JA, Forni L, Francoz C, Asrani SK, Ostermann M, Allegretti AS, Neyra JA, Olson JC, Piano S, VanWagner LB, Verna EC, Akcan-Arikan A, Angeli P, Belcher JM, Biggins SW, Deep A, Garcia-Tsao G, Genyk YS, Gines P, Kamath PS, Kane-Gill SL, Kaushik M, Lumlertgul N, Macedo E, Maiwall R, Marciano S, Pichler RH, Ronco C, Tandon P, Velez JCQ, Mehta RL, Durand F. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol 2024; 81:163-183. [PMID: 38527522 PMCID: PMC11193657 DOI: 10.1016/j.jhep.2024.03.031] [Citation(s) in RCA: 47] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 02/28/2024] [Accepted: 03/07/2024] [Indexed: 03/27/2024]
Abstract
Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
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Affiliation(s)
- Mitra K Nadim
- Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, USA
| | - John A Kellum
- Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Lui Forni
- School of Medicine, University of Surrey and Critical Care Unit, Royal Surrey Hospital Guildford UK
| | - Claire Francoz
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, Paris, France
| | | | - Marlies Ostermann
- King's College London, Guy's & St Thomas' Hospital, Department of Critical Care, London, UK
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Javier A Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jody C Olson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Padova, Italy
| | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Elizabeth C Verna
- Division of Digestive and Liver Diseases, Columbia University, New York, NY, USA
| | - Ayse Akcan-Arikan
- Department of Pediatrics, Divisions of Critical Care Medicine and Nephrology, Baylor College of Medicine, Houston, TX, USA
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, University and Teaching Hospital of Padua, Italy
| | - Justin M Belcher
- Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA
| | - Scott W Biggins
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Akash Deep
- Pediatric Intensive Care Unit, King's College Hospital, London, UK
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Yale University School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA
| | - Yuri S Genyk
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Division of Abdominal Organ Transplantation at Children's Hospital of Los Angeles, Los Angeles, CA, USA
| | - Pere Gines
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer and Ciber de Enfermedades Hepàticas y Digestivas, Barcelona, Catalonia, Spain
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Sandra L Kane-Gill
- Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
| | - Manish Kaushik
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Nuttha Lumlertgul
- Excellence Centre in Critical Care Nephrology and Division of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Etienne Macedo
- Division of Nephrology, Department of Medicine, University of California San Diego, CA, USA
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Raimund H Pichler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Claudio Ronco
- International Renal Research Institute of Vicenza, Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza-Italy
| | - Puneeta Tandon
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Juan-Carlos Q Velez
- Department of Nephrology, Ochsner Health, New Orleans, LA, USA; Ochsner Clinical School, The University of Queensland, Brisbane, QLD, Australia
| | - Ravindra L Mehta
- Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - François Durand
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, Paris, France; University Paris Cité, Paris, France.
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13
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Lekakis V, Gkoufa A, Vlachogiannakos J, Papatheodoridis GV, Cholongitas E. Incidence and risk factors of acute kidney injury in cirrhosis: a systematic review and meta-analysis of 5,202,232 outpatients, inpatients, and ICU-admitted patients. Expert Rev Gastroenterol Hepatol 2024; 18:377-388. [PMID: 39001566 DOI: 10.1080/17474124.2024.2380299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/11/2024] [Indexed: 07/18/2024]
Abstract
INTRODUCTION Acute kidney injury (AKI) is a commonly seen condition in the natural course of cirrhosis. The aim of this study was to evaluate the pooled incidence and risk factors of AKI in different clinical stages and situations in patients with cirrhosis. METHODS Search was conducted on 13 December 2023 across MEDLINE (PubMed), Embase, and Cochrane databases. Meta-analysis was performed using a generalized linear mixed model. RESULTS In total, 73 studies with 5,202,232 patients were finally enrolled in the meta-analysis. AKI commonly occurs among hospitalized cirrhotics experiencing any decompensation event (29%) as well as among stable outpatients (28%) throughout a 1-year follow-up period. On admission, patients with infection or sepsis/septic shock had the highest AKI rate (47%), followed by those with hepatic encephalopathy (41%). Furthermore, the severity of liver disease proved to be a substantial driver for AKI development, while patients at intensive care unit had the greatest AKI incidence (61%). CONCLUSIONS Both hospitalized patients and stable outpatients with cirrhosis exhibited an elevated susceptibility to AKI. Patients at intensive care unit and those with severe liver disease, infection, sepsis/septic shock, hepatic encephalopathy, or acute on chronic liver failure upon admission are at higher risk for AKI. TRIAL REGISTRATION PROSPERO, registered 09/12/23, CRD42023487736.
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Affiliation(s)
- Vasileios Lekakis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Aikaterini Gkoufa
- First Department of Internal Medicine, "Laiko", General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, "Laiko", General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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14
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Maiwall R, Singh SP, Angeli P, Moreau R, Krag A, Singh V, Singal AK, Tan SS, Puri P, Mahtab M, Lau G, Ning Q, Sharma MK, Rao PN, Kapoor D, Gupta S, Duseja A, Wadhawan M, Jothimani D, Saigal S, Taneja S, Shukla A, Puri P, Govil D, Pandey G, Madan K, Eapen CE, Benjamin J, Chowdhury A, Singh S, Salao V, Yang JM, Hamid S, Shalimar, Jasuja S, Kulkarni AV, Niriella MA, Tevethia HV, Arora V, Mathur RP, Roy A, Jindal A, Saraf N, Verma N, De A, Choudhary NS, Mehtani R, Chand P, Rudra O, Sarin SK. APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure. Hepatol Int 2024; 18:833-869. [PMID: 38578541 DOI: 10.1007/s12072-024-10650-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 01/20/2024] [Indexed: 04/06/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Paolo Angeli
- Department of Internal Medicine and Hepatology, University of Padova, Padua, Italy
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)-CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Centre de Recherche sur l'Inflammation (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Cité, Paris, France
- Service d'Hépatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Clichy, France
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Virender Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India
| | - Ashwani K Singal
- Department of Medicine, University of Louisville School of Medicine, Trager Transplant Center and Jewish Hospital, Louisville, USA
| | - S S Tan
- Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia
| | - Puneet Puri
- Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mamun Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - George Lau
- Humanity and Health Medical Group, Humanity and Health Clinical Trial Center, Hong Kong SAR, China
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- State Key Laboratory for Zoonotic Diseases, Wuhan, China
- Department of Pediatrics, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - P N Rao
- Department of Hepatology and Nutrition, Asian Institute of Gastroenterology, Hyderabad, India
| | - Dharmesh Kapoor
- Department of Hepatology, Gleneagles Global Hospitals, Hyderabad, Telangana, India
| | - Subhash Gupta
- Department of Surgery, Center for Liver and Biliary Sciences, Max Healthcare, Saket, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Manav Wadhawan
- Institute of Digestive & Liver Diseases, BLK Superspeciality Hospital Delhi, New Delhi, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharat Institute of Higher Education and Research, Chennai, India
| | - Sanjiv Saigal
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, India
| | - Deepak Govil
- Department of Critical Care and Anaesthesia, Medanta-The Medicity, Gurugram, Haryana, India
| | - Gaurav Pandey
- Gastroenterology and Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Kaushal Madan
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - C E Eapen
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Jaya Benjamin
- Department of Clinical Nutrition, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashok Chowdhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Shweta Singh
- Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Vaishali Salao
- Department of Critical Care, Fortis Hospital, Mulund, Mumbai, India
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Saeed Hamid
- Department of Hepatology, Aga Khan University, Karachi, Pakistan
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjiv Jasuja
- Department of Nephrology, Indraprastha Apollo Hospitals, New Delhi, India
| | | | - Madund A Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | - Harsh Vardhan Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - R P Mathur
- Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akash Roy
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Hospitals, Kolkata, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Delhi (NCR), India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Narendra S Choudhary
- Department of Hepatology and Liver Transplantation, Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | - Rohit Mehtani
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Phool Chand
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Omkar Rudra
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
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15
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Raja K, Panackel C. Post Liver Transplant Renal Dysfunction-Evaluation, Management and Immunosuppressive Practice. J Clin Exp Hepatol 2024; 14:101306. [PMID: 38274509 PMCID: PMC10806298 DOI: 10.1016/j.jceh.2023.101306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 11/21/2023] [Indexed: 01/27/2024] Open
Abstract
Liver transplantation (LT) is an effective and lifesaving treatment for patients with end-stage liver disease and hepatocellular carcinoma. Significant improvement in intermediate and long-term survival has been possible due to advancements in immunosuppressive therapy, perioperative care, and surgical techniques. Despite these advances, metabolic complications, including diabetes mellitus, cardiovascular diseases, malignancies, and renal dysfunction, are challenging issues after LT. Acute kidney injury (AKI) and chronic kidney disease (CKD) after LT are common and result in significant morbidity and mortality. Early diagnosis of kidney injury after LT is challenging, and no technique has yet proven effective in prediction of renal dysfunction. The methods for assessing renal function range from formulas that predict glomerular filtration rate to non-invasive biomarkers. The universal adoption of the model for end-stage liver disease has a direct impact on the incidence of peri-transplant AKI and development of CKD in the long-term. Post-LT renal dysfunction is multifactorial and is usually a result of pre-transplantation comorbidities, occurrence of renal dysfunction on the waiting list, perioperative events, and post-transplant nephrotoxic immunosuppressive medication use. Early identification of patients at risk for renal dysfunction and adoption of preventive measures are crucial in the pre-transplant period. No data are currently available to suggest a surgical technique that reliably demonstrates renal protection. Nephroprotective strategies during LT follow accepted surgical practice guidelines, such as maintenance of intravascular volume and mean arterial pressure. The management of kidney disease following LT is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Early nephroprotective measures are strongly advised and they mostly center on delaying the administration of calcineurin inhibitors (CNIs) during the initial postoperative period, lowering CNI dosage and combining CNI with mycophenolate mofetil and everolimus. The reasons for renal failure following LT, the techniques used to diagnose it, and the therapies designed to preserve renal function both immediately and late after LT are all critically evaluated in this review.
