Arterial hypertension - Causes, pathogenesis and degrees

Parenchymatous kidney diseases include acute and chronic glomerulonephritis, chronic pyelonephritis, obstructive nephropathy, polycystic kidney disease, diabetic nephropathy, hydronephrosis, congenital renal hypoplasia, kidney injury, renin-secreting tumors, renoprivative conditions, primary sodium retention (Liddle, Gordon syndromes).

The frequency of detection of arterial hypertension in parenchymatous kidney diseases depends on the nosological form of renal pathology and the state of renal function. In almost 100% of cases, the arterial hypertension syndrome accompanies a renin-secreting kidney tumor (reninoma) and lesions of the main renal vessels (renovascular hypertension).

In diffuse kidney diseases, arterial hypertension syndrome is most often detected in diseases of the renal glomeruli and vessels: primary glomerulonephritis, systemic connective tissue diseases (systemic lupus erythematosus, systemic scleroderma), vasculitis (nodular periarteritis), diabetic nephropathy. The frequency of arterial hypertension in these diseases and preserved renal function fluctuates within 30-85%. In chronic glomerulonephritis, the frequency of arterial hypertension is on average 50-60% and largely depends on the morphological variant of kidney damage. Most often (up to 70-85%), arterial hypertension is detected in the mesangiocapillary variant of glomerulonephritis and focal segmental glomerulosclerosis, less often in membranous, mesangioproliferative and IgA-GN (from 40 to 50%). Least often, arterial hypertension is recorded in glomerulonephritis with minimal changes. The frequency of arterial hypertension in diabetic nephropathy is from 50 to 70%. Much less often (about 20%), arterial hypertension is detected in diseases of the renal tubules and interstitium (renal amyloidosis, interstitial, drug-induced nephritis, tubulopathy). As kidney function decreases, the frequency of arterial hypertension increases sharply, reaching 85-90% at the stage of renal failure in all kidney diseases.

At the present stage, several factors in the pathogenesis of renal arterial hypertension are identified: sodium and water retention, dysregulation of pressor and depressor hormones, increased formation of free radicals, renal ischemia, and gene disorders.

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Water and sodium retention

The most significant factor in the pathogenesis of arterial hypertension in diffuse kidney diseases is sodium retention, accompanied by an increase in the volume of extracellular fluid and the magnitude of cardiac output. This is the most common mechanism for the development of renal arterial hypertension. Volume-dependent hypertension is detected in 80-90% of patients with acute glomerulonephritis and chronic renal failure.

As a result of sodium retention, the electrolyte content in the vessel wall changes (accumulation of sodium and calcium ions in it), its edema occurs, which leads to an increase in the sensitivity of the vessels to the pressor effects of vasoconstrictor hormones (angiotensin II, catecholamines, vasopressin, vasoconstrictor hormones of the endothelium). The listed changes are the basis for the development of high peripheral resistance (HPR) and total renal vascular resistance.

Thus, sodium and water retention by the kidneys affects both factors of blood pressure regulation - the magnitude of cardiac output and TPR.

The main causes of sodium retention in kidney diseases are damage to the renal glomeruli with subsequent reduction in the mass of active nephrons, inflammation in the renal parenchyma, increased reabsorption in the proximal, distal tubules and collecting duct, and primary tubulointerstitial disorders.

The presented data on the role of sodium in the mechanism of development of arterial hypertension and the existence of many factors leading to sodium retention determine the need for limiting table salt in the diet and, if necessary, prescribing diuretics in the treatment of renal arterial hypertension.

Dysregulation of pressor and depressor systems

Renal arterial hypertension, independent of volume, is detected in 5-10% of patients. In this variant of hypertension, the circulating blood volume and cardiac output, as a rule, remain within normal values. The cause of the increase in blood pressure is an increase in vascular tone due to dysregulation of the pressor and depressor hormonal systems, which leads to an increase in the peripheral arterial resistance.

Physiological regulators of vascular tone are vasoactive hormones: vasoconstrictor (angiotensin II, catecholamines, endothelins) and vasodilating (kinins, prostaglandins, endothelium-relaxing factor, calcitonin-gene-related peptide, etc.). In kidney diseases, a violation of the physiological balance in the vasoconstrictor-vasodilator system in favor of vasoconstrictors is detected.

In kidney diseases, activation of one of the strongest vasoconstrictors - angiotensin II - occurs when renal hemodynamics are impaired as a result of acute immune inflammation or sclerotic processes. In addition to increased formation of systemic angiotensin II, local RAAS is activated in the kidneys with production of the vasoconstrictor hormone directly in the renal tissue. The combined effect of activated systemic and renal angiotensin II provokes constriction of both resistive vessels (medium-diameter arterioles), which mainly determine the renal vascular resistance, and intrarenal vessels, which leads to an increase in the renal vascular resistance.

