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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Prognostic Value of Computed Tomographic Coronary Angiography for Long-Term Major Adverse Cardiac Events after Liver Transplantation. J Clin Med 2021; 10:jcm10143132. [PMID: 34300296 PMCID: PMC8303180 DOI: 10.3390/jcm10143132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 12/26/2022] Open
Abstract
Computed tomographic coronary angiography (CTCA) has prognostic value for early major adverse cardiac events (MACEs) after liver transplantation. However, the association between CTCA and long-term MACEs in liver transplant (LT) recipients remains unknown. We evaluated the association between CTCA and long-term MACEs within 5 years after living donor liver transplantation (LDLT). A total of 628 LDLT recipients who underwent CTCA were analyzed between 2010 and 2012. MACEs were investigated within 5 years after LDLT. The factors associated with long-term MACEs in transplant recipients were evaluated. Only 48 (7.6%) patients developed MACEs. In the Fine and Gray competing risk regression, a coronary artery calcium score (CACS) of >400 combined with obstructive coronary artery disease (CAD) (subdistribution hazard ratio: 5.01, 95% confidence interval: 2.37–10.58, p < 0.001), age (1.05, 1.01–1.10, p = 0.018), diabetes mellitus (2.43, 1.37–4.29, p = 0.002), dyslipidemia (2.45, 1.23–4.70, p = 0.023), and creatinine (1.19, 1.08–1.30, p < 0.001) were independently associated with long-term MACEs. CACS (>400) combined with obstructive CAD may be associated with MACEs within 5 years after LDLT, suggesting the importance of preoperative noninvasive CTCA in LT recipients. The evaluation of coronary artery stenosis on CTCA combined with CACS may have a prognostic value for long-term MACEs in LT recipients.
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Osseointegration of Dental Implants in Organ Transplant Patients Undergoing Chronic Immunosuppressive Therapy. IMPLANT DENT 2019; 28:447-454. [DOI: 10.1097/id.0000000000000916] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Leiskau C, Rajanayagam J, Pfister ED, Goldschmidt I, Junge N, Karch A, Lerch C, Richter N, Lehner F, Schrem H, Baumann U. Side effects and efficacy of renal sparing immunosuppression in pediatric liver transplantation-A single center matched cohort study. Pediatr Transplant 2018; 22:e13207. [PMID: 29729061 DOI: 10.1111/petr.13207] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/31/2018] [Indexed: 11/29/2022]
Abstract
Immunosuppressive combination therapy with MMF can reduce CNI associated nephrotoxicity. We investigated effectiveness and safety of de novo MMF-tacrolimus based immunosuppression after pLTx. Patients after pLTx receiving immunosuppression with MMF/tacrolimus (MMF/TAC) were compared to retrospectively selected age- and diagnosis-matched patients with tacrolimus monotherapy (TAC) and cyclosporine/prednisolone therapy (CSA) (19 patients each, n = 57). Effectiveness, renal function and side effects were analyzed for 1 year after pLTx. Tacrolimus reduction in combination therapy (0.7 μg/L over the year) was lower than aspired (2 μg/L). Acute BPAR occurred equally in MMF/TAC and TAC groups (31.6% each), being slightly higher in CSA group (42.1%; OR = 1.5; 95% CI = 0.42-5.44; P = .5). GFR deteriorated comparably in all 3 groups (P < .01 each) without significant differences between the groups. Septicemia was detected significantly more often in MMF/TAC (73.6%) than in TAC (31.6%) (OR 4.17; 1.07-16.27; P = .04). EBV reactivation occurred more often in CSA patients (84.2%) than in MMF/TAC (47.4%; OR 5.16; 0.98-27.19; P = .05) and TAC patients (52.6%; OR 8.16; 1.48-44.89; P = .02) the same was true for other viral infections (47.4% (CSA) vs 15.8% (TAC); OR 4.21; 0.95-18.55; P = .05). Our study does not provide additional evidence for a benefit of initial use of MMF/TAC over TAC regarding renal function, but raises concerns regarding a potentially increased risk of serious infections under MMF/TAC compared to TAC monotherapy at equivalent renal outcome; our study is, however, limited by the minor CNI reduction in combination therapy.