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Affiliation(s)
- Kaiser Raja
- Department of Gastroenterology and Hepatology, King's College Hospital London, Dubai, United Arab Emirates
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16
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Jung CY, Jung HY, Kim HW, Ryu GW, Lee JI, Ahn SH, Kim SU, Kim BS. Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes. J Infect Dis 2024; 229:108-116. [PMID: 37470458 DOI: 10.1093/infdis/jiad273] [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: 03/30/2023] [Revised: 07/06/2023] [Accepted: 07/18/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. RESULTS The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. CONCLUSIONS Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.
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Affiliation(s)
- Chan-Young Jung
- Department of Internal Medicine, Yonsei University College of Medicine
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine
| | - Hui-Yun Jung
- Department of Internal Medicine, Yonsei University College of Medicine
| | - Hyung Woo Kim
- Department of Internal Medicine, Yonsei University College of Medicine
| | - Geun Woo Ryu
- Department of Internal Medicine, Yonsei University College of Medicine
| | - Jung Il Lee
- Division of Gastroenterology, Gangnam Severance Hospital
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Seok Kim
- Department of Internal Medicine, Yonsei University College of Medicine
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17
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Yepes Barreto I, Romero Florez D, Coronado Daza J. Factores de riesgo para fibrosis hepática en pacientes diabéticos con enfermedad renal cronica terminal. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:278-289. [DOI: 10.22516/25007440.1061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Introducción: la cirrosis hepática es la cuarta causa de muerte en el mundo. Actualmente, la enfermedad hepática por depósito de grasa es la causa más frecuente de hepatopatía crónica en la mayoría de los países. La identificación de factores de riesgo para la presencia de fibrosis hepática en una población con enfermedad renal crónica terminal puede facilitar el diagnóstico temprano de esta complicación y permitir la activación de protocolos de seguimiento para disminuir la morbimortalidad en estos pacientes.
Metodología: se realizó un estudio de corte transversal y analítico. Se incluyeron pacientes en hemodiálisis, mayores de 18 años con diagnóstico de diabetes mellitus y de enfermedad renal crónica terminal. El contraste de hipótesis se realizó a través de la prueba de chi cuadrado y la T de Student, según correspondiera. La significación estadística se estableció con un valor p = 0,05.
Resultados: se observó una prevalencia de fibrosis hepática significativa y cirrosis del 17%. Los factores asociados a la presencia de fibrosis hepática fueron los antecedentes de enfermedad cerebrovascular, la enfermedad vascular periférica, el índice de masa corporal (IMC), el colesterol total, la hemoglobina glicosilada, el sodio y el aspartato-aminotransferasa (AST). No se observó relación entre el puntaje de NAFLD (enfermedad del hígado graso no alcohólico), el índice APRI (AST to Platelet Ratio Index) y la presencia de fibrosis.
Conclusión: la prevalencia de fibrosis hepática significativa en pacientes con diabetes y ERCT es similar a la reportada en otras poblaciones de pacientes con diabetes. Sin embargo, algunos factores, como el IMC, podrían comportarse de forma diferente y favorecer la aparición de lesión hepática con grados menores de obesidad a los reportados previamente en la literatura.
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Maiwall R, Pasupuleti SSR, Hidam AK, Rastogi A, Thomas S, Kumar G, Kumar A, Sarin SK. Non-resolution of acute kidney injury in the first week portends the development of chronic kidney disease in critically ill patients with cirrhosis. Aliment Pharmacol Ther 2023; 58:593-610. [PMID: 37455381 DOI: 10.1111/apt.17639] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/11/2023] [Accepted: 06/27/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND Renal tubular epithelial cells (RTECs) cause maladaptive repair and perpetuate renal fibrosis. AIM To evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and RTEC as risk factors for non-resolution of acute kidney injury (AKI-NR) at day seven and chronic kidney disease (CKD) in critically ill patients with cirrhosis. METHODS We performed urinary NGAL and microscopy at enrolment and day 7 in all patients. We assessed 17 renal injury, endothelial injury and repair markers, genes for mitochondrial biogenesis by qRT-PCR in RTEC, and post-mortem renal biopsies for understanding mechanisms of AKI non-resolution (n = 30). RESULTS We enrolled 310 patients, aged 48.1 ± 11.6 years, 87% male, 90% alcoholic. Of these, 36% had RTEC at enrolment, and 53% had AKI-NR on day 7. On mean follow-up of 136 days (range 43-365), 150 (48.3%) developed CKD. The presence of RTEC or granular casts, NGAL and AKI-NR were independent predictors of CKD development on competing risk analysis. Higher MCP-1, renal endothelial injury, decrease in tubular repair markers and failure of mitochondrial biogenesis in RTEC were seen in patients with AKI-NR compared with AKI-R (p < 0.05). Renal biopsies showed infiltration with monocyte-macrophage, increased α-SMA, and tubulointerstitial fibrosis. CONCLUSION Almost two-thirds of critically ill patients with cirrhosis have AKI, which resolves in only one-half at day seven and predicts the development of CKD. Higher NGAL, RTEC, or granular casts were independent predictors of AKI-NR and CKD development. Enhanced tubular and endothelial injury, decreased repair, monocyte-macrophage infiltration and mitochondrial dysfunction in RTEC are associated with AKI non-resolution and risk of renal fibrosis.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Samba Siva Rao Pasupuleti
- Department of Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India
- Department of Applied Mathematics and Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India
| | - Ashini Kumar Hidam
- Department of Clinical and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sherin Thomas
- Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Anupam Kumar
- Department of Clinical and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Arnold J, Avila E, Idalsoaga F, Diaz LA, Ayala Valverde M, Ayares G, Arrese M, Roessler E, Huidobro JP, Hudson D, Khan MQ, Arab JP. Advances in the diagnosis and management of hepatorenal syndrome: insights into HRS-AKI and liver transplantation. EGASTROENTEROLOGY 2023; 1:e100009. [PMID: 39943997 PMCID: PMC11770447 DOI: 10.1136/egastro-2023-100009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/27/2023] [Indexed: 01/04/2025]
Abstract
In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI-liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.
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Affiliation(s)
- Jorge Arnold
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Avila
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Gustavo Ayares
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eric Roessler
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Huidobro
- Departamento de Nefrología, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - David Hudson
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Mohammad Qasim Khan
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Medicine, London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
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20
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Ma AT, Solà E. Editorial: composite kidney outcomes in studies with patients with cirrhosis and AKI-Are we ready to "MAKE" the switch? Aliment Pharmacol Ther 2023; 57:1473-1474. [PMID: 37243463 DOI: 10.1111/apt.17527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Affiliation(s)
- Ann T Ma
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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21
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Patidar KR, Naved MA, Kabir S, Grama A, Allegretti AS, Cullaro G, Asrani SK, Worden A, Desai AP, Ghabril MS, Nephew LD, Orman ES. Longer time to recovery from acute kidney injury is associated with major adverse kidney events in patients with cirrhosis. Aliment Pharmacol Ther 2023; 57:1397-1406. [PMID: 36883210 PMCID: PMC10441172 DOI: 10.1111/apt.17457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/27/2022] [Accepted: 02/25/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE). AIMS To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis. METHODS Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine <0.3 mg/dL of baseline) from AKI-onset was grouped by Acute-Disease-Quality-Initiative Renal Recovery consensus: 0-2, 3-7, and >7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with the development of de-novo chronic-kidney-disease (CKD) stage ≥3 or CKD progression (≥50% reduction in eGFR compared with baseline) or new haemodialysis or death. Landmark competing-risk multivariable analysis was performed to determine the independent association between timing of AKI-recovery and risk of MAKE. RESULTS 4655 (75%) achieved AKI-recovery: 0-2 (60%), 3-7 (31%), and >7-days (9%). Cumulative-incidence of MAKE was 15%, 20%, and 29% for 0-2, 3-7, >7-days recovery groups, respectively. On adjusted multivariable competing-risk analysis, compared to 0-2-days, recovery at 3-7 and >7-days was independently associated with an increased risk for MAKE: sHR 1.45 (95% CI 1.01-2.09, p = 0.042), sHR 2.33 (95% CI 1.40-3.90, p = 0.001), respectively. CONCLUSION Longer time to recovery is associated with an increased risk of MAKE in patients with cirrhosis and AKI. Further research should examine interventions to shorten AKI-recovery time and its impact on subsequent outcomes.