In recent years, great importance has been attached to the increase in the activity of the sympathetic nervous system in the genesis of renal arterial hypertension. The sclerotically altered kidney acts as a source of afferent signals to the hypothalamus, under the influence of which the secretion of norepinephrine and a previously unknown, even stronger than norepinephrine, catecholamine - vasoactive neuropeptide Y - is activated. Neuropeptide Y is released together with norepinephrine in perivascular nerve endings. Its period of action is longer than that of norepinephrine. This peptide promotes the secretion of other vasoactive hormones. In kidney diseases, a direct dependence of the activity of angiotensin II secretion and the level of catecholamines is noted, which significantly enhances the constrictor effect of hormones. Increased activity of the sympathetic nervous system in kidney diseases is usually accompanied by vasoconstriction and an increase in OPS, as well as the formation of a characteristic hyperkinetic type of blood circulation.

The physiological system of renal vasodilator hormones is represented by renal prostaglandins, the kallikrein-kinin system. Their physiological properties: vasodilation and increased sodium excretion - counteract the development of arterial hypertension. In kidney diseases, their synthesis is sharply reduced. Genetic damage to the renal receptor system of the kallikrein-kinin system may be important, which contributes to the development of renal arterial hypertension.

An important role in the development of arterial hypertension is also played by a decrease in the production of the vasodilator lipid medullin by the renal medulla, the effects of which are currently being studied in detail.

Endothelial hormones also play an important role in the genesis of renal arterial hypertension: the active vasodilator NO and the most powerful of the known endogenous vasoconstrictors - endothelins. Experiments have shown that blockade of NO formation leads to the development of arterial hypertension. Enhanced synthesis of NO from L-arginine is necessary for the development of a normal natriuretic response under sodium load. In salt-sensitive hypertensive rats, blockade of NO formation leads to an increase in arterial pressure, and sequential administration of L-arginine is accompanied by normalization of arterial pressure. In chronic renal failure, a sharp increase in the concentration of endothelin-1 and inhibition of NO release are detected. In kidney diseases, an imbalance of this system with a decrease in NO synthesis and an increase in the concentration of endothelins in the blood leads to the development of arterial hypertension due to a sharp increase in TPS, which is enhanced by sodium retention in the body.

As renal failure progresses, the frequency and severity of arterial hypertension increase. The role of sodium and water retention in the pathogenesis of arterial hypertension increases, and most other mechanisms common to all arterial hypertensions retain their significance, including increased renin production by shrunken kidneys, depletion of their production of depressor hormones, and dysregulation of endothelial hormones. With the development of uremia, additional factors arise that contribute to the development and maintenance of arterial hypertension.

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Formation of free radicals

In recent years, the attention of researchers studying the mechanisms of arterial hypertension development in chronic renal failure has been attracted by the activation of lipid peroxidation and the role of the protein metabolism metabolite asymmetric dimethylarginine. In chronic renal failure, the activity of free radicals is sharply increased, antioxidant activity is significantly reduced, which can potentiate arterial hypertension, contributing to an increase in the OPS due to various mechanisms. These include inactivation of NO production, increased formation of vasoconstrictor metabolites due to oxidation of arachidonic acid inside glomerular membranes, direct vasoconstrictor action of free oxygen radicals, increased fibrosis and atherosclerosis in blood vessels. Accumulation of asymmetric dimethylarginine in chronic renal failure leads to blockade of NO synthetase, which causes an increase in the OPS of blood vessels and blood pressure.

Renal ischemia

In recent years, the role of ischemic kidney damage has been actively discussed as a concept for the development of chronic renal failure and arterial hypertension in elderly patients who have not previously suffered from renal diseases. In this category of patients, chronic renal failure arose against the background of generalized atherosclerosis with damage to the renal arteries (see "Ischemic kidney disease").

Genetic disorders

The problem of gene disorders in the genesis of renal arterial hypertension is currently under active study. The pathogenetic role of renin gene expression, gene disorders in the reception of KKS hormones has already been indicated above. There have been reports of gene disorders of the NO-synthetase enzyme, endothelin receptors. Researchers have paid close attention to the polymorphism of the angiotensin-converting enzyme (ACE) gene as a factor in the development and establishment of renal arterial hypertension, determining its severity, the degree of damage to target organs and the rate of progression of renal failure.

Summarizing the data on the pathogenesis of renal arterial hypertension, it should be emphasized that each of the presented mechanisms can be the only cause of its development, but in most patients, several factors are involved in the pathogenesis of the disease.

Degrees of arterial hypertension

Currently, the degree of arterial hypertension is determined by three main criteria: blood pressure level, etiological factor, and degree of damage to target organs.

