Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria.
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.


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.
Andersen
Steen
S
Steno Diabetes Center, Gentofte, Denmark. stan@dadlnet.dk
Bröchner-Mortensen
Jens
J
Parving
Hans-Henrik
HH
D000419:Albuminuria / Q000517:prevention & control*; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D000077405:Irbesartan; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D010919:Placebos; D013777:Tetrazoles; D000804:Angiotensin II; D000077405:Irbesartan