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Affiliation(s)
- Kavish R. Patidar
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Mobasshir A. Naved
- Department of Computer Science, Purdue University, West Lafayette, Indiana, USA
| | - Shaowli Kabir
- College of Public Health, University of Kentucky, Lexington, Kentucky, USA
| | - Ananth Grama
- Department of Computer Science, Purdue University, West Lafayette, Indiana, USA
| | - Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Giuseppe Cullaro
- Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | | | - Astin Worden
- Division of Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Archita P. Desai
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Marwan S. Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Lauren D. Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Eric S. Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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22
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Abstract
The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.
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Affiliation(s)
- Florence Wong
- Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada,Corresponding author : Florence Wong Division of Gastroenterology and Hepatology, Toronto General Hospital, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto Ontario M5G2C4, Canada Tel: +1-416-3403834, Fax: +1-416-3405019, E-mail:
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23
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Abstract
AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.
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Affiliation(s)
- Giuseppe Cullaro
- Department of Medicine, University of California, San Francisco, California
| | - Swetha Rani Kanduri
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, The University of Queensland, Brisbane, Queensland, Australia
| | - Juan Carlos Q. Velez
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, The University of Queensland, Brisbane, Queensland, Australia
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24
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Abstract
Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Catalonia, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain
| | - Ann T Ma
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Catalonia, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Catalonia, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain.,Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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25
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Campion D, Rizzi F, Bonetto S, Giovo I, Roma M, Saracco GM, Alessandria C. Assessment of glomerular filtration rate in patients with cirrhosis: Available tools and perspectives. Liver Int 2022; 42:2360-2376. [PMID: 35182100 DOI: 10.1111/liv.15198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 11/08/2021] [Accepted: 12/09/2021] [Indexed: 12/07/2022]
Abstract
Renal dysfunction often complicates the course of liver disease, resulting in higher morbidity and mortality. The accurate assessment of kidney function in these patients is essential to early identify, stage and treat renal impairment as well as to better predict the prognosis, prioritize the patients for liver transplantation and decide whether to opt for simultaneous liver-kidney transplants. This review analyses the available tools for direct or indirect assessment of glomerular filtration rate, focusing on the flaws and strengths of each method in the specific setting of cirrhosis. The aim is to deliver a clear-cut view on this complex issue, trying to point out which strategies to prefer in this context, especially in the peculiar setting of liver transplantation. Moreover, a glance is given at future promising tools for glomerular filtration rate assessment, including new biomarkers and new equations specifically modelled for the cirrhotic population.
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Affiliation(s)
- Daniela Campion
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Felice Rizzi
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Silvia Bonetto
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Ilaria Giovo
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Michele Roma
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Giorgio M Saracco
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Carlo Alessandria
- Department of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
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26
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Schulte B, Tergast TL, Griemsmann M, Menti D, Deveci N, Kahlhöfer J, Dörge P, Hüffner L, Kraft ARM, Behrendt P, Wedemeyer H, Cornberg M, Stichtenoth DO, Maasoumy B. Metamizole-Associated Risks in Decompensated Hepatic Cirrhosis. DEUTSCHES ARZTEBLATT INTERNATIONAL 2022; 119:687-693. [PMID: 35912424 PMCID: PMC9830680 DOI: 10.3238/arztebl.m2022.0280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 01/11/2022] [Accepted: 07/04/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Because of the increased risk of acute renal failure (ARF), the use of cyclooxygenase (COX) inhibitors is not recommended in patients with decompensated hepatic cirrhosis. Metamizole is not a classic COX inhibitor, but there are insufficient data to support its safe use. In this study, we investigate the effect of metamizole on the risk of ARF in these patients. METHODS Metamizole use, ARF incidence, and patient mortality were examined in a large, retrospective, exploratory cohort and validated with data from a prospective registry. RESULTS 523 patients were evaluated in the exploratory cohort. Metamizole use at baseline was documented in 110 cases (21%) and was independently associated with the development of ARF, severe (grade 3) ARF, and lower survival without liver transplantation at follow-up on day 28 (HR: 2.2, p < 0.001; HR: 2.8, p < 0.001; and HR: 2.6, p < 0.001, respectively). Interestingly, the risk of ARF depended on the dose of metamizole administered (HR: 1.038, p < 0.001). Compared to patients who were treated with opioids, the rate of ARF was higher in the metamizole group (49% vs. 79%, p = 0.014). An increased risk of ARF with metamizole use was also demonstrated in the independent validation cohort (p < 0.001). CONCLUSION Metamizole therapy, especially at high doses, should only be used with a high level of caution in patients with decompensated cirrhosis.
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Affiliation(s)
| | - Tammo L. Tergast
- * Joint first authors,Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School
| | - Marie Griemsmann
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School
| | - Denise Menti
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School,Center for Individualized Infection Medicine (CiiM), Hannover
| | - Neslihan Deveci
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School
| | - Julia Kahlhöfer
- German Center for Infection Research (DZIF), German Liver Foundation, HepNet, Hannover
| | - Petra Dörge
- German Center for Infection Research (DZIF), German Liver Foundation, HepNet, Hannover
| | - Lucas Hüffner
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School,Twincore, Center for Experimental and Clinical Infection Research, Hannover
| | - Anke R. M. Kraft
- * Joint first authors,German Center for Infection Research (DZIF), Hannover-Braunschweig
| | - Patrick Behrendt
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School,German Center for Infection Research (DZIF), Hannover-Braunschweig
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School,German Center for Infection Research (DZIF), Hannover-Braunschweig
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School,Center for Individualized Infection Medicine (CiiM), Hannover,Twincore, Center for Experimental and Clinical Infection Research, Hannover,German Center for Infection Research (DZIF), Hannover-Braunschweig
| | | | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School,German Center for Infection Research (DZIF), Hannover-Braunschweig,*Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover Carl-Neuberg-Str. 1, 30625 Hannover, Germany
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27
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Patidar KR, Naved MA, Grama A, Adibuzzaman M, Aziz Ali A, Slaven JE, Desai AP, Ghabril MS, Nephew L, Chalasani N, Orman ES. Acute kidney disease is common and associated with poor outcomes in patients with cirrhosis and acute kidney injury. J Hepatol 2022; 77:108-115. [PMID: 35217065 DOI: 10.1016/j.jhep.2022.02.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS Acute kidney disease (AKD) is the persistence of acute kidney injury (AKI) for up to 3 months, which is proposed to be the time-window where critical interventions can be initiated to alter downstream outcomes of AKI. In cirrhosis, AKD and its impact on outcomes have been scantly investigated. We aimed to define the incidence and outcomes associated with AKD in a nationwide US cohort of hospitalized patients with cirrhosis and AKI. METHODS Hospitalized patients with cirrhosis and AKI in the Cerner-Health-Facts database from 1/2009-09/2017 (n = 6,250) were assessed for AKD and were followed-up for 180 days. AKI and AKD were defined based on KDIGO and ADQI AKD and renal recovery consensus criteria, respectively. The primary outcome measure was mortality, and the secondary outcome measure was de novo chronic kidney disease (CKD). Competing-risk multivariable models were used to determine the independent association of AKD with primary and secondary outcomes. RESULTS AKD developed in 32% of our cohort. On multivariable competing-risk analysis adjusting for significant confounders, patients with AKD had higher risk of mortality at 90 (subdistribution hazard ratio [sHR] 1.37; 95% CI 1.14-1.66; p = 0.001) and 180 (sHR 1.37; 95% CI 1.14-1.64; p = 0.001) days. The incidence of de novo CKD was 37.5%: patients with AKD had higher rates of de novo CKD (64.0%) compared to patients without AKD (30.7%; p <0.001). After adjusting for confounders, AKD was independently associated with de novo CKD (sHR 2.52; 95% CI 2.01-3.15; p <0.001) on multivariable competing-risk analysis. CONCLUSIONS AKD develops in 1 in 3 hospitalized patients with cirrhosis and AKI and it is associated with worse survival and de novo CKD. Interventions that target AKD may improve outcomes of patients with cirrhosis and AKI. LAY SUMMARY In a nationwide US cohort of hospitalized patients with cirrhosis and acute kidney injury, acute kidney disease developed in 1 in 3 patients and was associated with worse survival and chronic kidney disease. Interventions that target acute kidney disease may improve outcomes of patients with cirrhosis and acute kidney injury.