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Blood pressure level

Degrees of arterial hypertension by blood pressure level in people aged 18 years and older

Category	Systolic blood pressure, mmHg	Diastolic blood pressure, mmHg
Optimal	<120	<80
Normal	120-129	80-84
Increased normal	130-139	85-89
Arterial hypertension:
1st degree	140-159	90-99
II degree	160-179	100-109
III degree	>180	>110
Isolated systolic	>140	<90

In 2003, American cardiologists proposed the 7th revision of the classification of arterial hypertension by stages (New Hypertension Guidelines: JNC 7).

Classification of arterial hypertension by stages

Categories	Systolic blood pressure, mmHg	Diastolic blood pressure, mmHg
Normal	<120	<80
Increased normal	120-139	80-89
Stage I	140-159	90-99
Stage II	160 and above	100 and above

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Etiological factor of arterial hypertension

According to etiology, arterial hypertension is divided into 2 groups: hypertension with unknown etiology - essential arterial hypertension, which makes up the vast majority of patients with arterial hypertension (more than 95%) and hypertension with known etiology, or secondary arterial hypertension.

Among the causative factors of secondary arterial hypertension are diseases of the kidneys, aorta, endocrine and nervous systems, as well as pregnancy, complications during surgical interventions, and medications.

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Complications of renal arterial hypertension

Complications of arterial hypertension are the same as with hypertension. Accelerated development of atherosclerosis, coronary heart disease, and the occurrence of heart rhythm disturbances are possible. With the development of left ventricular failure, shortness of breath with attacks of cardiac asthma appears, and pulmonary edema may develop. Congestion in the systemic circulation subsequently develops. Hypertensive encephalopathy occurs as a result of ischemia and edema of the brain and is manifested by the same symptoms as with hypertension (weakness, drowsiness, decreased memory and concentration, headache, decreased intelligence, depression).

Hypertensive crises (additional acute rise in blood pressure) may be associated with exacerbation of kidney disease, as well as with emotional or physical stress, excessive salt and/or fluid intake. Crises most often occur in patients undergoing hemodialysis treatment. Clinically, they are manifested by worsening cerebral, cardiac or, less commonly, ocular symptoms, acute left ventricular failure.

Accelerated development of nephrosclerosis and chronic renal failure are also considered as complications of arterial hypertension. Population studies in recent years have shown that in patients with kidney disease, the rate of decrease in glomerular filtration was higher, the higher the arterial pressure. Analysis of the causes of this phenomenon showed that a "sick" kidney, compared to a "healthy" one, is much more sensitive to even a slight increase in arterial pressure. In kidney disease, there are a number of factors that are activated under conditions of exposure to high arterial pressure. There is a violation of autoregulation of renal blood flow with subsequent transmission of increased systemic arterial pressure to glomerular capillaries and with the development of intraglomerular hypertension and hyperfiltration - the most important factors in the accelerated development of nephrosclerosis.

As a result of renal blood supply disturbance and endothelial dysfunction in kidney diseases occurring with arterial hypertension, dysregulation of vasoactive hormones (angiotensin II, endothelium, prostaglandins, nitric oxide, etc.) occurs. This increases renal blood supply disturbances, stimulates the production of cytokines, growth factors (TGF-beta, platelet growth factor and other biologically active substances), activates the processes of interstitial fibrosis and glomerular sclerosis.

The dependence of the rate of development of renal failure on the value of arterial pressure in nephrological patients has been confirmed by multicenter controlled studies, first of all by the MDRD study. In this study, in patients with various kidney diseases and proteinuria exceeding 1 g/day, the rate of decrease in glomerular filtration was about 9 ml/min per year with an average arterial pressure of 107 mm Hg (approximately 140/90 mm Hg), while, all other things being equal, in patients with an average arterial pressure not exceeding 90 mm Hg (approximately 120/80 mm Hg), the decrease in filtration was about 3 ml/min per year. This means that terminal renal failure requiring treatment with extracorporeal methods of blood purification would develop in the first case in about 7-10 years, and in the second - in 20-30 years. The presented data, later confirmed by other studies, showed that a blood pressure level significantly lower than 140/90 mmHg is optimal in terms of survival in patients with kidney disease. This approach was the basis for the concept of "target pressure" for patients with kidney disease.

The current recommendations of international expert groups are that to prevent the progression of chronic kidney disease, it is necessary to maintain blood pressure below 130/80 mm Hg. In patients with chronic renal failure and/or proteinuria exceeding 1 g/day, the optimal blood pressure should not exceed 125/75 mm Hg. Achieving such values is a rather difficult task due to a large number of objective and subjective factors. At the same time, it is not recommended to reduce systolic blood pressure < 110 mm Hg.

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