scholarly journals Calcineurin Inhibitor Toxicity in Solid Organ Transplantation

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Andrea Karolin ◽  
Vera Genitsch ◽  
Daniel Sidler

Calcineurin inhibitors (CNIs) have a substantial role in maintaining immunosuppression after solid organ transplantation (SOT). These drugs have a narrow therapeutic window, and individual doses and drug treatment monitoring are necessary. Still, a substantial proportion of patients suffer from short- or long-term calcineurin inhibitor toxicity (CNT), including kidney function impairment, hypertension, neurotoxicity, and metabolic disturbances. The authors discuss pathophysiology, clinical presentation, and histological features of CNT, with focus on renal manifestations. Furthermore, we elucidate recent and ongoing attempts to reduce the burden of CNT in SOT including CNI-sparing and CNI-free regimens.

2020 ◽  
Vol 8 (7) ◽  
pp. 977 ◽  
Author(s):  
Lorenzo Cavagna ◽  
Elena Seminari ◽  
Giovanni Zanframundo ◽  
Marilena Gregorini ◽  
Angela Di Matteo ◽  
...  

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.


Author(s):  
A. V. Shabunin ◽  
S. P. Loginov ◽  
P. A. Drozdov ◽  
I. V. Nesterenko ◽  
D. A. Makeev ◽  
...  

Rationale. To date, liver transplantation is the most effective method of treating end-stage liver failure, and therefore this treatment has become widespread throughout the world. However, due to the improvement in the quality of transplant care and an increase in the long-term survival of patients, the development of concomitant pathology, which often requires medical treatment, is inevitably associated with a higher life expectancy of liver transplant recipients. Thus, in patients who underwent liver transplantation, there is. a significant increase in the incidence of dyslipidemia. However, a long-term immunosuppressive therapy in organ transplant patients can adversely modify the effect of the prescribed drugs, which requires careful monitoring and consideration of drug interactions.Purpose. Using a clinical example to demonstrate the importance of taking drug interactions into account in the treatment of patients after organ transplantation receiving immunosuppressive drugs.Material and methods. In the presented clinical case, a patient after orthotopic liver transplantation performed in 2005 underwent a staged treatment of cicatricial stricture of choledochal anastomosis in the S.P. Botkin City Clinical Hospital. During the following hospitalization, the patient complained of minor muscle pain when walking. At doctor's visit 3 weeks before hospitalization, a local physician prescribed therapy with atorvastatin 10 mg per day due to an increase in blood plasma cholesterol levels. The patient underwent removal of the self-expanding nitinol stent. During the follow-up examination, the patient had no evidence of an impaired bile outflow, however, muscle pain and weakness progressively increased, the rate of diuresis decreased, and in the biochemical analysis of blood there was an abrupt increase in the concentration of creatinine, aspartate aminotransferase, alanine aminotransferase. Atorvastatin was canceled, a diagnosis of acute non-traumatic rhabdomyolysis was established, treatment with hemodialysis and plasma exchange was started on 03/05/2020. The last session of renal replacement therapy was 03/30/20.Results. With the restoration of the diuresis rate, there was a spontaneous decrease in the level of creatinine to 170 μmol/L. The patient was discharged with satisfactory renal and hepatic function. The pain syndrome completely resolved. Conclusion. Drug interactions between atorvastatin and cyclosporine have resulted in acute rhabdomyolysis with life-threatening consequences. This once again confirms the importance of taking drug interactions into account when managing patients after solid organ transplantation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Manuel Alfredo Podestà ◽  
Giuseppe Remuzzi ◽  
Federica Casiraghi

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.


2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Kara L. Watts ◽  
Ethan B. Fram ◽  
Mark Schoenberg ◽  
Farhang Rabbani

Perfusion ◽  
2020 ◽  
pp. 026765912093936
Author(s):  
Ernest G Chan ◽  
Matthew R Morrell ◽  
Patrick G Chan ◽  
Pablo G Sanchez

The ethical concerns of refusing lifesaving treatments after receiving an already limited resource such as a solid organ transplantation in a Jehovah’s Witness patient have been discussed in the literature. Many of these studies have concluded that with a multidisciplinary approach, solid organ transplantation is possible in the setting of Jehovah’s Witness patients. To date, there are no reported cases of bilateral sequential lung transplantation in the literature. We report two successful cases of bilateral sequential lung transplantation in Jehovah’s Witness patients with excellent long-term follow-up.


2018 ◽  
Vol 13 (11) ◽  
pp. 1760-1764 ◽  
Author(s):  
Paloma Leticia Martin-Moreno ◽  
Sudipta Tripathi ◽  
Anil Chandraker

The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.


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