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Jiménez-Romero C, Justo Alonso I, Caso Maestro O, Manrique Municio A, García-Sesma Á, Calvo Pulido J, Cambra Molero F, Loinaz Segurola C, Martín-Arriscado C, Nutu A, Marcacuzco Quinto A. Indications and Long-Term Outcomes of Using Mycophenolate Mofetil Monotherapy in Substitution for Calcineurin Inhibitors in Liver Transplantation. Transpl Int 2025; 38:13790. [PMID: 40060933 PMCID: PMC11886422 DOI: 10.3389/ti.2025.13790] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 01/27/2025] [Indexed: 05/13/2025]
Abstract
Switching the use of calcineurin inhibitors (CNIs), as basal immunosuppression in liver transplantation (LT) patients, for that of mycophenolate mofetil monotherapy (MMF-MT) is currently considered a good measure in recipients with chronic kidney disease (CKD) and other CNI-related adverse effects. We analyzed a retrospective cohort series of 324 LT patients who underwent long-term follow-up and were switched from CNI immunosuppression to MMF-MT due to CKD and other CNI-related adverse effects (diabetes, hypertension, infection). The median time on MMF-MT was 78 months. The indication for MMF-MT was CKD alone or associated with CNI-related adverse effects in 215 patients, diabetes in 61, hypertension in 42, and recurrent cholangitis in 6. Twenty-four (7.4%) patients developed non-resistant acute rejection post-MMF-MT, and 48 (14.8%) patients experienced MMF-related adverse effects, with MMF-MT withdrawn in only 8 (2.5%) patients. In the comparison between the pre-MMF-MT period and the last outpatient review, using a repeated measures model and taking each patient as its own comparator, we demonstrated a significant increase in GFR and significant decrease in creatinine and ALT values, remaining the other variables (diabetes, hypertension, and hematological and AST) within similar levels. Five-year survival post-MMF-MT conversion was 75.3%. MMF-MT significantly improved renal function, was well tolerated, and had a low rejection rate.
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Affiliation(s)
- Carlos Jiménez-Romero
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Iago Justo Alonso
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Oscar Caso Maestro
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Alejandro Manrique Municio
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Álvaro García-Sesma
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Jorge Calvo Pulido
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Félix Cambra Molero
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Carmelo Loinaz Segurola
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | | | - Anisa Nutu
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Alberto Marcacuzco Quinto
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital, Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
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2
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Kaye AD, Shah SS, Johnson CD, De Witt AS, Thomassen AS, Daniel CP, Ahmadzadeh S, Tirumala S, Bembenick KN, Kaye AM, Shekoohi S. Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients. Curr Issues Mol Biol 2024; 47:2. [PMID: 39852117 PMCID: PMC11763814 DOI: 10.3390/cimb47010002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 01/26/2025] Open
Abstract
Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care.
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Affiliation(s)
- Alan D. Kaye
- Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA
| | - Shivam S. Shah
- School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA; (S.S.S.); (C.D.J.); (C.P.D.)
| | - Coplen D. Johnson
- School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA; (S.S.S.); (C.D.J.); (C.P.D.)
| | - Adalyn S. De Witt
- School of Medicine, Indiana University, 340 W 10th St., Indianapolis, IN 46202, USA
| | - Austin S. Thomassen
- School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA; (S.S.S.); (C.D.J.); (C.P.D.)
| | - Charles P. Daniel
- School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA; (S.S.S.); (C.D.J.); (C.P.D.)
| | - Shahab Ahmadzadeh
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA
| | - Sridhar Tirumala
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA
| | - Kristin Nicole Bembenick
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA
| | - Adam M. Kaye
- Department of Pharmacy Practice, Thomas J. Long School of Pharmacy, University of the Pacific, 751 Brookside Road, Stockton, CA 95207, USA
| | - Sahar Shekoohi
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA
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3
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Xiong D, Yue B, Ye S, Wang H, Ban L, Chen Y, Lv J, Zhou M, Yin P, Chen J. The impact of long-term exposure to tacrolimus on chronic kidney disease after lung transplantation: A retrospective analysis from a single transplantation center. Transpl Immunol 2023; 78:101810. [PMID: 36918103 DOI: 10.1016/j.trim.2023.101810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 01/06/2023] [Accepted: 02/26/2023] [Indexed: 03/14/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a progressive and irreversible complication in lung transplant patients who have received long-term treatment with tacrolimus. This study aimed to verify long-term tacrolimus exposure values in CKD progression. METHODS We retrospectively analyzed the clinical data of adult lung transplant recipients performed at our center between 2012 and October 2015. Patients who completed the 5-year follow-up period were enrolled in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS Eighty patients were analyzed. Compared with baseline (109 ± 38.1 mL/min/1.73 m2), the average eGFR values of our patients gradually decreased during the fifth-year post transplantation (46.5%, 58.3 ± 28.3 mL/min/1.73 m2), and the decline in eGFR values was particularly pronounced in the first year (31.2%, 74.6 ± 28.91 mL/min/1.73 m2). Moreover, 10 (12.7%), 21 (26.9%), 24 (31.2%), 28 (41.2%), and 48 (60%) patients had eGFR <60 mL/min/1.73 m2 at 3, 6, 1, 3, and 5 years after lung transplantation (LT), respectively. A significant negative correlation was found between tacrolimus dose and eGFR 6 months after LT (P = 0.0414). We found no correlation between the serum tacrolimus concentration and CKD progression. CONCLUSION eGFR constantly decreased and the incidence of CKD increased during the 5-year follow-up period after LT. The tacrolimus dose had a significant negative correlation with eGFR at 6 months after LT. Meanwhile, whole-blood tacrolimus trough concentrations were not correlated with eGFR decline. When possible, lower dosing within 1 year after LT can reduce potential nephrotoxic side effects.
