Pharmacogenomics-Guided Precision Therapy for Chronic Kidney Disease with Resistant Hypertension: A Prospective Cohort Study.

Abstract

Introduction: Managing blood pressure in patients with chronic kidney disease (CKD) complicated by resistant hypertension (RH) remains a major clinical challenge. The clinical utility of pharmacogenomics (PGx) in this high-risk population has not been well established. This study aimed to evaluate the effectiveness of PGx-guided precision therapy on blood pressure control, medication optimization, and treatment safety in CKD patients with RH.

Methods: A single-center prospective cohort study was conducted using the Yidu Cloud big data platform at People's Hospital of Xinjiang Uygur Autonomous Region. Sixty-five patients with CKD and RH were enrolled and randomized into either an empirical treatment group (Empirical group, n = 22) or a PGx-guided group (PGx group, n = 43). Patients in the PGx group received individualized therapy based on genetic testing covering 21 antihypertensive drugs, whereas the Empirical group received conventional empirical treatment. The primary endpoint was the rate of achieving target blood pressure (systolic BP <140 mm Hg, diastolic BP <90 mm Hg) at 24 months. Secondary endpoints included medication optimization, incidence of adverse events, and changes in kidney function.

Results: The PGx group demonstrated earlier and greater improvement in blood pressure control compared with the Empirical group. At 0.5 months, the proportion of patients achieving systolic BP targets was significantly higher in the PGx group (20.93% vs. 0%, p = 0.021). By 3 months, the diastolic BP target achievement rate had markedly increased (72.09% vs. 27.27%, p = 0.001) and was sustained through 24 months (systolic BP target rate 44.18% vs. 13.63%, p = 0.014). Medication optimization analysis showed a 46.5% reduction in the proportion of patients requiring four to 5 antihypertensive agents in the PGx group, compared with 31.8% in the Empirical group, alongside a 41% lower risk of adverse events (34.88% vs. 59.09%, p = 0.016). Genotyping revealed high responsiveness to angiotensin II receptor blockers (candesartan 86.05%, telmisartan 79.07%, irbesartan 76.74%) and calcium channel blockers (amlodipine, nitrendipine, and felodipine all 81.40%), whereas angiotensin-converting enzyme inhibitors showed generally poor efficacy. Moreover, the decline in estimated glomerular filtration rate at 24 months was significantly less pronounced in the PGx group compared with the Empirical group (8.82% vs. 30.00%, p < 0.001), indicating a potential renal-protective effect.

Conclusion: PGx-guided precision therapy enables more rapid and sustained blood pressure control, reduces polypharmacy and adverse events, and slows kidney function decline in CKD patients with RH. This study represents the first PGx-based clinical trial in a multi-ethnic population from Northwest China, providing valuable evidence to support personalized treatment strategies for CKD with RH in East Asian populations.