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KMID : 0648320030090020109
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Journal of The Korean Society of Hypertension
2003 Volume.9 No. 2 p.109 ~ p.116
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Short-Term Effect of ACE Inhibitor and ATII Receptor Blocker in Patients with Advanced Stage of Diabetic Nephropathy with Renal Dysfunction
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Lim Hee-Jung
Lee Sun-Young
Park Geun-Ho
Kang Seong-Ryul
Song Joon-Ho
Lee Seoung-Woo
Kim Moon-Jae
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Abstract
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Background: The additive antiproteinuric effect of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists has been inconsistent according to underlying renal diseases in previous studies. To examine the possibility that the benefit of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists.
Methods: we underwent a crossover therapeutic trial of the combination therapy in patients with diabetic
nephropathy showing mild to moderate stage of renal dysfunction. The BP-reducing effect was excluded during the study.
Results: Twenty-four type 2 diabetic nephropathy patients were selected as study subjects, who met criteria
of creatinine clearance (Ccr) between 25 and 90 ml/min/1.73m2, 24-hr urinary protein excretion more than 1.0 g/day, and BP maintained less than 130/80 mmHg with more than six-month therapy of ramipril (5.7± 0.4 mg/day, 13±2 month). After a 12-week stabilization period (control period), 4 mg once daily dose of candesartan (combination period) followed by placebo (placebo period), or vice versa, were added on ramipril each for 12 weeks. The combination of candesartan did not change Ccr, BP, and serum and urinary electrolytes and urea. Twenty-four hour urinary protein excretion was not significantly reduced by the combination therapy (3.8±0.2 g/day in combination, 3.9±0.3 in control, and 4.1±0.3 in placebo; P=NS). The change in proteinuria showed no relationship with the change of BP.
Conclusions: In conclusion, the benefit of combination therapy in antiproteinuric effect was not shown in patients with diabetic nephropathy our short 12-week trial. Complexity of pathophysiological mechanism other than the activation of renin-angiotensin system in diabetic nephropathy might contribute to this unexpected result. Further studies with prolonged period of the combination therapy and elevation of drug doses are required.
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KEYWORD
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ACE inhibitors, Angiotensin II receptor blockade, Diabetic nephropathy
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