Nephrogenic (renal) hypertension: a review of information

Nephrogenic (renal) hypertension - Renovascular hypertension is a pathological condition characterized by a persistent increase in blood pressure.

Of a large number of patients suffering from hypertension, in a third it has a nephrogenic character, i.e. Is caused by kidney disease and their blood vessels.

[1], [2], [3], [4], [5],

Epidemiology

Nephrogenic hypertension occupies one of the first places among secondary, or symptomatic, arterial hypertension and is found in 5-16% of patients. It leads to complications that are the cause of the decline or loss of ability to work and death of patients.

Vasorenal hypertension occurs in 1-7% of patients with arterial hypertension.

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

Causes of the nephrogenic (renal) hypertension

The causes of nephrogenic hypertension are acquired and congenital diseases or pathological conditions.

[12], [13], [14], [15]

Congenital causes of nephrogenic (renal) hypertension

• Fibromuscular dysplasia of the renal artery (the most common congenital cause), arteriovenous fistula of the kidney, calcification, aneurysm, thrombosis or embolism of the renal artery, renal artery hypoplasia, aortic and renal artery anomalies (atresia and hypoplasia of the renal arteries), stenoses, vein thrombosis, vascular injuries kidney, horseshoe, dystopic and pathologically moving kidney.
• Anomalies of the bladder, urethra and ureters.

[16], [17], [18]

Acquired causes of nephrogenic (renal) hypertension

Atherosclerosis of the renal artery (the most common cause of vasorenal hypertension), nephroptosis, renal artery thrombosis or major branches, nonspecific aortoarteritis (pulseless disease, Takayasu disease) with renal artery disease, nodular periarteritis, renal artery aneurysm, arteriovenous fistula (most often as a result trauma), compression of the renal artery from the outside (tumor, kidney cyst, spikes, hematoma).

Vasorenal hypertension in 99% of observations is determined by two diseases: atherosclerotic lesion of the renal artery (60-70%) and fibromuscular dysplasia (30-40%). The remaining causes are extremely rare and in the aggregate constitute no more than 1% of cases.

Thrombosis and embolism, being occlusal forms of lesions of the renal arteries, often lead to arterial hypertension. Finally, vasorenal hypertension can develop as a result of compression of the main renal arteries with a tumor, cyst, spikes, organized hematoma, etc.

The parenchymal form of renal arterial hypertension can occur against the background of acute and chronic glomerulonephritis, chronic pyelonephritis, obstructive nephropathy, polycystic kidney disease, simple kidney cysts, including multiple, diabetic nephropathies, hydronephrosis, congenital renal hypoplasia, renal injury, renin secretion tumors, renoprival conditions, primary delay of sodium (syndromes Liddle, Gordon), systemic connective tissue diseases (systemic lupus erythematosus, systemic scleroderma), tuberculosis kidney. Significantly less often (about 20%), renal hypertension is detected in renal diseases with tubular lesions and interstitium (amyloidosis of the kidney, interstitial drug nephritis, tubulopathy).

[19], [20], [21], [22], [23]

Pathogenesis

At the end of XIX century. Tigerstedt and Bergman (1898), experimenting with extracts from the cortical layer of the kidneys, discovered renin - a hormone, which played a huge role in the doctrine of arterial hypertension.

Studies have shown that any narrowing of the renal arteries, leading to ischemia of the renal parenchyma, causes an increase in renin production in the juxtaglomerular apparatus (SOHA) of the kidneys. The formation of renin is a complex process. The first link in this process is the synthesis of preproenin, a protein consisting of a signal peptide and a prorenic structure. The signal peptide is cleaved in the endoplasmic reticulum, and the glycosylated prorenin passes through the Golgi apparatus, where it is converted to active renin. Renin molecules form granules, which are then pushed into the intercellular space. The synthesis of renin by cells of SOUTH depends on the tone of the afferent arterioles or their intramural pressure. Renin secretion is regulated by renal baro-regulation. Stenosis of the renal artery, leading to a decrease in arterial pressure in the distal vessels and reducing the tonus of the afferent arterioles stimulates the baroreceptors of the macula densa, a closely connected tubular structure to the SOUTH, resulting in increased synthesis of renin.

