Screening for the earliest stages of renal damage and aggressively controlling blood glucose and blood pressure can help prevent more severe renal involvement. Sensitive tests are available to identify patients with renal involvement early in the clinical course, when preventive measures may have greatest impact.
Pathophysiology of Diabetic Nephropathy Creator: Luigi Gnudi Diabetic nephropathy is a devastating chronic microvascular diabetic complication, which represents the major cause of end stage renal failure today.
The mechanisms leading to the development and progression of this most feared diabetic complication are mainly poor metabolic and haemodynamic control. We should direct all our efforts into achieving good glycaemic and blood pressure control.
Prevention of diabetic nephropathy is our only tool to beat this disease currently. The prevention and management of diabetes and its renal complication is a huge global challenge: The concomitant increase in associated cardiovascular mortality and morbidity nearly 40 times higher in patients with nephropathy than in patients without nephropathyand end stage renal disease ESRD will result in significant social and economic impact, particularly in the developing world; this is particularly so for populations of Afro-Caribbean and Asian origin, who are known to have a significantly higher risk for renal disease.
Endothelial dysfunction precedes altered vascular permeability and albuminuria.
Markers of endothelial dysfunction such as soluble intercellular and vascular adhesion molecules, Von Willebrand Factor, and altered microvascular reactivity can be observed in patients with diabetes before any clinical manifestation of DN .
In this early phase, the prominent clinical manifestation of diabetic renal disease is characterised by an elevation of renal plasma flow and by an increase in glomerular filtration rate GFR.
Studies on filtration fraction, an indirect measure of glomerular capillary pressure, have shown that, in patients with diabetes, glomerular capillary pressure is elevated and may synergise with the metabolic perturbation in the pathophysiology of the disease.
Indeed many studies in experimental models of diabetes and hypertension and in the clinical setting have described an important synergistic effect of metabolic hyperglycaemia and haemodynamic glomerular hypertension perturbations in the development and progression of DN .
In the glomerulus hyperglycemia is paralleled by local upregulation of angiotensin-2 that, by reducing afferent and, to a lower degree, efferent arteriolar tone, alters glomerular capillary auto-regulation.
The resulting increase in glomerular pressure and the consequent disproportionate transmission of the systemic pressure to the glomerular circulation synergise with the raised glucose levels in mediating glomerular damage. Endothelial Changes in Later Disease In subsequent more advanced stages of the disease an increase in oxidative stress is the basis of activation of different cellular pathways leading to an increase in inflammation, diffuse inflammatory cell infiltrates, increased extracellular matrix deposition, altered angiogenesis and progressive tissue damage.
Typically a progressive accumulation of extracellular matrix is observed in the glomerular and tubular compartment resulting respectively in diffuse glomerulosclerosis and fibrosis of the tubular interstitium and tubular damage .
Changes in Other Components of the Glomerular Filtration Barrier Parallel changes occur in the glomerular filtration barrier with glomerular endothelial cell injury, with loss of glycocalyx and cell apoptosis.
The glycocalyx is an aqueous extracellular layer that covers the glomerular capillary lumen side, and plays an important role in glomerular vascular function and permeability .
Further thickening of the glomerular basement membrane and podocyte foot process effacement and loss of podocytes in the urine are other mechanisms that characterise the alteration of the permselective properties of the glomerular filtration barrier and disease progression.
Podocyte detachment has been positively correlated with urinary albumin excretion and increasing podocyte detachment is associated with decreased permselectivity of the glomerulus and progressive albuminuria.
Although the terms normoalbuminuria albumin: Further the classification of albuminuria has been revisited and 3 categories have been proposed: It is widely accepted that the rise in albuminuria reflects an increased transglomerular flux of albumin as a consequence of an increased transglomerular pressure gradient and damage of the glomerular filtration barrier.
In these patients GFR gradually declines in a linear fashion at variable rates average 3. Although variations in fall in GFR exist between patients, in the last few decades with the introduction of inhibitors of the renin angiotensin aldosterone system RAASand more intense glycaemic and hypertension treatment, the time from the onset of clinical albuminuria to death has increased from 7 to 21 years.
The decrease in annual incidence rate for diabetes-related ESRD in the last years where treatments of risk factors mostly hypertension have significantly contributed to this reduction has been significant; nevertheless the pandemic of type 2 diabetes should be considered as a likely determinant for the predicted future absolute increase in number of patients with diabetes-related ESRD.
Future better understanding of the pathophysiology of DN will hopefully open novel drug development for this chronic diabetic vascular complication.
Endothelial factors and diabetic nephropathy. Diabetes Care 34 Suppl 2: Mechanical forces in diabetic kidney disease: Cellular and molecular mechanisms of diabetic glomerulopathy. Nephrol Dial Transplant What is the mechanism of microalbuminuria in diabetes: J Am Soc Nephrol Diabetic nephropathy is detected clinically by the presence of microalbuminuria or proteinuria; The time course to nephropathy is usually years following the onset of diabetes.
Radiocontrast media (RCM) are medical drugs used to improve the visibility of internal organs and structures in X-ray based imaging techniques. They may have side effects ranging from itching to a life-threatening emergency, known as contrast-induced nephropathy (CIN).
We define CIN as acute renal failure occurring within 24–72 hrs of exposure to RCM that cannot be attributed to other causes. Diabetic nephropathy is the single most important cause of end-stage renal disease. 1 It results from the gradual accumulation of extracellular matrix in glomerular and tubular basement membranes.
Available online pfmlures.com Journal of Chemical and Pharmaceutical Research, , 8(4) Research Article ISSN: Diabetic kidney disease, commonly termed diabetic nephropathy (DN), is the most common cause of end-stage kidney disease (ESKD) worldwide.
The characteristic histopathology of DN includes glomerular basement membrane thickening, mesangial expansion, nodular glomerular sclerosis, and . Malnutrition, Anthropometric, and Biochemical Abnormalities in Patients With Diabetic Nephropathy Biochemical parameters did not show any significant change across nutritional grades, except for hemoglobin, which showed a significant reduction with advanced malnutrition.
L. Schram, E. Melzer, et pfmlures.comvascular risk factors in.