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1
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Gabrielli F, Bernasconi E, Toscano A, Avossa A, Cavicchioli A, Andreone P, Gitto S. Side Effects of Immunosuppressant Drugs After Liver Transplant. Pharmaceuticals (Basel) 2025; 18:342. [PMID: 40143120 PMCID: PMC11946649 DOI: 10.3390/ph18030342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/18/2025] [Accepted: 02/26/2025] [Indexed: 03/28/2025] Open
Abstract
Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal immunosuppression and minimal side effects is a cornerstone of the post-LT period. Today, there are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring, and immunosuppression regimens vary from center to center and from country to country. Currently, there are many drugs with different efficacy and safety profiles. Using different agents permits a decrease in the dosage and minimizes the toxicities. A small subset of recipients achieves immunotolerance with the chance to stop immunosuppressive therapy. This article focuses on the side effects of immunosuppressive drugs, which significantly impact long-term outcomes for LT recipients. The primary aim is to highlight the balance between achieving effective immunosuppression and minimizing adverse effects, emphasizing the role of personalized therapeutic strategies. Moreover, this review evaluates the mechanisms of action and specific complications associated with immunosuppressive agents. Finally, special attention is given to strategies for reducing immunosuppressive burdens, improving patient quality of life, and identifying immunotolerant individuals.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Elisa Bernasconi
- Postgraduate School of Internal Medicine, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Arianna Toscano
- Division of Internal Medicine, University Hospital of Policlinico G. Martino, 98124 Messina, Italy
| | - Alessandra Avossa
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Alessia Cavicchioli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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Naldi GDAR, Minari AB, Pereira TDM, Fossaluza V, Eugenio NW, Ferreira MA, Gregório GH, Nacif L, D Albuquerque LAC, di Lazzaro Filho R, Cançado ELR, Ono SK. CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus - a cohort study. THE PHARMACOGENOMICS JOURNAL 2025; 25:4. [PMID: 39994182 DOI: 10.1038/s41397-025-00363-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/30/2025] [Accepted: 02/14/2025] [Indexed: 02/26/2025]
Abstract
Liver transplantation is the only curative option for patients with advanced stages of liver disease, with tacrolimus used as the immunosuppressive drug of choice. Genetic variability can interfere with drug response, potentially leading to overexposure or underexposure. This study aims to investigate the association of CYP3A4 (rs2740574, rs2242480, rs35599367), CYP3A5 (rs776746, rs10264272), POR (rs1057868) and ABCB1 (rs1128503, rs2229109, rs9282564) gene polymorphisms with infection, acute rejection, and renal failure. The logistic regression model found an influence of CYP3A5 (rs776746) and POR28 (rs1057868) on the development of acute rejection after liver transplantation (p = 0.028). It also found an association between carriers of the variant allele of the POR*28 gene and infection.
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Affiliation(s)
| | - Ariane Boccoli Minari
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Thales D M Pereira
- Institute of Mathematics and Statistics of the University of São Paulo, São Paulo, Brazil
| | - Victor Fossaluza
- Institute of Mathematics and Statistics of the University of São Paulo, São Paulo, Brazil
| | | | | | | | - Lucas Nacif
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | | | | | | | - Suzane Kioko Ono
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
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Tovikkai C, Sawetwanichakul J, Kositamongkol P, Mahawithitwong P, Dumronggittigule W, Sangserestid P, Assawasirisin C, Limsrichamrern S, Sirivatanauksorn Y. Incidence and Risk Factors Associated With Chronic Kidney Disease After Liver Transplantation: A Review of a 20-Year Experience at a Single Center. Transplant Proc 2024; 56:613-619. [PMID: 38388291 DOI: 10.1016/j.transproceed.2023.11.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 11/18/2023] [Indexed: 02/24/2024]
Abstract
BACKGROUND Chronic kidney disease (CKD) is one of the major complications after liver transplantation (LT), with a significant impact on patient outcomes. This study aims to investigate the incidence and risk factors of CKD in LT recipients at Siriraj Hospital over the past 20 years. METHODS There were 366 adult patients undergoing LT at Siriraj Hospital between January 2002 and December 2021. After excluding patients with pretransplant CKD stages 4 to 5, simultaneous liver-kidney transplantation, and patients who died after LT within 90 days, we retrospectively reviewed a total of 288 patients. Univariable and multivariable binary logistic regression analyses were used to identify the risk factors of post-transplant CKD. RESULTS Of the 288 patients, 171 (59.4%) developed CKD after LT. The median time to develop CKD was 5.8 months (IQR, 3.8-15.3). Univariable and multivariable analyses revealed that age ≥55 years (odds ratio [OR] = 2.44; 95% CI, 1.34-4.42; P = .003), pretransplant kidney dysfunction defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 (OR = 2.23; 95% CI, 1.16-4.27; P = .016), and postoperative acute kidney injury (OR = 3.06; 95% CI, 1.73-5.42; P < .001) were significantly associated with post-transplant CKD. Patients with preexisting kidney dysfunction who received delayed calcineurin inhibitor introduction without antibody induction protocol had a significantly lower incidence of post-transplant CKD (OR = 0.28; 95% CI, 0.11-0.70; P = .007). CONCLUSIONS Advanced age, pre-transplant kidney dysfunction, and postoperative acute kidney injury are risk factors for CKD after LT. Importantly, delayed calcineurin inhibitor introduction can protect patients with pretransplant kidney dysfunction from developing post-transplant CKD. These results may have important clinical implications in reducing the incidence of CKD after LT.
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Affiliation(s)
- Chutwichai Tovikkai
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Jirasawet Sawetwanichakul
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Prawat Kositamongkol
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Prawej Mahawithitwong
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Wethit Dumronggittigule
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pholasith Sangserestid
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Charnwit Assawasirisin
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Somchai Limsrichamrern
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Yongyut Sirivatanauksorn
- Hepato-Pancreato-Biliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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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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Stylemans D, Vandecruys M, Leunis S, Engelborghs S, Gargioli D, Monbaliu D, Cornelissen V, Van Craenenbroeck AH, De Smet S. Physical Exercise After Solid Organ Transplantation: A Cautionary Tale. Transpl Int 2024; 37:12448. [PMID: 38414660 PMCID: PMC10898592 DOI: 10.3389/ti.2024.12448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 02/02/2024] [Indexed: 02/29/2024]
Abstract
An increasing body of randomized controlled trials suggests the safety of engaging in moderate to vigorous intensity exercise training following solid organ transplantation. Fueled by emerging sport events designed for transplant recipients and the ever-growing body of research highlighting the diverse health benefits of physical activity, transplant recipients are now increasingly participating in strenuous and occasionally competitive physical endeavors that largely surpass those evaluated in controlled research settings. This viewpoint article adopts a cautionary stance to counterbalance the prevalent one-sided optimistic perspective regarding posttransplant physical activity. While discussing methodological limitations, we explore plausible adverse impacts on the cardiovascular, immunological, and musculoskeletal systems. We also examine the physiological consequences of exercising in the heat, at high altitude, and in areas with high air pollution. Risks associated with employing performance-enhancing strategies and the conceivable psychological implications regarding physical activity as a tribute to the 'gift of life' are discussed. With a deliberate focus on the potential adverse outcomes of strenuous posttransplant physical activity, this viewpoint aims to restore a balanced dialogue on our comprehension of both beneficial and potentially detrimental outcomes of physical activity that ultimately underscores the imperative of well-informed decision-making and tailored exercise regimens in the realm of posttransplant care.
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Affiliation(s)
- Dimitri Stylemans
- Department of Respiratory Diseases, Pulmonary Rehabilitation, University Hospitals Leuven, Leuven, Belgium
| | - Marieke Vandecruys
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Sofie Leunis
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Sofie Engelborghs
- Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium
| | - Davide Gargioli
- Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
- Transplantoux Foundation, Leuven, Belgium
| | - Véronique Cornelissen
- Research Group for Rehabilitation in Internal Disorders, Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium
| | - Amaryllis H. Van Craenenbroeck
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Stefan De Smet
- Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium
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Azpilicueta-Idarreta M, Prieto-Torre M, Montijano-Herrero L, Fernández-Ruiz L, Antón-Gamero M. Kidney injury associated with liver transplantation. An Pediatr (Barc) 2023; 99:232-239. [PMID: 37598081 DOI: 10.1016/j.anpede.2023.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 06/04/2023] [Indexed: 08/21/2023] Open
Abstract
INTRODUCTION Kidney injury associated with paediatric liver transplantation (LT) is common, but its evaluation is challenging. Our aim was to analyse the presence of perioperative acute kidney injury (AKI) and study the prevalence of chronic kidney disease (CKD) using different glomerular filtration rate (GFR) estimation formulas. METHODS We conducted a cross-sectional study in a cohort of children aged less than 18 years with a history of LT followed up for 5.42 years. We estimated the GFR using the creatinine-based Schwartz bedside formula (2009), the cystatin C-based Caucasian Asian Pediatric and Adult cohort (CAPA) equation and the combined Full-Age Spectrum (FAS) formula as modified by Pottel. We analysed the agreement between them using the Bland-Altman method and the kappa statistic. We measured the albumin level in urine, the urine volume adjusted to 100 mL of GFR and blood pressure. We performed univariate and multivariate analyses of the risk factors associated with CKD. RESULTS The sample included 52 patients with a median age of 9.21 years. Fifteen (28.8%) had AKI. Five (10%) had CKD and the only associated risk factor was acute liver failure at the time of LT (odds ratio, 8.57; P = 0.04). There was poor agreement between the different estimation formulas. One patient was classified as having CKD with the Schwartz formula compared to four patients with the CAPA and the Pottel combined FAS formulas. Up to 42% of children without CKD had some positive marker of kidney injury. CONCLUSIONS The exclusive use of the 2009 Schwartz bedside formula to estimate GFR may lead to underdiagnosis of CKD in children post LT. Other markers of kidney injury are common, and their detection may help prevent the progression of CKD.
