Personalized immunosuppression after kidney transplantation.

Abstract

With advances in immunosuppressive therapy, there have been significant improvements in acute rejection rates and short-term allograft survival in kidney transplant recipients. However, this success has not been translated into long-term benefits by the same magnitude. Optimization of immunosuppression is important to improve the clinical outcome of transplant recipients. It is important to note that each patient has unique attributes and immunosuppression management should not be a one-size-fits-all approach. Elderly transplant patients are less likely to develop acute rejection but more likely to die from infectious and cardiovascular causes than younger patients. For those with post-transplant cancers and BK polyomavirus-associated nephropathy, reduction of immunosuppression can increase the risk of rejection. Therapeutic drug monitoring (TDM) is routinely used for dosage adjustment of several immunosuppressive drugs. It has been hoped that pharmacogenetics can be used to complement TDM in optimizing drug exposure. Among the various drug-genotype pairs being investigated, tacrolimus and CYP3A5 gives the most promising results. Different studies have consistently shown that CYP3A5 expressers require a higher tacrolimus dose and take longer time to achieve target blood tacrolimus levels than nonexpressers. However, for pharmacogenetics to be widely used clinically, further trials are necessary to demonstrate the clinical benefits of genotype-guided dosing such as reduction of rejection and drug-related toxicities. The development of different biomarkers in recent years may help to achieve true personalized therapy in transplant patients.