Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.
Background: Kidney transplantation outcomes in resource-limited settings remain underreported. This 10-year retrospective review examined the clinical characteristics, long-term pharmacokinetics, and outcomes of kidney transplant recipients at a South African public hospital. Methods: Data from kidney transplant recipients between January 2012 and December 2022 were analysed. Graft and patient survival were assessed using Kaplan–Meier analysis. Cox proportional hazards models were used to evaluate the associations between clinical and pharmacokinetic variables and outcomes. Results: The one- and five-year graft survival rates were 87.9% and 65.6%, respectively. Acute rejection, as confirmed by biopsy, was associated with graft failure (HR, 2.46; p = 0.010). Increasing recipient age at transplantation increased the graft failure risk by about 5.0% per year (HR: 1.05, p = 0.006). Tacrolimus trough and normalised trough levels were lower in the graft loss group 73% and 93% of the time, respectively, despite similar tacrolimus doses. Whereas achieving optimal tacrolimus concentration did not significantly affect graft survival, maintaining a haemoglobin level >10 g/dL improved the chances of 3-, 4-, and 5-year graft survival (p-value, 0.001, 0.001, and <0.001, respectively). Patient survival rates were more favourable than graft survival rates. The 1-year and 5-year patient survival rates were 90.0% and 77.4%, respectively. Conclusions: This study offers insights into transplant outcomes in low-resource public health settings. The findings emphasise the impact of rejection and age on the risk of graft failure and the significance of maintaining adequate haemoglobin levels after transplantation. The results also indicate the need for more nuanced and personalised approaches to tacrolimus monitoring in the long-term following transplantation.