Search

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 m2, is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function. [ABSTRACT FROM PUBLISHER]

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. The renal microvascular disease is progressive as the disease severity progresses and eventually induces chronic renal ischemia and a progressive tubulointerstitial fibrosis. Further study has revealed that early DN is associated with an adequately functional vascular homeostasis. Therefore, recognition and treatment of early renal microvascular disease at early DN (stages 1-2) could enhance renal perfusion and restore renal function. [ABSTRACT FROM AUTHOR]

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. Second, intraglomerular hypertension and hemodynamic maladjustment secondary to glomerular endothelial dysfunction increases filtration pressure and enhances sized selective proteinuria leakage. Third, podocyte injury leads to a vicious cycle of hemodynamic maladjustment and endothelial and podocyte injuries. All three of these mechanisms induce glomerular endothelial injury and microalbuminuria, which reflects renal microvascular disease. [ABSTRACT FROM AUTHOR]

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. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process. [ABSTRACT FROM AUTHOR]

Renal hemodynamic study was performed in eight patients associated with type 1, early childhood diabetes mellitus (DM) and seven patients associated with type 2, early childhood DM. The results in both types of DM revealed a significant reduction in peritubular capillary flow and a high value of glomerular filtration rate (GFR) in the presence of reduced renal perfusion characteristic of glomerular hyperfiltration. These findings imply that renal ischemia has already developed in both types of early stage childhood DM and GFR is overestimated in DM, which may mislead to improper interpretation of renal function. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about the role of vascular endothelial growth factors on endothelial cell loss and impaired renal function.