scholarly journals Renal Dysfunction in Liver Transplantation: The Problem and Preventive Strategies

2004 ◽  
Vol 18 (suppl c) ◽  
pp. 27C-40C ◽  
Author(s):  
Marcelo Cantarovich
Keyword(s):  
Liver Transplantation ◽  
Adverse Effects ◽  
Renal Dysfunction ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Therapeutic Monitoring ◽  
Wide Range ◽  
Nephrotoxic Drugs ◽  
Poor Outcomes

Ongoing improvements in survival following liver transplantation have necessitated a re-evaluation of immunosuppression protocols. Corticosteroids and calcineurin inhibitors (CNIs) are the most frequently used immunosuppressive drugs for liver transplantation but are associated with a wide range of adverse effects, such as hypertension, hyperlipidemia and nephrotoxicity. The need for hemodialysis after liver transplantation is associated with poor outcomes. Renal dysfunction in this setting may be caused by pre-existing renal disease, hepatorenal syndrome and/or post-transplant factors, including the use of nephrotoxic drugs, most notably CNIs such as cyclosporine and tacrolimus. The methods that address this problem include the diligent control of metabolic factors (eg, hypertension and hyperlipidemia), therapeutic monitoring of CNIs and withdrawal or reduction of the dosage of CNIs, combined with the use of newer non-nephrotoxic agents. Although there is no clear consensus about the most effective strategy, the optimal long-term immunosuppressive regimen would prevent rejection without causing nephrotoxicity or other significant adverse effects. Recent evidence suggests that the liver is a tolerogenic organ and that some patients may need little, if any, long-term immunosuppression.

Immunosuppression in Liver Transplantation: State of the Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3389-3401
Author(s):  
Geir I. Nedredal ◽  
Rafael V. Picon ◽  
Marcio F. Chedid ◽  
Aksel Foss
Keyword(s):  
Liver Transplantation ◽  
Adverse Effects ◽  
Mtor Inhibitor ◽  
Patient Survival ◽  
Interleukin 2 ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Antibody Mediated Rejection ◽  
Novel Drugs

Background: Novel drugs and combinations for immunosuppression (IS) after liver transplantation is one main reason for improved graft and patient survival seen in the last decades. The backbone of IS is still steroids and calcineurin inhibitors, although novel drugs are being introduced, such as the mammalian target of rapamycin inhibitors (mTOR inhibitor). The challenge today, along with increased patient survival, is the adverse effects of long-term use of immunosuppressive drugs, mainly nephrotoxicity and other serious adverse effects. Concepts: The ultimate outcome after liver transplantation would be achieving tolerance, a state where all IS can be withdrawn. In the meantime, different approaches to reduce and withdraw IS have been tested out in different clinical trials with the aim to reduce the adverse effects of steroids and calcineurin inhibitors. This has formed the basis of today’s clinical practice. The different combinations of immunosuppressive drugs have included mTOR inhibitor such as everolimus and different induction drugs such as anti-interleukin 2 receptor antibodies. Regarding induction drugs, lymphocyte depleting (alemtuzumab and ATG) and non-depleting agents, such as basiliximab, have shown advantageous effects. Summary: Alongside steroid and calcineurin inhibitors reduction or elimination, current strategies for post-liver transplantation immunosuppression explore combinations of novel agents. The gauge (or yardstick) here is the fine balance between the adverse effects of IS drugs and the risk of rejection. Long-term maintenance IS regimens, development of tolerance and antibody-mediated rejection are also discussed in this review.

Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation

2003 ◽  
Vol 75 (2) ◽  
pp. 186-190 ◽  
Author(s):  
Maria Luisa Raimondo ◽  
Lucy Dagher ◽  
George V. Papatheodoridis ◽  
Nancy Rolando ◽  
David W. Patch ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mycophenolate Mofetil ◽  
Renal Dysfunction ◽  
Calcineurin Inhibitors

Posttransplant Calcineurin Inhibitors Levels and Intrapatient Variability Are Not Associated With Long-term Outcomes Following Liver Transplantation

