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

Objective: Managing blood pressure in patients with chronic kidney disease (CKD) complicated by resistant hypertension (RH) presents significant challenges. The clinical utility of pharmacogenomics (PGx) in this high-risk patient population requires investigation. This study aimed to assess the impact of PGx-guided precision therapy on blood pressure control, medication optimization, and safety in CKD patients with RH.
Methods: A single-center prospective cohort study was conducted utilizing the "Yidu Cloud" big data platform from Xinjiang Uygur Autonomous Region People's Hospital. Sixty-five CKD patients with RH were enrolled and randomized into either an empirical medication control group (Empirical group, n=22) or a PGx-guided group (PGx group, n=43). The PGx group received individualized treatment based on gene testing for 21 antihypertensive drugs, while the Empirical group received conventional treatment. The primary outcome was the BP target achievement rate (systolic BP <140 mmHg, diastolic BP <90 mmHg) at 24 months. Secondary outcomes included medication optimization, adverse events, and changes in kidney function. adverse eventadverse events.
Results: The PGx group exhibited significant improvements early in the intervention, achieving a higher systolic BP target rate at 0.5 months compared to the Empirical group (20.93% vs 0%, P=0.021). At 3 months, the diastolic BP target achievement rate increased significantly in the PGx group (72.09% vs 27.27%, P=0.001), maintaining an advantage through the 24-month endpoint (systolic BP target rate 44.18% vs 13.63%, P=0.014). Medication optimization in the PGx group showed a 46.5% reduction in patients requiring 4-5 drug combinations from baseline, compared to 31.8% in the Empirical group, along with a 41% reduction in overall adverse event risk (34.88% vs 59.09%, P=0.016). Genetic testing revealed high sensitivity to ARB drugs (candesartan 86.05%, telmisartan 79.07%, irbesartan 76.74%) and CCB drugs (amlodipine, nitrendipine, felodipine all 81.40%), with ACEI drugs generally showing poor efficacy. Additionally, the decline in eGFR at 24 months was significantly lower in the PGx group compared to the Empirical group (8.82% vs 30.00%, P<0.001), suggesting a protective effect on kidney function.
Conclusion: PGx-guided precision therapy facilitates rapid BP control, reduces polypharmacy and adverse events, and delays kidney function decline in CKD patients with RH. This study, the first PGx clinical trial targeting a multi-ethnic population in Northwest China, offers valuable insights into personalized treatment approaches for CKD with RH in East Asia.