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Affiliation(s)
- Kavish R Patidar
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA.
| | - Mobasshir A Naved
- Department of Computer Science, Purdue University, West Lafayette, IN USA
| | - Ananth Grama
- Department of Computer Science, Purdue University, West Lafayette, IN USA
| | - Mohammad Adibuzzaman
- Department of Medical Informatics and Clinical Epidemiology, Oregon Health Sciences University, OR USA
| | - Arzina Aziz Ali
- Division of Internal Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - James E Slaven
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis IN, USA
| | - Archita P Desai
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Marwan S Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Lauren Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
| | - Eric S Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis IN, USA
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Schleicher EM, Kremer WM, Kalampoka V, Gairing SJ, Kaps L, Schattenberg JM, Galle PR, Wörns MA, Nagel M, Weinmann-Menke J, Labenz C. Frailty as Tested by the Clinical Frailty Scale Is a Risk Factor for Hepatorenal Syndrome in Patients With Liver Cirrhosis. Clin Transl Gastroenterol 2022; 13:e00512. [PMID: 35905416 PMCID: PMC10476772 DOI: 10.14309/ctg.0000000000000512] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Frailty is common in patients with cirrhosis and increases the vulnerability to internal and external stressors. This study aimed to investigate the impact of frailty, as defined by the Clinical Frailty Scale (CFS), on the risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS-AKI) in hospitalized patients with liver cirrhosis. METHODS We analyzed data of 201 nonelectively hospitalized patients with cirrhosis and without higher-grade chronic kidney disease. Patient characteristics were captured within the first 24 hours of hospital admission, and frailty was assessed using the CFS. Patients were followed for the development of AKI and/or HRS-AKI during the hospital stay. RESULTS In the total cohort, median CFS was 3 (interquartile range 3-4), and 34 (16.9%) patients were frail (CFS >4). During the hospital stay, 110 (54.7%) and 49 (24.3%) patients developed AKI or HRS-AKI, respectively. Patients with AKI or HRS-AKI had a significantly higher CFS than patients without kidney injury (P < 0.001 each). In multivariable analyses, a higher CFS was independently associated with the development of AKI (odds ratio [OR] 1.467, 95% confidence interval (CI) 1.065-2.021) in the total cohort and HRS-AKI (OR 1.809, 95% CI 1.263-2.591) in the subcohort of patients with a history of ascites. In addition, there was a strong association between frailty (OR 3.717, 95% CI 1.456-9.491) and HRS-AKI. DISCUSSION Frailty in patients with cirrhosis is associated with AKI and HRS-AKI. In this context, CFS appears to be a reliable tool to identify patients at high risk for developing AKI or HRS-AKI on hospital admission.
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Affiliation(s)
- Eva Maria Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Wolfgang Maximilian Kremer
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Vasiliki Kalampoka
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Leonard Kaps
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Jörn M. Schattenberg
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Metabolic Liver Research Program, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
| | - Marcus-Alexander Wörns
- Department of Gastroenterology, Hematology, Oncology and Endocrinology, Klinikum Dortmund, Germany;
| | - Michael Nagel
- Department of Gastroenterology, Hematology, Oncology and Endocrinology, Klinikum Dortmund, Germany;
| | - Julia Weinmann-Menke
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;
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Clinical Value of Prognostic Nutritional Index and Neutrophil-to-Lymphocyte Ratio in Prediction of the Development of Sepsis-Induced Kidney Injury. DISEASE MARKERS 2022; 2022:1449758. [PMID: 35711566 PMCID: PMC9197608 DOI: 10.1155/2022/1449758] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/17/2022] [Accepted: 05/25/2022] [Indexed: 11/27/2022]
Abstract
Background Sepsis-related acute kidney injury (S-AKI) is a frequent complication of hospitalized patients and is linked to increased morbidity and mortality. Early prediction and detection remain conducive to optimizing treatment strategies and limiting further insults. This study was aimed at evaluating the potential predictive value of the combined prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) to predict the risk of AKI in septic patients. Methods In this retrospective study, 1238 adult patients with sepsis who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to June 2021 were enrolled. Patients were divided into two groups: the non-AKI group (n = 731) and the S-AKI group (n = 507). Univariate and multivariate logistic regression analyses were performed to screen the independent predictive factors of S-AKI. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of PNI and NLR. Results Multivariate logistic regression analysis indicated that age, chronic liver disease, cardiovascular disease, respiratory rate (RR), white blood cells (WBC), blood urea nitrogen (BUN), creatinine (CRE), international normalized ratio (INR), neutrophil-to-lymphocyte ratio (NLR), and prognostic nutrition index (PNI) were independent prognostic factors of S-AKI. In the three models, the adjusted OR of PNI for S-AKI was 0.802 (0.776-0.829), 0.801 (0.775-0.829), and 0.717 (0.666-0.772), while that of NLR was 1.094 (1.078-1.111), 1.097 (1.080-1.114), and 1.044 (1.016-1.072), respectively. In addition, the area under the ROC curve of the PNI plus NLR group was significantly greater than that of the CRE plus BUN group (0.801, 95% CI: 0.775-0.827 vs. 0.750, 95% CI: 0.722-0.778, respectively; P < 0.001). Conclusions PNI and NLR have been identified as readily available and independent predictors in septic patients with S-AKI. PNI, in combination with NLR, is of vital significance for early warning and efficient intervention of S-AKI and is superior to combined BUN and CRE.
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Yu Y, Xie S, Wang K, Zhang F, Jiang C, Qiu C, Zhu J, Shen W. Perfusion Analysis of Kidney Injury in Rats With Cirrhosis Induced by Common Bile Duct Ligation Using Arterial Spin Labeling MRI. J Magn Reson Imaging 2022; 55:1393-1404. [PMID: 34499757 DOI: 10.1002/jmri.27917] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/26/2021] [Accepted: 08/27/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Arterial spin labeling (ASL) has been proven to be effective in ischemia-induced acute kidney injury (AKI); however, validation of ASL magnetic resonance imaging (MRI) is limited in AKI in the presence of cirrhosis. PURPOSE To investigate the feasibility of ASL in revealing renal blood flow (RBF) changes in kidney injury in the presence of cirrhosis and to assess its value in the early diagnosis of disease. STUDY TYPE Longitudinal. ANIMAL MODEL Rats were randomized into baseline group (N = 3), sham surgery group (N = 18), and common bile duct ligation (BDL) group (N = 48). All groups were divided into six subgroups based on different sacrificed time points. FIELD STRENGTH/SEQUENCE 3 T scanner, prototypic pulsed ASL sequence using flow-sensitive alternating inversion recovery preparation, half-Fourier acquisition single-shot turbo spin echo sequence. ASSESSMENT RBF measurement was performed by ASL. Hematoxylin-eosin (HE) score, Hypoxia-inducible factor-1alpha (HIF-1α) score, peritubular capillar (PTC) density, alanine aminotransferase, aspartate aminotransferase, serum total bilirubin, total bile acids, serum creatinine (Scr), and blood urea nitrogen (BUN) were harvested. STATISTICAL TESTS Analysis of variance, Pearson's correlation coefficient, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS RBF, HE score, HIF-1α score, and PTC density after BDL were significantly different from baseline. RBF was highly correlated with HE score, HIF-1α score, and PTC density (r = -0.7598, r = -0.7434, r = 0.6406, respectively). RBF and Scr began to differ significantly from baseline at day 3 and 7 after intervention, respectively. The areas under the curves of RBF, Scr, and BUN for distinguishing non-AKI from AKI in cirrhosis were 1.00, 0.888, and 0.911, while those for distinguishing mild from severe kidney injury were 0.961, 0.830, and 0.857, respectively. DATA CONCLUSION ASL allows the longitudinal assessment of the degree of AKI induced by cholestatic cirrhosis in rats and can serve as a noninvasive marker for the early and accurate diagnosis of AKI. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Yongquan Yu
- Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China
- Department of Radiology, Weihai Central Hospital, Shandong, China
| | - Shuangshuang Xie
- Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Kaiqi Wang
- School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, China
| | - Fuzhi Zhang
- Department of Pathology, Rushan People's Hospital, Shandong, China
| | - Chao Jiang
- Department of Public Health, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, China
| | - Caixin Qiu
- Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Jinxia Zhu
- MR Collaboration, Siemens Healthcare Ltd, Beijing, China
| | - Wen Shen
- Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
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Ma AT, Juanola A, Solà E. Assessment of kidney function in cirrhosis: Are we moving closer to accurate estimation of glomerular filtration rate? Liver Int 2022; 42:957-959. [PMID: 35447007 DOI: 10.1111/liv.15238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 02/12/2022] [Accepted: 03/05/2022] [Indexed: 02/13/2023]
Affiliation(s)
- Ann T Ma
- Liver Unit, Hospital Clínic Barcelona. School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.,Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Ciber de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Adrià Juanola
- Liver Unit, Hospital Clínic Barcelona. School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.,Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Ciber de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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Jung CY, Kim HW, Ahn SH, Kim SU, Kim BS. Higher risk of kidney function decline with entecavir than tenofovir alafenamide in patients with chronic hepatitis B. Liver Int 2022; 42:1017-1026. [PMID: 35220649 DOI: 10.1111/liv.15208] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 01/03/2022] [Accepted: 02/16/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS Entecavir (ETV) and tenofovir alafenamide (TAF) are the preferred agents in patients with predisposing factors for nephrotoxicity, but no studies to date have directly compared the renal safety of the two antiviral agents. Hence, we compared the risk of kidney function decline among patients with treatment-naïve chronic hepatitis B (CHB) treated with ETV or TAF. METHODS This study included 1988 patients with treatment-naïve CHB who were treated with ETV (n = 1839) or TAF (n = 149) between 2007 and 2020 for ETV and between 2017 and 2020 for TAF. The primary outcome was chronic kidney disease (CKD) progression, defined as an increase in CKD stage by at least one stage for at least three consecutive months. RESULTS A 1:1 propensity score match yielded 149 patients in each treatment group. The mean estimated glomerular filtration rate (eGFR) was 100.6 ml/min/1.73 m2 vs. 101.3 ml/min/1.73 m2 in the ETV and TAF groups respectively. A total of 61 patients developed a progression in CKD stage ≥ 1, of which 47 and 14 patients were from the ETV- and TAF-treated groups respectively (19.9 vs. 5.1 per 1000 person-years; p < .001). The risk of progression in CKD stage ≥1 was significantly higher in patients treated with ETV, even when adjusted for potential confounders (adjusted hazard ratio 4.05; 95% CI 2.14-7.68; p < .001). CONCLUSIONS ETV was associated with a higher risk of kidney function decline than TAF in patients with treatment-naïve CHB. Therefore, further prospective randomized studies are needed.
