Causes and pathogenesis of diabetic nephropathy

Classification of diabetic nephropathy

The classification of diabetic nephropathy was developed by C.E. Mogensen.

The identification of three preclinical reversible stages optimized the possibilities of preventing the development and progression of diabetic nephropathy with timely and adequate pathogenetic therapy.

5-7 years of persistent proteinuria leads to the development of stage V diabetic nephropathy - the uremia stage in 80% of patients with type 1 diabetes (in the absence of the necessary treatment). In patients with type 2 diabetes, the proteinuric stage of diabetic nephropathy is less aggressive and chronic renal failure develops much less frequently. However, the high prevalence of type 2 diabetes leads to the fact that an equal number of patients with type 1 and type 2 diabetes need hemodialysis treatment.

At present, it is accepted worldwide to diagnose diabetic nephropathy at the stage of microalbuminuria, which allowed the approval of a new formulation of the diagnosis of diabetic nephropathy (2001).

• Diabetic nephropathy, microalbuminuria stage;
• Diabetic nephropathy, stage of proteinuria with preserved nitrogen-excreting function of the kidneys;
• Diabetic nephropathy, stage of chronic renal failure.

Pathogenesis of diabetic nephropathy

Diabetic nephropathy is the result of the impact of metabolic and hemodynamic factors on renal microcirculation, modulated by genetic factors.

Hyperglycemia is the main metabolic factor in the development of diabetic nephropathy, which is realized through the following mechanisms:

• non-enzymatic glycosylation of renal membrane proteins, disrupting their structure and function;
• direct glucotoxic effect associated with the activation of the enzyme protein kinase-C, which regulates vascular permeability, smooth muscle contraction, cell proliferation processes, and the activity of tissue growth factors;
• activation of the formation of free radicals that have a cytotoxic effect.

Hyperlipidemia is another powerful nephrotoxic factor. The process of nephrosclerosis development under hyperlipidemia conditions is similar to the mechanism of vascular atherosclerosis formation.

Intraglomerular hypertension is the leading hemodynamic factor in the development and progression of diabetic nephropathy, which manifests itself in its early stages as hyperfiltration (SCF over 140-150 ml/min x 1.73 m2 ⁾. An imbalance in the regulation of the tone of the afferent and efferent glomerular arterioles in diabetes mellitus is considered responsible for the development of intraglomerular hypertension and the subsequent increase in the permeability of the glomerular capillary basement membranes. The cause of this imbalance is primarily the high efficiency of the renal renin-angiotensin system and the key role of angiotensin II.

In patients with type 1 diabetes, arterial hypertension is usually secondary and develops as a result of diabetic kidney damage. In patients with type 2 diabetes, arterial hypertension precedes the development of diabetes in 80% of cases. However, in both cases, it becomes the most powerful factor in the progression of renal pathology, surpassing metabolic factors in its significance. Pathophysiological features of patients with diabetes are circadian rhythm disturbance. Blood pressure with weakening of its physiological decrease at night and orthostatic hypotension.

Diabetic nephropathy develops in 40-45% of patients with diabetes mellitus types 1 and 2, so it is entirely justified to search for genetic defects that determine the structural features of the kidneys as a whole, as well as to study genes encoding the activity of various enzymes, receptors, and structural proteins involved in the development of diabetic nephropathy.

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