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 doublemasked 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 Ϯ 2 (mean Ϯ SE), 103 Ϯ 2, and 102 Ϯ 2 mmHg, respectively (P Ͻ 0.05 versus baseline), and urinary albumin excretion rate reduced by 8% (Ϫ16 to 27) (NS), 34% (95% CI 8 -53), and 60% (46 -70) (P Ͻ 0.05). Rates of decline in GFR were 1.3 Ϯ 0.7, 1.2 Ϯ 0.7, and 1.0 Ϯ 0.8 ml ⅐ min -1 ⅐ 1.73 m -2 per month, respectively, during the initial 3 months of the study and 0.3 Ϯ 0.1, 0.3 Ϯ 0.1, and 0.4 Ϯ 0.1 ml ⅐ min -1 ⅐ 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 Ϯ 2 mmHg, but increased significantly in the irbesartan groups, to 109 Ϯ 2 and 108 Ϯ 2 mmHg, respectively. Compared with baseline, urinary albumin excretion rate was increased by 14% (Ϫ17 to 54) in the placebo group and by 11% (Ϫ26 to 65) in the irbesartan 150-mg group but was persistently reduced by 47% (24 -73) in the irbesartan 300-mg group (P Ͻ 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. Diabetes Care 26:3296 -3302, 2003S everal vasoactive hormones exhibit effects on renal hemodynamics, but angiotensin II is the major intrarenal hormone to regulate glomerular filtration rate (GFR) (1). Angiotensin II plays an important role in the initiation and progression of diabetic and nondiabetic glomerulopathies (2,3), but the recognized role of angiotensin II in the pathogenesis of diabetic renal disease cannot be attributed exclusively to its hemodynamic effects (4). Accumulating data suggest that angiotensin II exerts several nonhemodynamic effects, such as growth stimulation, fibrogenesis, and impairment of endothelial function (4). Studies in type 2 diabetic patients with incipient and overt diabeti...

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