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

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¹Fellow of The Royal Institute, Academy of Science.
²Department of Physiology, King Chulalongkorn 
Memorial Hospital, Bangkok.

Abstract 

Chronic kidney disease is underrecognized worldwide. This is mainly due to the lack of sensitivity of present diagnostic markers in common medical practice, such as serum creatinine, and microalbuminuria which usually detect late stage chronic kidney disease (actual creatinine clearance less than 60 ml/min/1.73m²) but are unable to screen for early stage chronic kidney disease (actual creatinine clearance over 60 ml/min/1.73m²)  insensitiveness of the present diagnostic markers unrecognizes the pres ence of underlying early stage of chronic kidney disease, and usually allow the dis eased stage to slowly progress towards late stage, without any appropriate therapeutic intervention. It is very unfortunate for the patient to generally receive treatment at the late stage of chronic kidney disease, since it has recently been demonstrated that the hanism of vascular repair is markedly impaired at the late stage. Therefore, it is not surprising to realize the progressive increment in number of chronic kidney disease patients entering end-stage renal disease, which is a growing public health threat. 

In contrast to the present therapeutic failure observed in late stage chronic kidney disease, we have recently demonstrated that the mechanism of vascular repair for renal regeneration appears to function (adequately) at the early stage of chronic kidney disease. Treatment initiated at the early stage of chronic kidney disease can improve renal perfusion, with clinical impact on the restoration of renal function, since integrity of renal structure and function is modulated by renal perfusion. 

In accordance with the preceding information, a new therapeutic paradigm to effectively prevent end-stage renal disease can be implemented by (1) all physicians to discard the old conceptual view attached to low sensitivity diagnostic markers, and to treatment at late stage of chronic kidney disease, and change to a new therapeutic paradigm at the early stage of chronic kidney disease by using a new sensitive diagnostic marker such as fractional excretion of magnesium (FE Mg) (2) appropriate treatment to improve renal perfusion by correcting the hemodynamic maladjustment which is the crucial determinant inducing renal disease progression, 

Key words: chronic kidney disease, vascular repair, renai regeneration, hemodynamic 

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