Diabetic Nephropathy: An Overview of Information

Diabetic nephropathy is a specific lesion of kidney vessels in diabetes mellitus, accompanied by the formation of nodular or diffuse glomerulosclerosis, the terminal stage of which is characterized by the development of chronic renal failure.

Diabetes mellitus is a group of metabolic diseases characterized by the development of persistent hyperglycemia due to a defect in the secretion of insulin, the action of insulin or both of these factors (World Health Organization, 1999). In clinical practice, the main group of patients with diabetes mellitus are patients with type 1 diabetes mellitus (insulin-dependent diabetes mellitus) and type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus).

With prolonged exposure to hyperglycemia, specific structural and functional changes in target organs arise on the vessels and nervous tissue of the body, which is manifested by the development of complications of diabetes mellitus. Conditionally these complications can be divided into microangiopathy (damage of small and medium-sized vessels, macroangiopathy (damage to large-caliber vessels) and neuropathy (damage to nervous tissue).

Dmabetic nephropathy is referred to as microangiopathy. It is considered as a late complication of diabetes mellitus of both 1st and 2nd type.

[1], [2], [3], [4]

Epidemiology of diabetic nephropathy

Throughout the world, diabetic nephropathy with the formation of chronic renal failure is considered as the main cause of death of patients with type 1 diabetes. In patients with type 2 diabetes, diabetic nephropathy is the second most common cause of death after cardiovascular disease. In the United States and Japan, diabetic nephropathy ranks first in the prevalence of all kidney diseases (35-40%), pushing to the second or third position such primary kidney diseases as glomerulonephritis, pyelonephritis, and polycystic kidney disease. In Europe, the "epidemic" of diabetic nephropathy is less threatening, but in the structure of the causes of extracorporeal treatment of chronic renal failure is 20-25%.

In Russia, mortality from renal failure in type 1 diabetes mellitus, according to the State Register (1999-2000), does not exceed 18%, which is 3 times lower than the level registered in the world over the past 30 years. In type 2 diabetes mellitus, mortality from chronic renal failure in Russia is 1.5%, which is 2 times lower than in the world.

Diabetic nephropathy has become the most common cause of chronic renal failure in the US and European countries. The causes of this phenomenon were mainly a rapid decrease in the incidence of type 2 diabetes and an increase in the life expectancy of diabetic patients.

The prevalence of diabetic nephropathy depends primarily on the duration of the disease. This is especially clear for patients with type 1 diabetes who have a relatively accurate date of debut. Nephropathy rarely develops in the first 3-5 years in patients with type 1 diabetes, after 20 years they are found in almost 30% of patients. Most often, diabetic nephropathy develops in 15-20 years from the onset of the disease. For patients with type 1 diabetes, the age at onset of the disease is very important. The maximum frequency of diabetic nephropathy is in people with a debut of diabetes at the age of 11-20 years, which is determined by the pathological effect on the kidneys in conjunction with the age-related hormonal changes in the body.

The prevalence of diabetic nephropathy in type 2 diabetes is less studied primarily because of the uncertainty of the onset of the disease of type 2 diabetes, usually develops after 40 years and often aggravates already existing kidney diseases. Therefore, already at the time of diagnosis of type 2 diabetes, 17-30% of patients can be diagnosed with microalbuminuria, 7-10% with proteinuria, and 1% with chronic kidney failure.

[5], [6], [7]

Causes and pathogenesis of diabetic nephropathy

Development of kidney damage in diabetes mellitus is associated with simultaneous exposure to two pathogenetic factors - metabolic (hyperglycemia and hyperlipidemia) and hemodynamic (systemic and glomerular hypertension).

Hyperglycemia acts as the main initiating metabolic factor in the development of diabetic kidney damage. In the absence of hyperglycemia, changes in renal tissue, characteristic of diabetes mellitus, are not detected.

There are several mechanisms of nephrotoxic action of hyperglycemia:

• nonenzymatic glycosylation of renal membrane proteins, changing their structure and function;
• direct toxic effects of glucose on the kidney tissue, leading to activation of the protein kinase C enzyme, which increases the permeability of renal vessels;
• activation of oxidative reactions leading to the formation of a large number of free radicals that have a cytotoxic effect.

Hyperlipidemia is another metabolic factor involved in the development and progression of diabetic nephropathy. The kidneys are damaged by modified LDL, which penetrate through the damaged endothelium of the capillaries of the renal glomeruli and promote the development of sclerotic processes in them.

Inside, the glomerular hypertension (high hydrostatic pressure in the capillaries of the renal glomeruli) acts as the main hemodynamic factor in the development of diabetic nephropathy. At the heart of this phenomenon in diabetes mellitus is an imbalance in the tonus of the renal glomerulus that carries and carries the arteriolus: on the one hand, there is a "gaping" of the glomerular arteriolus due to the toxic effect of hyperglycemia and the activation of vasodilating hormones, and on the other, the constriction of the renal arterioles extinguishing due to the action of local angiotensin II.

However, in diabetes mellitus of both types 1 and 2, arterial hypertension is the most powerful factor in the progression of renal insufficiency, which by the force of its damaging effect is many times greater than the influence of metabolic factors (hyperglycemia and hyperlipidemia).

Causes and pathogenesis of diabetic nephropathy

[8], [9], [10], [11], [12], [13], [14],

Symptoms of diabetic nephropathy

In the initial stages (I and II), the course of diabetic nephropathy is asymptomatic. In the Reberg sample, there is an increase in GFR (> 140-150 ml / min x 1.73 m ² ).

At stage III (stage of beginning diabetic nephropathy), symptoms are also absent, microalbuminuria (20-200 mg / L) is detected with normal or elevated GFR.

Beginning with the stage of severe diabetic nephropathy (stage IV), patients develop clinical symptoms of diabetic nephropathy, which primarily include:

• arterial hypertension (appears and rapidly increases);
• edema.

Symptoms of diabetic nephropathy

Diagnosis of diabetic nephropathy

Diagnosis and establishment of the stage of diabetic nephropathy are based on the history of the disease (duration and type of diabetes mellitus), the results of laboratory studies (detection of microalbuminuria, proteinuria, azotemia and uremia).

The earliest method of diagnosing diabetic nephropathy is the recognition of microalbuminuria. The criterion of microalbuminuria is highly selective excretion of albumin with urine in the amount from 30 to 300 mg / day or from 20 to 200 μg / min in the night portion of urine. Microalbuminuria is also diagnosed by the albumin / creatinine ratio in the morning urine, which excludes the errors of daily urine collection.

Diagnosis of diabetic nephropathy

[15], [16], [17], [18], [19], [20], [21], [22]

Treatment of diabetic nephropathy

At the heart of effective therapy for diabetic nephropathy are early diagnosis and treatment conducted in accordance with the stage of the disease. Primary prevention of diabetic nephropathy is aimed at preventing the appearance of mycoalbumiuria, i.e. Influence on its modifiable risk factors (the level of compensation of carbohydrate metabolism, the state inside the glomerular hemodynamics, the violation of lipid metabolism, smoking).

The basic principles of the prevention and treatment of diabetic nephropathy include:

• glycemic control;
• control of blood pressure (blood pressure level should be <135/85 mm Hg in patients with diabetes mellitus in the absence of mycoralbuminuria <130/80 mm Hg in the presence of microalbuminuria and <120/75 mm Hg in patients with proteinuria) ;
• control of dyslipidemia.

Treatment of diabetic nephropathy