Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

New insight of immunosuppressive drugs related nephrotoxicity

E. Thervet

Ann Transplant 2008; 13(1): 10-10 :: ID: 880165


Even though the incidence of acute rejection episode has been dramatically lowered after organ transplantation, long-term results have not improved consequently. Nephrotoxicity is a major side effect of the powerful immunosuppressive drugs used and may precluded long-term outcome. This side effect is well-recognized for calcineurine inhibitors but sirolimus (SRL), a mTOR inhibitor, also exhibit nephrotoxicity especially after delayed graft function. For calcineurine inhibitors, in vivo and in vitro data demonstrate that P-glycoproteine may play a critical role in protecting renal epithelial cells from cyclosporine A (CsA) toxicity. Regarding the molecular mechanisms, transcriptional profiles of human proximal tubular cells exposed to CsA found that it preferentially alters biological processes located at the cell membrane, such as ion transport or signal transduction. Wide expression analysis suggested that CsA may induce an endoplasmic reticulum (ER) stress in tubular cells in vitro and in vivo, because of cyclophilin A inhibition. Furthermore, CsA induces epithelial phenotypic changes reminiscent of an incomplete epithelial-to-mesenchymal transition in a TGF-b independent manner, as did various ER stress inducers. Finally, in primary cultured human tubular cells CsA induces autophagy dependant of ER stress. SRL modifies biological processes within the nucleus and related to transcriptional activity. It inhibits the proliferative response to mitogenic stimuli, and causes cell cycle arrest in the early G(1) phase, by a nonspecifi c process due to inhibition of the p70(S6k) pathway and by a direct effect on cyclin D3 mRNA stability. All these data demonstrate that new pathways have been defined recently to better understand the immunosuppressive drug associated nephrotoxicity giving possible clues to prevent this complication.

Keywords: Organ Transplantation, nephrotoxicity, carcinomatosis, intraperitoneal chemotherapy, cancer


In Press

06 May 2022 : Original article  

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of D...

Ann Transplant In Press; DOI: 10.12659/AOT.936293  

27 Apr 2022 : Review article  

A Systematic Review of the Literature on Chronic Kidney Disease Following Liver Transplantation

Ann Transplant In Press; DOI: 10.12659/AOT.935170  

Most Viewed Current Articles

31 Dec 1969 : Original article  

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...

DOI :10.12659/AOT.933588

Ann Transplant 2021; 26:e933588

31 Dec 1969 : Review article  

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

DOI :10.12659/AOT.934924

Ann Transplant 2022; 27:e934924

31 Dec 1969 : Review article  

Kidney Transplantation in the Times of COVID-19 – A Literature Review

DOI :10.12659/AOT.925755

Ann Transplant 2020; 25:e925755

31 Dec 1969 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358