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Abstract
Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life. Significant improvements in one-year renal allograft and patients’ survival rates have been achieved over the last 10 years primarily as a result of newer immunosuppressive regimens. Despite these notable achievements in the short-term outcome, long-term graft function and survival rates remain less than optimal. Death with a functioning graft and chronic allograft dysfunction result in an annual rate of 3%–5%. In this context, drug toxicity and long-term chronic adverse effects of immunosuppressive medications have a pivotal role. Unfortunately, at the moment, except for the evaluation of trough drug levels, no clinically useful tools are available to correctly manage immunosuppressive therapy. The proper use of these drugs could potentiate therapeutic effects minimizing adverse drug reactions. For this purpose, in the future, “omics” techniques could represent powerful tools that may be employed in clinical practice to routinely aid the personalization of drug treatment according to each patient’s genetic makeup. However, it is unquestionable that additional studies and technological advances are needed to standardize and simplify these methodologies.
Highlights
Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life
CYP3A5*3 allele is a splice variant with a premature stop codon and encodes an enzyme with a reduced activity. Patients homozygous for this variant require a dose of TAC approximately 50% lower to reach the blood target concentration compared with carriers of the CYP3A5*1 allele [24,25,26,27]
The DeKAF study, a pharmacogenomic analysis of 945 Kidney transplant recipients has shown that a number of single-nucleotide polymorphism (SNP) in several genes were associated with early cyclosporin A (CsA)-related nephrotoxicity [139]
Summary
The completion of the Human Genome Project [123,124] and the development of innovative high-throughput screening technologies (e.g., genome wide scans, haplotype analysis and candidate gene approaches) has led to the development of pharmacogenomics, a new science that, screening the entire genome, is able to recognize determinants of drug responses or toxicities. The use of pharmacogenetics/pharmacogenomics in clinical practice to personalize the dosage of a specific medication avoiding/minimizing its toxicity and enhancing its therapeutic effects, is referred as “personalized medicine”. There have been numerous clinical studies and molecular genetics research in this area, we are still far from the possibility of extensive use of pharmacogenomics in clinical practice, primarily because the clear-cut demonstration that genotype-based dosing could definitely improve clinical outcomes is still lacking. Medical students and practicing physicians must be educated and trained to use pharmacogenetic tests and properly interpret their clinical relevance [135,136]. As previously mentioned, the Clinical Pharmacogenetics Implementation Consortium has published guidelines on the use of TPMT genotyping in clinical practice [122]. The DeKAF study, a pharmacogenomic analysis of 945 Kidney transplant recipients has shown that a number of SNPs in several genes were associated with early CsA-related nephrotoxicity [139]
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