Pathogenesis of diabetic nephropathy

Abstract

Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy, nephropathy and atherosclerosis, both in IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified completely yet.

Pathological influence of obesity on renal structural changes in chronic kidney disease

“…An increase in glomerular volume is usually the consequence of glomerular hyperfiltration, and can be associated with expansion of capillary loops [8,9,10]. Obesity can accelerate renal dysfunction in patients with glomerulonephritis such as IgA nephropathy (IgAN).…”

Diabetic Nephropathy Is Associated with Oxidative Stress and Decreased Renal Nitric Oxide Production

“…doi: 10.1681 Despite several recent advances, the pathogenesis of diabetic nephropathy (DN) remains far from clear. 1 The lack of suitable diabetic animal models that develop nephropathy akin to human disease is a major barrier for progress in this field. Notwithstanding the contribution to mechanistic pathways, the in vitro models to study DN have compounded the problem, necessitating more dependable in vivo animal models.…”

Therapeutic Potential of Angiostatin in Diabetic Nephropathy

“…Approximately 20 to 40% of the patients with type 1 diabetes and 10 to 20% of those with type 2 diabetes develop nephropathy (3). The earliest pathologic changes of DN are characterized by glomerular hypertrophy, the thickening of glomerular basement membrane, and expanded extracellular matrix (ECM), which lead to glomerular hyperfiltration and microalbuminuria (2,4). Although intensified controls of hyperglycemia, BP, and hyperlipidemia reduce the risks of DN, they do not sufficiently prevent the progression from microalbuminuria to overt nephropathy in patients with diabetes (1,5,6).…”

“…iabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes as well as the leading cause of ESRD in the United States (1,2). Approximately 20 to 40% of the patients with type 1 diabetes and 10 to 20% of those with type 2 diabetes develop nephropathy (3).…”