Diabetes Care. 2003 Dec;26(12):3296-302. Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria. (IRMA-2) Andersen S， Brochner-Mortensen J， Parving HH; Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria Study Group. Steno Diabetes Center， Gentofte， Denmark. stan@dadlnet.dk

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% CI 8-53)， 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. min(-1). 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.