Causes and pathogenesis of diabetic nephropathy

Classification of diabetic nephropathy

The classification of diabetic nephropathy was developed in S.E. Mogensen.

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

5-7 years of persistent proteinuria leads to the development of the V stage of diabetic nephropathy - the stage of uremia 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 hemodialysis treatment needs an equal number of patients with type 1 and type 2 diabetes.

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

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

The pathogenesis of diabetic nephropathy

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

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

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

Hyperlipidemia is another powerful nephrotoxic factor. The development of nephrosclerosis in hyperlipidemia is similar to the mechanism of atherosclerosis of the vessels.

Intra-tubular hypertension is the leading hemodynamic factor in the development and progression of diabetic nephropathy, whose manifestation in its early stages is hyperfiltration (GFR more than 140-150 ml / min x l, 73 m ² ). An imbalance in the regulation of the tonus of the glomerulus and arthritis-bearing glomeruli in diabetes mellitus is considered responsible for the development of intra-cerebral hypertension and the subsequent increase in the permeability of the basal membranes of the glomerular capillaries. The reason for this imbalance is, first of all, 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 in 80% of cases precedes the development of diabetes. However, in both cases, and in another case it becomes the most powerful factor in the progression of renal pathology, surpassing the importance of metabolic factors. Pathophysiological features of patients with diabetes mellitus are a disruption of the circadian rhythm. Arterial pressure with a weakening of his physiological decline at night and orthostatic hypotension.

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

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