The tradeoff between the efficacy of calcineurin inhibitors: prevention of allograft rejection vs. post-transplant renal and cardiovascular complications.

Solid organ transplantation has emerged as a crucial intervention in the field of medicine. During transplantation, our human body perceives the organ as an exogenous entity or graft, initiating an immune reaction to eliminate it. This immune response ultimately culminates in the rejection of the graft. So, to mitigate the possibility of graft rejection, implementing immune suppression is imperative. In this context, the utilization of calcineurin inhibitors (CNIs) assumes a pivotal role. Calcineurin inhibitors significantly preserve immunosuppression following solid organ transplantation. Calcineurin inhibitors have considerably improved short-term results in renal transplantation by reducing acute rejection rates. Concerning the limited therapeutic window of these medications, careful monitoring of pharmacological treatment and individual doses is required. However, a significant number of patients do experience CNI toxicity. Side effects of CNIs include renal failure, hypertension, respiratory disorders, gastrointestinal damage, gingivitis, and so on. Higher trough level of the drug causes acute nephrotoxicity, which is of three types: functional toxicity, tubular toxicity, and vascular toxicity. Acute nephrotoxicity, if untreated, leads to irreversible, progressive deterioration of allograft function, leading to chronic nephrotoxicity. Cardiovascular toxicity of CNIs includes atrial hypertension caused by vasoconstriction of the afferent arteriole, vascular remodeling, hypertrophy, dyslipidemia, and also the onset of diabetes. Such clinical complications further affect the patient's survivability and subjective well-being, possibly leading to graft loss. This review focuses on the most severe side effects of CNIs: renal and cardiovascular toxicity.