สำนักราชบัณฑิตยสภา

The Journal of the Royal Institute of Thailand Volume II - 2010 Restoration of Renal Function in Diabetes Mellitus : Is It Plausible ? 88 There is a general consensus that treatment of diabetic nephropathy under common practice fails to restore renal function. It is noted that such diabetic patients are associated with altered serum creatinine concentrations, or the presence of proteinuria which reflects a rather late stage of chronic kidney disease (creatinine clearance less than 60 ml/min/1.73m 2 ). This is due to the lack of sensitivity of the available diagnostic markers such as serum creatinine or microalbuminuria, which become abnormal only when renal function impairment is approaching the 50 percent level. 1 Since renal microvascular disease is believed to be the crucial determinant inducing chronic renal ischemia and renal disease progression, the therapeutic target should be the administration of vasodilators to improve renal perfusion and function. 2 Surprisingly renal microvascular disease does not seem to respond to vasodilators in this late stage of diabetic nephropathy. We then decide to explore this issue further by studying the mechanism of vascular repair in order to explain why there is no response to vasodilators in these patients. Mechanism of vascular repair in the late stage of diabetic nephropathy (creatinine clearance less than 60 ml/min/1.73m 2 ) A defective mechanism of vascular repair was observed in these patients with the late stage of chronic kidney disease. 3 A defective angiogenic or classical pathway (VEGF → VEGF receptor 1) due to an impaired VEGF receptor 1 would trigger an abnormal activation of VEGF through the alternative (antiangiogenic) pathway (VEGF → VEGF receptor 2), which would be unable to induce coupling of endothelial nitric oxide synthase, and therefore unable to enhance nitric oxide production. This would explain the unresponsiveness of renal microvessels to vasodilators, and thus, the inability to induce vasodilation, and the failure to enhance renal perfusion and function in late stage diabetic nephropathy. Mechanism of vascular repair observed in the early stage of diabetic nephropathy (normal serum creatinine, normoalbuminuria, a mildly impaired creatinine clearance, an abnormally elevated fractional excretion of magnesium reflecting chronic kidney disease) In contrast to the above finding documented in the late stage diabetic nephropathy, the mechanism of vascular repair appears to be normal at an early stage of diabetic nephropathy. 4 In this regard, a normal status of angiogenic factors namely VEGF, VEGF receptor 1, would allow normal activation through the classical pathway, which would be able to induce coupling of endothelial nitric oxide