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Affiliation(s)
- Christoph Leiskau
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.,Core Facility Quality Management & Health Technology Assessment in Transplantation, Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
| | - Jeremy Rajanayagam
- Department of Gastroenterology and Nutrition, Royal Children's Hospital, Melbourne, Australia
| | - Eva-Doreen Pfister
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Imeke Goldschmidt
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Norman Junge
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - André Karch
- Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Christian Lerch
- Core Facility Quality Management & Health Technology Assessment in Transplantation, Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.,Division of Pediatric Nephrology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Nicolas Richter
- General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Frank Lehner
- General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Harald Schrem
- Core Facility Quality Management & Health Technology Assessment in Transplantation, Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.,General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Ulrich Baumann
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.,Birmingham Children´s Hospital, Liver Unit and University of Birmingham, Institute of Immunology and Immunotherapy, UK
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Koppelstaetter C, Kern G, Leierer G, Mair SM, Mayer G, Leierer J. Effect of cyclosporine, tacrolimus and sirolimus on cellular senescence in renal epithelial cells. Toxicol In Vitro 2018; 48:86-92. [PMID: 29309803 DOI: 10.1016/j.tiv.2018.01.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 01/02/2018] [Accepted: 01/04/2018] [Indexed: 01/09/2023]
Abstract
INTRODUCTION In transplantation medicine calcineurin inhibitors (CNI) still represent the backbone of immunosuppressive therapy. The nephrotoxic potential of the CNI Cyclosporine A (CsA) and Tacrolimus (FK506) is well recognized and CNI not only have been linked with toxicity, but also with cellular senescence which hinders parenchymal tissue regeneration and thus may prime kidneys for subsequent insults. To minimize pathological effects on kidney grafts, alternative immunosuppressive agents like mTOR inhibitors or the T-cell co-stimulation blocker Belatacept have been introduced. METHODS We compared the effects of CsA, FK506 and Sirolimus on the process of cellular senescence in different human renal tubule cell types (HK2, RPTEC). Telomere length (by real time PCR), DNA synthesis (by BrdU incorporation), cell viability (by Resazurin conversion), gene expression (by RT-PCR), protein (by western blotting), Immuncytochemistry and H2O2 production (by Amplex Red® conversion) were evaluated. RESULTS DNA synthesis was significantly reduced when cells were treated with cyclosporine but not with tacrolimus and sirolimus. Resazurin conversion was not altered by all three immunosuppressive agents. The gene expression as well as protein production of the cell cycle inhibitor p21 (CDKN1A) but not p16 (CDKN2A) was significantly induced by cyclosporine compared to the other two immunosuppressive agents when determined by western blotting an immuncytochemistry. Relative telomere length was reduced and hydrogen peroxide production increased after treatment with CsA but not with FK506 or sirolimus. CONCLUSION In summary, renal tubule cells exposed to CsA show clear signs of cellular senescence where on the contrary the second calcineurin inhibitor FK506 and the mTOR inhibitor sirolimus are not involved in such mechanisms. Chronic renal allograft dysfunction could be in part triggered by cellular senescence induced by immunosuppressive medication and the choice of drug could therefore influence long term outcome. Tacrolimus and Sirolimus are equally effective in avoiding cellular senescence compared to cyclosporine at least in parts due to a lack of induction of reactive oxygen species.
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Affiliation(s)
| | - Georg Kern
- Department of Physiology, Medical University Innsbruck, Austria
| | - Gisela Leierer
- Division of Genetic Epidemiology, Medical University Innsbruck, Austria
| | - Sabine Maria Mair
- Department of Internal Medicine II; Infectious Diseases, Medical University Innsbruck, Austria
| | - Gert Mayer
- Department of Internal Medicine IV Nephrology, Medical University Innsbruck, Austria
| | - Johannes Leierer
- Department of Internal Medicine IV Nephrology, Medical University Innsbruck, Austria
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Dalla Torre D, Burtscher D. Ridge augmentation in an organ transplant patient. Int J Oral Maxillofac Surg 2016; 45:658-61. [DOI: 10.1016/j.ijom.2015.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Revised: 09/13/2015] [Accepted: 11/04/2015] [Indexed: 11/28/2022]
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Hao JC, Wang WT, Yan LN, Li B, Wen TF, Yang JY, Xu MQ, Zhao JC, Wei YG. Effect of low-dose tacrolimus with mycophenolate mofetil on renal function following liver transplantation. World J Gastroenterol 2014; 20:11356-11362. [PMID: 25170222 PMCID: PMC4145776 DOI: 10.3748/wjg.v20.i32.11356] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2014] [Revised: 03/05/2014] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether low-dose tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is a safe approach to decrease the incidence of chronic kidney disease (CKD) in liver transplantation (LT) recipients.
