Arterial hypertension: causes, pathogenesis and degrees

Parenchymal diseases of the kidney include acute and chronic glomerulonephritis, chronic pyelonephritis, obstructive nephropathy, polycystic kidney disease, diabetic nephropathy, hydronephrosis, congenital kidney hypoplasia, renal injuries, renin secretion tumors, renoprive conditions, primary sodium retention (Liddle and Gordon syndromes).

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

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

At the present stage, several factors of pathogenesis of renal arterial hypertension are singled out: sodium and water retention, pressor and depressor hormone dysregulation, increased free radical formation, kidney ischemia, gene disorders.

[1], [2]

Water and sodium retention

The most significant factor in the pathogenesis of arterial hypertension in diffuse kidney disease is considered to be sodium retention, accompanied by an increase in the volume of extracellular fluid and the magnitude of cardiac output. This is the most frequent mechanism of development of renal arterial hypertension. Hypertension, dependent on volume, is revealed in 80-90% of patients with acute glomerulonephritis and chronic renal failure.

As a result of sodium retention, the content of electrolytes in the vessel wall changes (the accumulation of sodium and calcium ions in it), its edema, which leads to an increase in vascular sensitivity to pressor effects of vasoconstrictor hormones (angiotensin II, catecholamines, vasopressin, vasoconstrictor endothelial hormones). These changes are the basis for the development of high peripheral resistance (OPS) and general renal vascular resistance.

Thus, the delay of sodium and water by the kidneys affects both factors of the regulation of blood pressure - the value of cardiac output and OPS.

The main causes of sodium retention in renal diseases are renal glomeruli, followed by a decrease in the weight of the active nephrons, inflammation in the kidney parenchyma, increased reabsorption in the proximal, distal tubules and collecting tube, primary tubulointerstitial disorders.

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

Dysregulation of pressor and depressor systems

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

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

With kidney disease, the activation of one of the strongest vasoconstrictors - angiotensin II - occurs when the kidney hemodynamics is broken as a result of the development of acute immune inflammation or sclerotic processes. In addition to the enhanced formation of systemic angiotensin II, the local RAAS is activated in the kidneys with the production of the vasoconstrictor hormone directly in the kidney tissue. The combined effect of activated systemic and renal angiotensin II provokes a narrowing of both the resistive vessels (arterioles of medium diameter), which basically determine the OPS and the intrarenal vessels, which leads to an increase in OPS.

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

The physiological system of renal vasodilator hormones is represented by renal prostaglandins, kallikrein-kinin system. Their physiological properties: vasodilation and increased sodium excretion - counteract the development of arterial hypertension. With 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 played by a decrease in the production by the medulla of the kidneys of the vasodilating lipid of the medullin, the effects of which are being developed in detail at the present time.

An important role in the genesis of renal arterial hypertension is played by endothelial hormones: the active vasodilator N0 and the most powerful of the known endogenous vasoconstrictors are endothelin. In experiments it was shown that the blockade of N0 formation leads to the development of arterial hypertension. The enhanced synthesis of N0 from L-arginine is necessary for the development of a normal natriuretic response when loaded with sodium. In salt-sensitive hypertensive rats, blockade of N0 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 endothelin-1 concentration and inhibition of N0 release are revealed. With kidney diseases, the imbalance of this system with a decrease in the synthesis of N0 and an increase in the concentration in the blood of endothelin leads to the development of arterial hypertension due to a sharp increase in OPS, which increases against the background of sodium retention in the body.

In the process of progression of renal failure, the frequency and severity of hypertension increase. The role of sodium and water retention in the pathogenesis of arterial hypertension is increasing, and most other mechanisms common to all hypertension, including increased renin production by wrinkled kidneys, exhaustion of their production of depressant hormones and dysregulation of endothelial hormones, remain important. With the development of uremia, there are also additional factors that contribute to the emergence and maintenance of arterial hypertension.

[3], [4], [5]

Free radical formation

In recent years, the attention of researchers studying the mechanisms of the development of arterial hypertension in chronic renal failure attracts the activation of lipid peroxidation and the role of metabolite of protein metabolism of asymmetric dimethyl arginine. 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 OPS due to various mechanisms. These include the inactivation of NO production, the enhanced formation of vasoconstrictor metabolites due to oxidation of arachidonic acid inside the glomerular membranes, direct vasoconstrictor action of free oxygen radicals, increased fibrosis and atherosclerosis in the vessels. Accumulation of asymmetric dimethylarginine in chronic renal failure leads to blockade of NO-synthetase, which causes an increase in blood vessel OVC and blood pressure.