The synthesis of renin SOA kidney affects a number of factors. Stimulation of sympathetic neurohumoral activity leads to increased renin production independent of renal blood flow and glomerular filtration. This effect is mediated by exposure to beta-adrenergic receptors. In addition, there are inhibitory alpha-adrenergic receptors in the kidneys. The response to stimulation of both types of receptors depends on the combined effect of changes in perfusion pressure, renal blood flow and glomerular filtration, all of which can vary under the influence of sympathetic activity. The sodium load inhibits, and the depletion of its stocks stimulates the expression of the renin gene and the secretion of renin. Reduction of perfusion pressure stimulates, and its increase inhibits the secretion of renin. At the same time, many other factors influence the secretion of renin, in particular, angiotensin II, the active product of renin metabolism, an enzyme with a powerful hypertensive effect. Angiotensin II suppresses the secretion of renin by the feedback mechanism.

Now it is known that renin synthesized in kidneys under the influence of liver enzyme angiotensinogen combines with blood a1-globulin, forming an angiotensin polypeptide, which has a vasopressor effect. Angiotensin exists in two forms: inactive angiotensin I and having a potent vasopressor effect of angiotensin II. The first form is transformed into the second under the influence of angiotensin-converting enzyme (ACE). It refers to zinc-containing metalloproteases. Most of the ACE is bound to the cell membranes. It exists in two forms: endothelial and testicular. ACE is widely distributed in most body tissues. Unlike renin, ACE does not have specificity and is able to affect many substrates. One of such substrates is bradykinin, a substance that has depressor properties and belongs to the kallikrenne-kinin system. Decreased ACE activity, causes a decrease in angiotensin II production and simultaneously increases the sensitivity of the vessels to bradykinin, leading to a decrease in blood pressure.

Angiotensin II has a hypertensive effect both directly, affecting the tone of the arterioles, and through stimulation of the secretion of aldosterone. The hypertensive action of aldosterone is associated with its effect on sodium reabsorption. As a result, the volume of extracellular fluid and plasma increases, the sodium content in the walls of the arterioles increases, which leads to their swelling, increased tone and increased sensitivity to pressor influences. The interactions of renin, angiotensin and aldosterone, characterized by both positive and negative feedbacks, have been called the renin-angiotensin-aldosterone system.

It is established that the tissue of the kidney is capable of producing substances having direct or indirect depressor properties. The depressor effect of the kallikrein-kinin system, vasodilating action of prostacyclin, simultaneously stimulating the secretion of renin, was found. Between the pressor and depressor substances produced by the kidneys, there is a close relationship.

Thus, the pathogenesis of nephrogenic arterial hypertension is very complex and is associated with several major factors: sodium and water retention, pressor and depressor hormone dysregulation (increased renal and non-renal pressor hormone activity and insufficient depressor function of the kidney), stimulation of vasopressin secretion, oppression of natriuretic factor release, increasing the formation of free radicals, kidney ischemia, gene disorders.

The kidney function can be normal, but more often it slowly but progressively decreases, reaching 85-90% of the deficit in the development of chronic renal failure.

[24], [25], [26], [27], [28], [29], [30]

Symptoms of the nephrogenic (renal) hypertension

Symptoms of nephrogenic hypertension are due to impaired perfusion of the renal tissue due to a disease or pathological condition leading to a sharp restriction of renal blood flow. In this case, the kidneys can simultaneously cause arterial hypertension and the target organ of this pathological condition, aggravating the course and symptoms of nephrogenic (renal) hypertension. The most common cause of nephrogenic (renal) hypertension is atherosclerotic narrowing of the main renal arteries. Vasorenal hypertension with nephroptosis is usually of an orthostatic nature and is caused by the inflection or tension of the renal artery.

If a nephrogenic (renal) arterial hypertension is suspected, the diagnostic algorithm is complex and consists of several stages that end with the clarification of its cause (vasorenal or parenchymal), the determination of the functional significance of the revealed renal artery lesions with vasorenal hypertension, since this has a dramatic effect on the choice of treatment tactics . For a urologist, in practice, this amounts to confirming or eliminating the vasorenal cause of hypertension. In the case of a vasorenal nature of the disease, the patient is under the supervision of a urologist (vascular surgeon) in conjunction with a therapist (cardiologist), during which the question of the possibility of surgical treatment of the disease is solved in order to reduce or stabilize blood pressure. If there is no data for a vasorenal hypertension or if the patient's condition does not allow performing radical surgical treatment with vasorenal hypertension, it is transmitted under observation and treatment from the therapist (cardiologist).

At the first stage, a thorough general medical examination is envisaged, including a targeted study of the patient's complaints and the collection of an anamnesis, measurement of blood pressure on the arms and legs, auscultation of the heart and large vessels. Unfortunately, the history and course of vasorenal hypertension do not have sensitivity and specificity for establishing a diagnosis. Some anamnestic data and symptoms only suggest the presence of vasorenal hypertension. 

