Autoregulation of Glomerular Filtration Rate in Patients With Type 2 Diabetes During Isradipine Therapy

Abstract

OBJECTIVE—Calcium-channel blockade impairs renal autoregulation in animals. Impaired renal autoregulation leads to transmission of the systemic blood pressure (BP) into the glomerulus, resulting in capillary hypertension. Information on the impact of calcium antagonist treatment on renal autoregulation in humans is lacking. This study examines the effect of isradipine treatment on the autoregulation of the glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS—We performed a randomized double-blind crossover study with 5 mg o.d. isradipine retard and matching placebo in 16 hypertensive patients with type 2 diabetes. Each treatment arm lasted 4 weeks. On the last day of each treatment period, GFR (single-shot 51Cr-EDTA plasma clearance technique for 4 h) was measured twice between 8:00 a.m. and 5:00 p.m., first without clonidine and then after intravenous injection of 75 μg clonidine. BP was measured every 10 min (Takeda TM2420; A&D, Tokyo). RESULTS—Clonidine reduced mean arterial BP (MABP) by 15 ± 1 vs. 11 ± 1 mmHg (means ± SE) during placebo and isradipine treatment, respectively (P < 0.05). GFR was reduced from 102 ± 4 to 99 ± 4 ml · min−1 · 1.73 m−2 with placebo (P < 0.01) and from 106 ± 5 to 98 ± 5 ml · min−1 · 1.73 m−2 during treatment with isradipine (P < 0.01). Mean difference (95% CI) between changes in GFR with placebo and isradipine was −4.6 ml · min−1 · 1.73 m−2 (−10.0 to 0.6) (P = 0.08). Six patients had a reduction in GFR >13% (exceeding the normal limit of autoregulation) combined with a complete pressure-passive vasculature (defined as ΔMABP% ≤ ΔGFR%) during isradipine treatment versus none during the placebo treatment (P < 0.05). CONCLUSIONS—Isradipine impairs GFR autoregulation in a sizeable proportion of hypertensive type 2 diabetic patients.