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Affiliation(s)
- Chan-Young Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Seok Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Cullaro G, Verna EC, Duarte‐Rojo A, Kappus MR, Ganger DR, Rahimi RS, Boyarsky B, Segev DL, McAdams‐DeMarco M, Ladner DP, Volk ML, Hsu C, Lai JC. Frailty and the Risk of Acute Kidney Injury Among Patients With Cirrhosis. Hepatol Commun 2022; 6:910-919. [PMID: 34676697 PMCID: PMC8948591 DOI: 10.1002/hep4.1840] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/10/2021] [Accepted: 09/05/2021] [Indexed: 12/16/2022] Open
Abstract
Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 . Our primary outcome, AKI, was defined as an increase in serum creatinine ≥0.3 mg/dL or a serum creatinine ≥1.5-fold increase. Wait-list mortality was defined as either a death on the wait list or removal for being too sick. We performed Cox regression analyses to estimate the hazard ratios (HRs) for AKI and wait-list mortality. Of 1,033 participants, 41% were frail and 23% had CKD. Twenty-one percent had an episode of AKI during follow-up. Frail versus nonfrail patients were more likely to develop AKI (25% vs. 19%) and wait-list mortality (21% vs. 13%) (P < 0.01 for each). In multivariable Cox regression, each of the following groups was associated with a higher risk of AKI as compared with not frail/no CKD: frail/no CKD (adjusted HR [aHR] = 1.87, 95% confidence interval [CI] = 1.29-2.72); not frail/CKD (aHR = 4.30, CI = 2.88-6.42); and frail/CKD (aHR = 4.85, CI = 3.33-7.07). We use a readily available metric, LFI, to identify those patients with cirrhosis most at risk for AKI. We highlight that serum creatinine and creatinine-based estimations of glomerular filtration rate may not fully capture a patient's vulnerability to AKI among the frail phenotype. Conclusion: Our work lays the foundation for implementing physical frailty in clinical practice to identify AKI earlier, implement reno-protective strategies, and expedite liver transplantation.
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Affiliation(s)
- Giuseppe Cullaro
- Department of MedicineUniversity of California‐San FranciscoSan FranciscoCAUSA
| | - Elizabeth C. Verna
- Center for Liver Disease and TransplantationColumbia UniversityVagelos College of Physicians and SurgeonsNew YorkNYUSA
| | - Andres Duarte‐Rojo
- Center for Liver DiseasesThomas A. Starzl Transplantation Institute, and Pittsburgh Liver Research CenterUniversity of PittsburghPittsburghPAUSA
| | - Matthew R. Kappus
- Division of GastroenterologyDepartment of MedicineDuke University School of MedicineDurhamNCUSA
| | - Daniel R. Ganger
- Division of Gastroenterology and HepatologyDepartment of MedicineNorthwestern MedicineChicagoILUSA
| | - Robert S. Rahimi
- Annette C. and Harold C. Simmons Transplant InstituteBaylor University Medical CenterBaylor Scott and WhiteDallasTXUSA
| | - Brian Boyarsky
- Department of SurgeryJohns Hopkins School of MedicineBaltimoreMDUSA
| | - Dorry L. Segev
- Department of SurgeryJohns Hopkins School of MedicineBaltimoreMDUSA
| | - Mara McAdams‐DeMarco
- Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreMDUSA
| | - Daniela P. Ladner
- Division of TransplantationDepartment of SurgeryNorthwestern MedicineChicagoILUSA
- Comprehensive Transplant CenterFeinberg School of MedicineNorthwestern UniversityChicagoILUSA
| | - Michael L. Volk
- Division of Gastroenterology & Hepatology, and Transplantation InstituteLoma Linda University HealthLoma LindaCAUSA
| | - Chi‐yuan Hsu
- Division of NephrologyDepartment of MedicineUniversity of CaliforniaSan FranciscoCAUSA
| | - Jennifer C. Lai
- Department of MedicineUniversity of California‐San FranciscoSan FranciscoCAUSA
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Pacheco MP, Carneiro-D'Albuquerque LA, Mazo DF. Current aspects of renal dysfunction after liver transplantation. World J Hepatol 2022; 14:45-61. [PMID: 35126839 PMCID: PMC8790396 DOI: 10.4254/wjh.v14.i1.45] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 10/24/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.
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Affiliation(s)
- Mariana P Pacheco
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Sao Paulo, Brazil
| | - Luiz Augusto Carneiro-D'Albuquerque
- Division of Digestive Organs Transplant, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Sao Paulo, Brazil
| | - Daniel F Mazo
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Sao Paulo, Brazil
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences of University of Campinas, Campinas 13083-878, Sao Paulo, Brazil
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Gong J, Lu H. Regulator 1-Peroxisome Proliferator-Activated Receptor- γ Coactivator-1 α Signaling Pathway in Investigating the Pathological Characteristics and Molecular Mechanism of Liver Cirrhosis Complicated by Acute Kidney Injury. J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.2859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The objective of this study was to investigate the molecular mechanism of the histopathological characteristics of liver cirrhosis (LC) complicated with acute kidney injury (AKI) and the signaling pathway of silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-γ
coactivator 1α (PGC-1α) during the pathogenesis of LC. 20 healthy male rats with AKI complicated by laparoscopic cholecystectomy were selected and divided randomly into control group (C group), lipopolysaccharide (LPS) group, bile duct ligation (BDL) group, and model
group (lipopolysaccharide+BDL) (D group). The indexes of all the rats were determined, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), sarcoplasmic enzyme (Scr), and blood urea nitrogen (BUN); the SIRT1 and PGC-1α expressions in renal tissues
of rats from each group was detected. Results showed that the AST and ALT levels in BDL group and D group were higher markedly than those before surgery (P < 0.05). The serum levels of Scr and BUN in D group 4 hours after LPS injection increased hugely compared with before injection
(P < 0.05). Compared with BDL group, the protein levels of SIRT1 and PGC-1α in renal tissue of group D were decreased sharply (P < 0.05), and the SIRT1 protein expression was positively correlated with PGC-1α (r = 0.836 and P < 0.01).
When LC were complicated with AKI, SIRT1 activity was reduced and PGC-1α expression was inhibited. Moreover, SIRT1-PGC-1α signaling pathway played a protective role in pathogenesis of LC complicated with AKI.
