Metabolic Consequences of Solid Organ Transplantation

2020 ◽  
Author(s):  
Mamatha Bhat ◽  
Shirine E Usmani ◽  
Amirhossein Azhie ◽  
Minna Woo
Keyword(s):  
Metabolic Disease ◽  
Weight Gain ◽  
Dietary Habits ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Metabolic Effects ◽  
Current Evidence ◽  
Solid Organ ◽  
Metabolic Complications ◽  
Nonalcoholic Fatty Liver

Abstract Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/− donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.

scholarly journals Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

2013 ◽  
Vol 70 (9) ◽  
pp. 848-853 ◽  
Author(s):  
Ljiljana Ignjatovic ◽  
Rajko Hrvacevic ◽  
Dragan Jovanovic ◽  
Zoran Kovacevic ◽  
Neven Vavic ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Immunosuppressive Therapy ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Solid Organ ◽  
Kidney Graft ◽  
Group I ◽  
Grade Iii

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ? 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ? 13 months. Nine patients (the group I) had early postransplant conversion after 4 ? 3 months and 15 patients (the group II) late conversion after 46 ? 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ? 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ? 12.7 to 69 ? 15 mL/min), while the increase in proteinuria (from 265 ? 239 to 530.6 ? 416.7 mg/day) and lipidemia (cholesterol from 4.71 ? 0.98 to 5.61 ? 1.6 mmol/L and triglycerides from 2.04 ? 1.18 to 2.1 ? 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ? 232 to 1639 ? 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/min) and significantly improved proteinuria (from 1639 ? 1641 to 529 ? 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ? 88 to 202 ? 91 mmol/L), decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/day) and increased proteinuria (from 528.9 ? 688 to 850 ? 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications.

scholarly journals Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy

2020 ◽  
Vol 8 (7) ◽  
pp. 977 ◽  
Author(s):  
Lorenzo Cavagna ◽  
Elena Seminari ◽  
Giovanni Zanframundo ◽  
Marilena Gregorini ◽  
Angela Di Matteo ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Calcineurin Inhibitor ◽  
Clinical Course ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Infectious Complications ◽  
Study Data ◽  
Solid Organ ◽  
The North

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to 28 April 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48–69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.

scholarly journals COVID-19 vaccine use in immunocompromised patients: A commentary on evidence and recommendations

2021 ◽  
Author(s):  
Kristine Duly ◽  
Francis A Farraye ◽  
Shubha Bhat
Keyword(s):  
Hiv Infection ◽  
Significant Proportion ◽  
Safety Data ◽  
Solid Organ Transplantation ◽  
British Society ◽  
Vaccine Hesitancy ◽  
Current Evidence ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Phase 3

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose While COVID-19 vaccine emergency use authorization (EUA) deemed the vaccines to be effective and safe for public use, the phase 3 trials leading to EUA predominantly excluded patients with immunocompromising conditions. Immunocompromised patients make up a significant proportion of the population, and in light of recent mass vaccination efforts, we aim to review current evidence and recommendations of COVID-19 vaccines in 4 patient populations with immunocompromising disorders or conditions: human immunodeficiency virus (HIV) infection, solid organ transplantation, rheumatoid arthritis, and inflammatory bowel disease. Summary Given the evolving data on safety and efficacy of the approved COVID-19 vaccines in the immunocompromised population, it is vital that pharmacists and other immunizing providers understand the current data and recommendations and provide the public with accurate information. To date, the only immunocompromised subgroup included in phase 3 COVID-19 vaccine trials have been those with HIV infection. However, recent retrospective trials have provided reassuring safety data of the COVID-19 vaccine in immunocompromised patients, and the interim analysis of the Moderna phase 3 trial produced promising efficacy data on HIV-infected patients. Presently, the US Centers for Disease Control and Prevention, British Society for Immunology, and various other governmental and professional societies and organizations endorse COVID-19 vaccination in the immunocompromised population. Conclusion While additional data is warranted to determine the effects of immunocompromising medical conditions and immunosuppressing medications on the efficacy of the vaccine, the benefits of the vaccine is anticipated to outweigh theoretical risks. Thus, the COVID-19 vaccine is recommended to be given to immunocompromised patients at this time, and providers should make efforts to decrease vaccine hesitancy in this population through education and reassurance.

scholarly journals Long-term dietary habits and interventions in solid-organ transplantation

2015 ◽  
Vol 34 (11) ◽  
pp. 1357-1365 ◽  
Author(s):  
Stuart M. Zeltzer ◽  
David O. Taylor ◽  
W.H. Wilson Tang
Keyword(s):  
Organ Transplantation ◽  
Dietary Habits ◽  
Solid Organ Transplantation ◽  
Solid Organ

scholarly journals Recent options in drug therapy after solid organ transplantation

2012 ◽  
Vol 153 (33) ◽  
pp. 1294-1301
Author(s):  
Balázs Pőcze ◽  
Péter Németh ◽  
Róbert Langer
Keyword(s):  
Immune Response ◽  
Organ Transplantation ◽  
Survival Rates ◽  
Solid Organ Transplantation ◽  
Tolerance Induction ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Solid Organ ◽  
Patient And Graft Survival

