Effects of therapy on renal impairment in essential hypertension

The effect of hydrochlorothiazide 50 mg, amiloride 5 mg (HCTZ-A) (Moduretic; MSD) and its combination with pindolol and nadolol on renal function were compared in patients with mild to moderate essential hypertension (mean untreated supine blood pressure 179 +/- 5.7/108 +/- 2.6 mmHg) with compromised renal function (glomerular filtration rate (GFR) < 85 ml/min). After randomisation to a beta-blocker plus diuretic, the beta-blocker was washed out (diuretic-only period) and the other beta-blocker added. Eleven patients completed the randomised cross-over comparative study, 5 receiving pindolol 15 mg plus 1 dose of HCTZ-A daily for 6 weeks, and 6 nadolol 120 mg plus 1 dose of HCTZ-A daily. The beta-blocker was then withdrawn for 4 weeks, after which each group of patients received 1 dose of HCTZ-A plus the alternative beta-blocker daily for 6 weeks. The GFR was measured using chromium-51-ethylenediamine-tetra-acetic acid at the end of each treatment phase. The mean GFR (+/- SE) fell from 69.6 +/- 5.8 to 60.6 +/- 5.1 ml/min (P < 0.01) during HCTZ-A therapy, whereas the addition of pindolol or nadolol caused no further drop in the GFR. We conclude that mild degrees of renal impairment in essential hypertension may be aggravated by HCTZ-A therapy when given as one tablet of Moduretic daily.