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Kidney Week

Abstract: PO2370

A Genotype-Guided Antihypertensive Therapy and CKD Care Precision Health Initiative

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Maddatu, Judith, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moorthi, Ranjani N., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Spiech, Katherine M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Sheth, Nehal, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

A precision health initiative was implemented, wherein pharmacogenomic predictors of antihypertensive response and genomic predictors of chronic kidney disease (CKD) were provided to clinicians caring for nephrology patients.

Methods

This is a prospective cohort study of 580 individuals who presented to outpatient nephrology clinics. Subjects were genotyped for 60 antihypertensive response variants and chronic kidney disease (CKD) predictors. Predictors included variants of CYP2D6 for metoprolol dosing and CYP2C9 for angiotensin receptor blocker dosing. Variants in APOL1, UMOD, and SHROOM3 were markers of CKD risk prediction. Subjects were followed to ascertain utilization of the genetic information by nephrologists.

Results

The cohort was 46% female and 43% African-American. Actionable variants were found in 85% of subjects. These variants are known to affect metabolism of a drug or contribute to CKD progression. The prevalence of actionable genotypes was 66% for CYP2D6, and 36% for CYP2C9. In African American subjects, 23% of CKD patients had two APOL1 risk variants. Clinicians adapted treatment for 43% of individuals with actionable genotypes. The primary nephrologist was surveyed for each subject. In the 143 subjects who completed follow-up, nephrologists reported a change in diagnosis in 44% of their patients and a change in management in 28.0% based on genotype. Clinicians discussed the genetic testing results with their patients in 83.9% of cases.

Conclusion

Nephrologists utilized a genetic testing panel of up to 60 variants in the routine care of their CKD patients. Pharmacogenomics predictors of disease response may prove to be very valuable the care of patients with chronic kidney disease .

Funding

  • NIDDK Support