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Affiliation(s)
| | - María Prieto-Torre
- Servicio de Gastroenterología, Hospital Universitario Reina Sofía, Córdoba, Spain
| | | | | | - Montserrat Antón-Gamero
- Unit de Nefrología Pediátrica, Hospital Universitario Reina Sofía, Córdoba, Spain; Universidad de Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
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7
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Caragata R, Emerson S, Santema ML, Selzner N, Sapisochin G, Wang S, Huszti E, Van Klei W, McCluskey SA. Intraoperative hypotension and the risk of acute kidney injury following liver transplantation. Clin Transplant 2023; 37:e15053. [PMID: 37350742 DOI: 10.1111/ctr.15053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 06/07/2023] [Accepted: 06/11/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) is a frequent adverse outcome following liver transplantation (LT) with a multifactorial etiology. It is critical to identify modifiable risk factors to mitigate the risk. One key area of interest is the role of intraoperative hypotension, which remains relatively unexplored in liver transplant cohorts. METHODS This was a retrospective observational cohort study of 1292 adult patients who underwent LT (between 2009 and 2019). Multivariable logistic regression analysis was used to explore the association between intraoperative hypotension, quantified by time duration (in min) under various mean arterial pressure (MAP) thresholds, and the primary outcome of early postoperative AKI according to the KDIGO criteria. RESULTS AKI occurred in 40% of patients and was independently associated with greater than 20 min spent below MAP thresholds of 55 mm Hg (adjusted OR = 1.866; 95% CI = 1.037-3.44; P = 0.041) and 50 mm Hg (adjusted OR = 1.801; 95% CI = 1.087-2.992; P = 0.023). Further sensitivity analyses demonstrated that the association between intraoperative hypotension and postoperative AKI was accentuated after restricting the analysis to patients with a normal preoperative renal function. CONCLUSIONS Prolonged (>20 min) intraoperative hypotension (below a MAP of 55 mm Hg) was independently associated with AKI following LT, after adjusting for several known confounders.
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Affiliation(s)
- Rebecca Caragata
- Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Anesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sophia Emerson
- Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Michael L Santema
- Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Stella Wang
- Biostatistics Research Unit, University Health Network, Toronto, Ontario, Canada
| | - Ella Huszti
- Biostatistics Research Unit, University Health Network, Toronto, Ontario, Canada
| | - Wilton Van Klei
- Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Anesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Departement of Anesthesiology, University of Utrecht, Utrecht, The Netherlands
| | - Stuart A McCluskey
- Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Anesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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8
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Odenwald MA, Roth HF, Reticker A, Segovia M, Pillai A. Evolving challenges with long-term care of liver transplant recipients. Clin Transplant 2023; 37:e15085. [PMID: 37545440 DOI: 10.1111/ctr.15085] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/08/2023]
Abstract
The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.
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Affiliation(s)
- Matthew A Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Hannah F Roth
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Anesia Reticker
- Department of Pharmacy, University of Chicago Medicine, Chicago, USA
| | - Maria Segovia
- Department of Medicine, Section of Gastroenterology, Duke University School of Medicine, Durham, USA
| | - Anjana Pillai
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
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Khan BA, Khalid A, Saeed Z, Ihsan-Ul-Haq, Khan MY, Rashid S, Naveed A, Dar FS. Exploring safety and efficacy of rivaroxaban after living donor liver transplantation: a retrospective study. Langenbecks Arch Surg 2023; 408:308. [PMID: 37578661 DOI: 10.1007/s00423-023-03042-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 08/02/2023] [Indexed: 08/15/2023]
Abstract
PURPOSE Thromboembolic complications remain a significant concern in postoperative patients, particularly those who have undergone liver transplantation. Warfarin has been the standard oral anticoagulant. Direct oral anticoagulants (DOACs) have several advantages over warfarin, including rapid onset of action and standardized dose guidelines. We aimed to assess the safety of rivaroxaban in living donor liver transplantation (LDLT) recipients. METHODS This study was a single-center, retrospective descriptive analysis of LDLT recipients who received rivaroxaban between December 2020 and April 2022. A total of 27 recipients received rivaroxaban postoperatively. Liver function tests, immunosuppression levels, serum creatinine, and INR were recorded before the initiation of rivaroxaban and then on post-therapy days 1, 7, 14, 28, 90, and 180. RESULTS Among the 27 recipients receiving rivaroxaban postoperatively, portal venous thrombosis was the most prevalent indication for anticoagulation (44.4%), followed by Budd-Chiari syndrome (29.6%). Nine patients had a twofold increase in either ALT or AST values, two of whom were treated for biliary strictures and the others for rejection. Eighteen patients were given tacrolimus, and eight were on cyclosporine, with one patient switched from tacrolimus to cyclosporine due to insufficient therapeutic levels. There were no incidents of bleeding or re-thrombosis during the 180-day follow-up period. CONCLUSION Rivaroxaban may be a safe and effective alternative in LDLT recipients with no significant adverse incidents. Further studies with larger sample sizes are needed to confirm these findings and determine this population's optimal dose and duration of rivaroxaban therapy.
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Affiliation(s)
- Bilal Ahmed Khan
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan.
| | - Abdullah Khalid
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan
| | - Zubair Saeed
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan
| | - Ihsan-Ul-Haq
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan
| | - Ammara Naveed
- Gastroenterology and Hepatology Department, PKLI&RC, Lahore, Pakistan
| | - Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery and Liver Transplant Unit, Pakistan Kidney & Liver Institute & Research Center (PKLI&RC), DHA Phase VI, Lahore, Pakistan
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10
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Huwyler F, Eden J, Binz J, Cunningham L, Sousa Da Silva RX, Clavien P, Dutkowski P, Tibbitt MW, Hefti M. A Spectrofluorometric Method for Real-Time Graft Assessment and Patient Monitoring. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2301537. [PMID: 37265001 PMCID: PMC10427358 DOI: 10.1002/advs.202301537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 05/03/2023] [Indexed: 06/03/2023]
Abstract
Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real-time measurements of fluorescent and non-fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real-time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post-transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real-time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery.
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Affiliation(s)
- Florian Huwyler
- Macromolecular Engineering Lab, Department of Mechanical and Process EngineeringETH ZurichZurich8092Switzerland
- Department of Surgery and Transplantation, Swiss Hepato‐Pancreato‐Biliary (HPB) and Transplant CenterUniversity Hospital ZurichZurich8091Switzerland
- Wyss Zurich Translational CenterETH Zurich and University of ZurichZurich8092Switzerland
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss Hepato‐Pancreato‐Biliary (HPB) and Transplant CenterUniversity Hospital ZurichZurich8091Switzerland
| | - Jonas Binz
- Macromolecular Engineering Lab, Department of Mechanical and Process EngineeringETH ZurichZurich8092Switzerland
| | - Leslie Cunningham
- Macromolecular Engineering Lab, Department of Mechanical and Process EngineeringETH ZurichZurich8092Switzerland
- Department of Surgery and Transplantation, Swiss Hepato‐Pancreato‐Biliary (HPB) and Transplant CenterUniversity Hospital ZurichZurich8091Switzerland
- Wyss Zurich Translational CenterETH Zurich and University of ZurichZurich8092Switzerland
| | - Richard X. Sousa Da Silva
- Department of Surgery and Transplantation, Swiss Hepato‐Pancreato‐Biliary (HPB) and Transplant CenterUniversity Hospital ZurichZurich8091Switzerland
- Wyss Zurich Translational CenterETH Zurich and University of ZurichZurich8092Switzerland
| | - Pierre‐Alain Clavien
- Department of Surgery and Transplantation, Swiss Hepato‐Pancreato‐Biliary (HPB) and Transplant CenterUniversity Hospital ZurichZurich8091Switzerland
- Wyss Zurich Translational CenterETH Zurich and University of ZurichZurich8092Switzerland
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss Hepato‐Pancreato‐Biliary (HPB) and Transplant CenterUniversity Hospital ZurichZurich8091Switzerland
| | - Mark W. Tibbitt
- Macromolecular Engineering Lab, Department of Mechanical and Process EngineeringETH ZurichZurich8092Switzerland
- Wyss Zurich Translational CenterETH Zurich and University of ZurichZurich8092Switzerland
| | - Max Hefti
- Wyss Zurich Translational CenterETH Zurich and University of ZurichZurich8092Switzerland
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11
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Velez JCQ, Wong F, Reddy KR, Sanyal AJ, Vargas HE, Curry MP, Gonzalez SA, Pappas SC, Jamil K. The Effect of Terlipressin on Renal Replacement Therapy in Patients with Hepatorenal Syndrome. KIDNEY360 2023; 4:1030-1038. [PMID: 37143199 PMCID: PMC10482068 DOI: 10.34067/kid.0000000000000132] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 03/21/2023] [Indexed: 05/06/2023]
Abstract
Key Points Hepatorenal syndrome type 1 (HRS-1) is an often fatal, but potentially reversible, kidney failure in patients with decompensated cirrhosis. Treatment with terlipressin in patients with HRS-1 is associated with a reduction in the need for RRT. Background Hepatorenal syndrome type 1 (HRS-1)—also known as hepatorenal syndrome-AKI (HRS-AKI)—is a rapidly progressing and usually fatal, but potentially reversible, kidney failure occurring in patients with decompensated cirrhosis. A large proportion of patients with HRS-1 require renal replacement therapy (RRT). Terlipressin demonstrated efficacy in reversing HRS and improving renal function in patients with HRS-1 in three phase III, randomized, clinical trials (RCTs; i.e. , OT-0401, REVERSE, and CONFIRM). However, these RCTs were not designed to evaluate the effect of terlipressin on the requirement of RRT. In this study, the effect of terlipressin on RRT requirements in the pooled phase III patient population was assessed. Methods For this retrospective analysis, data from patients who participated in the OT-0401, REVERSE, and CONFIRM studies were integrated in the largest-to-date randomized database (N =608). Results The need for RRT was significantly decreased in patients in the terlipressin group versus the placebo group by day 30 (28.1% versus 35.9%, respectively; P = 0.040) and day 60 (30.1% versus 37.9%, respectively; P = 0.045) in the pooled population and also postliver transplantation (LT) at day 60 (20.5% versus 40.3%, respectively; P = 0.008) and day 90 (25.3% versus 43.1%, respectively; P = 0.018). More patients were alive and RRT-free by day 90 in the overall population (36.9% versus 28.5%; P = 0.030) and among patients who received an LT (60.0% versus 39.7%; P = 0.010). Random assignment to receive terlipressin was an independent positive predictor of avoidance of RRT (P = 0.042); while higher baseline serum creatinine (sCr) level and Child-Pugh scores were negatively associated with RRT avoidance (P < 0.001 and P = 0.040, respectively). Conclusions Terlipressin decreased the requirement of RRT compared with placebo among patients with HRS-1, including those receiving LT. A lower sCr level at the beginning of therapy was associated with avoidance of RRT.
