Kidney Function during and after Withdrawal of Long-Term Irbesartan Treatment in Patients with Type 2 Diabetes and Microalbuminuria

Abstract

OBJECTIVE - Irbesartan is renoprotective in patients with type 2 diabetes and microalbuminuria. Whether the observed reduction in microalbuminuria is reversible (hemodynamic) or persistent (glomerular structural/biochemical normalization) after prolonged antihypertensive treatment is unknown. Therefore, the present substudy of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study (IRMA-2) investigated the reversibility of kidney function changes after withdrawal of 2 years' antihypertensive treatment. RESEARCH DESIGN AND METHODS - The substudy included 133 hypertensive type 2 diabetic patients with persistent microalbuminuria in IRMA-2, randomized to double-masked treatment with either placebo, irbesartan 150 mg, or irbesartan 300 mg o.d. for 2 years. Arterial blood pressure, overnight urinary albumin excretion rate, and glomerular filtration rate (GFR) were determined repeatedly. RESULTS - Baseline characteristics were similar in the placebo, irbesartan 150-mg, and irbesartan 300-mg groups. At the end of the study, mean arterial blood pressure (MABP) was similarly lowered to 105 ± 2 (mean ± SE), 103 ± 2, and 102 ± 2 mmHg, respectively (P < 0.05 versus baseline), and urinary albumin excretion rate reduced by 8% (-16 to 27) (NS), 34% (95% C118-53), and 60% (46-70) (P < 0.05). Rates of decline in GFR were 1.3 ± 0.7, 1.2 ± 0.7, and 1.0 ± 0.8 ml · min -1 · 1.73 m-2 per month, respectively, during the initial 3 months of the study and 0.3 ± 0.1, 0.3 ± 0.1, and 0.4 ± 0.1 ml · min1 · 1.73 m-2 per month in the remaining study period. One month after withdrawal of all antihypertensive medication, MABP remained unchanged in the placebo group, 105 ± 2 mmHg, but increased significantly in the irbesartan groups, to 109 ± 2 and 108 ± 2 mmHg, respectively. Compared with baseline, urinary albumin excretion rate was increased by 14% (-17 to 54) in the placebo group and by 11% (-26 to 65) in the irbesartan 150-mg group but was persistently reduced by 47% (24-73) in the irbesartan 300-mg group (P < 0.05). GFR levels increased to baseline values in the placebo group and approached initial levels in irbesartan groups. CONCLUSIONS - Persistent reduction of microalbuminuria after withdrawal of all antihypertensive treatment suggests that high-dose irbesartan treatment confers long-term renoprotective effects.