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Affiliation(s)
- Dian Xiong
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Bingqing Yue
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China; Department of Lung Transplant, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
| | - Shugao Ye
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Hongmei Wang
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Le Ban
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Yuan Chen
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Jian Lv
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Min Zhou
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China
| | - Pan Yin
- Department of Lung Transplant, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
| | - Jingyu Chen
- Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China; Department of Lung Transplant, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
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Swanson KJ. Kidney disease in non-kidney solid organ transplantation. World J Transplant 2022; 12:231-249. [PMID: 36159075 PMCID: PMC9453292 DOI: 10.5500/wjt.v12.i8.231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/07/2022] [Accepted: 07/11/2022] [Indexed: 02/05/2023] Open
Abstract
Kidney disease after non-kidney solid organ transplantation (NKSOT) is a common post-transplant complication associated with deleterious outcomes. Kidney disease, both acute kidney injury and chronic kidney disease (CKD) alike, emanates from multifactorial, summative pre-, peri- and post-transplant events. Several factors leading to kidney disease are shared amongst solid organ transplantation in addition to distinct mechanisms unique to individual transplant types. The aim of this review is to summarize the current literature describing kidney disease in NKSOT. We conducted a narrative review of pertinent studies on the subject, limiting our search to full text studies in the English language. Kidney disease after NKSOT is prevalent, particularly in intestinal and lung transplantation. Management strategies in the peri-operative and post-transplant periods including proteinuria management, calcineurin-inhibitor minimization/ sparing approaches, and nephrology referral can counteract CKD progression and/or aid in subsequent kidney after solid organ transplantation. Kidney disease after NKSOT is an important consideration in organ allocation practices, ethics of transplantation. Kidney disease after SOT is an incipient condition demanding further inquiry. While some truths have been revealed about this chronic disease, as we have aimed to describe in this review, continued multidisciplinary efforts are needed more than ever to combat this threat to patient and allograft survival.
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Affiliation(s)
- Kurtis J Swanson
- Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, MN 55414, United States
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5
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[Kidney failure after liver transplantation]. Nephrol Ther 2022; 18:89-103. [PMID: 35151596 DOI: 10.1016/j.nephro.2021.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 05/11/2021] [Accepted: 11/06/2021] [Indexed: 02/06/2023]
Abstract
One third of cirrhotic patients present impaired kidney function. It has multifactorial causes and has a harmful effect on patients' morbi-mortality before and after liver transplant. Kidney function does not improve in all patients after liver transplantation and liver-transplant recipients are at high risk of developing chronic kidney disease. Causes for renal dysfunction can be divided in three groups: preoperative, peroperative and postoperative factors. To date, there is no consensus for the modality of evaluation the risk for chronic kidney disease after liver transplantation, and for its prevention. In the present review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease to determine a risk stratification for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this setting, and highlight the indications of combined liver-kidney transplantation.
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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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Abstract
One-third of patients with cirrhosis present kidney failure (AKI and CKD). It has multifactorial causes and a harmful effect on morbidity and mortality before and after liver transplantation. Kidney function does not improve in all patients after liver transplantation, and liver transplant recipients are at a high risk of developing chronic kidney disease. The causes of renal dysfunction can be divided into three groups: pre-operative, perioperative and post-operative factors. To date, there is no consensus on the modality to evaluate the risk of chronic kidney disease after liver transplantation, or for its prevention. In this narrative review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease in order to establish a risk categorization for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this context, and highlight the indications of combined liver–kidney transplantation.