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Affiliation(s)
- Juan Carlos Q. Velez
- Department of Nephrology, Ochsner Health, New Orleans, Louisiana
- Ochsner Clinical School, The University of Queensland, Brisbane, Queensland, Australia
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Arun J. Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Hugo E. Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona
| | - Michael P. Curry
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Stevan A. Gonzalez
- Department of Medicine, Baylor Scott & White All Saints Medical Center, Fort Worth, Texas
| | | | - Khurram Jamil
- Mallinckrodt Pharmaceuticals, Bridgewater, New Jersey
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12
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Puri P. Renal Dysfunction After Liver Transplant: Is CNI Nephrotoxicity Overrated. J Clin Exp Hepatol 2023; 13:556-558. [PMID: 37440945 PMCID: PMC10333944 DOI: 10.1016/j.jceh.2023.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 05/12/2023] [Indexed: 07/15/2023] Open
Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi, 110025, India
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13
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Gonzalez SA, Farfan Ruiz AC, Ibrahim RM, Wadei HM. Essentials of Liver Transplantation in the Setting of Acute Kidney Injury and Chronic Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:356-367. [PMID: 37657882 DOI: 10.1053/j.akdh.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 06/06/2023] [Accepted: 06/26/2023] [Indexed: 09/03/2023]
Abstract
Kidney dysfunction is common among liver transplant candidates with decompensated cirrhosis and has a major impact on pre- and post-liver transplant survival. Updated definitions of acute kidney injury and criteria for the diagnosis of hepatorenal syndrome allow for early recognition and intervention, including early initiation of vasoconstrictor therapy for hepatorenal syndrome. The rise of the metabolic syndrome and nonalcoholic fatty liver disease as a cause of cirrhosis has coincided with an increase in intrinsic chronic kidney disease recognized in transplant candidates and recipients. Ultimately, the ability to accurately assess kidney function and associated risk is essential to decision-making in the context of transplantation, including selection of candidates for simultaneous liver and kidney transplantation.
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Affiliation(s)
- Stevan A Gonzalez
- Division of Hepatology, Annette C. and Harold C. Simmons Transplant Institute, Baylor Scott & White All Saints Medical Center Fort Worth and Baylor University Medical Center Dallas, TX; Department of Medicine, Burnett School of Medicine at TCU, Fort Worth, TX.
| | - Ana Cecilia Farfan Ruiz
- Division of Transplant Nephrology, Department of Transplant, Mayo Clinic College of Medicine and Science, Jacksonville, FL
| | - Ramez M Ibrahim
- Division of Transplant Nephrology, Department of Transplant, Mayo Clinic College of Medicine and Science, Jacksonville, FL
| | - Hani M Wadei
- Division of Transplant Nephrology, Department of Transplant, Mayo Clinic College of Medicine and Science, Jacksonville, FL
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14
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Ide R, Ohira M, Imaoka Y, Sato K, Kuroda S, Tahara H, Ide K, Kobayashi T, Ohdan H. Impact of Abdominal Aortic Calcification on Chronic Kidney Disease After Liver Transplantation: A Retrospective Study. Transplant Proc 2023; 55:956-960. [PMID: 37085382 DOI: 10.1016/j.transproceed.2023.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 03/13/2023] [Indexed: 04/23/2023]
Abstract
BACKGROUND With improved graft and patient survival after liver transplantation (LT), the onset of late complications, such as renal dysfunction, has become a problem. In this study, we aimed to investigate abdominal aortic calcification (AAC), a potential indicator of systemic atherosclerosis, and evaluate the relationship between preoperative AAC and postoperative chronic kidney disease (CKD), as the latter might be a long-term complication after LT. METHODS Among the 184 LTs performed at our center between 2008 and 2021, 110 LTs with normal renal function (estimated glomerular filtration rate [eGFR] 60 mL/min per 1.73 m2) before surgery were included. These were divided into high- (≥100 mm3) and low-AAC groups (<100 mm3) consisting of 51 and 59 patients, respectively. The AAC volume was automatically calculated for calcifications located in the abdominal aorta using the Agatston method. RESULTS The high-AAC group was older, consisted of more men, and had lower preoperative creatinine and eGFR levels. No significant difference in the onset of postoperative CKD was found between the 2 groups. However, the cumulative incidence of postoperative CKD was significantly higher in the high-AAC group compared with the low-AAC group. Multivariate analysis of postoperative CKD using the Cox proportional hazards model showed significant differences in preoperative AAC ≥100 mm3, recipient age ≥50 years, and preoperative eGFR <75 mL/min per 1.73 m2. CONCLUSIONS The development of postoperative CKD should be monitored in liver transplant recipients despite normal preoperative renal function. Our study suggests that preoperative AAC may influence postoperative renal dysfunction.
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Affiliation(s)
- Ryuta Ide
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
| | - Yuki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kouki Sato
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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15
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Stämmler F, Derain-Dubourg L, Lemoine S, Meeusen JW, Dasari S, Lieske JC, Robertson A, Schiffer E. Impact of race-independent equations on estimating glomerular filtration rate for the assessment of kidney dysfunction in liver disease. BMC Nephrol 2023; 24:83. [PMID: 37003973 PMCID: PMC10064726 DOI: 10.1186/s12882-023-03136-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 03/23/2023] [Indexed: 04/03/2023] Open
Abstract
BACKGROUND Altered hemodynamics in liver disease often results in overestimation of glomerular filtration rate (GFR) by creatinine-based GFR estimating (eGFR) equations. Recently, we have validated a novel eGFR equation based on serum myo-inositol, valine, and creatinine quantified by nuclear magnetic resonance spectroscopy in combination with cystatin C, age and sex (GFRNMR). We hypothesized that GFRNMR could improve chronic kidney disease (CKD) classification in the setting of liver disease. RESULTS We conducted a retrospective multicenter study in 205 patients with chronic liver disease (CLD), comparing the performance of GFRNMR to that of validated CKD-EPI eGFR equations, including eGFRcr (based on creatinine) and eGFRcr-cys (based on both creatinine and cystatin C), using measured GFR as reference standard. GFRNMR outperformed all other equations with a low overall median bias (-1 vs. -6 to 4 ml/min/1.73 m2 for the other equations; p < 0.05) and the lowest difference in bias between reduced and preserved liver function (-3 vs. -16 to -8 ml/min/1.73 m2 for other equations). Concordant classification by CKD stage was highest for GFRNMR (59% vs. 48% to 53%) and less biased in estimating CKD severity compared to the other equations. GFRNMR P30 accuracy (83%) was higher than that of eGFRcr (75%; p = 0.019) and comparable to that of eGFRcr-cys (86%; p = 0.578). CONCLUSIONS Addition of myo-inositol and valine to creatinine and cystatin C in GFRNMR further improved GFR estimation in CLD patients and accurately stratified liver disease patients into CKD stages.
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Affiliation(s)
- Frank Stämmler
- Department of Research and Development, Numares AG,, Am BioPark 9, 93053, Regensburg, Germany
| | - Laurence Derain-Dubourg
- Department Néphrologie, Dialyse, Hypertension Et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Université Claude Bernard, Lyon 1, Lyon, France
| | - Sandrine Lemoine
- Department Néphrologie, Dialyse, Hypertension Et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Université Claude Bernard, Lyon 1, Lyon, France
| | - Jeffrey W Meeusen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Surendra Dasari
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - John C Lieske
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Andrew Robertson
- Department of Research and Development, Numares AG,, Am BioPark 9, 93053, Regensburg, Germany
| | - Eric Schiffer
- Department of Research and Development, Numares AG,, Am BioPark 9, 93053, Regensburg, Germany.
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16
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Stewart E, Nydam TL, Hendrickse A, Pomposelli JJ, Pomfret EA, Moore HB. Viscoelastic Management of Coagulopathy during the Perioperative Period of Liver Transplantation. Semin Thromb Hemost 2023; 49:119-133. [PMID: 36318962 PMCID: PMC10366939 DOI: 10.1055/s-0042-1758058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Viscoelastic testing (VET) in liver transplantation (LT) has been used since its origin, in combination with standard laboratory testing (SLT). There are only a few, small, randomized controlled trials that demonstrated a reduction in transfusion rates using VET to guide coagulation management. Retrospective analyses contrasting VET to SLT have demonstrated mixed results, with a recent concern for overtreatment and the increase in postoperative thrombotic events. An oversight of many studies evaluating VET in LT is a single protocol that does not address the different phases of surgery, in addition to pre- and postoperative management. Furthermore, the coagulation spectrum of patients entering and exiting the operating room is diverse, as these patients can have varying anatomic and physiologic risk factors for thrombosis. A single transfusion strategy for all is short sighted. VET in combination with SLT creates the opportunity for personalized resuscitation in surgery which can address the many challenges in LT where patients are at a paradoxical risk for both life-threatening bleeding and clotting. With emerging data on the role of rebalanced coagulation in cirrhosis and hypercoagulability following LT, there are numerous potential roles in VET management of LT that have been unaddressed.
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Affiliation(s)
- Erin Stewart
- Department of Anesthesia, University of Colorado School of Medicine, Aurora, Colorado
| | - Trevor L. Nydam
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Adrian Hendrickse
- Department of Anesthesia, University of Colorado School of Medicine, Aurora, Colorado
| | - James J. Pomposelli
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Elizabeth A. Pomfret
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Hunter B. Moore
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
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17
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Liu JK, Vutien P, Huang DQ, Ishigami M, Landis CS, Nguyen MH. Renal Outcomes With Tenofovir Alafenamide in Liver Transplant Recipients. Clin Gastroenterol Hepatol 2023; 21:538-540.e4. [PMID: 35123081 PMCID: PMC9346095 DOI: 10.1016/j.cgh.2022.01.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/18/2021] [Accepted: 01/20/2022] [Indexed: 02/07/2023]
Abstract
Tenofovir disoproxil fumarate (TDF) is associated with a higher risk of nephrotoxicity compared with entecavir (ETV) or tenofovir alafenamide (TAF).1,2 One-fifth of transplant recipients develop chronic kidney disease (CKD) within 5 years after transplantation, contributed by the use of nephrotoxic immunosuppressive medications.3 Prior studies conducted in the nontransplant setting reported superior renal safety in TAF compared with TDF but data in liver transplant (LT) recipients have so far been limited to small case series.1,4-6 Therefore, the goals of this study were to examine changes in renal function in a large multicenter cohort of LT recipients with chronic hepatitis B who were treated with TAF, TDF, or ETV for the prevention of hepatitis B virus (HBV) reinfection or reactivation from receipt of a positive HBV core antibody graft.
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Affiliation(s)
| | - Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Masatoshi Ishigami
- Division of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Charles S Landis
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California.