2020 ◽  
Vol 104 (6) ◽  
pp. 1201-1209
Author(s):  
Tommaso Di Maira ◽  
Gonzalo Sapisochin ◽  
Les Lilly ◽  
Victoria Fonés ◽  
Marina Berenguer
Keyword(s):  
Liver Transplantation ◽  
Calcineurin Inhibitors ◽  
Long Term Outcomes ◽  
Intrapatient Variability

Treatment of Cyclosporine-Related Adverse Effects by Conversion to Tacrolimus After Liver Transplantation: Long-Term Results

1998 ◽  
Vol 30 (4) ◽  
pp. 1419-1421 ◽  
Author(s):  
J Pratschke ◽  
R Neuhaus ◽  
S.G Tullius ◽  
S Jonas ◽  
W.O Bechstein ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Adverse Effects ◽  
Long Term Results

scholarly journals The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence

2014 ◽  
Vol 2014 ◽  
pp. 1-45 ◽  
Author(s):  
Goran B. Klintmalm ◽  
Björn Nashan
Keyword(s):  
Metabolic Syndrome ◽  
Liver Transplantation ◽  
Renal Function ◽  
De Novo ◽  
Immunosuppressive Agents ◽  
Mammalian Target Of Rapamycin ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors

Despite the success of liver transplantation, long-term complications remain, includingde novomalignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms,de novotumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity.

Pets and Health

1998 ◽  
Vol 83 (3) ◽  
pp. 1011-1024 ◽  
Author(s):  
James Robert Brasić
Keyword(s):  
Adverse Effects ◽  
Objective Assessment ◽  
Wide Range ◽  
Follow Up Studies ◽  
Long Term Follow Up

Beneficial and adverse effects of pets for individuals in a wide range of circumstances have been reported. Nevertheless, well-designed unbiased experiments and long-term follow-up studies are needed. Pets appear to be therapeutic for some individuals and deleterious for others. The controversies concerning the effects of pets on health merit objective assessment by unbiased researchers.

scholarly journals Steroid induced psychiatric adverse effects: an overview of risk factors, clinical features and management

2020 ◽  
Vol 8 (6) ◽  
pp. 2365
Author(s):  
Anant Parasher ◽  
Jeplin Bez
Keyword(s):  
Adverse Effects ◽  
Steroid Therapy ◽  
Wound Repair ◽  
Glucocorticoid Receptors ◽  
Psychiatric Symptoms ◽  
Immunosuppressive Drugs ◽  
Psychotic Symptoms ◽  
Metabolic Disturbances ◽  
Duration Of Treatment

Corticosteroids have been in use since the past five decades as anti-inflammatory and immunosuppressive drugs for the treatment of several pathologies such as asthma, allergy, rheumatoid arthritis, and dermatological disorders. Adverse effects include growth retardation in children, immunosuppression, hypertension, hyperglycemia, inhibition of wound repair, osteoporosis, metabolic disturbances, glaucoma, and cataracts. The psychiatric effects of steroids are due to the wide expression of Glucocorticoid Receptors in the brain, and their long-term modulation can lead to functional and anatomical alterations along with hippocampal dysfunction. In most cases, the psychiatric symptoms disappear on cessation of steroid therapy; others may require some form of therapeutic management. A search was conducted for clinically relevant articles from 1971 to 2016 by including the terms corticosteroids, mania, depression, psychosis and cognitive defects. About one-fifth of patients receiving high doses of corticosteroids develop psychiatric symptoms. These symptoms are observed to be dose-dependent and generally occur during the first few weeks of therapy. Lithium has a preventive as well as therapeutic role, while antipsychotics are reserved for high risk cases with predominant psychotic symptoms. Psychiatric effects of long term steroid therapy have become increasingly common nowadays due to long duration of treatment of many chronic respiratory and orthopedic illnesses. Reduction in the dose or complete discontinuation of steroid therapy has been proven beneficial in many patients. Among the therapeutic options, lithium has a definitive role, both in the prevention as well as treatment of psychiatric symptoms. Better co-ordination between the physician and psychiatrist can go a long way to improve the quality of life in these patients. 

scholarly journals Positive and Negative Effects of Antipsychotic Medication: An International Online Survey of 832 Recipients

2019 ◽  
Vol 14 (3) ◽  
pp. 173-181 ◽  
Author(s):  
John Read ◽  
James Williams
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Antipsychotic Medication ◽  
Online Survey ◽  
Negative Effects ◽  
Duration Of Treatment ◽  
Direct To Consumer ◽  
Poor Outcomes

