Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy.
BACKGROUND
Growth factors have been suggested to play a role in the development and progression of diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. The aim of the present study was to investigate plasma levels of VEGF in a large cohort of type 1 diabetic patients with diabetic nephropathy and in long-standing type 1 diabetic patients with persistent normoalbuminuria, and to evaluate VEGF as a predictor of nephropathy progression.


METHODS
We measured VEGF with an enzyme-linked immunosorbent assay (ELISA) technique in 199 type 1 diabetic patients with diabetic nephropathy (122 males, age 41 +/- 10 years, diabetes duration 28 +/- 8 years), glomerular filtration rate (GFR) (median [range]) 75 [10-143] mL/min/1.73 m2, and in 188 long-standing type 1 diabetic patients with persistent normoalbuminuria (115 males, age 43 +/- 10 years, diabetes duration 27 +/- 9 years). One hundred fifty-five of the proteinuric patients were followed for at least 3 years after baseline examination with yearly GFR measurements.


RESULTS
Plasma levels of VEGF were significantly increased in patients with nephropathy as compared to the normoalbuminuric group; (median [range]): 45.7 [22.0-410] versus 27.1 [22.0-355] ng/L, respectively, P < 0.001. This difference was ascribed to elevated VEGF levels in nephropathic men: 51.8 [22.0-410] versus 22.0 [22.0-308] ng/L, P < 0. 001. No differences were found between women with and without nephropathy: 37.8 [22.0-325] versus 36.6 [22.0-335] ng/L, NS. In proteinuric patients with GFR above and below the median value, there was no difference in the level of VEGF, NS. Plasma VEGF was below the detection limit (22.0 ng/L) in 60 patients with nephropathy and 93 patients with normoalbuminuria, P < 0.001. The mean rate of GFR decline was 3.5 (SE: 0.4) mL/min/year, and the following baseline variables acted as predictors of progression: albuminuria, mean arterial blood pressure and male gender. Hemoglobin A1c and plasma VEGF did not act as predictors. No significant differences between patients with and without proliferative retinopathy were detected.


CONCLUSIONS
Our data suggest that VEGF is elevated early in the course of diabetic nephropathy in men with type 1 diabetes mellitus. Baseline albuminuria, arterial blood pressure and male gender was predictors of diabetic nephropathy progression, while plasma VEGF and Hemoglobin A1c did not contribute. The importance of VEGF in the initiation of diabetic nephropathy remains to be established.
Hovind
P
P
Steno Diabetes Center, Gentofte, and Novo Nordisk, Bagsvaerd, Denmark.
Tarnow
L
L
Oestergaard
P B
PB
Parving
H H
HH
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008222:Lymphokines / Q000097:blood*; D008297:Male; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors