Biomarker for early renal microvascular and diabetic kidney diseases.

Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m, is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis.

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

Early stage of vascular disease and diabetic kidney disease (DKD stages 1 and 2) has been under-recognized, under common practice worldwide. The lack of sensitive diagnostic marker leads to late diagnosis and a progression of underlying vascular disease associated with chronic renal ischemia, which eventually intensifies the magnitude of DKD damage. Treatment at this late stage fails to correct the renal ischemia, or restore renal function, due to the altered vascular homeostasis associated with an impaired nitric oxide production.

Vascular response to vasodilator treatment in microalbuminuric diabetic kidney disease.

Under common practice, the conventional diagnostic marker such as microalbuminuria determination does not recognized early stage of diabetic kidney disease (normoalbuminuria, chronic kidney disease stage 1, 2); due to the insensitiveness of the available marker. Treatment at later stage (microalbuminuria) simply slows the renal disease progression, but is rather difficult to restore the renal perfusion. Intrarenal hemodynamic study in these patients revealed an impaired renal perfusion and abnormally elevated renal arteriolar resistances.

Urgent call for reconsideration of chronic kidney disease.

free radicals, cytokines and metabolic products induce glomerular endothelial dysfunction, hemodynamic maladjustment and chronic ischemic state;this leads to tubulointerstitial fibrosis in chronic kidney disease (CKD). Altered vascular homeostasis observed in late stage CKD revealed defective angiogenesis and impaired nitric oxide production explaining therapeutic resistance to vasodilator treatment in late stage CKD. Under current practice, CKD patients are diagnosed and treated at a rather late stage due to the lack of sensitivity of the diagnostic markers available.

Renal microvascular disease predicts renal function in diabetes.

Renal microvascular disease reflected directly by peritubular capillary flow reduction and indirectly by renal function impairment has been documented in early diabetic nephropathy (DN) associated with normoalbuminuria and normal serum creatinine concentration. The renal microvascular disease observed in early DN [chronic kidney disease (CKD) stages 1-2] could progress under current practice to late DN (CKD stages 3-5) with a further reduction in peritubular capillary flow. This advanced renal microvascular disease in late DN is characterized by therapeutic resistance to vasodilators and altered vascular homeostasis associated with impaired nitric oxide production.

Vascular homeostasis and angiogenesis determine therapeutic effectiveness in type 2 diabetes.

Under common practice, recognition and treatment of type 2 diabetic nephropathy (DN) are usually revealed at a rather late stage (CKD stages 3-5) due to the insensitiveness of available diagnostic markers. Accumulating data obtained from vascular homeostasis in late stage DN demonstrated (1) a defective angiogenesis and impaired NO production which explains the therapeutic resistance to vasodilators and the inability to correct chronic renal ischemia and (2) an abnormally elevated antiangiogenesis and a progressive vascular disease which correlates with the altered renal hemodynamics characterized by a progressive reduction in renal perfusion as the disease severity progressed. In contract, the vascular homeostasis is adequately functional in early stage DN.

A mildly altered vascular homeostasis in early stage of CKD.

Background: A continuous increase in number of CKD patients entering ESRD is a growing public health threat, which reflects the present therapeutic failure usually initiating at the late stage of CKD.

Objective: To study the mechanism of vascular repair in CKD patients associated with mildly impaired renal function, which included angiogenic factors such as VEFG, angiopoietin-1, and flt-1 (VEGFR1); and antiangiogenic factors such as angiopoietin-2 and KDR (VEGFR2).

Results: A mild defect in angiogenic factor-namely, angiopoietin-1-was observed, whereas VEGF and flt-1 (VEGFR1) were within normal limit.

Altered vascular homeostasis in type 2 diabetic nephropathy.

Type 2 diabetic nephropathy is a primary cause of ESRD worldwide. Therapeutic strategy in patients with microalbuminuric or macroalbuminuric type 2 diabetic nephropathy usually fails to restore renal function but merely slows the renal disease progression. In contrast, a recent study implies that the restoration of renal function as well as renal perfusion can be accomplished in early stage of type 2 diabetic nephropathy (normoalbuminuria) by correcting the hemodynamic maladjustment in renal microcirculation with vasodilators.

Microalbuminuria--a biomarker of renal microvascular disease.

Microalbuminuria (amount greater than 30-300 mg/day) reflects an abnormal glomerular capillary permeability to protein. It is usually dependent upon three mechanisms. First, loss of negatively charged surface of the glomerular capillary wall secondary to circulating toxic substances injury-namely, oxidative stress and proinflammatory cytokines-allows the albumin with negatively charged surface to freely escape into the urine.

Renal microvascular disease in an aging population: a reversible process?

Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis.

A defective angiogenesis in chronic kidney disease.

Background: A progressive reduction in peritubular capillary flow is observed in chronic kidney disease (CKD) patients as the disease severity progresses. This suggests an altered vascular homeostasis in CKD patients, but such a defective mechanism needs to be verified.

Methods: To study the vascular injury as reflected by circulating endothelial cell (CEC), the balance between angiogenic factor, vascular endothelial growth factor (VEGF), and antiangiogenic factor, endostatin.

Altered vascular homeostasis in chronic kidney disease.

Current treatments of chronic kidney disease (CKD) patients frequently result in progressive decline in renal perfusion, leading to the end-stage renal disease. Such renal failures may be a reflection of the progressive nature of renal microvascular disease. The aim of the present study is to elucidate the mechanism of microvascular homeostasis in CKD patients with moderately impaired renal function.