The Effect of ACE Gene Polymophism on the Antiproteinuric Effect of Angiotensin II Receptor Antagonist in Patients with Non-diabetic Chronic Renal Disease

Background : Angiotensin Ⅱ, a potent vasoconstrictor, plays a key role in renal injury and in the progression of chronic renal disease of diverse causes. In every organ system, the biologic effects of angiotensin Ⅱ are mediated through its interaction with specific receptors on cell membranes. Angiotensin Ⅱ receptor antagonist specifically inhibits angiotensin Ⅱ-mediated physiologic responses such as systemic and renal vasoconstriction, sodium reabsorption by renal proximal tubule, and stimulation of aldosterone and adrenergic hormone release by the adrenal gland. It has been reported that losartan angiotensin Ⅱ receptor antagonist, has a significant antiproteinuric effect in patients with diabetic and non-diabetic renal disease. This study was carried out to investigate the effect of angiotensin-converting enzyme (ACE) gene polymorphism on the renal response to angiotensin Ⅱ receptor antagonist in non-diabetic proteinuric chronic renal patients. Methods : Seventy patients with non-diabetic chronic renal disease with urinary protein excretion greater than 500 ㎎/day were enrolled in this prospective study. Subjects were given losartan 50 mg o.d. for the first 12 weeks, and then were given to 100 mg o.d. for another 12 weeks. Results : Twelve weeks and twenty-four weeks later, blood pressure, urinary protein excretion, total cholesterol, and triglyceride decreased significantly compared with baseline values. There was a significant correlation between the levels of baseline urinary protein excretion and the magnitudes of the reduction of urinary protein excretion after treatment with losartan. Baseline blood pressure, BUN, serum creatinine, and urinary protein excretion were not different in the responder group (patients with more than 30% reduction of urinary protein excretion after losartan treatment) compared with the nonresponder group. Systolic blood pressure and mean arterial pressure in the responder group were significantly lower than the nonresponder group after twelve and twenty-four weeks. Urinary protein excretion in the responder group was significantly lower than the nonresponder group after twelve weeks. When the patients were divided into three groups according to ACE gene polymorphism, Ⅱ, ID and DD, there were no significant differences in the blood pressure change, reduction of urinary protein excretion following losartan treatment and distributions of responder among three groups. Conclusion : Our results suggest that angiotensin Ⅱ receptor antagonist, losartan, significantly reduced blood pressure and proteinuria in patients with non-diabetic chronic renal disease. The magnitude of antiproteinuric effect of losartan was not influenced by ACE gene polymorphism. However, further studies with large number of patients are required to confirm the issues regarding the ACE gene polymorphism and the antiproteinuric effects of angiotensin disease.ope