- To inform clinicians about the role of genetic variants as risk factors for kidney diseases.
- To assist clinicians in understanding how genomics can influence kidney disease progression.
- To inform clinicians about the contribution of pharmacogenomics toward patient care for kidney disorders.
- To provide clinicians with an understanding of how polymorphisms in drug metabolism and disposition genes can influence risks for drug-induced nephrotoxicity.
Chronic kidney disease (CKD) afflicts at least 21 million persons in the United States.1 The majority of CKD is due to long-standing and uncontrolled diabetes mellitus and hypertension. In addition to treatments aimed at reducing blood sugar and blood pressure, other common approaches for preserving kidney function include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for reducing proteinuria, immunosuppressants and cytotoxic compounds for glomerulonephritis, and immunosuppressants for kidney transplantation. There has been a large expansion of studies within the nephrology research community to identify genetic variants that pose a risk for a particular form of CKD or serve as a risk factor for its progression (Table 17B–1). The role of genetic polymorphisms on drug metabolism and disposition (DMD) in patients with CKD has more recently gathered interest. This aspect is important as CKD, independent of genetic variants, is known to influence both the renal and nonrenal clearance of drugs. Together, genomic and nongenomic factors could considerably influence the pharmacokinetics of drugs and overall responses to treatments in the CKD population. This chapter undergoes an extensive review of genomics in order that a comprehensive understanding of its role in nephrology is provided to clinicians and researchers (Figure 17B–1). This information will be necessary for clinicians as the field evolves to treatments targeted toward genes or aberrant proteins. Additionally, clinicians will need to understand how to provide adequate therapy regimens in the face of physiological and genetic alterations that are present in CKD patients.
Table 17b–1 Chronic Kidney Diseases with Associated Genetic Polymorphisms. ||Download (.pdf)
Table 17b–1 Chronic Kidney Diseases with Associated Genetic Polymorphisms.
Implications for genomics and kidney diseases. DMD, drug metabolism and disposition.
Data are emerging that implicate a role for genetic polymorphisms ...