Diagram showing the basic outline of nephron structure and function:<unk>  is associated with changes in the afferent and efferent arterioles, causing capillary hypertension; and damage to the glomerular capillaries of multiple causes, including mesangial matrix deposition The disease progression of<unk>  involves various clinical stages: hyperfiltration, microalbuminuria, macroalbuminuria, nephrotic proteinuria to progressive chronic kidney disease leading to end-stage renal disease (ESRD). The damage is exerted on all compartments of the kidney: the glomerulus, the renal tubules, the vasculature (afferent and efferent renal arterioles) and the interstitium. Renal fibrosis is the final common pathway of<unk> . This fibrosis is a product of multiple mechanisms including renal hemodynamic changes, glucose metabolism abnormalities associated with oxidative stress as well as inflammatory processes and an overactive renin-angiotensin-aldosterone system (RAAS). The pathophysiology of<unk>  is thought to involve an interaction between hemodynamic and metabolic factors. Hemodynamic factors include an increase in systemic and intraglomerular pressure, as well as the over-activation of the RAAS. Studies have shown that in the setting of diabetes, various factors stimulate the RAAS, which is one of the most important pathways in<unk>  pathophysiology. Due to the higher load of filtered glucose, there is an up-regulation in the sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules, which cotransports sodium and glucose back into circulation. This leads to a decrease in the delivery of sodium chloride to the macula densa in the distal tubules, promoting the release of renin and over-activating RAAS. Hyperfiltration is one of the earliest features of<unk> . Several mechanisms have been proposed to cause hyperfiltration. One of these mechanisms is that as glomeruli becomes hypertrophied, filtration surface area initially increases. Another possible mechanism is that abnormal vascular control in<unk>  leads to a reduction in afferent glomerular arteriolar resistance and an increase in efferent glomerular arteriolar resistance, leading to a net increase in renal blood flow (RBF) and glomerular filtration rate (GFR). Glomerular hyperfiltration and an aberrant regulation of RAAS lead to increased intraglomerular pressure, causing stress on the endothelial cells, the mesangial cells and the podocytes. This exacerbates the dysfunction caused by the metabolic effects of hyperglycemia. Metabolic factors include the formation of Advanced glycation end-products (AGEs), which have a central role in the pathophysiology of many of the complications of diabetes mellitus, including cardiovascular complications. AGEs are chemical groups that form when a reducing sugar (glucose in this case) reacts non-enzymatically with an amine group, predominantly lysine and arginine, which are attached on proteins, lipids and nucleic acids. These glycation products accumulate on the proteins of vessel wall collagen, forming an irreversible complex of cross-linked AGEs. An important way AGEs exert their effect is through a receptor-mediated mechanism, most importantly by the receptor for advanced glycation end products (RAGE). RAGE is a signal transduction receptor found on a number of cell types including macrophages, endothelial cells, renal mesangial cells and podocytes in the glomerulus. Bindings of AGEs to RAGE receptors enhances production of cytosolic Reactive Oxygen Species (ROS) as well as stimulates intracellular molecules such as Protein Kinase C (PKC), NF-kB and the activation of growth factors TGF-B and vascular endothelial growth factor (VEGF). These factors, along with the hemodynamic changes that occur, lead to podocyte injury, oxidative stress, inflammation and fibrosis. As injury worsens, kidney function decreases and glomerular basement membrane (GBM) become more permeable and less efficient at filtration. This is accompanied by a steady decline in kidney function.
Diabetic nephropathy
Analgesic nephropathy
IgA nephropathy
Benign nephrosclerosis
Malarial nephropathy
Phosphate nephropathy
Reflux nephropathy
Sickle cell nephropathy