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18
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Morales Junior R, Telles JP, Kwiatkowski SYC, Juodinis VD, de Souza DC, Santos SRCJ. Pharmacokinetic and pharmacodynamic considerations of antibiotics and antifungals in liver transplantation recipients. Liver Transpl 2023; 29:91-102. [PMID: 35643926 DOI: 10.1002/lt.26517] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/10/2022] [Accepted: 05/18/2022] [Indexed: 01/14/2023]
Abstract
The liver plays a major role in drug metabolism. Liver transplantation impacts the intrinsic metabolic capability and extrahepatic mechanisms of drug disposition and elimination. Different levels of inflammation and oxidative stress during transplantation, the process of liver regeneration, and the characteristics of the graft alter the amount of functional hepatocytes and activity of liver enzymes. Binding of drugs to plasma proteins is affected by the hyperbilirubinemia status and abnormal synthesis of albumin and alpha-1-acid glycoproteins. Postoperative intensive care complications such as biliary, circulatory, and cardiac also impact drug distribution. Renally eliminated antimicrobials commonly present reduced clearance due to hepatorenal syndrome and the use of nephrotoxic immunosuppressants. In addition, liver transplantation recipients are particularly susceptible to multidrug-resistant infections due to frequent manipulation, multiple hospitalizations, invasive devices, and frequent use of empiric broad-spectrum therapy. The selection of appropriate anti-infective therapy must consider the pathophysiological changes after transplantation that impact the pharmacokinetics and pharmacodynamics of antibiotics and antifungal drugs.
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Affiliation(s)
- Ronaldo Morales Junior
- Clinical Pharmacokinetics Center, School of Pharmaceutical Sciences , University of São Paulo , São Paulo , Brazil
- Pediatric Intensive Care Unit, Department of Pediatrics , Hospital Sírio-Libanês , São Paulo , Brazil
| | - João Paulo Telles
- Department of Infectious Diseases , AC Camargo Cancer Center , São Paulo , Brazil
| | | | - Vanessa D'Amaro Juodinis
- Pediatric Intensive Care Unit, Department of Pediatrics , Hospital Sírio-Libanês , São Paulo , Brazil
| | - Daniela Carla de Souza
- Pediatric Intensive Care Unit, Department of Pediatrics , Hospital Sírio-Libanês , São Paulo , Brazil
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19
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Peng B, Lu J, Guo H, Liu J, Li A. Regional citrate anticoagulation for replacement therapy in patients with liver failure: A systematic review and meta-analysis. Front Nutr 2023; 10:1031796. [PMID: 36875829 PMCID: PMC9977825 DOI: 10.3389/fnut.2023.1031796] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 01/09/2023] [Indexed: 02/18/2023] Open
Abstract
Background Citrate refers to an anticoagulant agent commonly used in extracorporeal organ support. Its application is limited in patients with liver failure (LF) due to the increased risk of citrate accumulation induced by liver metabolic dysfunction. This systematic review aims to assess the efficacy and safety of regional citrate anticoagulation in extracorporeal circulation for patients with liver failure. Methods PubMed, Web of Science, Embase, and Cochrane Library were searched. Studies regarding extracorporeal organ support therapy for LF were included to assess the efficacy and safety of regional citrate anticoagulation. Methodological quality of included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS). Meta-analysis was performed using R software (version 4.2.0). Results There were 19 eligible studies included, involving 1026 participants. Random-effect model showed an in-hospital mortality of 42.2% [95%CI (27.2, 57.9)] in LF patients receiving extracorporeal organ support. The during-treatment incidence of filter coagulation, citrate accumulation, and bleeding were 4.4% [95%CI (1.6-8.3)], 6.7% [95%CI (1.5-14.4)], and 5.0% [95%CI (1.9-9.3)], respectively. The total bilirubin(TBIL), alanine transaminase (ALT), aspartate transaminase(AST), serum creatinine(SCr), blood urea nitrogen(BUN), and lactate(LA) decreased, compared with those before the treatment, and the total calcium/ionized calcium ratio, platelet(PLT), activated partial thromboplastin time(APTT), serum potential of hydrogen(pH), buffer base(BB), and base excess(BE) increased. Conclusion Regional citrate anticoagulation might be effective and safe in LF extracorporeal organ support. Closely monitoring and timely adjusting during the process could reduce the risk for complications. More prospective clinical trials of considerable quality are needed to further support our findings. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022337767.
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Affiliation(s)
- Bo Peng
- Beijing Ditan Hospital, Capital Medical University, Beijing, China.,Beijing Fengtai Hospital, Beijing, China
| | - Jiaqi Lu
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hebing Guo
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jingyuan Liu
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ang Li
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
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20
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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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21
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Okumura K, Lee JS, Dhand A, Sogawa H, Veillette G, John D, Misawa R, Bodin R, Wolf DC, Diflo T, Nishida S. Trends and outcomes of liver transplantation among older recipients in the United States. World J Transplant 2022; 12:259-267. [PMID: 36159074 PMCID: PMC9453296 DOI: 10.5500/wjt.v12.i8.259] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/30/2022] [Accepted: 08/01/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited.
AIM To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States.
METHODS We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old).
RESULTS Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI.
CONCLUSION While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Joon Sub Lee
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Devon John
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Roxana Bodin
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - David C Wolf
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Thomas Diflo
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, United States
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22
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Kim DG, Hwang S, Kim JM, Ryu JH, You YK, Choi D, Kim BW, Kim DS, Nah YW, Kim TS, Cho JY, Hong G, Yang JD, Han J, Suh SW, Kim KW, Jung YK, Moon JI, Lee JY, Kim SH, Lee JG, Kim MS, Lee KW, Joo DJ. Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month. J Clin Med 2022; 11:4203. [PMID: 35887972 PMCID: PMC9315935 DOI: 10.3390/jcm11144203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/14/2022] [Accepted: 07/18/2022] [Indexed: 01/27/2023] Open
Abstract
Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06−3.53) and infection (HR = 1.44, 95% CI 1.12−1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients’ renal functional reserve.
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Affiliation(s)
- Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea; (D.-G.K.); (J.G.L.); (M.S.K.)
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea;
| | - Je Ho Ryu
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan 49241, Korea;
| | - Young Kyoung You
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Donglak Choi
- Department of Surgery, Catholic University of Daegu, Daegu 42472, Korea;
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon 16499, Korea;
| | - Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul 02841, Korea;
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea;
| | - Tae-Seok Kim
- Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu 42601, Korea;
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea;
| | - Geun Hong
- Department of Surgery, EWHA Womans University College of Medicine, Seoul 07804, Korea;
| | - Jae Do Yang
- Department of Surgery, Jeonbuk National University Hospital, Jeonju 54896, Korea;
| | - Jaryung Han
- Department of Surgery, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Suk-Won Suh
- Department of Surgery, College of Medicine, Chung-Ang University, Seoul 06974, Korea;
| | - Kwan Woo Kim
- Department of Surgery, Dong-A University Hospital, Busan 49201, Korea;
| | - Yun Kyung Jung
- Department of Surgery, Hanyang University, Seoul 04764, Korea;
| | - Ju Ik Moon
- Department of Surgery, Konyang University Hospital, Daejeon 35365, Korea;
| | - Jun Young Lee
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea;
| | - Sung Hwa Kim
- Department of Biostatistics, Yonsei University Wonju College of Medicine, Wonju 26426, Korea;
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea; (D.-G.K.); (J.G.L.); (M.S.K.)
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea; (D.-G.K.); (J.G.L.); (M.S.K.)
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul 03087, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea; (D.-G.K.); (J.G.L.); (M.S.K.)
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23
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Januszko-Giergielewicz B, Kobryń A, Donderski R, Trzcinska J, Theda-Pawelska J, Romaszko-Wojtowicz A, Shevchuk A, Słupski M. Hepatorenal Syndrome and Other Post-Liver Transplantation Complications: Case Studies and Literature Review. Transplant Proc 2022; 54:1029-1036. [PMID: 35760626 DOI: 10.1016/j.transproceed.2022.03.036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 03/05/2022] [Accepted: 03/14/2022] [Indexed: 01/09/2023]
Abstract
Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment.
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Affiliation(s)
- Beata Januszko-Giergielewicz
- Clinic of General, Liver and Transplant Surgery, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland.
| | - Andrzej Kobryń
- Clinic of General, Liver and Transplant Surgery, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland
| | - Rafał Donderski
- Department of Nephrology, Internal Diseases and Hypertention, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland
| | - Joanna Trzcinska
- Clinic of General, Liver and Transplant Surgery, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland
| | - Joanna Theda-Pawelska
- Clinic of General, Liver and Transplant Surgery, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland
| | - Anna Romaszko-Wojtowicz
- Department of Pulmonology, Faculty of Public Health, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Poland
| | - Andii Shevchuk
- Clinic of General, Liver and Transplant Surgery, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland
| | - Maciej Słupski
- Clinic of General, Liver and Transplant Surgery, University Hospital No 1 in Bydgoszcz named after Dr A. Jurasz, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland
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24
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Lee J, Lee JG, Hwang S, Lee KW, Kim JM, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Yu HC, Hong G, Choi D, Moon JI, Kim MS. Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study. Hepatol Int 2022; 16:537-544. [PMID: 35467324 DOI: 10.1007/s12072-022-10320-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 02/20/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation. METHODS This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1 month post-transplantation). Median duration of follow-up was 29 months (interquartile range 19-42). RESULTS A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; p = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Overall survival rate was significantly lower in patients with renal dysfunction than in those without. CONCLUSIONS In this nationwide study, the use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.
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Affiliation(s)
- Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Republic of Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong-Sik Kim
- Division of HBP Surgery & Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
| | - Koo Jeong Kang
- Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hee Chul Yu
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Geun Hong
- Department of Surgery, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Ju Ik Moon
- Department of Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
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25
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Minjares RO, Martin P, Carrion AF. Chronic Kidney Disease After Liver Transplantation. Clin Liver Dis 2022; 26:323-340. [PMID: 35487614 DOI: 10.1016/j.cld.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Improved survival after liver transplantation has led to an aging cohort of recipients at risk of renal dysfunction. The etiology of renal dysfunction is typically multifactorial; calcineurin inhibitors nephrotoxicity, pretransplant renal dysfunction, and perioperative acute kidney injury are important risk factors. Metabolic complications such as hypertension, diabetes mellitus, and metabolic-associated fatty liver disease also contribute to the development of renal disease. Most LT recipients will eventually develop some degree of renal dysfunction. Criteria to select candidates for simultaneous liver and kidney transplantation have been established. Both delayed introduction of CNIs and renal-sparing immunosuppressive regimens may reduce progression of renal dysfunction.
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Affiliation(s)
- Ramon O Minjares
- Department of Internal Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA.
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA
| | - Andres F Carrion
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA
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26
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Lee CY, Wu MY, Chan HC, Chen TT, Hsu LY, Wu MS, Cherng YG. The Influence of Diabetes Mellitus on the Risks of End-Stage Kidney Disease and Mortality After Liver Transplantation. Transpl Int 2022; 35:10023. [PMID: 35185375 PMCID: PMC8842258 DOI: 10.3389/ti.2022.10023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 01/10/2022] [Indexed: 11/18/2022]
Abstract
This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78–3.99) and 2.61 (95% CI, 1.63–4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72–1.55) and 1.28 (95% CI, 1.04–1.59) for PLTDM group and pre-existing DM group compared to those without DM group, respectively. The sensitivity analysis for the risk of ESKD and death also revealed the consistent result. Pre-existing DM has significant increase the risk of post-LT ESKD and mortality. The role of PLTDM should be explored to explain postoperative morbidity and mortality.