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Successful Treatment of Mucocutaneous Lupus Erythematosus in a Dog with Prednisolone, Mycophenolate Mofetil and Tacrolimus. Vet Sci 2021; 8:vetsci8050072. [PMID: 33922817 PMCID: PMC8146856 DOI: 10.3390/vetsci8050072] [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: 04/01/2021] [Revised: 04/22/2021] [Accepted: 04/22/2021] [Indexed: 11/16/2022] Open
Abstract
A 6-year-old, intact male miniature Pinscher dog had erosive lesions on perilabial, peripenial and perianal mucocutaneous areas, which were exacerbated by ulcerations, crusts, with pain while defecating and urinating. The lesions were symmetrical, and no systemic signs were observed. Histopathological evaluation showed parakeratotic hyperkeratosis, ulceration and cell-rich lymphoplasmacytic interface dermatitis with basal keratinocyte apoptosis. Immunohistochemistry revealed strong reaction in the dermoepidermal junction against goat-canine IgG and mild-to-moderate reaction against goat-canine IgA, IgM and C3. Based on these findings, the dog was diagnosed with mucocutaneous lupus erythematosus (MCLE). Oral prednisolone 1 mg/kg twice daily, mycophenolate mofetil (MMF) 18.3 mg/kg twice daily and 0.1% tacrolimus ointment were prescribed as initial treatment. The lesions showed remarkable improvement within 4 weeks, but the dog exhibited polyuria, polydipsia and hepatomegaly with high dosage of prednisolone. Hence, the dosage of prednisolone was gradually tapered for 9 weeks and discontinued, but MMF and tacrolimus were continued. No new lesion or associated side effect was observed while reducing the MMF dose to 10 mg/kg twice daily and with continuous use of tacrolimus ointment after steroid discontinuation. In conclusion, this case report emphasizes the usefulness of MMF and tacrolimus as steroid-sparing agents in the treatment of dogs with MCLE. To the best of our knowledge, this is the first case report of MCLE that was successfully managed long-term with MMF and tacrolimus.
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Cai X, Li R, Sheng C, Tao Y, Zhang Q, Zhang X, Li J, Shen C, Qiu X, Wang Z, Jiao Z. Systematic external evaluation of published population pharmacokinetic models for tacrolimus in adult liver transplant recipients. Eur J Pharm Sci 2020; 145:105237. [DOI: 10.1016/j.ejps.2020.105237] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 12/19/2022]
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10
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Jouve T, Noble J, Rostaing L, Malvezzi P. An update on the safety of tacrolimus in kidney transplant recipients, with a focus on tacrolimus minimization. Expert Opin Drug Saf 2019; 18:285-294. [DOI: 10.1080/14740338.2019.1599858] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Thomas Jouve
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
| | - Johan Noble
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
| | - Paolo Malvezzi
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
- Université Grenoble Alpes, Grenoble, France
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Tan PS, Muthiah MD, Koh T, Teoh YL, Chan A, Kow A, Zheng Q, Kwon CHD, Lee GH, Lesmana CRA, de Villa V, Fung J, Lim K. Asian Liver Transplant Network Clinical Guidelines on Immunosuppression in Liver Transplantation. Transplantation 2019; 103:470-480. [PMID: 30422953 DOI: 10.1097/tp.0000000000002532] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.
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Affiliation(s)
- Poh Seng Tan
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore
- National University Centre for Organ Transplantation, National University Hospital, National University Health System, Singapore
| | - Mark D Muthiah
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore
- National University Centre for Organ Transplantation, National University Hospital, National University Health System, Singapore
| | - Tsingyi Koh
- Department of Pharmacy, National University Hospital, National University Health System, Singapore
| | | | - Albert Chan
- Division of Hepatobiliary and Pancreatic Surgery, and Liver Transplantation, Department of Surgery, Queen Mary Hospital, Hong Kong
| | - Alfred Kow
- National University Centre for Organ Transplantation, National University Hospital, National University Health System, Singapore
- Division of Hepatopancreatobiliary Surgery and Division of Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, National University of Singapore, Singapore
| | - Qishi Zheng
- Singapore Clinical Research Institute, Singapore
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Guan Huei Lee
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore
- National University Centre for Organ Transplantation, National University Hospital, National University Health System, Singapore
| | - Cosmas Rinaldi A Lesmana
- Hepatobiliary Division, Department of Internal Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
- Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta, Indonesia
| | - Vanessa de Villa
- Department of Surgery and Center for Liver Disease Management and Transplantation, The Medical City, Pasig City, Philippines
| | - James Fung
- Department of Medicine, Queen Mary Hospital, Hong Kong
| | - Kieron Lim
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore
- National University Centre for Organ Transplantation, National University Hospital, National University Health System, Singapore
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Verma R, Satapathy SK. Medical Course and Complications After Liver Transplantation. PSYCHOSOCIAL CARE OF END-STAGE ORGAN DISEASE AND TRANSPLANT PATIENTS 2019:169-179. [DOI: 10.1007/978-3-319-94914-7_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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13
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Yee ML, Tan HH. Use of everolimus in liver transplantation. World J Hepatol 2017; 9:990-1000. [PMID: 28878864 PMCID: PMC5569278 DOI: 10.4254/wjh.v9.i23.990] [Citation(s) in RCA: 16] [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: 01/16/2017] [Revised: 05/20/2017] [Accepted: 06/12/2017] [Indexed: 02/06/2023] Open
Abstract
In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy. Adverse effects of proteinuria, hypercholesterolemia and hyperlipidemia are significantly higher as compared to standard CNI and long-term implications on graft and patient survival in LT is still unclear. Future research to explore strategies to minimise EVR adverse effects will be crucial for the success of EVR as an important alternative or adjunct immunosuppressive therapy in LT.
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Affiliation(s)
- Mei-Ling Yee
- Department of Pharmacy, Singapore General Hospital, Singapore 169608, Singapore.
| | - Hui-Hui Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
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