The physical examination data have a great preliminary value in the detection of vasorenal hypertension than the anamnestic data, however the absence of such objective signs does not exclude the diagnosis of vasorenal hypertension. The detection of vascular noise or other manifestations of systemic vascular lesions presupposes the presence of vasorenal hypertension, but does not serve as a basis for establishing a diagnosis. Typical symptoms of nephrogenic hypertension are a sudden and rapid increase in blood pressure, hypertension resistance to potent combined therapy, or "causeless" loss of control of blood pressure. Stenosis of the renal arteries is more common among patients with systemic, and in particular atherosclerotic, lesions of the arteries. In addition, by percussion, it is possible to detect pronounced hypertrophy of the left ventricle, resulting from prolonged severe hypertension.

For vasorenal hypertension is not necessary, but a symptom is very characteristic when the patient has very high blood pressure against the background of a normal heart rate, or even a bradycardia.

Clinical and biochemical blood tests are carried out (the latter includes determination of blood urea, creatinine and electrolytes in the blood), general urine analysis, Zimnitsky urine analysis, Kakovsky-Addis test and bacteriological urine analysis. Mandatory examination of the fundus. A sample with a single dose of captopril is performed.

The instrumental methods used at this stage include ultrasound and kidneys, dynamic nephroscintnography with I-hippuran. In the second stage, angiography (traditional aortography, selective angiography of the renal arteries or digital subtraction angiography) is performed to identify lesions of the renal arteries.

In the third stage, central hemodynamics, radioimmunoassay studies of renin level in blood obtained from renal veins and inferior vena cava, and a pharmacoradiological test with captopril are performed to determine the nature of arterial hypertension, to determine the functional significance of renal artery lesions, and to optimize intraoperative tactics.

Forms

Nephrogenic arterial hypertension is divided into two forms: vasorenal and parenchymal.

Vasorenal hypertension is a symptomatic arterial hypertension that has arisen as a result of ischemia of the renal parenchyma on the background of the defeat of the main renal arterial vessels. Less often, vasorenal hypertension is called fibromuscular dysplasia of the renal arteries and arteriovenous malformation, vasorenal hypertension is divided into two forms: congenital and acquired.

With parenchymal renal arterial hypertension, almost all diffuse diseases of the kidney can occur, in which hypertension is associated with the lesion of its glomeruli and intragroup small arterial vessels.

[31], [32]

Diagnostics of the nephrogenic (renal) hypertension

Diagnosis of nephrogenic hypertension includes the following stages:

[33], [34], [35]

Determination of renin level in peripheral blood

It was found that a decrease in the intake and excretion of sodium leads to an increase in the level of renin. In humans, the plasma renin level fluctuates sharply during the day, and therefore its single measurement is not informative. In addition, virtually all antihypertensive drugs have a significant effect on blood renin levels. Therefore, they must be canceled, at least 2 weeks. Before the study, which is dangerous for patients with severe hypertension.

[36], [37], [38], [39]

Disposable captopril test

After the first experimental inhibitor of angiotensin II was created, and then other angiotensin II and ACE inhibitors, studies showed that under the influence of angiotensin II inhibitors renal artery stenosis increases the secretion of renin by an ischemic kidney. The positive result of a one-time trial with captopril indicates a renin-dependent nature of hypertension, but does not allow the diagnosis of vasorenal hypertension. That is why the use of only a single-dose captopril test for screening of vasorenal hypertension is not enough.

[40], [41],

General blood analysis

Rare erythrocytosis is possible due to excessive production of erythropoietin by the affected kidney.

There is an isolated stimulation of the red bone marrow: reticulocytosis, an excessively large number of red blood cells, an excessively high hemoglobin level corresponding to erythrocytosis, although each individual red blood cell or reticulocyte is perfectly normal.

General urine analysis

Possible a small proteinuria (up to 1 g / day), erythrocyturia, less often - a slight leukocyturia.

Blood chemistry. In the absence of severe chronic renal failure, changes can not be detected, and in patients with concomitant diseases, changes characteristic of these diseases are revealed (in patients with advanced atherosclerosis, high levels of low and very low density lipoproteins, cholesterol, etc.).

Reberg's test is for all patients with prolonged and severe hypertension of any origin, including suspected nephrogenic, for the detection of chronic renal failure.

Daily protein excretion is investigated when differential diagnosis is required with primary glomerular lesions.