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Affiliation(s)
- Chung-Ying Lee
- Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Mei-Yi Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Hsiu-Chen Chan
- Department of Pharmacy, Shuang Ho Hospital, New Taipei City, Taiwan
| | - Tzu-Ting Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
| | - Le-Yin Hsu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yih-Giun Cherng
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- *Correspondence: Yih-Giun Cherng,
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27
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Wadei HM, Burcin Taner C, Keaveny AP, Mai ML, Hodge DO, White LJ, Harnois DM, Mao SA, Jarmi T, Croome KP. The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center. Ann Hepatol 2022; 24:100317. [PMID: 33545403 DOI: 10.1016/j.aohep.2021.100317] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/27/2020] [Accepted: 01/04/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.
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Affiliation(s)
- Hani M Wadei
- Department of Transplant, Mayo Clinic Florida, United States.
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, United States
| | | | - Martin L Mai
- Department of Transplant, Mayo Clinic Florida, United States
| | - David O Hodge
- Department of Health Sciences Research, Mayo Clinic Florida, United States
| | - Launia J White
- Department of Health Sciences Research, Mayo Clinic Florida, United States
| | - Denis M Harnois
- Department of Transplant, Mayo Clinic Florida, United States
| | - Shennen A Mao
- Department of Transplant, Mayo Clinic Florida, United States
| | - Tambi Jarmi
- Department of Transplant, Mayo Clinic Florida, United States
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28
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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: 6] [Impact Index Per Article: 2.0] [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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29
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Guo D, Wang H, Liu J, Liu H, Zhang M, Fu Z, Liu X. Prediction of chronic kidney disease after orthotopic liver transplantation: development and validation of a nomogram model. BMC Nephrol 2022; 23:33. [PMID: 35034618 PMCID: PMC8761273 DOI: 10.1186/s12882-021-02650-1] [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: 08/14/2021] [Accepted: 12/15/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT). METHODS The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed. RESULTS The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p < 0.001), preoperative hypertension (HR 1.670, 95% CI 0.962-2.898; p = 0.068), preoperative eGFR (HR 0.996, 95% CI 0.991-1.001; p = 0.143), uric acid at 3 months (HR 1.002, 95% CI 1.001-1.004; p = 0.028), haemoglobin at 3 months (HR 0.970, 95% CI 0.956-0.983; p < 0.001), and average concentration of cyclosporine A at 3 months (HR 1.002, 95% CI 1.001-1.003; p < 0.001). According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function. CONCLUSIONS With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.
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Affiliation(s)
- Dandan Guo
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China
| | - Huifang Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China
| | - Jun Liu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China
| | - Hang Liu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China
| | - Ming Zhang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China
| | - Zixuan Fu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China
| | - Xuemei Liu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China.
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Lim SY, Wang R, Tan DJH, Ng CH, Lim WH, Quek J, Syn N, Nah BKY, Wong ETY, Huang DQ, Vathsala A, Siddiqui MS, Fung J, Muthiah MD, Tan EXX. A meta-analysis of the cumulative incidence, risk factors, and clinical outcomes associated with chronic kidney disease after liver transplantation. Transpl Int 2021; 34:2524-2533. [PMID: 34714569 DOI: 10.1111/tri.14149] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/19/2021] [Accepted: 09/29/2021] [Indexed: 12/15/2022]
Abstract
Chronic kidney disease (CKD) remains a relatively common complication after liver transplantation (LT), and significantly impacts overall survival. We sought to assess the cumulative incidence, risk factors and mortality associated with post-LT CKD. CKD was defined as eGFR <60 ml/min/1.73 m2 as estimated by the Modified Diet in Renal Disease (MDRD) formula. Single-arm meta-analysis was done to evaluate the cumulative incidence of CKD at 1-, 3-, and 5-year timepoints post-LT. Risk factors for CKD were evaluated using hazard ratios (HR). Twenty-one studies involving 44 383 patients were included. Cumulative incidence of stage 3-5 CKD was 31.44% (CI 0.182-0.447), 36.71% (CI 0.188-0.546), and 43.52% (CI 0.296-0.574) at 1, 3, and 5 years after LT, respectively. Stage 5 CKD cumulative incidence increased from 0.274% (CI 0.001-0.005) at 1 year to 2.06% (CI 0.009-0.045) at 5 years post-LT. Age, female sex, diabetes, and peri-operative acute kidney injury (AKI) were significant risk factors for CKD. Stage 4-5 CKD was associated with a decrease in overall survival (HR 3.23, 95% CI 1.74-5.98, P < 0.01). CKD after LT is relatively common, and is associated with significantly reduced overall survival. Identification of patients at high risk of developing CKD allows physicians to prophylactically use renal-sparing immunosuppression which may be crucial in achieving desirable clinical outcomes.
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Affiliation(s)
- Sze Yinn Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Renaeta Wang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Benjamin Kai Yi Nah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Emmett Tsz-Yeung Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Anantharaman Vathsala
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, VA, USA
| | - James Fung
- Division of Gastroenterology and Hepatology, Department of Medicine, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Eunice Xiang-Xuan Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
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31
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Teo VXY, Heng RRY, Tay PWL, Ng CH, Tan DJH, Ong Y, Tan EY, Huang D, Vathsala A, Muthiah M, Tan EXX. A meta-analysis on the prevalence of chronic kidney disease in liver transplant candidates and its associated risk factors and outcomes. Transpl Int 2021; 34:2515-2523. [PMID: 34773291 DOI: 10.1111/tri.14158] [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] [Received: 06/07/2021] [Revised: 10/20/2021] [Accepted: 11/07/2021] [Indexed: 12/15/2022]
Abstract
Pre-liver transplant (LT) chronic kidney disease (CKD) has emerged as a leading cause of post-operative morbidity. We aimed to report the prevalence, associated risk factors, and clinical outcomes in patients with pre-LT CKD. Meta-analysis and systematic review were conducted for included cohort and cross-sectional studies. Studies comparing healthy and patients with s pre-LT CKD were included. Outcomes were assessed with pooled hazard ratios. 15 studies were included, consisting of 82,432 LT patients and 26,754 with pre-LT CKD. Pooled prevalence of pre-LT CKD was 22.35% (CI: 15.30%-32.71%). Diabetes mellitus, hypertension, viral hepatitis, and non-alcoholic fatty liver disease, and older age were associated with increased risk of pre-LT CKD: (OR 1.72 CI: 1.15-2.56, P = 0.01), (OR 2.23 CI: 1.76-2.83, P < 0.01), (OR 1.09; CI: 1.05-1.13, P < 0.01), (OR 1.73; CI: 1.10-2.71 P = 0.03), and (MD: 2.92 years; CI: 1.29-4.55years; P < 0.01) respectively. Pre-LT CKD was significantly associated with increased mortality (HR 1.38; CI: 1.2-1.59; P < 0.01), post-LT end-stage renal disease and post-LT CKD. Almost a quarter of pre-LT patients have CKD and it is significantly associated with post-operative morbidity and mortality. However, long-term outcomes remain unclear due to a lack of studies reporting such outcomes.
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Affiliation(s)
- Vanessa Xin Yi Teo
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Ryan Rui Yang Heng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Yuki Ong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - En Ying Tan
- Department of Medicine, National University Hospital, Singapore
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Anantharaman Vathsala
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Nephrology, Department of Medicine, National University Hospital, Singapore.,Kidney and Pancreas Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
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32
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Dong V, Nadim MK, Karvellas CJ. Post-Liver Transplant Acute Kidney Injury. Liver Transpl 2021; 27:1653-1664. [PMID: 33963666 DOI: 10.1002/lt.26094] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/19/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022]
Abstract
Acute kidney injury (AKI) is a common condition following liver transplantation (LT). It negatively impacts patient outcomes by increasing the chances of developing chronic kidney disease and reducing graft and patient survival rates. Multiple definitions of AKI have been proposed and used throughout the years, with the International Club of Ascites definition being the most widely now used for patients with cirrhosis. Multiple factors are associated with the development of post-LT AKI and can be categorized into pre-LT comorbidities, donor and recipient characteristics, operative factors, and post-LT factors. Many of these factors can be optimized in an attempt to minimize the risk of AKI occurring and to improve renal function if AKI is already present. A special consideration during the post-LT phase is needed for immunosuppression as certain immunosuppressive medications can be nephrotoxic. The calcineurin inhibitor tacrolimus (TAC) is the mainstay of immunosuppression but can result in AKI. Several strategies including use of the monoclonoal antibody basilixamab to allow for delayed initiation of tacrolimus therapy and minimization through combination and minimization or elimination of TAC through combination with mycophenolate mofetil or mammalian target of rapamycin inhibitors have been implemented to reverse and avoid AKI in the post-LT setting. Renal replacement therapy may ultimately be required to support patients until recovery of AKI after LT. Overall, by improving renal function in post-LT patients with AKI, outcomes can be improved.
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Affiliation(s)
- Victor Dong
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Alberta, Canada.,Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Mitra K Nadim
- Division of Nephrology and Hypertension, University of Southern California, Los Angeles, CA
| | - Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada.,Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
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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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34
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Bluhme E, Malenicka S, Fischler B, Nemeth A, Berg UB, Jorns C. Comparison of cystatin C, creatinine, and iohexol clearance in pediatric liver transplantation-a retrospective cohort study. Pediatr Transplant 2021; 25:e13993. [PMID: 34010490 DOI: 10.1111/petr.13993] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/10/2020] [Accepted: 02/06/2021] [Indexed: 12/01/2022]
Abstract
Impaired renal function after pediatric (LT) is a recognized problem. Accurate monitoring of (GFR) is imperative to detect declining renal function. GFR can be estimated via s-creatinine and/or p-cystatin C or measured by inulin and or/iohexol clearances. We retrospectively compared eGFRcrea and eGFRcyst, to mGFRiohex after LT. Data from 91 children with 312 concomitant measurements of s-creatinine, p-cystatin C, and iohexol clearance, obtained between 2007 and 2015, were analyzed. eGFR was calculated by using the p-cystatin C-based CAPA and CKD-EPI formulas, and the s-creatinine-based Schwartz-LYON, FAS, revised Schwartz and MDRD formulas. Also, the arithmetic means of cystatin C-based and creatinine-based equations were used. Every calculated eGFR was compared to mGFRiohex in statistical correlation, accuracy, precision, bias, and misclassifications. Among the different equations, p-cystatin C-based formulas (CAPA and CKD-EPI) as well as the s-creatinine-based Schwartz-LYON formula showed the most correct estimates regarding accuracy (84-87.5%), bias (0.19-4.0 ml/min/1.73 m2 ), and misclassification rate (24.7-25%). In patients with renal function <75 ml/min/1.73 m2 , cystatin C-based formulas were significantly more accurate and less biased than creatinine-based formulas. In conclusion, S-creatinine could be used in a clinical setting on a regular basis in liver transplanted pediatric patients, with reliable results, if eGFR is calculated by the Schwartz-LYON formula. When suspected renal dysfunction, cystatin C-based eGFR should be calculated, since it gives more accurate and less biased estimates than creatinine-based eGFR, and should be confirmed by mGFR (iohexol).
