Prasit Futrakul 1
and Narisa Futrakul 2
1 Fellow of the Royal Institute, Academy of Science
2 Department of Physiology, King Chulalongkorn Memorial Hospital, Bangkok
Abstract
The present therapeutic strategy fails to improve renal function in diabetes mellitus, which commonly leads to end-stage renal failure. It is noted that treatment is generally initiated at a late stage due to the lack of sensitivity of available diagnostic markers such as serum creatinine or microalbuminuria. We plan to study the mechanism of vascular repair in order to explain such therapeutic failure in diabetes mellitus. The study indicates that the mechanism of vascular repair is markedly defective in the late stage chronic kidney disease associated with diabetes mellitus. A defective angiogenic factor namely vascular endothelial growth factor (VEGF) receptor 1 induces an abnormal activation through the antiangiogenic pathway (VEGF → VEGF receptor 2) preventing enhancement of nitric oxide production. In contrast, adequate angiogenic factors namely VEGF, VEGF receptor 1 observed in the early stage diabetic nephropathy (normal serum creatinine, normoalbuminuria, a slightly impaired creatinine clearance, an abnormally elevated fractional excretion of magnesium reflecting chronic kidney disease), would activate through the classical pathway (VEGF → VEGF receptor 1), inducing coupling of endothelial nitric oxide synthase, and enhancing nitric oxide production. In accordance with the preceding information treatment at the early stage of diabetic nephropathy can restore renal perfusion and function.
Key words: diabetic nephropathy, vascular repair, renal perfusion, renal function, fractional excretion of magnesium, vasodilators