Immunosuppressive Minimization Strategies in Kidney Transplantation

Abstract

The long-term graft survival in renal transplantation results is still controversial, the toxicity and adverse reactions of the immunosuppressive drugs are implicated, as well as cellular and humoral antigen-specific immune mechanisms; therefore, different strategies for adapting immunosuppression are used to reduce the complications associated with the use of these drugs. Calcineurin inhibitors (CNI) require an adequate dose-dependent concentration leading to the appearance of drug-related adverse reactions. The variability in the required dose of CNI leads to minimization strategies that do not result in a higher acute rejection (AR) incidence when compared to other immunosuppressive agents. Early steroid withdrawal is another strategy, although with an increase in AR, but without an impact on the function and survival of the renal graft. The reduction of mycophenolate mofetil to 1.5 g/day seems to be a therapeutic option, decreasing the infectious, hematological and gastrointestinal adverse reactions. Finally, alemtuzumab, bortezomib, belatacept and cellular therapies are in the search for the new treatments, whose premise is the induction of donor-specific nonresponse in the context of operational tolerance or mixed chimerism. The use of adapted and adequate immunosuppression has led to variable results and some are very encouraging; however, they must be validated with experimental studies.

Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study

“…Additionally, since the study relies on medication dispensation data where dosage is lacking, this information has not been taken into consideration. However, different minimization strategies can be applied to reduce the dosage of immunosuppressive maintenance drugs in order to limit complications associated with them, especially CNIs [ 60 ]. Since the study involved a long monitoring period, it’s plausible to assume that the different treatment groups encompassed patients assuming both low and high dosage therapies.…”

“…order to limit complications associated with them, especially CNIs [60]. Since the study involved a long monitoring period, it's plausible to assume that the different treatment groups encompassed patients assuming both low and high dosage therapies.…”

Validation and Adaptation of the “Modified Transplant Symptom Occurrence and Symptom Distress Scale” for Kidney Transplant Recipients

“…To prevent rejection, organ transplant recipients require life-long immunosuppression treatment [ 2 ]. Unfortunately, these extended drug treatments can trigger various side effects, including diabetes, heart disease, cancer, or infections [ 3 ]. Since these adverse side effects can have a negative impact on patients’ quality of life (QOL) [ 3 , 4 ], both objective and subjective evaluations of symptoms associated with immune system suppression are essential [ 5 , 6 ].…”

“…Unfortunately, these extended drug treatments can trigger various side effects, including diabetes, heart disease, cancer, or infections [ 3 ]. Since these adverse side effects can have a negative impact on patients’ quality of life (QOL) [ 3 , 4 ], both objective and subjective evaluations of symptoms associated with immune system suppression are essential [ 5 , 6 ]. Compared to those with end-stage kidney disease, kidney transplant recipients maintain a much higher quality of life [ 7 , 8 ], but side effects from the administration of immunosuppressants could limit this advantage in quality of care compared to the general population.…”