Yaghoub Mollaei-Kandelous; Pedram Ahmadpoor; Mohsen Nafar; Mohammad Reza Khatami; Samad Farashi Bonab; Nader Tajik; Mahdi Shekarabi; Aliakbar Amirzargar
Abstract
Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.Objective: ...
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Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.Objective: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.Methods: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.Results: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.Conclusions: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.
Nasrollah Ghahramani
Abstract
The subject of transplant immunosuppression has generated significant interest in recent years. Excellent immunosuppression, advances in surgical technique, post-transplantation care, and infection control have resulted in excellent outcomes. There is widespread support for the notion that the fundamental ...
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The subject of transplant immunosuppression has generated significant interest in recent years. Excellent immunosuppression, advances in surgical technique, post-transplantation care, and infection control have resulted in excellent outcomes. There is widespread support for the notion that the fundamental objective in transplant immunology should be the achievement of specific graft tolerance. However, until this objective evolves into reality, investigators are in search of the “ideal immunosuppressant”, which should target predominantly the immune system with minimal consequences for other tissues and minimal metabolic, cardiovascular and renal complications. While immunosuppressants have been associated with a tremendous trade-off in terms of morbidity, new agents have provided the investigators with the opportunity to formulate strategies that employ combination therapies with the goal of decreasing doses of individual agents and minimizing their toxicities. Multiple small studies have addressed the issue of minimizing immunosuppressants, but there is a need for well-designed clinical trials which should evaluate protocols that will reduce acute rejection, as well as chronic allograft nephropathy. They should address methods to identify subsets of patients who would maximally benefit from avoidance or withdrawal of steroids or calcineurin inhibitors. Other promising areas of research include tolerance studies among the sensitized recipients, and development of optimal immunosuppression based on genotype. In general, future trials must include a more diverse population of recipients, particularly the immunologically high risk groups.