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Affiliation(s)
- Jieqi Gong
- Department of General Surgery, Qingpu Branch, Zhongshan Hospital, Fudan University, Qingpu District, Shanghai 201700, China
| | - Huanhua Lu
- Department of General Surgery, Qingpu Branch, Zhongshan Hospital, Fudan University, Qingpu District, Shanghai 201700, China
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36
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Duan Y, Li Z, Wang X, Cui L, Gao Z, Zhang H. Risk Factors and Prognosis of New-Onset Chronic Kidney Disease Following Orthotopic Liver Transplantation: A Retrospective Case-Control Study. Med Sci Monit 2021; 27:e931834. [PMID: 34537807 PMCID: PMC8459623 DOI: 10.12659/msm.931834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 06/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND We have undertaken this investigation to explore the perioperative risk factors of new-onset chronic kidney disease (NOCKD) after orthotopic liver transplantation (OLT), and to provide an early prediction model for the screening of NOCKD high-risk populations. MATERIAL AND METHODS A retrospective case-control study was performed in adult recipients who received OLT in our center between January 2018 and January 2020. Perioperative data were collected using the center's electronic medical record system. Logistics regression analysis was used to determine risk factors for NOCKD within 1 year following OLT. Kaplan-Meier and log-rank tests were used to evaluate the 1-year survival of recipients with NOCKD or without NOCKD. RESULTS A total of 174 patients were included in this study, and 29 patients developed NOCKD after OLT. Logistic multivariate regression analysis showed that preoperative diabetes, high model for end-stage liver disease (MELD) score, postoperative acute kidney injury (AKI), and postoperative renal replacement therapy (RRT) were independent risk factors for NOCKD 1 year after OLT. The 1-year survival rate of NOCKD recipients waas significantly lower than that of patients who did not receive NOCKD. CONCLUSIONS Diabetes mellitus, MELD score, postoperative AKI, and requirement for postoperative RRT are independent risk factors for NOCKD after OLT, which may have great potential for personalized decision making and predicting the 1-year postoperative mortality of the recipient.
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Affiliation(s)
- Yi Duan
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China
| | - Zuozhi Li
- Special Care Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China
| | - Xiaoyu Wang
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China
| | - Lei Cui
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China
| | - Zhifeng Gao
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China
| | - Huan Zhang
- Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, PR China
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Pyne JD, Brickman AM. The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline. NEURODEGENER DIS 2021; 21:1-23. [PMID: 34348321 PMCID: PMC8678181 DOI: 10.1159/000518581] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/19/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19), the far-reaching pandemic, has infected approximately 185 million of the world's population to date. After infection, certain groups, including older adults, men, and people of color, are more likely to have adverse medical outcomes. COVID-19 can affect multiple organ systems, even among asymptomatic/mild severity individuals, with progressively worse damage for those with higher severity infections. SUMMARY The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily attaches to cells through the angiotensin-converting enzyme 2 (ACE2) receptor, a universal receptor present in most major organ systems. As SARS-CoV-2 binds to the ACE2 receptor, its bioavailability becomes limited, thus disrupting homeostatic organ function and inducing an injury cascade. Organ damage can then arise from multiple sources including direct cellular infection, overactive detrimental systemic immune response, and ischemia/hypoxia through thromboembolisms or disruption of perfusion. In the brain, SARS-CoV-2 has neuroinvasive and neurotropic characteristics with acute and chronic neurovirulent potential. In the cardiovascular system, COVID-19 can induce myocardial and systemic vascular damage along with thrombosis. Other organ systems such as the lungs, kidney, and liver are all at risk for infection damage. Key Messages: Our hypothesis is that each injury consequence has the independent potential to contribute to long-term cognitive deficits with the possibility of progressing to or worsening pre-existing dementia. Already, reports from recovered COVID-19 patients indicate that cognitive alterations and long-term symptoms are prevalent. This critical review highlights the injury pathways possible through SARS-CoV-2 infection that have the potential to increase and contribute to cognitive impairment and dementia.
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Affiliation(s)
- Jeffrey D. Pyne
- Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
| | - Adam M. Brickman
- Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
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Cheng JH, Yip CW, Jiang YK, Zhou LH, Que CX, Luo Y, Wang X, Zhao HZ, Zhu LP. Clinical Predictors Impacting Cryptococcal Dissemination and Poor Outcome in Patients With Cirrhosis. Open Forum Infect Dis 2021; 8:ofab296. [PMID: 34250196 PMCID: PMC8266647 DOI: 10.1093/ofid/ofab296] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 06/04/2021] [Indexed: 01/03/2023] Open
Abstract
Background Cirrhosis is an end-stage liver disease and is reported as an independent risk factor for cryptococcosis. Information about cryptococcosis in patients with cirrhosis remains sparse. Methods Human immunodeficiency virus–uninfected patients with cryptococcosis and cirrhosis admitted to Huashan Hospital from July 2005 to June 2020 were reviewed. Efficacy and safety of antifungal treatments, clinical outcome, and prognostic factors of mortality were evaluated. Results A total of 49 cryptococcosis patients with cirrhosis were included. Sites of infection involved central nervous system (n = 38), lung (n = 21), bloodstream (n = 11), skin (n = 1), and bone (n = 1). Nine patients (18.4%) had pulmonary cryptococcosis alone. Viral hepatitis B infection (57.1%) was the most common cause of cirrhosis. Patients with decompensated cirrhosis (Child-Pugh class B and C) were more likely to have extrapulmonary cryptococcosis than those with compensated cirrhosis (90.7% vs 64.7%; P = .049). In patients with cryptococcal meningitis (CM), 7 were treated with amphotericin B with/without flucytosine, 5 with amphotericin B plus fluconazole with/without flucytosine, and 12 with fluconazole with/without flucytosine. Fluconazole (>400 mg/day) was well tolerated and only 1 patient had a mild adverse drug reaction. At 1-year follow-up, all patients treated with fluconazole with or without flucytosine survived, whereas the mortality rate was 14.3%–20.0% in the remaining groups. In addition, Child-Pugh class C cirrhosis (hazard ratio [HR], 7.555 [95% confidence interval {CI}, 1.393–40.971]) and time to diagnosis >120 days (HR, 18.619 [95% CI, 2.117–163.745]) were independent factors for 1-year mortality in patients with CM. Conclusions Severity of cirrhosis was associated with developing extrapulmonary cryptococcosis and mortality in CM. Early diagnosis and intervention of cryptococcosis are key for outcome.
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Affiliation(s)
- Jia-Hui Cheng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Ching-Wan Yip
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Ying-Kui Jiang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Ling-Hong Zhou
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Chun-Xing Que
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yu Luo
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xuan Wang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Hua-Zhen Zhao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Li-Ping Zhu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China
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Piano S, Gambino C, Vettore E, Calvino V, Tonon M, Boccagni P, Gringeri E, Germani G, Burra P, Cillo U, Angeli P. Response to Terlipressin and Albumin Is Associated With Improved Liver Transplant Outcomes in Patients With Hepatorenal Syndrome. Hepatology 2021; 73:1909-1919. [PMID: 32870499 DOI: 10.1002/hep.31529] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 07/27/2020] [Accepted: 08/07/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Although terlipressin and albumin are effective at treating acute kidney injury-hepatorenal syndrome (AKI-HRS), liver transplantation (LT) is the best treatment. However, it is unclear if an effective treatment with terlipressin and albumin improves post-LT outcomes in these patients. The aim of this study was to evaluate the impact of response to treatment with terlipressin and albumin on posttransplant outcomes in patients with AKI-HRS. APPROACH AND RESULTS We analyzed two cohorts of patients with cirrhosis listed for LT between 2012 and 2016: 82 patients who developed AKI-HRS before LT and were treated with terlipressin and albumin and 259 patients without AKI-HRS who received transplants during the study period (control group). After LT, patients were followed up until discharge, every month for the first 3 months, and every 3 months thereafter. Of the patients, 43 (52%) responded to terlipressin and albumin. Responders had a better 30-day transplant-free survival (60% vs. 33%, P = 0.006), longer LT waiting list time (37 vs. 17 days, P = 0.041), and lower Model for End-Stage Liver Disease score at the time of LT (23 vs. 29, P = 0.007). Among patients with AKI-HRS receiving transplant, nonresponders required renal replacement therapy (RRT) more frequently than responders (20% vs. 0%, P = 0.024). Nonresponders had a significantly higher incidence of chronic kidney disease (CKD) at 1 year after LT than responders (65% vs. 31%, P = 0.019). In multivariate analysis, nonresponse to terlipressin and albumin was found to be an independent predictor for CKD at 1 year after LT (subdistribution hazard ratio [SHR] = 2.76, P = 0.001), whereas responders did not have an increased risk (SHR = 1.53, P = 0.210). CONCLUSIONS In patients with AKI-HRS, response to terlipressin and albumin reduces the need for RRT after LT and reduces the risk of CKD at 1 year after LT.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Carmine Gambino
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Elia Vettore
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Valeria Calvino
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Patrizia Boccagni
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
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Juanola A, Solé C, Toapanta D, Ginès P, Solà E. Monitoring Renal Function and Therapy of Hepatorenal Syndrome Patients with Cirrhosis. Clin Liver Dis 2021; 25:441-460. [PMID: 33838860 DOI: 10.1016/j.cld.2021.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis. Patients with cirrhosis can develop AKI due to different causes. Hepatorenal syndrome (HRS) is a unique cause of AKI occurring in patients with advanced cirrhosis and is associated with high short-term mortality. The differential diagnosis between different causes of AKI may be challenging. In this regard, new urine biomarkers may be helpful. Liver transplantation is the definitive treatment of patients with HRS-AKI. Vasoconstrictors and albumin represent the first-line pharmacologic treatment of HRS-AKI. This review summarizes current knowledge for the diagnosis and management of HRS in cirrhosis.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain
| | - Cristina Solé
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - David Toapanta
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain.
