Pharmacogenetics and pharmacogenomics of chronic kidney disease comorbidities and kidney transplantation

Abstract

Chronic kidney disease (CKD) is a worldwide major public health problem associated with increased risk of mortality and rate of hospitalization and decreased life expectancy. Progression from early to late stages of CKD generally results in the onset of new symptoms and concomitant complications. Frequent complications and comorbidities of CKD include fluid and electrolyte abnormalities, secondary hyperparathyroidism and renal osteo (known as Chronic Kidney Disease-Bone Mineral Disorder - CKD-BMD), hypertension and hyperlipidemia, anemia, metabolic acidosis, and several other comorbidities involving malnutrition, pruritus, and uremic bleeding. CKD patients are at increased risk of cardiovascular disease (CVD), which includes coronary heart disease (CHD), cerebrovascular disease, peripheral vascular disease, and heart failure. The management and prevention of these comorbidities, as well as the kidney transplant complications, are complex. Pharmacogenetics and pharmacogenomics have been applied to the management of CKD patients in both conservative and renal replacement treatments (dialysis and transplantation) trying to avoid the occurrence of drug-related problems and appearance of comorbidities. This chapter will discuss important findings in CKD pharmacogenetic and pharmacogenomic studies conducted to date and future research directions in this field. The focus will be on the CKD comorbidities (CKD-BMD and CVD) and calcineurin inhibitors (cyclosporine and tacrolimus) as immunosuppressive therapy. Although many studies are limited by small sample sizes and replication of the fi ndings is needed, several candidate genes have been identifi ed and are discussed here: CYP3A5, CYP3A4, ABCB1, CASR, VDR, GC, MTHFR, and RFC1. Thus, the future is promising for a personalized treatment of CKD, which will improve therapeutic outcomes, minimize side effects, and lead to a more cost-effective care.