Diabetic nephropathy is a specific pathological changes in the renal vessels that occur in diabetes mellitus of both types and lead to glomerulosclerosis, decreased filtration function of the kidneys and the development of chronic renal failure (CRF). Disease is clinically manifested by microalbuminuria and proteinuria, arterial hypertension, nephrotic syndrome, signs of uremia and CRF. The diagnosis is based on determining the level of albumin in urine, clearance of endogenous creatinine, protein and lipid spectrum of blood, kidney ultrasound, ultrasound of the renal vessels. In the treatment of diabetic nephropathy, diet, correction of carbohydrate, protein, fat metabolism, taking ACE and ARA inhibitors, detoxification therapy, if necessary, hemodialysis, kidney transplantation are indicated.
Meaning
Diabetic nephropathy is a late complication of type 1 and type 2 diabetes mellitus and one of the main causes of death in patients with this disease. The damage of large and small blood vessels developing in diabetes (diabetic macroangiopathy and microangiopathies) contribute to the damage of all organs and systems, primarily the kidneys, eyes, and nervous system.
Diabetic nephropathy is observed in 10-20% of patients with diabetes mellitus; somewhat more often nephropathy complicates the course of an insulin-dependent type of disease. DN is detected more often in male patients and in persons with type 1 diabetes mellitus who developed at puberty. The peak of DN (CRF stage) is observed with the duration of diabetes 15-20 years.
Causes
Diabetic nephropathy is caused by pathological changes in the renal vessels and glomeruli of capillary loops (glomeruli) that perform a filtration function. Despite the various theories of the pathogenesis of diabetic nephropathy considered in endocrinology, the main factor and trigger of its development is hyperglycemia. DN occurs due to prolonged insufficient compensation of carbohydrate metabolism disorders.
According to the metabolic theory of diabetic nephropathy, constant hyperglycemia gradually leads to changes in biochemical processes: non-enzymatic glycosylation of protein molecules of the renal glomeruli and a decrease in their functional activity; disruption of water-electrolyte homeostasis, fatty acid metabolism, a decrease in oxygen transport; activation of the polyol pathway of glucose utilization and toxic effects on kidney tissue, increased permeability of renal vessels.
Hemodynamic theory in the development of diabetic nephropathy assigns the main role to arterial hypertension and disorders of intrarenal blood flow: imbalance of the tone of the bringing and carrying arterioles and increased blood pressure inside the glomeruli. Prolonged hypertension leads to structural changes in the glomeruli: first to hyperfiltration with accelerated formation of primary urine and protein release, then to replacement of the renal glomerular tissue with connective (glomerulosclerosis) with complete occlusion of the glomeruli, a decrease in their filtration capacity and the development of chronic renal failure.
The genetic theory is based on the presence of genetically determined predisposing factors in a patient with diabetic nephropathy, manifested in metabolic and hemodynamic disorders. All three developmental mechanisms are involved in the pathogenesis of DN and closely interact with each other.
Risk factors for DN are arterial hypertension, prolonged uncontrolled hyperglycemia, urinary tract infections, disorders of fat metabolism and overweight, male sex, smoking, use of nephrotoxic drugs.
Symptoms
Diabetic nephropathy is a slowly progressive disease, its clinical picture depends on the stage of pathological changes. In the development of diabetic nephropathy, there are stages of microalbuminuria, proteinuria and the terminal stage of chronic renal failure.
Diabetic nephropathy has been asymptomatic for a long time, without any external manifestations. At the initial stage of diabetic nephropathy, there is an increase in the size of the glomeruli of the kidneys (hyperfunctional hypertrophy), increased renal blood flow and an increase in the glomerular filtration rate (GFR). A few years after the onset of diabetes mellitus, initial structural changes in the glomerular apparatus of the kidneys are observed. A high volume of glomerular filtration remains, the excretion of albumin in the urine does not exceed normal values (<30 mg / day).
Incipient diabetic nephropathy develops more than 5 years after the onset of pathology and is manifested by constant microalbuminuria (>30-300 mg / day. or 20-200 mg / ml in the morning portion of urine). There may be a periodic increase in blood pressure, especially during exercise. The deterioration of the well-being of patients with diabetic nephropathy is observed only in the later stages of the disease.
Clinically pronounced diabetic nephropathy develops after 15-20 years in type 1 diabetes mellitus and is characterized by persistent proteinuria (protein level in urine – > 300 mg / day), indicating the irreversibility of the lesion. Renal blood flow and GFR decrease, arterial hypertension becomes permanent and difficult to correct. Nephrotic syndrome develops, manifested by hypoalbuminemia, hypercholesterolemia, peripheral and abdominal edema. Blood creatinine and urea levels are normal or slightly elevated.
