Role of pharmacogenomics in dialysis and transplantation

Abstract

Purpose of Review Pharmacogenomics is the study of differences in drug response based on individual genetic background. With rapidly advancing genomic technologies and decreased costs of genotyping, the field of pharmacogenomics continues to develop. Application to patients with kidney disease provides growing opportunities for improving drug therapy. Recent Findings Pharmacogenomics studies are lacking in patients with chronic kidney disease and dialysis but are abundant in the kidney transplant field. A clinically actionable genetic variant exists in the CYP3A5 gene, with the initial tacrolimus dose selection optimized based on CYP3A5 genotype. Though many pharmacogenomics studies have focused on transplant immunosuppression pharmacokinetics, an expanding literature on pharmacodynamic outcomes like calcineurin inhibitor toxicity and new onset diabetes is providing new information on patients at risk. Summary Appropriately powered pharmacogenomics studies with well-defined phenotypes are needed to validate existing studies and unearth new findings in patients with kidney disease, especially the chronic kidney disease and dialysis population.

Prevalence of CYP3A5 Genomic Variances and Their Impact on Tacrolimus Dosing Requirements among Kidney Transplant Recipients in Eastern North Carolina

“…Other studies are looking beyond pharmacokinetics and pharmacodynamics. For example, research into intracellular lymphocyte concentrations of TAC and T‐lymphocyte proportions may yield beneficial information for improving drug therapy …”

“…For example, research into intracellular lymphocyte concentrations of TAC and Tlymphocyte proportions may yield beneficial information for improving drug therapy. 32,33 In recent years, growing evidence on the impact of CYP3A5 on TAC trough concentrations has been reported. However, clinicians and pharmacists are largely unfamiliar with current information supporting clinical use of these types of data.…”

Tacrolimus Utilization and Expenditure in Serbia

“…Current recommended protocols in the patients subjected to solid organ transplantation include calcineurin inhibitors (tacrolimus or cyclosporine) and antiproliferative agents (mycophenolate mofetil or azathioprine), with or without regimens of corticosteroids (4, 7, 8). …”

Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature

“…Gender, age, body mass index, hematocrit, diabetes status, liver dysfunction, drug interactions, etc., can also influence the variability in response to these drugs among patients ( 14 , 16 ). In addition, genetic factors are likely to play a major role as well ( 17 , 18 ).…”

“…Current recommended immunosuppression protocols in the patients subjected to renal transplantation include a combination of calcineurin inhibitors (tacrolimus or cyclosporine) and antiproliferative agents (mycophenolate mofetil or azathioprine), with and without regimens of corticosteroids ( 18 , 22 , 23 ). Tacrolimus as the first-line treatment is recommended by the Kidney Disease Improving Global Outcomes Transplant Work Group (KDIGO) ( 23 ).…”