METHODS: We analyzed the medical records of 689 patients who underwent LT between March 1999 and December 2012 in a single Chinese center. Immunosuppression was initiated with a calcineurin inhibitor (TAC or CSA) and prednisone with or without MMF. CKD is defined by the glomerular filtration rate (GFR), estimated by an abbreviated Modification of Diet in Renal Disease formula, < 60 mL/min per 1.73 m2 for at least 3 consecutive months after LT. Individuals with TAC trough concentrations ≤ 8 ng/mL at 3 mo after LT were defined as the low-dose group. The incidence of CKD within 5 years was compared between the TAC group and the CSA group, as well as between four subgroups (low-dose and high-dose TAC groups with or without MMF).
RESULTS: No difference regarding the occurrence of pre-LT renal dysfunction or that of post-LT rejection was found between the TAC and CSA groups or between the four subgroups. With a definition of GFR < 60 mL/min per 1.73 m2, the overall incidence of CKD was significantly higher in the CSA group than in the TAC group. The incidence of CKD in the low-dose TAC + MMF group (7.7%) was significantly lower than that observed in the low-dose TAC group (15.9%), high-dose TAC group (24.6%) and high-dose TAC + MMF group (18.5%). The cumulative 1-, 3- and 5-year incidence rates of CKD were 12.7%, 14.5% and 16.7%, respectively. The cumulative 5-year survival rates were 61.7% and 82.2% in patients with or without CKD, respectively.
CONCLUSION: In LT patients, the choice of immunosuppressive therapy appears to affect renal function and patient survival.
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Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update. Arch Toxicol 2014; 88:1351-89. [PMID: 24792322 DOI: 10.1007/s00204-014-1247-1] [Citation(s) in RCA: 145] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Accepted: 04/15/2014] [Indexed: 12/22/2022]
Abstract
This review aims to provide an update of the literature on the pharmacology and toxicology of mycophenolate in solid organ transplant recipients. Mycophenolate is now the antimetabolite of choice in immunosuppressant regimens in transplant recipients. The active drug moiety mycophenolic acid (MPA) is available as an ester pro-drug and an enteric-coated sodium salt. MPA is a competitive, selective and reversible inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), an important rate-limiting enzyme in purine synthesis. MPA suppresses T and B lymphocyte proliferation; it also decreases expression of glycoproteins and adhesion molecules responsible for recruiting monocytes and lymphocytes to sites of inflammation and graft rejection; and may destroy activated lymphocytes by induction of a necrotic signal. Improved long-term allograft survival has been demonstrated for MPA and may be due to inhibition of monocyte chemoattractant protein 1 or fibroblast proliferation. Recent research also suggested a differential effect of mycophenolate on the regulatory T cell/helper T cell balance which could potentially encourage immune tolerance. Lower exposure to calcineurin inhibitors (renal sparing) appears to be possible with concomitant use of MPA in renal transplant recipients without undue risk of rejection. MPA displays large between- and within-subject pharmacokinetic variability. At least three studies have now reported that MPA exhibits nonlinear pharmacokinetics, with bioavailability decreasing significantly with increasing doses, perhaps due to saturable absorption processes or saturable enterohepatic recirculation. The role of therapeutic drug monitoring (TDM) is still controversial and the ability of routine MPA TDM to improve long-term graft survival and patient outcomes is largely unknown. MPA monitoring may be more important in high-immunological recipients, those on calcineurin-inhibitor-sparing regimens and in whom unexpected rejection or infections have occurred. The majority of pharmacodynamic data on MPA has been obtained in patients receiving MMF therapy in the first year after kidney transplantation. Low MPA area under the concentration time from 0 to 12 h post-dose (AUC0-12) is associated with increased incidence of biopsy-proven acute rejection although AUC0-12 optimal cut-off values vary across study populations. IMPDH monitoring to identify individuals at increased risk of rejection shows some promise but is still in the experimental stage. A relationship between MPA exposure and adverse events was identified in some but not all studies. Genetic variants within genes involved in MPA metabolism (UGT1A9, UGT1A8, UGT2B7), cellular transportation (SLCOB1, SLCO1B3, ABCC2) and targets (IMPDH) have been reported to effect MPA pharmacokinetics and/or response in some studies; however, larger studies across different ethnic groups that take into account genetic linkage and drug interactions that can alter a patient's phenotype are needed before any clinical recommendations based on patient genotype can be formulated. There is little data on the pharmacology and toxicology of MPA in older and paediatric transplant recipients.