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Affiliation(s)
- Emil Bluhme
- Department of Transplantation Surgery, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Silvia Malenicka
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Bjorn Fischler
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Antal Nemeth
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Ulla B Berg
- Department of Pediatric Nephrology, Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Carl Jorns
- Department of Transplantation Surgery, Karolinska University Hospital Huddinge, CLINTEC, Karolinska Institutet, Stockholm, Sweden
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Vimalesvaran S, Souza LN, Deheragoda M, Samyn M, Day J, Verma A, Vilca-Melendez H, Rela M, Heaton N, Dhawan A. Outcomes of adults who received liver transplant as young children. EClinicalMedicine 2021; 38:100987. [PMID: 34505022 PMCID: PMC8413260 DOI: 10.1016/j.eclinm.2021.100987] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/06/2021] [Accepted: 06/10/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Patient and graft survival 20-years after pediatric liver transplantation (pLT) are excellent. In children, attainment of normal growth, education and social adaptation to be an independent adult are equally important. This is particularly relevant for children who receive liver transplant at a young age, where infantile-onset liver disease, surgery and immunosuppression can adversely affect growth and neurodevelopment. The aim of this study was to evaluate the long-term physical and psychosocial outcomes of pLT recipients with normal graft function. We coin the term 'meaningful survival'. METHODS We performed a cross-sectional study of pLT recipients who received transplants between 1985 and 2004. A 20-year evaluation of physical health (growth, renal function), mental wellbeing and social outcomes (substance abuse, adherence, education, employment) was performed. All patients included were considered to have normal graft function. FINDINGS Eighty-four patients met study criteria. Median age at transplantation was 1.3 years (IQR 0·7-3·3 years), with median duration of follow-up of 20.2 years (18·0-23·5). At median of 20-years, 19 patients (23%) had chronic renal dysfunction and 3 patients (4%) had a BMI of >30 (mean 20·4). Evaluation of long-term psychosocial outcomes demonstrated 22 patients (26%) with mental health disorders. Substance abuse was lower than national average. 62 patients (74%) were in education, employment or training. Overall, only 26% of our cohort achieved a composite outcome of 'meaningful survival'. INTERPRETATION This is the largest reported long-term study of biopsychosocial outcomes of pLT recipients with normal liver biochemistry, with follow-up upon completion of physical growth and senior school education. Importantly, despite normal liver function, many patients did not demonstrate 'meaningful survival'. We must refocus our efforts towards better understanding the long-term outcomes of children. A 'meaningful survival' rather than mere survival should be our goal. FUNDING None.
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Key Words
- ALP, alkaline phosphatase
- AST, aspartate aminotransferase
- BA, biliary atresia
- BMI, body mass index
- GGT, gamma-glutamyl transferase
- IMPARTS, Integrating Mental and Physical Healthcare: Research, Training and Services
- IQR, interquartile range
- Liver transplantation
- SD, standard deviation
- biopsychosocial
- eGFR, estimated glomerular filtration rate
- long-term
- outcomes
- pLT, pediatric liver transplantation
- pediatric
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Affiliation(s)
- Sunitha Vimalesvaran
- Paediatric Liver, GI and Nutrition Center and Mowat Labs, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
| | - Lara Neves Souza
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Maesha Deheragoda
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Marianne Samyn
- Paediatric Liver, GI and Nutrition Center and Mowat Labs, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
| | - Jemma Day
- Paediatric Liver, GI and Nutrition Center and Mowat Labs, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
| | - Anita Verma
- Paediatric Liver, GI and Nutrition Center and Mowat Labs, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
| | - Hector Vilca-Melendez
- Liver and Intestinal Transplant Surgical Service, King's College Hospital, London, United Kingdom
| | - Mohamed Rela
- Institute of Liver disease and Transplantation, Dr Rela Institute and Medical Center, Bharat Institute of Higher Education and Research, Chennai, India
| | - Nigel Heaton
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Center and Mowat Labs, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
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36
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Kim KS, Moon YJ, Kim SH, Kim B, Jun IG, Kwon HM, Song JG, Hwang GS. Low Preoperative Antithrombin III Level Is Associated with Postoperative Acute Kidney Injury after Liver Transplantation. J Pers Med 2021; 11:jpm11080716. [PMID: 34442360 PMCID: PMC8401622 DOI: 10.3390/jpm11080716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/21/2021] [Accepted: 07/23/2021] [Indexed: 12/17/2022] Open
Abstract
We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII < 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII < 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII < 50% group (54.7% vs. 75.5%, p < 0.001); odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81–0.92; p < 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.
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Affiliation(s)
| | | | | | | | | | | | - Jun-Gol Song
- Correspondence: ; Tel.: +82-2-3010-3869; Fax: +82-2-470-1363
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Yeh H, Chiang CC, Yen TH. Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges. World J Gastroenterol 2021; 27:4104-4142. [PMID: 34326614 PMCID: PMC8311541 DOI: 10.3748/wjg.v27.i26.4104] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/17/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.
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Affiliation(s)
- Hsuan Yeh
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
| | - Chun-Cheng Chiang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
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Sarno G, Montalti R, Giglio MC, Rompianesi G, Tomassini F, Scarpellini E, De Simone G, De Palma GD, Troisi RI. Hepatocellular carcinoma in patients with chronic renal disease: Challenges of interventional treatment. Surg Oncol 2021; 36:42-50. [PMID: 33307490 DOI: 10.1016/j.suronc.2020.11.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 11/15/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available: thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.
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Affiliation(s)
- Gerardo Sarno
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" -University Hospital, Scuola Medica Salernitana, Salerno, Italy.
| | - Roberto Montalti
- Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Naples, Italy
| | - Mariano Cesare Giglio
- Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Naples, Italy
| | | | - Federico Tomassini
- Department of Human Structure and Repair, Ghent University Faculty of Medicine, Belgium
| | - Emidio Scarpellini
- Internal Medicine Unit, San Benedetto General Hospital, San Benedetto Del Tronto, Italy
| | - Giuseppe De Simone
- Department of Anesthesiology, Federico II University of Naples, Naples, Italy
| | - Giovanni Domenico De Palma
- Department of Clinical Medicine and Surgery, Interuniversity Center for Technological Innovation Interdepartmental Center for Robotic Surgery, Federico II University Naples, Italy
| | - Roberto Ivan Troisi
- Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Naples, Italy; Oxford University Hospitals NHS Foundation Trust, UK; Department of Human Structure and Repair, Ghent University Faculty of Medicine, Belgium
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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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40
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Arnold K, Xu Y, Liao YE, Cooley BC, Pawlinski R, Liu J. Synthetic anticoagulant heparan sulfate attenuates liver ischemia reperfusion injury. Sci Rep 2020; 10:17187. [PMID: 33057098 PMCID: PMC7566620 DOI: 10.1038/s41598-020-74275-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 09/29/2020] [Indexed: 12/18/2022] Open
Abstract
Heparan sulfate (HS) is a sulfated glycosaminoglycan abundant on the cell surface and in the extracellular matrix and has several biological activities including anticoagulation and anti-inflammation. Liver ischemia reperfusion injury is associated with coagulation and inflammatory responses. Here, we synthesized HS oligosaccharides with defined sulfation patterns and show that synthetic anticoagulant HS oligosaccharides limit liver ischemia reperfusion injury in a mouse model. Using a small targeted HS library, we demonstrate that an oligosaccharide that possesses both anticoagulant activity and binding affinity to HMGB1, the inflammatory target, decreases injury greater than oligosaccharides that only bind to HMGB1 or only have anticoagulant activity. HS oligosaccharides may represent a potential new therapeutic option for decreasing liver damage resulting from ischemia reperfusion injury.
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Affiliation(s)
- Katelyn Arnold
- Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
| | - Yongmei Xu
- Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
| | - Yi-En Liao
- Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
| | - Brian C Cooley
- Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Rafal Pawlinski
- Division of Hematology/Oncology, Department of Medicine, UNC Blood Research Center, University of North Carolina, Chapel Hill, NC, USA
| | - Jian Liu
- Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
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Kim SJ, Rhu J, Lee SH, Kim JM, Choi GS, Kim K, Joh JW. Tenofovir does not induce renal dysfunction compared to entecavir in post-liver-transplant hepatitis B virus patients. Ann Surg Treat Res 2020; 99:180-187. [PMID: 32908850 PMCID: PMC7463039 DOI: 10.4174/astr.2020.99.3.180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 06/19/2020] [Accepted: 07/14/2020] [Indexed: 01/05/2023] Open
Abstract
Purpose Tenofovir disoproxil fumarate is accepted as an effective and tolerable drug for treatment of HBV, similar to entecavir. However, there are some concerns about the nephrotoxicity of tenofovir. The aim of this study is to compare the renal-function change of liver recipients who received tenofovir or entecavir for HBV. Methods Among 468 patients with HBV who underwent liver transplantation at Samsung Medical Center between January 2008 and December 2015, the patients treated with tenofovir (n = 39) or entecavir (n = 429) were reviewed retrospectively. Baseline characteristics and renal-function change after 1 month, 1 year, and 2 years were compared. Propensity-score matching was performed for 37 patients using tenofovir and 132 patients using entecavir. We also analyzed risk factors of renal dysfunction. Results Age, preoperative creatinine, estimated glomerular filtration rate (e-GFR), and hepatic encephalopathy score showed statistical difference between the tenofovir and entecavir groups. The proportion of patients with ‘decreased renal function (e-GFR < 60 mL/min/1.73 m2)’ was higher in the tenofovir group than in the entecavir group (33.3% vs. 12.4% at postoperative one year, P < 0.005). After propensity-score matching, there was no statistical difference in preoperative characteristics. Postoperative 1-, 2-, and 3-year e-GFR and creatinine showed no statistical difference in either group. On multivariate analysis, only preoperative high e-GFR showed a protective effect on renal-function change (odds ratio, 0.97; P < 0.001), and there was no aggravating factor. Conclusion Tenofovir disoproxil fumarate does not induce renal dysfunction in liver-transplanted patients with HBV more than does entecavir.
