Long-Term Effects of Amlodipine and Hydrochlorothiazide Combination Therapy on Creatinine Clearance in Hypertensive Nigerians

Blacks respond to therapy with amlodipine (AML) and hydrochlorothiazide (HCZ) with greater diuresis and natriuresis than whites, a situation that may lead to prerenal azotaemia and other problems. Although AML and HCZ are frequently used as antihypertensive agents in Nigeria, the effects of the combination treatment on renal function has been poorly examined. Therefore, to evaluate the effects of dual treatment with these drugs on creatinine clearance (Clcr), we enrolled 90 Nigerians of both gender 31-86 years with uncomplicated essential hypertension (blood pressure [BP] > 160/90 = 180/120 mmHg), into a randomized, open-label, prospective, two-centre, outpatient, 48-week study. Patients, who were 30 each (15 males (M) + 15 females (F)) in AML, HCZ and AML-HCZ groups, were treated, respectively, with AML 5mg for 6 weeks (wks) and the dose increased to 10mg till wk 12 (monotherapy) after which HCZ 25mg was added; HCZ 25mg till wk 6 (monotherapy) after which AML 5-10mg was added; and AML 5-10mg + HCZ 25mg. Body mass index (BMI), systolic BP (SBP) and diastolic BP (DBP), 24hrs urine volume, urine creatinine, serum creatinine and the corresponding Clcr were evaluated at baseline before treatment and at the end of wks 1, 3, 6, 12, 24, 36 and 48 during treatment. The 3 treatment regimens comparably significantly (P < 0.05) reduced BP. At week 48 M vs F reductions in SBP/DBP in AML, HCZ and AML-HCZ groups were, respectively, 37.88±2.46/30.86±1.45 vs 37.75±2.15/31.76±1.86, 37.66±1.50/28.67±1.56 vs 34.43±1.57/27.34±1.92 and 33.00±3.05/30.33±1.55 vs 31.67±2.86/31.33±1.95 mmHg. Diuresis was greatest and significant (P < 0.05) in HCZ group at week 1 with M vs F AML, HCZ and AML-HCZ levels being, respectively, 1523.33±57.34 vs 1486.00±56.09, 1621.33±36.49 vs 1586.67±37.01 and 1506.00±42.26 vs 1514.67±45.30 ml. Gender effect on Clcr was significant, for M values, respectively, in AML, HCZ and AML-HCZ groups (114.27±4.40, 108.36±4.19, 111.13±3.02 ml/min) were higher than the corresponding F values (107.20±2.30, 105.80±2.94, 104.80±2.69 mil/min, P < 0.0001). Duration of treatment effect was significant (P < 0.05) and while Clcr values appeared to increase in AML group, the reverse was the case in HCZ and AML-HCZ groups. However, changes in Clcr values were within normal range. It is concluded that long-term combination treatment with AML and HCZ does not cause clinically significant changes in Clcr; and also that it seems prudent to initiate treatment with AML to which HCZ is subsequently added instead of HCZ to which AML is later added or ab initio AML-HCZ combination.