Kidney ischemia

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

Genetic disorders

The problem of gene disorders in the genesis of renal arterial hypertension is now in the active study stage. We have already mentioned the pathogenetic role of the expression of the renin gene, gene disorders in the reception of the hormones CCS. There have been reports of gene disorders of the NO synthetase enzyme, endothelin receptors. Close attention is being paid to the polymorphism of the angiotensin-converting enzyme (ACE) gene as a factor in the development and development of renal arterial hypertension, determining its severity, the degree of damage to target organs and the rate of progression of renal failure.

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

Degrees of hypertension

At present, the degree of arterial hypertension is carried out according to three main characteristics: the level of blood pressure, the etiologic factor, the degree of damage to target organs.

[6], [7], [8], [9], [10], [11], [12],

Blood pressure level

The degree of arterial hypertension in terms of blood pressure in people aged 18 years and over

Category	Systolic BP, mmHg	Diastolic blood pressure, mmHg
Optimal	<120	<80
Normal	120-129	80-84
Increased normal	130-139	85-89
Arterial hypertension:
I 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 BP, mmHg	Diastolic blood pressure, mmHg
Normal	<120	<80
Increased normal	120-139	80-89
Stage I	140-159	90-99
II stage	160 and above	100 and above

[13], [14], [15], [16], [17]

Etiological factor of arterial hypertension

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

Among the causative factors of secondary arterial hypertension, renal, aortic, endocrine and nervous system diseases, as well as pregnancy, complications in surgical interventions, drugs are isolated.

[18], [19], [20], [21], [22]

Complications of renal arterial hypertension

Complications of hypertension are the same as in hypertensive disease. Perhaps the accelerated development of atherosclerosis, coronary heart disease, the occurrence of heart rhythm disturbances. With the development of left ventricular failure, dyspnea with attacks of cardiac asthma appears, it is possible the development of pulmonary edema. In the future, stagnation develops over a large range of blood circulation. Hypertensive encephalopathy occurs as a result of ischemia and edema of the brain and manifests itself with the same symptoms as hypertensive disease (weakness, drowsiness, memory and concentration decrease, headache, decreased intelligence, depression).

Hypertensive crises (an additional acute increase in blood pressure) may be associated with exacerbation of kidney disease, as well as with emotional or physical exertion, with excessive consumption of salt and / or liquid. The most common crises occur in patients undergoing hemodialysis treatment. Clinically, they are manifested by worsening of cerebral, cardiac or, more rarely, ocular symptoms, acute left ventricular failure.

As a complication of hypertension, the accelerated rate of development of nephrosclerosis and chronic renal failure is also considered. Population studies of recent years have shown that in patients with kidney disease, the rate of decrease in glomerular filtration was higher, the higher the level of blood pressure. Analysis of the causes of this phenomenon showed that the "sick" kidney, in comparison with the "healthy" kidney, is much more sensitive even to a slight increase in blood pressure. In kidney diseases, there are a number of factors that are activated in conditions of high blood pressure. There is a violation of autoregulation of the renal blood flow followed by the transfer of increased systemic arterial pressure to the glomerular capillaries and the development of intra-cerebral hypertension and hyperfiltration, the most important factors in the accelerated development of nephrosclerosis.

As a result of impaired renal blood supply and endothelial dysfunction in diseases of the kidneys that occur with arterial hypertension, dysregulation of vasoactive hormones (angiotensin II, endothelium, prostaglandins, nitric oxide, etc.) occurs. This increases the disturbances in the renal blood supply, stimulates the production of cytokines, growth factors (TGF-beta, platelet-derived 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 was confirmed by multicentre controlled studies, primarily 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 with other conditions being equal, in patients with mean arterial pressure not exceeding 90 mm Hg. (approximately 120/80 mm Hg), the filtration drop was about 3 ml / min per year. This means that terminal renal failure, requiring treatment with extracorporeal methods of blood purification, in the first case would develop after about 7-10 years, and in the second - in 20-30 years. Presented data, then confirmed by other studies, showed that the blood pressure level, significantly lower than 140/90 mm Hg, is optimal for the survival of patients with kidney diseases. This approach was used as the basis for the concept of "target pressure" for patients with kidney disease.

Current recommendations of international expert groups are that to prevent the progression of chronic kidney diseases, 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 mmHg.

[23], [24], [25], [26], [27]