Diabetic angiopathies are late complications of diabetes mellitus. Diabetic angiopathy is a generalized vascular lesion that spreads to both small vessels and vessels of medium and large caliber.
With the defeat of small vessels, such as arterioles, venules and capillaries, microangiopathy develops. With the defeat of medium and large caliber vessels, macroangiopathy develops. Microangiopathies lead to the development of diabetic nephropathy and retinopathy. In macro-angiopathies, the vessels of the heart, brain, and great vessels of the lower extremities are affected. The main role of the development of diabetic angiopathy belongs to hyperglycemia. Hazardous products are glycosylation. Their action is to change the structure and metabolism of proteins in the body, primarily proteins of cell membranes. This leads to thickening and increased permeability of the latter. Also, glycosylation products enhance cytokine production, which, in turn, stimulates cell proliferation and hyperplasia, increases blood clotting due to increased platelet aggregation. In diabetic angiopathy, superoxide anion is formed. This substance inactivates nitric oxide, leading to dysfunction of the vascular endothelium. These changes cause a decrease in the ability of the endothelium to cause vasodilation, an increase in the permeability of the vascular wall and a violation of the rheological properties of blood, which causes the development of hemostasis and thrombus formation.
Diabetic nephropathy is a specific lesion of the kidneys in diabetes mellitus, which is accompanied by morphological changes in the capillaries and arterioles of the renal glomeruli, leading to their occlusion, sclerotic change, progressive reduction in renal filtration function and the development of chronic renal failure.
The initial signs of diabetic nephropathy are detected 5–10 years after the onset of diabetes. This complication is the main cause of death in diabetes mellitus type I.
There are a number of mechanisms in the development of diabetic nephropathy. Under the influence of persistent hyperglycemia, the arteriole-bearing glomerulus is dilated. Damage to the renal vessels causes a thickening of the basement membrane, impaired renal perfusion, and, as a result, an increase in blood pressure. Since dilatation of the bringing arterioles occurs and the outgoing tone rises, the intraglomerular pressure rises, which progresses under the influence of an increase in the volume of primary urine. An increase in pressure inside the glomeruli leads to a change in the vessels and the parenchyma of the kidney. The permeability of the renal filter is impaired, which is manifested by microalbuminuria, and then by proteinuria. The progression of the process leads to the development of glomerulosclerosis, which is manifested by chronic renal failure.
Diabetic nephropathy is characterized by several stages: microalbuminuria, proteinuria, and chronic renal failure. The stage of microalbuminuria and proteinuria is not diagnosed in a routine examination.
The microalbuminuria stage is characterized by an increase in urinary albumin excretion from 30 to 300 mg per day. With a general analysis of urine protein is not detected. A characteristic clinical picture at this stage does not develop. In some cases there may be a slight increase in blood pressure.
The proteinuria stage is characterized by an increase in urinary protein excretion of more than 300 mg per day. At first, only albumin is detected in the urine, i.e. proteinuria is selective. With the progression of the disease, the selectivity of proteinuria decreases, which is manifested by the excretion with the urine of coarse-grained proteins – globulins. If proteinuria is more than 3.5 g per day, this indicates the development of nephrotic syndrome. It is clinically manifested by edema localized to the face. An increase in blood pressure develops in 65–80% of patients, and this increases both systolic and diastolic pressure. Arterial hypertension in diabetic nephropathy is distinguished by its stability and lack of sensitivity to antihypertensive drugs. Nephrotic syndrome leads to the development of dysproteinaemia, and as it progresses, it leads to hypoproteinemia.
Since resistant proteinuria is established, there is a decrease in glomerular filtration rate of less than 80 ml / min, a decrease in kidney concentration, which leads to hypoisostenuria, and then an increase in creatinine and urea levels in the blood. This is the stage of chronic renal failure. At this stage, all symptoms characteristic of chronic renal failure are added to proteinuria. This stage has a progressive course, the tempo of which may be different.
The stage of chronic renal failure is characterized by a decrease in the need these bodies are in exogenous insulin. This fact is explained by a decrease in the activity of insulin, as well as a decrease in insulin binding to plasma proteins as a result of hypoproteinemia. Clinically, this stage is manifested by an increased tendency to hypoglycemic states. For their prevention it is necessary to reduce the dose of insulin injected and at the same time increase the carbohydrate content in food. The most powerful factor in the progression of chronic renal failure is arterial hypertension. In most cases, at this stage, various inflammatory processes of the urinary system occur, such as ascending pyelonephritis and others.
Laboratory and instrumental diagnostic methods
The first two stages of diabetic nephropathy are diagnosed when microalbuminuria is detected in two or more urine tests, with albuminuria being 30–300 mg / day. These figures characterize the stage of microalbuminuria. The stage of proteinuria is diagnosed if the amount of albumin is more than 300 mg per day. With diabetic nephropathy increases the glomerular filtration rate, which is determined using the
At the same time the glomerular filtration rate is more than 140 ml per minute. The stage of chronic renal failure is characterized by massive proteinuria of more than 3.5 g per day, hypoalbuminemia, and hypercholesterolemia.
To achieve a positive effect, it is necessary to begin treatment at the first stage of diabetic nephropathy. The goal of therapy at this stage is to normalize the level of arterial pressure. The drugs of choice are ACE inhibitors.
The preparations of this group normalize the indices of arterial pressure, as well as reduce the intraglomerular pressure and the permeability of the glomerular basement membranes. The drugs used are enalapril, perindopril, lisinopril, etc. Monotherapy is usually given. In the case of a normal level of blood pressure, drugs of this group are also prescribed, but in a small dose. Also, in the first stage, sulodexide, a drug from the group of glycosaminoglycans, is administered to restore the damaged basement membranes of the glomeruli.
Treatment at the stage of proteinuria should include the administration of insulin to patients with type 2 diabetes mellitus, the appointment of a diet with a reduced amount of salt in the case of arterial hypertension. Treatment of arterial hypertension with medicament is also carried out with ACE inhibitors. Monotherapy with these drugs is usually performed. The level of arterial pressure to be reached is 130/85 mm Hg. Art. In the case of failure of monotherapy with ACE inhibitors, additional therapy with calcium antagonists, such as verapamil or diltiazem, is given.
In addition, α-blockers (atenolol), diuretics (furosemide), angiotensin receptor antagonists (lo-sartan) can be prescribed.
Therapy for the development of chronic renal insufficiency is determined by its stage. There are conservative and terminal stage. The conservative stage is characterized by a glomerular filtration rate of 30–60 ml / min. Major in this stage is dieting. In the case of arterial hypertension, the amount of salt is limited to 3 g per day, the amount of carbohydrates must be increased in order to cover energy costs. Of the medications at this stage, insulin, ACE inhibitors, is mandatory. For the correction of lipid metabolism disorders, simvastatin is used; calcium phosphate metabolism disorders — calcium carbonate or acetate, of an acid-base state, namely, an acid dose — sodium bicarbonate. If necessary, drugs are used to treat anemia, as well as sorbents. In the case of end-stage chronic renal failure, which is characterized by a decrease in glomerular filtration rate of less than 15 ml / min, the treatment is carried out in specialized nephrological hospitals. Methods of treatment are chronic hemodialysis or peritoneal dialysis. If necessary and possible, kidney transplantation is performed.