Improvement of Renal Function in Type 2 Diabetic Nephropathy

Abstract

FE Mg appears to be a more sensitive marker than microalbuminuria for the early detection of DN. Increased endothelial cell injury is reflected by enhanced circulating endothelial cell loss in conjunction with the increased TGF B and the decreased ratio between VEGF and TGF B. This is further supported by the dysfunctioning glomerular endothelium, which is characterized by hemodynamic maladjustment and a reduction in the peritubular capillary flow. A correction of such hemodynamic maladjustment by multidrug vasodilators effectively improves renal perfusion and restores renal function in type 2 DN.

Vascular repair is vulnerable to renal regeneration in early stage of diabetic nephropathy

“…The above view is further supported by clinical trial with multi-drug vasodilators such as enalapril 5-10 mg/D, angiotensin receptor blocker (Micardis) 40-80 mg/D, in addition to the correction of metabolic disorders, which has indeed increased renal plasma flow and peritubular capillary flow in conjunction with the increase in actual creatinine clearance [6,7]. The reduction in fractional excretion of magnesium following treatment implies that there is likely reduction in the degree of tubulointerstitial fibrosis, or it reflects renal regeneration.…”

Normalization of kidney dysfunction in normotensive, normo-albuminuric type 2 diabetes

“…Under common general medical practice, therapeutic intervention of renal ischemia is usually initiated at a rather late stage (chronic kidney disease (CKD) stage 3; creatinine clearance less than 60 mL/min/1.73 m 2 ) due to the insensitiveness of the available diagnostic marker such as serum creatinine determination or microalbuminuria, which recognizes only late stages CKD, but is unable to screen the early stages CKD. 1,2 In this stage, therapeutic vasodilators fail to enhance the peritubular capillary flow, which is due to the altered vascular homeostasis associated with an impaired nitric oxide production. 7 This would explain the therapeutic resistance observed under conventional medical practice at the late stage of diabetic nephropathy, as well as the progressive increment in number of diabetic nephropathic patients entering end-stage renal failure.…”

“…Such early impaired renal function usually correlates with (i) the altered renal hemodynamics characterized by reductions in renal plasma flow and peritubular capillary flow, 1 an abnormally elevated renal arteriolar resistance and a glomerular hyperfiltration 2,3 and (ii) an abnormally elevated value of fractional excretion of magnesium (FE Mg) À a biomarker, which directly reflects the presence of tubulointerstitial fibrosis in this early stage of diabetic nephropathy, since FE Mg has previously been demonstrated to correlate directly with the magnitude of tubulointerstitial fibrosis. 4 The altered renal hemodynamics observed implies the presence of renal microvascular disease in this early stage of diabetic nephropathy.…”

Early stage of vascular disease and diabetic kidney disease: an under-recognized entity

“…Recently, we have an interesting observation to demonstrate a reversal of altered vascular homeostasis toward normal in early stage of chronic kidney disease under treatment, implying that a primary prevention of vascular disease as well as the development of target organ damage is likely plausible in the near future. 36,37,40,41 To further support this concept of early detection and prevention of vascular disease and DKD, the Bhumirajanagarindra Kidney Institute under The Royal Patronage and the Ministry of Public Health of Thailand have set up a policy to extend this pilot study which is presently on -going in several provinces in the country.…”

“…35,36 In fact, vasodilator treatment of both diabetic and non-DKD at this early stage, could improve renal perfusion as well as restore the renal function. 2,3,[37][38][39][40][41] An ability to correct renal ischemia and restore renal function would effectively prevent the progression of vascular disease as well as the entering of end-stage renal disease. Recently, we have an interesting observation to demonstrate a reversal of altered vascular homeostasis toward normal in early stage of chronic kidney disease under treatment, implying that a primary prevention of vascular disease as well as the development of target organ damage is likely plausible in the near future.…”