The exact causes responsible for the onset of diabetic nephropathy and its evolution towards renal failure are not yet clear. Currently, it is assumed that some factors, including hyperglycemia, arterial hypertension and an altered cellular transport of sodium, added to an innate genetic predisposition, are the main elements that favor the onset of diabetic nephropathy.
KEY CONCEPTS At the renal level, in the two million nephrons present approximately in each kidney, three fundamental processes take place:
Due to pathological processes of various nature (inflammatory, cicatricial, hypertensive ...) the meshes of the glomerular sieves can widen: the capillaries of the glomerulus are thus allowed to escape normally retained blood components: this is the case of proteins, which consequently found in excessive amounts in urine. In this case we talk about proteinuria or macroalbuminuria (albumin is the main plasma protein). Excessive filtration of glucose and proteins at the glomerular level leads to progressive renal damage which progresses to renal failure. Below we describe the pathogenetic mechanisms that lead to the appearance of such damage. |
The pathogenetic elements of diabetic nephropathy are represented by:
- Glomerular hyperfiltration: it is considered the first factor responsible for glomerulopathy in type I diabetes
- Structural alterations of the glomerular basement membrane: expression of microangiopathic damage that also occurs in other organs and systems
1) HYPERGLYCEMIA
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Glomerular glucose filtration increased
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Increased reabsorption of glucose and sodium at the tubular level
(The reabsorption of glucose in the proximal convoluted tubule occurs through a cotransport Na + / glucose, such that there will be an increase in blood volume and with it blood pressure)
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Increased volume and arterial pressure ↓ stimulation of atrial stretch receptors with increased secretion of ANP atrial natriuretic peptide↓ vasodilation of the afferent arteriole (to the glomerulus) | Reduction in the amount of sodium that reaches the dense macula ↓ vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole with release of antithrombin II |
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increase in glomerular pressure and glomerular filtration rate
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responsible for the onset of nephrotic syndrome: initially selective proteinuria without hematuria + hypoalbuminemia and edema + hyperlipidemia and lipiduria
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functional overload of nephrons with wear damage and activation of inflammatory phenomena → evolution towards chronic renal failure
2) HYPERGLYCEMIA
_____________________________ | ______________________________
| | activation of the polyol pathway | | | advanced glycation product formation | | | formation of free oxygen radicals | | | activation of the protein kinase C pathway | |
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increased vascular permeability and histological alterations with high synthesis of protein matrix at glomerular level and subsequent sclerosis
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reduction of capillary permeability and filtering surface
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reduction of glomerular filtration rate up to renal failure
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