The determination of aldosterone in the peripheral blood is performed to exclude or confirm secondary hyperaldosteronism simultaneously with the study of the level of renin.

Holter monitoring of arterial pressure and ECG is indicated for differential diagnosis in complex and ambiguous cases.

Instrumental methods of diagnosis of nephrogenic hypertension

The task of instrumental methods of investigation is to find the lesion of renal vessels and to prove the asymmetric nature of nephropathy. If the renal involvement is symmetrical, this usually indicates parenchymal renal hypertension due to different nephropathy and primary symmetrical nephrosclerosis.

These research methods are aimed at studying the structure of the kidneys, especially their vascularization, and allow us to judge the function of the kidneys. Structural and functional studies include excretory urography. Ultrasound examination methods, CT and magnetic resonance imaging of the urinary system.

Survey urography and excretory urography have several features of their implementation. Excretory urography is usually performed in the course of hagiographic research to assess the structural and functional state of the kidney. Against the background of an explicit decompensation of chronic renal failure, the introduction of RVT is contraindicated because of their nephrotoxicity (the risk of acute exacerbation of chronic renal failure). In addition, research on this background is of little informative.

It is necessary to refrain from excretory urography and at too high hypertension and to conduct it only after at least temporary lowering of arterial pressure by any short-acting drug (for example, clonidine).

The first image is taken immediately after the introduction of contrast, the second - after 3-5 minutes, then decisions are made according to the results obtained in the first pictures.

The delay in contrasting the kidney from the affected side, the asymmetry of the kidneys, the delayed secretion of contrast medium on the side of the lesion in the early radiographs, the early and persistent nephrogram, the hyperconcentration of the contrast medium in late urograms from the lesion, and the severe nephrosclerosis, the affected kidney generally can not be contrasted.

Ultrasonography of the kidneys and renal arteries

Ultrasonic evaluation of kidney size is not sensitive enough. Even with severe stenosis of the renal artery, the size of the kidneys remain normal. In addition, the ultrasonic determination of the size of the kidneys depends to a large extent on the method of investigation used. Therefore, the comparative size of the kidneys were useless for screening the stenosis of the renal arteries with vasorenal hypertension.

UZDG and duplex scanning (a combination of ultrasound scanning and Doppler ultrasound) are more effective methods of assessing the renal arteries. Arterial stenosis affects the character of intravascular blood flow, increasing its velocity in the area of injury and creating turbulence in the area of poststenotic enlargement. Since duplex ultrasound can provide information on the blood flow, it has a greater significance in the detection of hemodynamic disorders in the renal arteries than in the detection of stenosis of the renal arteries.

Thus, ultrasound and Doppler ultrasound may reveal signs of disturbed blood flow through the affected renal artery, signs of nephrosclerosis from the affected side and possible compensatory hypertrophy of the opposite kidney.

Intravascular ultrasound imaging of the renal arteries refers to the standard methods of studying their anatomical features in the clinic. In most cases, it makes it possible to identify the vasorenal hypertension and to conduct differential diagnosis between its two main causes - atherosclerosis and fibromuscular dysplasia. However, due to the invasive nature of the method, it can not be regarded as suitable for screening purposes.

Radioisotope renal scintigraphy

Methods of radioisotope diagnostics of nephrogenic (renal) hypertension determine the secretory function of proximal tubules, urodynamics of VMP, as well as topographic and anatomical, functional and structural features of the kidneys. For this purpose, dynamic nephroscintigraphy is used with the drug, the transport of which will be realized mainly through secretion in the proximal tubules of the kidney -131 I-hippuran.

Renography or dynamic nephroscintigraphy can reveal asymmetry of renographic curves or images of the kidneys. However, it is quite possible that the decrease in the diameter of the renal artery is completely compensated by an increase in blood pressure. In this case, there can be no significant asymmetry. Then you can not do without a test with captopril. To do this, the patient is reduced by arterial pressure with captopril (usually 25-50 mg at a time), then isotope testing is repeated. The asymmetry of curves or images should appear or intensify (significant is the fall of filtration from the affected side more than 10% of the original level). This event proves two facts:

• hypertension is vasorenal, since there is a significant drop in filtration from the affected side in response to a drop in systemic blood pressure;
• hypertension is highly prenitive, which is typical for the described syndrome and will later help in the appointment of a therapy regimen.

However, not always vasorenal hypertension is high-grade, sometimes it happens at a normal level of renin.

Since the main task of isotopic research methods is confirmation or refutation of the symmetry of nephropathy, it is pointless and economically impractical to perform them in a single kidney, when all questions related to kidney function are resolved by nephrological laboratory tests.