At the terminal stage of diabetic nephropathy, there is a sharp decrease in filtration and concentration functions of the kidneys: massive proteinuria, low GFR, a significant increase in the level of urea and creatinine in the blood, the development of anemia, pronounced edema. At this stage, hyperglycemia, glucosuria, urinary excretion of endogenous insulin, as well as the need for exogenous insulin can significantly decrease. Nephrotic syndrome progresses, blood pressure reaches high values, dyspeptic syndrome develops, uremia and CRF with signs of self-poisoning of the body by metabolic products and damage to various organs and systems.
Diagnostics
Early diagnosis of diabetic nephropathy is an important task. In order to establish the diagnosis of diabetic nephropathy, biochemical and general blood analysis, biochemical and general urine analysis, Rehberg test, Zimnitsky test, kidney vascular ultrasound are performed.
The main markers of the early stages of diabetic nephropathy are microalbuminuria and glomerular filtration rate. During the annual screening of patients with diabetes mellitus, the daily excretion of albumin in the urine or the ratio of albumin / creatinine in the morning portion is examined.
The transition of DN to the stage of proteinuria is determined by the presence of protein in the general urine analysis or the excretion of albumin in urine above 300 mg / day. There is an increase in blood pressure, signs of nephrotic syndrome. The late stage of diabetic nephropathy is not difficult to diagnose: to massive proteinuria and a decrease in GFR (less than 30 – 15 ml/min), an increase in creatinine and urea levels in the blood (azotemia), anemia, acidosis, hypocalcemia, hyperphosphatemia, hyperlipidemia, swelling of the face and whole body is added.
It is important to carry out differential diagnosis of diabetic nephropathy with other kidney diseases: chronic pyelonephritis, tuberculosis, acute and chronic glomerulonephritis. For this purpose, a bacteriological examination of urine for microflora, ultrasound of the kidneys, excretory urography can be performed. In some cases (with early-developing and rapidly increasing proteinuria, sudden development of nephrotic syndrome, persistent hematuria), a fine-needle aspiration biopsy of the kidney is performed to clarify the diagnosis.
Treatment
The main goal of diabetic nephropathy treatment is to prevent and delay further progression of the disease to CRF as much as possible, to reduce the risk of cardiovascular complications (coronary heart disease, myocardial infarction, stroke). Common in the treatment of different stages of diabetic nephropathy is strict control of blood sugar, blood pressure, compensation for violations of mineral, carbohydrate, protein and lipid metabolism.
The first-choice drugs in the treatment of diabetic nephropathy are angiotensin converting enzyme (ACE) inhibitors: enalapril, ramipril, trandolapril and angiotensin receptor antagonists (ARA): irbesartan, valsartan, losartan, normalizing systemic and intraclubular hypertension and slowing the progression of the disease. Drugs are prescribed even with normal blood pressure in doses that do not lead to the development of hypotension.
Starting from the stage of microalbuminuria, a low-protein, salt-free diet is indicated: limiting the consumption of animal protein, potassium, phosphorus and salt. To reduce the risk of developing cardiovascular diseases, correction of dyslipidemia is necessary due to a low-fat diet and taking medications that normalize the blood lipid spectrum (L-arginine, folic acid, statins).
At the terminal stage of diabetic nephropathy, detoxification therapy, correction of diabetes mellitus treatment, intake of sorbents, anti-azotemic agents, normalization of hemoglobin levels, prevention of osteodystrophy are required. With a sharp deterioration in kidney function, the question is raised about conducting hemodialysis, permanent peritoneal dialysis or surgical treatment by donor kidney transplantation.
Prognosis and prevention
Microalbuminuria with timely and adequate treatment is the only reversible stage of diabetic nephropathy. At the stage of proteinuria, it is possible to prevent the progression of the disease to CRF, while reaching the terminal stage of diabetic nephropathy leads to a condition incompatible with life.
Currently, diabetic nephropathy and CRF developing as a result of it are the leading indications for replacement therapy – hemodialysis or kidney transplantation. CRF due to diabetic nephropathy causes 15% of all deaths among patients with type 1 diabetes mellitus younger than 50 years.
Prevention of diabetic nephropathy consists in systematic observation of patients with diabetes mellitus by an endocrinologist-diabetologist, timely correction of therapy, constant self-monitoring of the level of glycemia, compliance with the recommendations of the attending physician.