The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression.
OBJECTIVE
The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the production of vascular endothelium growth factor (VEGF). Further, we sought to elucidate the correlation between VEGF level and certain clinical parameters, such as albumin excretion rate (AER), before and after treatment with angiotensin type 1 receptor blocker.


METHODS
We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study. We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF) levels were determined using ELISA.


RESULTS
In the cross-sectional study, hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor. Statistical analysis indicated that uVEGF level was independently correlated with the AER. In the longitudinal study involving the 6-month irbesartan treatment, we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group, n=10). Furthermore, the change in uVEGF was significantly correlated with the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan treatment. This result held true even after we had adjusted for the decrease in average blood pressure.


CONCLUSIONS
The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF. Accordingly, it may be possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN.
Chen
Hai-Bing
HB
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Lu
Jun-Xi
JX
Li
Qing
Q
Bao
Yu-Qian
YQ
Tang
Jun-Ling
JL
Lu
Hui-Juan
HJ
Xiang
Kun-San
KS
Jia
Wei-Ping
WP
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000652:urine*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D000077405:Irbesartan