TY - JOUR
T1 - Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy
AU - Andersen, Steen
AU - Tarnow, Lise
AU - Rossing, Peter
AU - Hansen, Birgitte V.
AU - Parving, Hans Henrik
PY - 2000/1/1
Y1 - 2000/1/1
N2 - Background. Angiotensin I-converting enzyme (ACE) inhibitors reduce angiotensin II formation and induce bradykinin accumulation. Animal studies suggest that bradykinin may play a role for the effects of ACE inhibition on blood pressure and kidney function. Therefore, we compared the renal and hemodynamic effects of specific intervention in the reninangiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition. Methods. A randomized, double-blind, cross-over trial was performed in 16 type 1 diabetic patients (10 men), age 42 ± 2 years (mean ± SEM). The study consisted of five periods, each lasting two months. The patients received losartan 50 mg, losartan 100 mg, enalapril 10 mg, enalapril 20 mg, and placebo in random order. At the end of each period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were determined. Results. Both doses of losartan and enalapril reduced albuminuria (P < 0.05) and mean arterial blood pressure (MABP; P < 0.05), whereas GFR remained stable. Albuminuria was reduced by 33% (95% CI, 12 to 51) on losartan 50 mg, 44% (95% CI, 26 to 57) on losartan 100 mg, 45% (95% CI, 23 to 61) on enalapril 10 mg, and 59% (95% CI, 39 to 72) on enalapril 20 mg, and MABP fell by 9 ± 2, 8 ± 2, 6 ± 3, and 11 ± 3 mm Hg (mean ± SEM), respectively. No significant differences were found between the effects of losartan 100 mg and enalapril 20 mg. HbA(1C) and sodium intake remained unchanged throughout the study, whereas a significant rise in serum potassium occurred during ACE inhibition. Conclusion. The angiotensin II subtype 1 receptor antagonist, losartan, reduces albuminuria and MABP similar to the effect of ACE inhibition. These results indicate that the reduction in albuminuria and blood pressure during ACE inhibition is primarily caused by interference in the renin-angiotensin system. Our study suggest that losartan represents a valuable new drug in the treatment of hypertension and proteinuria in type 1 diabetic patients with diabetic nephropathy.
AB - Background. Angiotensin I-converting enzyme (ACE) inhibitors reduce angiotensin II formation and induce bradykinin accumulation. Animal studies suggest that bradykinin may play a role for the effects of ACE inhibition on blood pressure and kidney function. Therefore, we compared the renal and hemodynamic effects of specific intervention in the reninangiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition. Methods. A randomized, double-blind, cross-over trial was performed in 16 type 1 diabetic patients (10 men), age 42 ± 2 years (mean ± SEM). The study consisted of five periods, each lasting two months. The patients received losartan 50 mg, losartan 100 mg, enalapril 10 mg, enalapril 20 mg, and placebo in random order. At the end of each period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were determined. Results. Both doses of losartan and enalapril reduced albuminuria (P < 0.05) and mean arterial blood pressure (MABP; P < 0.05), whereas GFR remained stable. Albuminuria was reduced by 33% (95% CI, 12 to 51) on losartan 50 mg, 44% (95% CI, 26 to 57) on losartan 100 mg, 45% (95% CI, 23 to 61) on enalapril 10 mg, and 59% (95% CI, 39 to 72) on enalapril 20 mg, and MABP fell by 9 ± 2, 8 ± 2, 6 ± 3, and 11 ± 3 mm Hg (mean ± SEM), respectively. No significant differences were found between the effects of losartan 100 mg and enalapril 20 mg. HbA(1C) and sodium intake remained unchanged throughout the study, whereas a significant rise in serum potassium occurred during ACE inhibition. Conclusion. The angiotensin II subtype 1 receptor antagonist, losartan, reduces albuminuria and MABP similar to the effect of ACE inhibition. These results indicate that the reduction in albuminuria and blood pressure during ACE inhibition is primarily caused by interference in the renin-angiotensin system. Our study suggest that losartan represents a valuable new drug in the treatment of hypertension and proteinuria in type 1 diabetic patients with diabetic nephropathy.
KW - Glomerular filtration rate
KW - Hypertension
KW - IDDM
KW - Losartan
KW - Proteinuria
KW - Renin- angiotensin system
UR - http://www.scopus.com/inward/record.url?scp=0033917552&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1755.2000.00880.x
DO - 10.1046/j.1523-1755.2000.00880.x
M3 - Article
C2 - 10652037
AN - SCOPUS:0033917552
SN - 0085-2538
VL - 57
SP - 601
EP - 606
JO - Kidney International
JF - Kidney International
IS - 2
ER -