| | - Elsa Solà
- Liver Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases. Stem Cell Res Ther 2021; 12:219. [PMID: 33789750 PMCID: PMC8011150 DOI: 10.1186/s13287-021-02289-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 03/15/2021] [Indexed: 12/14/2022] Open
Abstract
Kidney diseases pose a threat to human health due to their rising incidence and fatality rate. In preclinical and clinical studies, it has been acknowledged that mesenchymal stem cells (MSCs) are effective and safe when used to treat kidney diseases. MSCs play their role mainly by secreting trophic factors and delivering extracellular vesicles (EVs). The genetic materials and proteins contained in the MSC-derived EVs (MSC-EVs), as an important means of cellular communication, have become a research focus for targeted therapy of kidney diseases. At present, MSC-EVs have shown evident therapeutic effects on acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), and atherosclerotic renovascular disease (ARVD); however, their roles in the transplanted kidney remain controversial. This review summarises the mechanisms by which MSC-EVs treat these diseases in animal models and proposes certain problems, expecting to facilitate corresponding future clinical practice.
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Kumar R, Priyadarshi RN, Anand U. Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol 2021; 27:990-1005. [PMID: 33776368 PMCID: PMC7985728 DOI: 10.3748/wjg.v27.i11.990] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/17/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) in patients with liver cirrhosis has become a new frontier in hepatology. In recent years, a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis. The rising prevalence of risk factors, such as diabetes, hypertension and nonalcoholic fatty liver disease, appears to have contributed significantly to the high prevalence of CKD. Moreover, the diagnosis of CKD in cirrhosis is now based on a reduction in the estimated glomerular filtration rate of < 60 mL/min over more than 3 mo. This definition has resulted in a better differentiation of CKD from acute kidney injury (AKI), leading to its greater recognition. It has also been noted that a significant proportion of AKI transforms into CKD in patients with decompensated cirrhosis. CKD in cirrhosis can be structural CKD due to kidney injury or functional CKD secondary to circulatory and neurohormonal imbalances. The available literature on combined cirrhosis-CKD is extremely limited, as most attempts to assess renal dysfunction in cirrhosis have so far concentrated on AKI. Due to problems related to glomerular filtration rate estimation in cirrhosis, the absence of reliable biomarkers of CKD and technical difficulties in performing renal biopsy in advanced cirrhosis, CKD in cirrhosis can present many challenges for clinicians. With combined hepatorenal dysfunctions, fluid mobilization becomes problematic, and there may be difficulties with drug tolerance, hemodialysis and decision-making regarding the need for liver vs simultaneous liver and kidney transplantation. This paper offers a thorough overview of the increasingly known CKD in patients with cirrhosis, with clinical consequences and difficulties occurring in the diagnosis and treatment of such patients.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Rajeev Nayan Priyadarshi
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Tonon M, Rosi S, Gambino CG, Piano S, Calvino V, Romano A, Martini A, Pontisso P, Angeli P. Natural history of acute kidney disease in patients with cirrhosis. J Hepatol 2021; 74:578-583. [PMID: 32918956 DOI: 10.1016/j.jhep.2020.08.037] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 08/24/2020] [Accepted: 08/26/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS In 2012, the KDIGO group proposed new definitions for acute kidney injury (AKI), acute kidney disease (AKD) and chronic kidney disease (CKD). According to the definition adapted by the International Club of Ascites, AKI has been extensively investigated in patients with cirrhosis. On the contrary, there are currently no data on the epidemiology and clinical outcomes associated with AKD. The aim of the study was to assess the prevalence and the impact of AKD on the clinical course and survival of patients with cirrhosis. METHODS A total of 272 consecutive patients with cirrhosis attending our outpatient clinic were included in the study. Clinical and laboratory data were collected at inclusion. Patients were followed-up until death, liver transplant or the end of follow-up. RESULTS During follow-up, 80 patients developed AKD (29.4%). Forty-two (52.5%) recovered from the first episode of AKD and 26 maintained a normal renal function up to the end of follow-up. Sixteen patients developed a second episode of AKD. Globally, 36 patients (45.0%) died with AKD. Finally, AKD progressed to CKD in 11 patients (13.8%). The 5-year survival rate was significantly lower in patients who developed AKD than in those who did not (34.8% vs. 88.8%, p <0.001). The 5-year rates of complications of cirrhosis and of hospitalizations were also higher in patients with AKD than in those without AKD. CONCLUSIONS AKD is frequent in patients with cirrhosis. It can be reversible, but it may recur and progress to CKD. AKD has a very negative impact on morbidity and mortality in patients with cirrhosis. LAY SUMMARY Renal impairment has a very negative impact on patients with cirrhosis. Renal impairment seems to be characterized by a very dynamic course, which is defined according to renal function and length of the impairment as acute kidney injury, acute kidney disease and chronic kidney disease. The role of acute kidney disease is currently unknown. Our study shows for the first time that acute kidney disease is frequent in patients with cirrhosis and has a very negative impact on survival.
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Affiliation(s)
- Marta Tonon
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Silvia Rosi
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Carmine Gabriele Gambino
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Valeria Calvino
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Antonietta Romano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Andrea Martini
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Patrizia Pontisso
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, University of Padova, Padova, Italy.
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Niewiński G, Smyk W, Graczyńska A, Kostrzewa K, Raszeja-Wyszomirska J, Ołdakowska-Jedynak U, Małyszko J, Wójcicki M, Zieniewicz K. Kidney Function After Liver Transplantation in a Single Center. Ann Transplant 2021; 26:e926928. [PMID: 33619240 PMCID: PMC7911851 DOI: 10.12659/aot.926928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Renal dysfunction in the peri-transplant period appears to complicate both short- and long-term outcome of liver transplantation (LT). The aim of this study was to analyze the impact of selected clinical features in the peri-liver transplant period, as well calcineurin inhibitor, particularly tacrolimus given after LT, on kidney function in a single liver transplant center’s experience. Material/Methods A total 125 consecutive liver-grafted individuals (82 M, 43 F), mean age 50±13 y (with alcohol-related liver disease in 48 (38%) patients) were included into the study. Their clinical data were collected in the database until 46 months of follow-up, and the Python packages Pandas (version 0.22.0) and scikit-learn (version 0.21.3) were used for data analysis. Results More advanced liver disease as judged by Child-Pugh class and MELD score differed significantly patients with preserved (serum creatinine SCr <1.5 mg/dL) and impaired (SCr ≥1.5 mg/dL) kidney function before LT. Older age and higher SCr pre-LT were associated with higher levels of SCr after LT in 2 time-points. SCr before LT was correlated with delta SCr for the highest and last recorded value (P<0.0001). Higher amounts of transfused colloids during surgery were associated with increased delta SCr for the highest value (P=0.019) after grafting in logistic regression analysis. There were no associations between SCr after LT and duration of anhepatic phase, urine output ≤100 mL/h, or post-reperfusion syndrome during transplantation (all P>0.05). There were no associations between SCr after LT and tacrolimus trough levels in analyses of correlations and linear regression analyses (all P>0.05). Conclusions We found that pretransplant serum creatinine was the only factor affecting kidney function after LT in our liver transplant center. The restricted fluid policy was safe and effective in terms of long-term renal function. The role of kidney-saving immunosuppressive protocols in preserving renal function long-term after LT was also confirmed.