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Affiliation(s)
- Sang Jin Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seo Hee Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyunga Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.,Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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42
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Lee J, Park JY, Yang SJ, Lee JY, Kim DG, Joo DJ, Kim MS, Kim SI, Lee JG. Renal safety of tenofovir disoproxil fumarate and entecavir with hepatitis B immunoglobulin in liver transplant patients. J Viral Hepat 2020; 27:818-825. [PMID: 32302037 DOI: 10.1111/jvh.13291] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/25/2020] [Accepted: 02/26/2020] [Indexed: 01/05/2023]
Abstract
Potent nucleos(t)ide analogues and hepatitis B immunoglobulin combinations are recommended after liver transplantation to prevent the recurrence of hepatitis B virus (HBV). Despite its proven efficacy, the renal safety of tenofovir disoproxil fumarate (TDF) has not been well established in liver transplant recipients. We aimed to assess the impacts of TDF and entecavir (ETV) on tubular and glomerular functions. We analysed 206 liver transplant patients treated with TDF (n = 102) or ETV (n = 104) plus hepatitis B immunoglobulin. Serum creatinine, phosphate and uric acid levels were measured. Proximal tubular dysfunction was defined as the presence of hypophosphatemia (<2 mg/dL) and hypouricemia (<2 mg/dL). Glomerular dysfunction was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 accompanied by a ≥25% eGFR decline from baseline. During a median follow-up of 42.5 months, 48 patients developed proximal tubular dysfunction (30.4% and 16.3% in the TDF and ETV groups; P = .017). Serum levels of phosphate and uric acid were significantly lower in the TDF group post-LT. TDF (OR, 2.34; 95% CI, 1.16-4.69; P = .017) and low body mass index (OR, 2.11; 95% CI, 1.06-4.21; P = .034) were independent risk factors for proximal tubular dysfunction. The prevalence of glomerular dysfunction was not significantly different between the two groups (TDF 51.0% and ETV 54.8%; P = .582). TDF significantly increased the risk of proximal tubular dysfunction. Although the effect of TDF on glomerular function was comparable to that of ETV, glomerular dysfunction was common after liver transplant.
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Affiliation(s)
- Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Jeong Yang
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jee Youn Lee
- Department of Surgery, Gangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Deok Gie Kim
- Department of Surgery, Wonju College of Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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43
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Lee YS, Choi YJ, Park KH, Park BS, Son JM, Park JY, Ri HS, Ryu JH. Liver Transplant Patients with High Levels of Preoperative Serum Ammonia Are at Increased Risk for Postoperative Acute Kidney Injury: A Retrospective Study. J Clin Med 2020; 9:jcm9061629. [PMID: 32481585 PMCID: PMC7356740 DOI: 10.3390/jcm9061629] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/18/2020] [Accepted: 05/18/2020] [Indexed: 01/09/2023] Open
Abstract
Acute kidney injury (AKI) is one of the most frequent postoperative complications after liver transplantation (LT). Increased serum ammonia levels due to the liver disease itself may affect postoperative renal function. This study aimed to compare the incidence of postoperative AKI according to preoperative serum ammonia levels in patients after LT. Medical records from 436 patients who underwent LT from January 2010 to February 2020 in a single university hospital were retrospectively reviewed. The patients were then categorized according to changes in plasma creatinine concentrations within 48 h of LT using the Acute Kidney Injury Network criteria. A preoperative serum ammonia level above 45 mg/dL was associated with postoperative AKI (p < 0.0001). Even in patients with a normal preoperative creatinine level, when the ammonia level was greater than 45 μg/dL, the incidence of postoperative AKI was significantly higher (p < 0.0001); the AKI stage was also higher in this group than in the group with preoperative ammonia levels less than or equal to 45 μg/dL (p < 0.0001). Based on the results of our research, an elevation in preoperative serum ammonia levels above 45 μg/dL is related to postoperative AKI after LT.
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Affiliation(s)
- Yoon Sook Lee
- Department of Anaesthesiology and Pain Medicine, Ansan Hospital, Korea University, College of Medicine, Ansan 15355, Korea; (Y.S.L.); (B.S.P.)
| | - Yoon Ji Choi
- Department of Anaesthesiology and Pain Medicine, Ansan Hospital, Korea University, College of Medicine, Ansan 15355, Korea; (Y.S.L.); (B.S.P.)
- Correspondence: ; Tel.: +82-10-7900-7825
| | - Kyu Hee Park
- Department of Pediatrics, Korea University Hospital, Ansan 15355, Korea;
| | - Byeong Seon Park
- Department of Anaesthesiology and Pain Medicine, Ansan Hospital, Korea University, College of Medicine, Ansan 15355, Korea; (Y.S.L.); (B.S.P.)
| | - Jung-Min Son
- Department of Biostatistics, Clinical Trial Center, Biomedical Research Institute, Pusan National University Hospital, Pusan 49241, Korea;
| | - Ju Yeon Park
- Department of Anesthesiology and Pain Medicine, Daedong Hospital, Busan 47737, Korea;
| | - Hyun-Su Ri
- Department of Anaesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Korea;
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Korea;
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Gojowy D, Kubis P, Gorecka M, Karkoszka H, Wiecek A, Adamczak M. Chronic Kidney Disease in Patients After Liver Transplantation: A Long-Term Retrospective Analysis From 1 Transplantation Center. Transplant Proc 2020; 52:2492-2496. [PMID: 32249052 DOI: 10.1016/j.transproceed.2020.02.081] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/17/2020] [Accepted: 02/22/2020] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Liver transplantation (LTx) is the only effective method of treating end-stage insufficiency of the liver. Coexisting chronic kidney disease (CKD) in these patients may worsen the long-term prognosis. The aim of this retrospective, a 1-center, observational study, was to determine the prevalence and predisposing factors of CKD in patients in the long run after LTx. PATIENTS AND METHOD Medical records were obtained, and the 130 patients after LTx (with a mean age of 49.3 ± 11.9 years) who completed the 24-month follow-up period were enrolled in the study. CKD was diagnosed in patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 or who had proteinuria for at least 3 months. Results are presented as means with standard deviation. RESULTS CKD was found in 17% of the patients before liver transplantation and in 32% and 39% 12 and 24 months after LTx, respectively. The eGFR values before, 12 months after, and 24 months after LTx were 98.6 ± 48.3, 79.1 ± 29.6, and 76.9 ± 21.3 mL/kg/1.73 m2, respectively. The prevalence of CKD was lower in transplant patients with an autoimmune disease (25%) compared with viral (52%) and ethanol abuse (47%) liver cirrhosis etiology (chi-square: P = .04; post hoc analyses: autoimmune vs viral; P = .01; autoimmune vs ethanol abuse; P = .07). A significant negative correlation was found between trough blood tacrolimus concentration and eGFR 12 and 24 months after LTx (P < .05). CONCLUSIONS The prevalence of CKD in patients after liver transplantation seems to be higher than in the general population. Patients with autoimmune etiology of the liver disease have better renal function than patients with viral or ethanol abuse liver cirrhosis etiology. Treatment with calcineurin inhibitors adversely influences renal function in patients after liver transplantations.
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Affiliation(s)
- Damian Gojowy
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland
| | - Piotr Kubis
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland
| | - Magdalena Gorecka
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland
| | - Henryk Karkoszka
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland
| | - Andrzej Wiecek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland.
| | - Marcin Adamczak
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland
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Santeusanio AD, Weinberg AD, Florman SS, Schiano TD. Safety of direct-acting oral anticoagulants relative to warfarin in a matched cohort of liver transplant recipients. Clin Transplant 2019; 34:e13756. [PMID: 31738454 DOI: 10.1111/ctr.13756] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 10/23/2019] [Accepted: 11/09/2019] [Indexed: 02/06/2023]
Abstract
Despite increasingly widespread utilization of direct-acting oral anticoagulants (DOACs), there remains limited experience with the use of these agents following liver transplantation. We performed a single-center, retrospective review of liver transplant recipients prescribed DOACs or warfarin between January 2014 and January 2018. Patients receiving DOACs were matched with warfarin-treated controls based on discrete clinical parameters and followed from the time of anticoagulant prescription, until treatment discontinuation or study conclusion. The primary endpoint for this review was the incidence of clinically relevant major or non-major bleeding among the treatment groups. Twenty-seven patients prescribed DOACs were identified for inclusion in the review, of which 20 could be matched with suitable warfarin controls. At the conclusion of the study, warfarin-treated patients had a significantly higher incidence of clinically relevant bleeding (45% vs 15%; P = .01). No statistically significant differences were found in the rate of new or recurrent thrombotic events. Multivariable logistic regression demonstrated that warfarin treatment was associated with a significantly higher odds of a bleeding event compared to treatment with a DOAC (OR = 6.9; 95% CI, 1.1-44.6). DOAC use appears relatively safe compared with warfarin in select liver transplant recipients. Patient-specific factors still bear consideration when selecting between the various anticoagulant options.
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Affiliation(s)
- Andrew D Santeusanio
- Recanati-Miller Transplantation Institute, Mount Sinai Hospital, New York, NY, USA.,Department of Pharmacy, Mount Sinai Hospital, New York, NY, USA
| | - Alan D Weinberg
- Department of Population Health Science and Policy, Mount Sinai Hospital, New York, NY, USA
| | - Sander S Florman
- Recanati-Miller Transplantation Institute, Mount Sinai Hospital, New York, NY, USA
| | - Thomas D Schiano
- Recanati-Miller Transplantation Institute, Mount Sinai Hospital, New York, NY, USA
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46
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Lima C, de Paiva Haddad LB, de Melo PDV, Malbouisson LM, do Carmo LPF, D'Albuquerque LAC, Macedo E. Early detection of acute kidney injury in the perioperative period of liver transplant with neutrophil gelatinase-associated lipocalin. BMC Nephrol 2019; 20:367. [PMID: 31615452 PMCID: PMC6794911 DOI: 10.1186/s12882-019-1566-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 09/26/2019] [Indexed: 12/28/2022] Open
Abstract
Background Acute kidney injury (AKI) is a common complication in patients undergoing liver transplant (LT) and is associated with high morbidity and mortality. We aim to evaluate the pattern of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) elevation during the perioperative period of LT and to assess it as a prognostic marker for AKI progression, need for dialysis and mortality. Methods We assessed NGAL levels before induction of anesthesia, after portal reperfusion and at 6, 18, 24, and 48 h after surgery. Patients were monitored daily during the first week after LT. Results Of 100 enrolled patients undergoing liver transplant, 59 developed severe AKI based on the KDIGO serum creatinine (sCr) criterion; 34 were dialysed, and 21 died within 60 days after LT. Applying a cut-off value of 136 ng/ml, UNGAL values 6 h after surgery was a good predictor of AKI development within 7 days after surgery, having a positive predictive value (PPV) of 80% with an AUC of 0.76 (95% CI 0.67–0.86). PNGAL at 18 h after LT was also a good predictor of AKI in the first week, having a PPV of 81% and AUC of 0.74 (95% CI 0.60–0.88). Based on PNGAL and UNGAL cut-off criteria levels, time to AKI diagnosis was 28 and 23 h earlier than by sCr, respectively. The best times to assess the need for dialysis were 18 h after LT by PNGAL and 06 h after LT by UNGAL. Conclusion In conclusion, the plasma and urine NGAL elevation pattern in the perioperative period of the liver transplant can predict AKI diagnosis earlier. UNGAL was an early independent predictor of AKI development and need for dialysis. Further studies are needed to assess whether the clinical use of biomarkers can improve patient outcomes. Trial registration Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title “Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)” and identifier NCT02095431, retrospectively registered.