Solid organ transplantation has shown improvement in patient and graft survival rates due to the development of immunosuppression in the last fifty years; however only the last two decades led to the development of new, baseline immunosuppressive drugs that avoid the unlikely side effects of calcineurin inhibitors, especially nephrotoxicity. The transplanted organ is foreign to the host and, therefore, it induces a complex immune response of the recipient. In this review, a brief outline of immune response is given, followed by the introduction of new immunosuppressive drugs acting via variant pathways. These are compounds which are already in use or becoming shortly available and are potential future alternatives for the calcineurin inhibitors. This paper highlights the role of co-stimulation blockade with belatacept and the recently even more intensively studied field of tolerance induction. Orv. Hetil., 2012, 153, 1294–1301.

scholarly journals COVID-19 in Patients with Solid Organ Transplantation: A Systematic Review

2020 ◽  
Vol 1 (1) ◽  
pp. 1-15 ◽  
Author(s):  
René Hage ◽  
Carolin Steinack ◽  
Christian Benden ◽  
Macé M. Schuurmans
Keyword(s):  
Systematic Review ◽  
Social Life ◽  
Case Reports ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Case Series ◽  
Google Scholar ◽  
Current Evidence ◽  
Solid Organ ◽  
Increased Risk

The novel coronavirus, SARS-CoV-2, is causing a pandemic of unknown precedent, with huge healthcare challenges and worldwide disruptions to economic and social life. Lung transplant recipients and other solid organ transplant (SOT) recipients are immunosuppressed, and therefore are generally considered at an increased risk for severe infections. Given the current gap in knowledge and evidence regarding the best management of these patients, we conducted a systematic review of studies on SARS-CoV-2 infections and Coronavirus Disease 2019 (COVID-19) in SOT recipients, to evaluate the association between immunosuppression in these patients, SARS-CoV-2 infection and COVID-19 outcomes. The focus was the severity of the disease, the need for mechanical ventilation and intensive care unit (ICU) admissions, and rate of death. The literature search was conducted repeatedly between 16 March and 8 April 2020. We searched original papers, observational studies, case reports, and meta-analyses published between 2019 and 2020 using two databases (PubMed, Google Scholar) with the search terms: [transplant OR immunosuppression] AND [COVID-19 OR SARS-CoV-2]. Further inclusion criteria were publications in English, French, German and Italian, and reference to humans. We also searched the reference lists of the studies encountered. From an initial search of PubMed and Google Scholar, 19 potential articles were retrieved, of which 14 were excluded after full-text screening (not being case reports or case series), leaving 5 studies for inclusion. No further studies were identified from the bibliographies of retrieved articles. Based on the limited research, no firm conclusions can be made concerning SOT recipients, but the current evidence suggests that immunosuppression is most likely associated with a better outcome of SARS-CoV-2 infection and COVID-19 because it prevents hyperinflammation (cytokine storm) in this particular population. There is a need for further research that would allow results to be adjusted for other factors potentially impacting COVID-19 severity and outcome.

scholarly journals Diffusion MRI Findings in Encephalopathy Induced by Immunosuppressive Therapy after Liver Transplantation

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Emanuele Tinelli ◽  
Nicoletta Locuratolo ◽  
Alberto Pierallini ◽  
Massimo Rossi ◽  
Francesco Fattapposta
Keyword(s):  
Liver Transplantation ◽  
Immunosuppressive Therapy ◽  
Cyclosporine A ◽  
Early Recognition ◽  
Brain Mri ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Neurological Complications ◽  
Solid Organ ◽  
Diffusion Weighted Images

Neurological complications are common after liver transplantation, as they affect up to one-third of the transplanted patients and are associated with significant morbidity. The introduction of calcineurin inhibitors, cyclosporine A and tacrolimus, in immunosuppressive regimens significantly improved the outcome of solid-organ transplantation even though immunosuppression-associated neurotoxicity remains a significant complication, particularly occurring in about 25% of cases after liver transplantation. The immunosuppressant cyclosporine A and tacrolimus have been associated with the occurrence of major neurological complications, diffuse encephalopathy being the most common. The biochemical and pathogenetic basis of calcineurin inhibitors-induced neurotoxicity are still unclear although several mechanisms have been suggested. Early recognition of symptoms could help reduce neurotoxic event. The aim of the study was to evaluate cerebral changes through MRI, in particular with diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps, in two patients undergoing liver transplantation after immunosuppressive therapy. We describe two patients in which clinical pictures, presenting as a severe neurological condition, early after orthotopic liver transplantation during immunosuppression therapy, showed a different evolution in keeping with evidence of focal-multifocal lesions at DWI and ADC maps. At clinical onset, DWI showed hyperintensity of the temporo-parieto-occipital cortex with normal ADC values in the patient with following good clinical recovery and decreased values in the other one; in the latter case, MRI abnormalities were still present after ten days, until the patient’s exitus. The changes in DWI with normal ADC may be linked to brain edema with a predominant vasogenic component and therefore reversible, while the reduction in ADC is due to cytotoxic edema and linked to more severe, nonreversible, clinical picture. Brain MRI and particularly DWI and ADC maps provide not only a good and early representation of neurological complications during immunosuppressant therapy but can also provide a useful prognostic tool on clinical outcome of the patient.

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