Background: Antipsychotic medication is currently the treatment of choice for psychosis, but few studies directly survey the first-hand experience of recipients. Objective: To ascertain the experiences and opinions of an international sample of users of antipsychotic drugs, regarding positive and negative effects. Methods: An online direct-to-consumer questionnaire was completed by 832 users of antipsychotics, from 30 countries – predominantly USA, UK and Australia. This is the largest such sample to date. Results: Over half (56%) thought, the drugs reduced the problems they were prescribed for, but 27% thought they made them worse. Slightly less people found the drugs generally ‘helpful’ (41%) than found them ‘unhelpful’ (43%). While 35% reported that their ‘quality of life’ was ‘improved’, 54% reported that it was made ‘worse’. The average number of adverse effects reported was 11, with an average of five at the ‘severe’ level. Fourteen effects were reported by 57% or more participants, most commonly: ‘Drowsiness, feeling tired, sedation’ (92%), ‘Loss of motivation’ (86%), ‘Slowed thoughts’ (86%), and ‘Emotional numbing’ (85%). Suicidality was reported to be a side effect by 58%. Older people reported particularly poor outcomes and high levels of adverse effects. Duration of treatment was unrelated to positive outcomes but significantly related to negative outcomes. Most respondents (70%) had tried to stop taking the drugs. The most common reasons people wanted to stop were the side effects (64%) and worries about long-term physical health (52%). Most (70%) did not recall being told anything at all about side effects. Conclusion: Clinical implications are discussed, with a particular focus on the principles of informed consent, and involving patients in decision making about their own lives.

scholarly journals Effect of cyclosporin and tacrolimus on kidney function in liver recipients

2018 ◽  
Vol 4 (3) ◽  
pp. 37-42
Author(s):  
Elena Kosmacheva ◽  
Anna Babich
Keyword(s):  
Chronic Kidney Disease ◽  
Liver Transplantation ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Kidney Function ◽  
Filtration Rate ◽  
Calcineurin Inhibitors

Introduction. Chronic renal failure is a significant issue regarding treatment of patients after liver transplantation. One of the factors determining the impaired renal function after liver transplantation is a long-term immunosuppressive therapy based on calcineurin inhibitors. The objective of the study was to evaluate the dynamics of renal function, depending on the use of various calcineurin inhibitors in the long-term postoperative period in liver recipients in real clinical practice. Materials and methods. A retrospective analysis of the renal function in patients operated in the State Public Health Budget Institution “Scientific Research Institute – S.V. Ochapovsky Regional Clinic Hospital № 1”, Krasnodar Region, was carried out. This article describes dynamics of creatinine level and glomerular filtration rate (GFR) in patients before liver transplant, as well as 6 months, 1, 2 and 3 years after surgery. GFR was calculated using the CKD-EPI formula (Chronic Kidney Disease Epidemiology Collaboration). Statistical processing of the results was carried out using the Statistica 10 software package. Results and discussion. Before transplantation, the level of creatinine in the blood plasma was 82.9±19.8 mmol/l, 6 months later a20.4% increase in creatinine was registered (p=0.004), 12, 24 and 36 months later – it increased by 24.8% (p=0.00001), 24.4% (p=0.0004), and 26.0% (p=0.0005), respectively. Both cyclosporine and tacrolimus caused an increase in the level of creatinine. Baseline GFR was 83.4±25.9, the reduction in GFR occurred in comparison with the baseline by 14.2% (p=0.0005), 18.8% (p=0.00001), 20.2% (p=0.00003), 22.6% % (p=0.00006) 6, 12, 24 and 36 months later, respectively. The degree of the decrease in GFR against the background of tacrolimus therapy did not differ significantly from that in case of cyclosporine. Verification of chronic kidney disease and the administration of statins were recorded in isolated cases. Conclusions. In liver recipients, the level of creatinine rises and GFR decreases. Reduction of kidney function occurs against the background of both inhibitors of calcineurin, in connection with which it is necessary to increase the doctors’ alertness for early detection of a decrease in glomerular filtration rate with further verification of chronic kidney disease.

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