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Wang XF, van Velkinburgh JC, Zhang Y, Ni B, Yang ZY. Effects of immunosuppressive agents on Th17 cells involved in transplantation. Clin Transplant 2013; 27:E12-20. [PMID: 23215778 DOI: 10.1111/ctr.12043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/01/2012] [Indexed: 12/13/2022]
Abstract
The lymphocyte-derived helper T (Th) cells are critical regulators of the adaptive immune response and are associated with inflammatory disease. The most recently recognized Th-cell lineage, Th17, plays an important role in host defense against extracellular pathogens by secreting the proinflammatory cytokine, interleukin 17, and recruiting reactive oxygen species (ROS)-producing monocytes to the site of infection. However, accumulating evidence has implicated Th17-cell dysregulation as an underlying cause for some immune-related pathogenic conditions, including allograft rejection. Recent studies of human transplant patients have indicated that Th17 cells exhibit resistance to current immunosuppressive therapies that would otherwise prevent allograft rejection. In this review, we will discuss the most current research findings related to Th17-cell function in various kinds of allografts.
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Affiliation(s)
- Xiao-Fei Wang
- Hepatobiliary Surgery Department, Southwest Hospital, PLA, Third Military Medical University, Chongqing, China
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Rao V, Haywood S, Abecassis M, Levitsky J. A Non-Induction Renal Sparing Approach After Liver Transplantation: High Dose Mycophenolate Mofetil With Delayed, Low-Dose Tacrolimus. Transplant Proc 2013; 45:320-2. [DOI: 10.1016/j.transproceed.2012.06.062] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 06/19/2012] [Indexed: 12/19/2022]
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Gu L, Yu YC. Clinical Outcome of Dental Implants Placed in Liver Transplant Recipients After 3 Years: A Case Series. Transplant Proc 2011; 43:2678-82. [DOI: 10.1016/j.transproceed.2011.06.037] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2011] [Revised: 05/05/2011] [Accepted: 06/03/2011] [Indexed: 01/13/2023]
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Evidence for the immunosuppressive potential of calcineurin inhibitor-sparing regimens in liver transplant recipients with impaired renal function. J Transplant 2011; 2011:483728. [PMID: 21785695 PMCID: PMC3139187 DOI: 10.1155/2011/483728] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Accepted: 05/09/2011] [Indexed: 12/19/2022] Open
Abstract
Patients requiring liver transplantation (LT) frequently experience renal insufficiency (RI), which affects their survival. Although calcineurin inhibitor-sparing immunosuppressive regimens (CSRs) are well known to prevent RI, the immune state in recipients receiving CSR remains to be intensively investigated. Among 60 cases of living-donor LT at our institute, 68% of the patients had none to mild RI (non-RI group) and 32% of the patients had moderate to severe RI (RI group). The RI group received a CSR comprising reduced dose of tacrolimus, methylprednisolone, and mycophenolate mofetil, while the non-RI group received a regimen comprising conventional dose of tacrolimus and methylprednisolone. One year after LT, the mean estimated glomerular filtration rate (eGFR) in the RI group had significantly improved, although it was still lower than that of the non-RI group. Serial mixed lymphocyte reaction assays revealed that antidonor T-cell responses were adequately suppressed in both groups. Thus, we provide evidence that CSR leads to improvement of eGFR after LT in patients with RI, while maintaining an appropriate immunosuppressive state.
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