PP.07.14

Abstract

Objective: Hypertensive patients with chronic kidney disease (CKD) usually need multidrug therapy to control blood pressure (BP). For these patients, angiotensin II receptor antagonists (ARB) are effective antihypertensive agents to prevent organ damage but require caution for hyperkalemia, while diuretics may have adverse effects on glucose, lipids and uric acid metabolism. However, the risk of ARB-induced hyperkalemia may be reduced by adding diuretics. Nevertheless, the effect of ARB/diuretics combination on BP regulation in patients with advanced CKD is unclear. Design and method: The study examined BP and other parameters in hypertensive (>140/90 mmHg) CKD patients treated by a fixed-dose combination product of losartan (50 mg) and hydrochlorothiazide (12.5 mg). Serum potassium and uric acid, BP, and the slope of 1/serum creatinine level (1/SCr; rate of decline of renal function) were measured at 0, 4, 8, 12 and 24 weeks of treatment. Patients were divided by estimated glomerular filtration rate (eGFR) into a CKD1–2 (eGFR > 60 ml/min/1.73 m2, 18 men and 11 women, aged 61 ± 9 years) and a CKD > 2 group (eGFR < 60 ml/min/1.73 m2, 16 men and 12 women, aged 60 ± 8 years). Results: The CKD1–2 group showed a significant (P < 0.01) decrease in BP (systolic/diastolic) from 153 ± 12/91 ± 10 to 143 ± 15/75 ± 5 mmHg at 4 weeks of treatment and maintained similar levels thereafter. In the CKD > 2 group, BP also decreased significantly (P < 0.01) from 151 ± 14/79 ± 5 to 142 ± 15/86 ± 4 mmHg at 8 weeks of treatment and stabilized thereafter. Serum potassium concentrations did not change both in the CKD1–2 (from 4.2 to 4.3 mEq/L at 24 weeks) and CKD > 2 groups (from 4.2 to 4.3 mEq/L). The 1/SCr during the 24-week study period did not differ between the CKD1–2 (0.0062 ± 0.0022 dL/mg/month) and CKD > 2 groups (0.0068 ± 0.0029 dL/mg/month). Serum uric acid levels did not increase both in the CKD1–2 (from 5.2 ± 1.6 to 6.7 ± 2.1 mg/dL at 24 weeks) and CKD > 2 groups (from 7.0 ± 1.8 to 7.6 ± 3.9 mg/dL). Conclusions: These results suggest that losartan/hydrochlorothiazide fixed combination therapy decreases BP effectively and safely without affecting serum potassium concentrations in hypertensive patients with CKD grade 3 and above. Thus, the fixed combination therapy may confer renoprotection even in advanced CKD.