만성 사구체 신염 환자에서 안지오텐신 수용체 차단제 투여가 단백뇨와 요중 TGF-β1에 미치는 효과

Abstract

Background : Urinary TGF-β1 reflects intrarenal TGF-β1 production and is increased in patients with progressive nephropathies. We studied the effects of angiotensin receptor blocker (ARB) on serum and urinary TGF-β1 excretion in chronic glomerulonephritis patients with proteinuria. Also the role of urinary TGF-β1 in ARB induced antiproteinuric responses was evaluated. Methods : Patients with non-diabetic chronic renal disease with proteinuria of 1 g or more were enrolled in this open, prospective study. After four weeks of washout period, the patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters and urinary indices including proteinuria and urinary TGF-β1 were measured at baseline and after each 12 week treatment period. Results : Among the 42 patients who completed the study, 31 responded to ARB therapy determined as a decrease in proteinuria by 30% (responders), and 11 did not respond (non-responders), ARB treatment controlled blood pressure to a similar degree in both responders and non-responders. Renal function and other biochemical parameters did not change during the study period. Both doses of losartan significantly lowered proteinuria and urinary TGF-β1 excretion in responders (50 mg : 33.4% and 29.0%, 100 mg : 64.1% and 45.8%, respectively, p<0.05). In contrast, non-responders showed no significant reduction in proteinuria and no further decrease in urinary TGF-β1 after 100 mg treatment. Urinary TGF-β1 excretion lacked any correlation between clinical parameters such as proteinuria or renal function. Responders were younger, showed lower baseline proteinuria and urinary TGF-β1 excretion and greater reduction in urinary TGF-β1 excretion after ARB treatment. However, lower baseline urinary TGF-β1 excretion was the only significant predictor of response to ARB therapy. Conclusion : Our data suggest that ARB therapy in nondiabetic proteinuric chronic glomerulonephritis patients reduces proteinuria and urinary TGF-β1 excretion and baseline urinary TGF-β1 excretion may predict antiproteinuric response to ARB therapy.