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Affiliation(s)
- Camila Lima
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil. .,Department of Medical Surgical Nursing, University of Sao Paulo Nursing School, Sao Paulo, Brazil.
| | - Luciana Bertocco de Paiva Haddad
- Department of Gastrointestinal Surgery, Clinical Surgery Division, University of Sao Paulo, Sao Paulo, Brazil.,Present Address: La Jolla, San Diego, USA
| | | | - Luiz Marcelo Malbouisson
- Department of Anaesthesiology, Clinical Surgery Division, University of Sao Paulo, Sao Paulo, Brazil
| | - Lilian Pires Freitas do Carmo
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil
| | | | - Etienne Macedo
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil.,Department of Medicine, Nephrology Division, University of California San Diego, San Diego, USA
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47
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Moon HH, Son HS, Shafqat M, Choi YI, Kim Y, Jung YS, Rim H, Seo KI, Chung HJ, Park JG, Shin DH. Clinical Course of Renal Disease in Recipients of Liver Transplant Who Required Peritransplant Dialysis. Transplant Proc 2019; 51:2771-2774. [PMID: 31563246 DOI: 10.1016/j.transproceed.2019.03.073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 03/12/2019] [Indexed: 01/23/2023]
Abstract
PURPOSE Renal dysfunction is a common complication and one of the factors that affects the outcomes of liver transplantation (LT). The aim of this study was to review the clinical course of recipients of LT who needed peritransplant dialysis at our center. METHODS We compared the clinical demographics, morbidity, and mortality between patients who required and those who did not require peritransplant dialysis among 26 recipients of LT from May 2015 to February 2018 at our center. RESULTS Among the recipients, 9 had pretransplant or posttransplant dialysis and 17 did not. The patients who underwent dialysis had a higher pretransplant Model for End-Stage Liver Disease score (42 vs 13; P < .001), older donor age (41 vs 24 years; P < .001), and longer post-LT hospital stay (37 vs 20 days; P < .001). However, there was no significant difference in the serum creatinine level between the 2 groups (1.36 vs 0.93 mg/dL; P = .187) at 2 weeks (1.10 vs 0.96 mg/dL; P = .341), 1 month (1.06 vs 0.86 mg/dL; P = .105), and 3 months after LT (0.92 vs 0.94 vs 0.89 mg/dL; P = .825). Mortality was higher in the peritransplant dialysis group (P = .043). The pre-LT dialysis duration was significantly related to post-LT dialysis (P = .028) and mortality (P = .011). CONCLUSIONS The pre-LT dialysis duration is considered an important factor in the survival and recovery of kidney function after LT. Therefore, if the patient has started dialysis, it may be beneficial to proceed to LT as soon as possible.
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Affiliation(s)
- Hyung Hwan Moon
- Department of Surgery, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Ho Sung Son
- Department of Surgery, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Musheer Shafqat
- Department of Surgery, Bach Christian Hospital, Abbottabad, Pakistan
| | - Young Il Choi
- Department of Surgery, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Yena Kim
- Division of Nephrology, Department of Medicine, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Yeon Soon Jung
- Division of Nephrology, Department of Medicine, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Hark Rim
- Division of Nephrology, Department of Medicine, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Kwang Il Seo
- Division of Hepatology, Department of Medicine, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Hyung-Joo Chung
- Department of Anesthesiology, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Jung Gu Park
- Department of Radiology, College of Medicine at Kosin University, Busan, Republic of Korea
| | - Dong Hoon Shin
- Department of Surgery, College of Medicine at Kosin University, Busan, Republic of Korea.
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Feltracco P, Barbieri S, Carollo C, Bortolato A, Michieletto E, Bertacco A, Gringeri E, Cillo U. Early circulatory complications in liver transplant patients. Transplant Rev (Orlando) 2019; 33:219-230. [PMID: 31327573 DOI: 10.1016/j.trre.2019.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 06/28/2019] [Accepted: 06/30/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Paolo Feltracco
- Department of Medicine, UO Anesthesia and Intensive Care, University of Padua, Italy.
| | - Stefania Barbieri
- Department of Medicine, UO Anesthesia and Intensive Care, University of Padua, Italy
| | - Cristiana Carollo
- Department of Medicine, UO Anesthesia and Intensive Care, University of Padua, Italy
| | - Andrea Bortolato
- Department of Medicine, UO Anesthesia and Intensive Care, University of Padua, Italy
| | - Elisa Michieletto
- Department of Medicine, UO Anesthesia and Intensive Care, University of Padua, Italy
| | - Alessandra Bertacco
- Hepatobiliary Surgery and Liver Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy
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Trunečka P, Klempnauer J, Bechstein WO, Pirenne J, Bennet W, Zhao A, Isoniemi H, Rostaing L, Settmacher U, Mönch C, Brown M, Undre N, Kazeem G, Tisone G. The Effect of Donor Age and Recipient Characteristics on Renal Outcomes in Patients Receiving Prolonged-Release Tacrolimus After Liver Transplantation: Post-Hoc Analyses of the DIAMOND Study. Ann Transplant 2019; 24:319-327. [PMID: 31160549 PMCID: PMC6568030 DOI: 10.12659/aot.913103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background The DIAMOND study of de novo liver transplant patients showed that prolonged-release tacrolimus exposure in the acute post-transplant period maintained renal function over 24 weeks of treatment. To assess these findings further, we performed a post-hoc analysis in patients according to baseline kidney function, Model for End-stage Liver Disease [MELD] scores, and donor age. Material/Methods Patients received prolonged-release tacrolimus (initial-dose, Arm 1: 0.2 mg/kg/day, Arm 2: 0.15–0.175 mg/kg/day, Arm 3: 0.2 mg/kg/day delayed until Day 5), mycophenolate mofetil and 1 steroid bolus. Arms 2 and 3 also received basiliximab. The recommended tacrolimus target trough levels to Day 42 post-transplantation were 5–15 ng/mL in all arms. In this post-hoc analysis, change in renal outcome, based on estimated glomerular filtration rate (eGFR), Modified Diet in Renal Disease-4 (MDRD4), values from baseline to Week 24 post-transplantation, were assessed according to baseline patient factors: eGFR (≥60 and <60 mL/min/1.73 m2), MELD score (<25 and ≥25) and donor age (<50 and ≥50 years). Results Baseline characteristics were comparable (Arms 1–3: n=283, n=287, n=274, respectively). Patients with baseline renal function, eGFR ≥60 mL/min/1.73 m2, experienced a decrease in eGFR in all tacrolimus treatment arms. In patients with lower baseline renal function (eGFR <60 mL/min/1.73 m2), an advantage for renal function was observed with both the early lower-dose and delayed higher-dose tacrolimus regimens compared with the early introduction of higher-dose tacrolimus. At Week 24, renal function was higher in the early-lower tacrolimus arm with older donors, and the delayed higher-dose tacrolimus arm with younger donors, both compared with early higher-dose tacrolimus. Conclusions Pre-transplantation factors, such as renal function and donor age, could guide the choice of prolonged-release tacrolimus regimen following liver transplantation.
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Affiliation(s)
- Pavel Trunečka
- Transplantcenter, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jürgen Klempnauer
- Department of General-, Visceral- and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Wolf Otto Bechstein
- Department of Surgery, Goethe University Hospital and Clinics, Frankfurt, Germany
| | - Jacques Pirenne
- Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - William Bennet
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Alexey Zhao
- Department of Abdominal Surgery, A.V. Vishnevsky Institute of Surgery, Moscow, Russian Federation
| | - Helena Isoniemi
- Department of Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - Lionel Rostaing
- Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany
| | - Christian Mönch
- Department of Surgery, Goethe University Hospital and Clinics, Frankfurt, Germany.,Department of General, Visceral and Transplantation Surgery, Westpfalz-Klinikum Hospital, Kaiserslautern, Germany
| | - Malcolm Brown
- Astellas Pharma, Medical Affairs - Global, Northbrook, IL, USA
| | | | - Gbenga Kazeem
- Astellas Pharma Europe Ltd., Chertsey, United Kingdom.,BENKAZ Consulting Ltd., Cambridge, United Kingdom
| | - Giuseppe Tisone
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
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Ding Y, Wu T, Zhang W, Zhang S, Wang W. Pretransplant renal function evaluated by serum cystatin C was associated with mortality after liver transplantation: a single-center experience. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:243. [PMID: 31317013 DOI: 10.21037/atm.2019.05.22] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background In the model for end-stage liver disease (MELD) score, renal function was well thought to be associated with the prognosis of liver recipients. Serum cystatin C (CystC)-based equations were considered more accurate for calculating estimated glomerular filtration rate (eGFR) than creatinine (Pcr) based equations. Thus, we aimed to assess the association between eGFR estimated by chronic kidney disease epidemiology collaboration (CKD-EPI)-CystC equation and post-transplantation mortality. Methods From January 2015 to January 2018, prior to liver transplantation (LT) and other clinical parameters, CystC was collected in all 307 consecutive patients who underwent LT at our center. Patients were divided into four groups according to the Kidney Disease Outcomes Quality Initiative (KDOQI) classification. Results Based on CKD-EPI-CystC and the KDOQI classification, 117 patients (38.1%) were stage I, 76 (24.8%) were stage II, 85 (27.7%) were stage III, and 29 (9.4%) were stage IV-V. After univariate and multivariate analysis, MELD score [hazard ratio (HR) =1.035; 95% confidence interval (CI), 1.006-1.066; P=0.018], associated HCC (HR =2.314; 95% CI, 1.253-4.273; P=0.007), and KDOQI stage III (HR =1.850; 95% CI, 1.001-3.419; P=0.049), and stage IV-V (HR =3.915; 95% CI, 1.843-8.316; P<0.001) according to CKD-EPI-CystC equation were confirmed to be independent prognostic factors for post-LT survival. Conclusions The pretransplant renal function evaluated by serum CystC was associated with mortality after LT and could be used for predicting post-transplant survival.
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Affiliation(s)
- Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
| | - Tianchun Wu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
| | - Wenyan Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Sitong Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, China.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
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