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Affiliation(s)
- Grzegorz Niewiński
- II Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | - Wiktor Smyk
- Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
| | - Agata Graczyńska
- II Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | | | | | | | - Jolanta Małyszko
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Maciej Wójcicki
- Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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Maiwall R, Pasupuleti SSR, Jain P, Sarin SK. Degree of Portal and Systemic Hemodynamic Alterations Predict Recurrent AKI and Chronic Kidney Disease in Patients With Cirrhosis. Hepatol Commun 2021; 5:293-308. [PMID: 33553976 PMCID: PMC7850308 DOI: 10.1002/hep4.1607] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 08/23/2020] [Indexed: 02/04/2023] Open
Abstract
The relevance of hemodynamic derangements on the incidence of recurrent acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with cirrhosis is largely unknown. Consecutive patients with cirrhosis with a complete record of baseline hemodynamics were followed for identifying risk factors for the development of recurrent AKI and CKD by using negative binomial regression and competing risk analysis, respectively. Consecutive patients with cirrhosis (n = 2013, age 50.1 ± 11.8 years, 80% male, Child A:B:C percentage 13.7:52.9:33.4, and mean Child-Turcotte-Pugh score 8.6 ± 1.8) were enrolled, 893 (44.3%) of whom received beta-blockers, with 44.2% responders. Prior AKI was noted in 12.4% at enrollment. At a median follow-up of 379 (interquartile range: 68-869) days, AKI developed at a rate of 0.37 episodes per person-year, and 26% patients developed CKD. A lower mean number of AKI episodes (0.05 ± 0.25 vs. 0.42 ± 0.868; P < 0.001), CKD (subdistribution hazard ratio 0.74 [0.54-1.02]), and mortality (hazard ratio 0.21 [0.06-0.73]) were observed in beta-blocker responders. Albuminuria was an independent risk factor for recurrent AKI, CKD, and mortality (P < 0.05). Lower systemic vascular resistance index predicted hemodynamic response (odds ratio 2.04 [1.29-3.22]), cumulative AKI episodes (ratio of means 0.10 [0.08-0.14]), and development of CKD (subdistribution hazard ratio 0.70 [0.58-0.83]). Higher hepatic venous pressure gradient (≥17 mm Hg) predicted AKI episodes (ratio of means 1.76 [1.32-2.35]) but not CKD. Conclusion: High portal pressure and severe vasodilatation predispose patients with cirrhosis to repeated AKI episodes and development of CKD. Response to beta-blockers and therapies targeting the vasodilatory state could prevent frequent AKI and the risk of CKD development. Albuminuria could serve as an early marker of renal dysfunction in patients with cirrhosis.
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Affiliation(s)
- Rakhi Maiwall
- Department of HepatologyInstitute of Liver and Biliary sciencesNew DelhiIndia
| | | | - Priyanka Jain
- Department of BiostatisticsInstitute of Liver and Biliary SciencesNew DelhiIndia
| | - Shiv Kumar Sarin
- Department of HepatologyInstitute of Liver and Biliary sciencesNew DelhiIndia
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Chou YT, Liu TT, Yang UC, Huang CC, Liu CW, Huang SF, Li TH, Liu HM, Lin MW, Yang YY, Lee TY, Huang YH, Hou MC, Lin HC. Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice. Int J Mol Sci 2021; 22:ijms22031233. [PMID: 33513830 PMCID: PMC7865325 DOI: 10.3390/ijms22031233] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 12/14/2022] Open
Abstract
In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction. Systemic and renal hemodynamics, intestinal dysbiosis [cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis], and direct renal vasoconstrictive response (renal vascular resistance (RVR) and glomerular filtration rate (GFR)) to cumulative doses of TNFα were measured in bile duct ligated (BDL)-cirrhotic ascitic mice. In SIRT1IEC-KO-BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation/barrier dysfunction, the upregulation of the expressions of intestinal/renal TNFα-related pathogenic signals, higher TNFα-induced increase in RVR, and decrease in GFR in perfused kidney. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Particularly, the negative correlations were identified between CDR and RVR, with the positive correlation between CDR and GFR. In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between intestinal dysbiosis and vasoconstriction/hypoperfusion-related renal dysfunction through the crosstalk between intestinal/renal TNFα-related pathogenic inflammatory signals.
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Affiliation(s)
- Yu-Te Chou
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
| | - Tze-Tze Liu
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Genomic Research Center, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan
| | - Ueng-Cheng Yang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Biomedical Informatics, Taipei 11267, Taiwan
| | - Chia-Chang Huang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Clinical Skills Training Center, Department of Medical Education, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
| | - Chih-Wei Liu
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
| | - Shiang-Fen Huang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Infection, Taipei Veterans General Hospital, Taipei 11267, Taiwan
| | - Tzu-Hao Li
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11267, Taiwan
| | - Hsuan-Miao Liu
- Graduate Institute of Traditional Chinese Medicine, Chang Guang Memorial Hospital, Linkou 33371, Taiwan; (H.-M.L.); (T.-Y.L.)
| | - Ming-Wei Lin
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Public Health, National Yang-Ming University, Taipei 11267, Taiwan
| | - Ying-Ying Yang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Clinical Skills Training Center, Department of Medical Education, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11267, Taiwan
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei 11267, Taiwan
- Correspondence: (Y.-Y.Y.); (H.-C.L.); Tel.: +886-2-2875-7725 (Y.-Y.Y.); +886-2-2875-2249 (H.-C.L.); Fax: +886-2-2875-7726 (Y.-Y.Y.); +886-2-2875-7809 (H.-C.L.)
| | - Tzung-Yan Lee
- Graduate Institute of Traditional Chinese Medicine, Chang Guang Memorial Hospital, Linkou 33371, Taiwan; (H.-M.L.); (T.-Y.L.)
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Institute of Public Health, National Yang-Ming University, Taipei 11267, Taiwan
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei 11267, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei 11267, Taiwan; (Y.-T.C.); (C.-W.L.); (Y.-H.H.); (M.-C.H.)
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
| | - Han-Chieh Lin
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11267, Taiwan; (T.-T.L.); (U.-C.Y.); (C.-C.H.); (S.-F.H.); (T.-H.L.); (M.-W.L.)
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei 11267, Taiwan
- Correspondence: (Y.-Y.Y.); (H.-C.L.); Tel.: +886-2-2875-7725 (Y.-Y.Y.); +886-2-2875-2249 (H.-C.L.); Fax: +886-2-2875-7726 (Y.-Y.Y.); +886-2-2875-7809 (H.-C.L.)
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Hiramine Y, Uto H, Mawatari S, Kanmura S, Imamura Y, Hiwaki T, Saishoji A, Oku M, Tokushige K, Maenohara S, Ido A. Impact of acute kidney injury on prognosis and the effect of tolvaptan in patients with hepatic ascites. J Gastroenterol 2021; 56:54-66. [PMID: 32959093 DOI: 10.1007/s00535-020-01727-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 09/07/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND In hepatic cirrhosis, ascites and acute kidney injury (AKI) portend poor prognosis. We examined the incidence and characteristics of AKI in patients with hepatic ascites and the impact of diuretics on AKI onset. METHODS This study included 337 patients with hepatic ascites treated with oral diuretics during September 2013-June 2019. Incidence of AKI, cumulative survival by AKI status, and prognostic factors were investigated. Patients were divided into those treated with tolvaptan (TLV) [TLV group (n = 244)] and those not treated with TLV [control group (n = 93)]. After propensity score matching, the incidence of AKI and changes in renal function and doses of diuretics were compared. RESULTS The incidence of AKI overall was 35% (n = 118). Patients with AKI had a significantly worse survival than those without AKI (P = 0.001), indicating that AKI is an independent prognostic factor for hepatic ascites (P = 0.025). After adjustment for background factors in the two groups (n = 77 each), the TLV group had a significantly lower incidence of AKI (27.6% vs. 44.7%, P = 0.028). While renal function worsened with higher natriuretic agent doses in the control group, no significant change was observed in the TLV group, suggesting that TLV is an independent prognostic factor for AKI onset. CONCLUSIONS Our study suggests that concomitant AKI significantly worsens survival in Japanese patients with hepatic ascites, and TLV and natriuretic agent combination therapy might lead to an excellent synergistic therapeutic effect of hepatic ascites and inhibition of AKI onset.
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Affiliation(s)
- Yasunari Hiramine
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan.
| | - Hirofumi Uto
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, 2-16 Takamatsu-cho, Miyazaki, 880-0003, Japan.,Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Yasushi Imamura
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan
| | - Takuya Hiwaki
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan
| | - Akiko Saishoji
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan.,Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Manei Oku
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.,Department of Nephrology, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan
| | - Koichi Tokushige
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan
| | - Shigeho Maenohara
- Department of Surgery, Kagoshima Kouseiren Hospital, 1-13-1 Yojiro, Kagoshima, 890-0062, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study. J Hepatol 2020; 73:1092-1099. [PMID: 32387698 PMCID: PMC7994029 DOI: 10.1016/j.jhep.2020.04.043] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/09/2020] [Accepted: 04/27/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. METHODS Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. RESULTS In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. CONCLUSIONS The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge. LAY SUMMARY Sudden damage to the kidneys is becoming more common in people who are hospitalized and have cirrhosis. Despite advances in cirrhosis care, those with damage to the kidneys remain at higher risk of dying.
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50
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Wong RJ, Cheung RC. Chronic Kidney Disease in Patients with Chronic Liver Disease: What Is the Price Tag? Hepatol Commun 2020; 4:1389-1391. [PMID: 33024910 PMCID: PMC7527759 DOI: 10.1002/hep4.1583] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology Veterans Affairs Palo Alto Health Care System Palo Alto CA
- Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology Veterans Affairs Palo Alto Health Care System Palo Alto CA
- Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA
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