Autoregulated glomerular filtration rate during candesartan treatment in hypertensive type 2 diabetic patients

Abstract

Background: Impaired autoregulation of the glomerular filtration rate (GFR) implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus, leading to capillary hypertension or hypotension dependent of the level of blood pressure. The impact on renal autoregulation of different antihypertensive drugs in animals has been elucidated, whereas information in humans is lacking.

Methods: A randomized, double-blind crossover study with candesartan cilexetil 16 mg o.d. and placebo was performed in 17 hypertensive type 2 diabetic patients without nephropathy. Each treatment arm lasted four weeks. On the last day, GFR (single shot [51Cr] EDTA plasma clearance technique for 4 hours) was measured twice between 8 a.m. and 5 p.m., first without clonidine and then after an intravenous injection of clonidine 75 microg. Blood pressure (Takeda TM2420, A&D, Tokyo, Japan) was measured every ten minutes, and the urinary albumin excretion rate (UAER) was measured by ELISA during each GFR determination.

Results: Candesartan induced a mean (SE) reduction in mean arterial blood pressure (MABP) of 6 (2) mm Hg (P < 0.02) and had a tendency to reduce UAER (P = 0.07), while GFR remained unchanged (95 vs. 93 mL/min/1.73 m2). Clonidine reduced MABP with 17 (2) versus 16 (1) mm Hg during placebo versus candesartan 16 mg o.d., respectively (NS). GFR diminished in average from 95 (3) to 92 (4) mL/min/1.73 m2 with placebo (NS), and from 93 (3) to 89 (4) mL/min/1.73 m2 during treatment with candesartan (NS). The mean difference (95% CI) in the changes in GFR between the examination with placebo and with candesartan was 0.1 (-5.5 to 5.8) mL/min/1.73 m2 (NS).

Conclusion: Candesartan reduces blood pressure without adversely altering the preserved ability to autoregulate GFR in hypertensive type 2 diabetic patients without nephropathy.