Computed tomography and magnetic resonance tomography CT allows you to assess the state of the vessels of the abdominal cavity, primarily the aorta and its branches, and reveals diseases of the kidney vessels. The use of intravenous administration of RKV in minimal quantities visualizes the walls of the vessels. CT data correlate well with the results of angiography. The most reliable in terms of identifying the causes of vasorenal hypertension MSCT, which is now virtually supplanted by renal arteriography performed for the same purpose. In some cases, an alternative to angiography may be an MRI.

Angiography in the diagnosis of lesions of the renal arteries

The most reliable method of studying the renal arteries for the diagnosis of vasorenal hypertension is radiocontrast study. Angiography determines the nature, extent and localization of renal vessels.

In the lifetime X-ray study of human vessels with the introduction of contrast media, Sicard and Forestier performed in 1923 for the first time. In the late 20's - early 30-ies of the last century, aortoarteriography due to the work of Dos Santos et al. Gradually enters into clinical practice, but does not receive a wide distribution in the diagnosis of diseases of the arterial system. A cautious attitude towards aortography at the time was due to the high toxicity of the contrast agents used and severe reactions to their administration, as well as the risk of complications caused by aortic and arterial puncture. In addition, the diagnosis of many diseases of the arterial system, including lesions of the arterial system of the kidneys, at that time was of purely academic interest, since most patients with vasorenal hypertension performed nephrectomy.

A new stage in the development of angiography refers to the second half of the 30s. This was facilitated by the synthesis of relatively low-toxicity RKV and the first successful radical surgery on the aorta and major arteries. In the late 40's and early 50's, aortography became increasingly popular as a highly informative method for diagnosing diseases of the arterial system, kidneys, retroperitoneal space, heart and brain. In 1953, SJ Seldinger reported on the method he developed for percutaneous catheterization of the aorta. This technique, using a special conductor, replaces the needle in the aorta with a polyethylene catheter. ON. Lopatkin - the first of domestic researchers - performs renal angiography in 1955.

An important role in the evolution of the method of aortoarteriography is played by the creation of powerful x-ray devices for angiography with electron-optical amplification and a television observation system, as well as the use of triiodic organic RCBs. The progress of electronics and computer technology in the late 70's leads to the creation of a radically new method for radiocontrast study of blood vessels - digital (or digital) subtraction angiography.

Further improvement of the method is possible due to the combination of X-ray and electronic computers, which simultaneously use the principle of enhancing the image of vessels and subtraction (subtraction) of images of soft tissues and bones. The essence of the method is that the computer processing of the x-ray image suppresses its background, i.e. Eliminates the image of soft tissues and bones and at the same time enhances the contrast of blood vessels. It well visualizes arteries and veins. Nevertheless, the doctor should be aware of the possibility of a technical error in identifying some forms of renal artery disease and in the presence of other strong arguments in favor of the diagnosis of vasorenal hypertension, to continue the research.

[42], [43], [44], [45], [46]

Indications for angiography:

• high stable or malignant hypertension, resistant to combined antihypertensive therapy;
• increased arterial pressure due to other diseases;
• parenchymal diseases of the kidneys (diffuse glomerulonephritis or chronic pyelonephritis);
• hormone-producing tumors of the adrenal glands;
• coarctation of the aorta, especially in young patients;
• generalized arterial diseases (atherosclerosis, fibromuscular dysplasia, nodular periarteritis, arteritis of the aorta and its branches);
• diseases characterized by the development of thrombosis and embolism of the arteries;
• decrease in secretory function of the kidney according to dynamic nephroscintigraphy.

The presence of signs of stenosis of the renal arteries, revealed at the stages of the previous examination, serves as an additional criterion for the expediency of angiography. Angiography is indicated for patients potentially having to undergo reconstructive operations on the kidney vessels, and allows to establish the shape, volume and localization of the lesion of the renal vessels. In this study, blood can be taken separately from each kidney for subsequent determination of renin level, which increases the reliability of the analysis.

The absence of any patient with a high stable arterial hypertension, refractory to complex therapy, any complaints, not only does not call into question the advisability of angiography of the renal arteries, but, on the contrary, serves as an additional argument in favor of it.

Contraindications for renal angiography are few and for the most part not absolute. Thus, with intolerance to patients with iodine preparations, the use of neiodic contrast agents is possible. Patients with renal insufficiency, in the presence of clear indications for angiographic examination, instead of traditional angiography, carry out arterial digital subtraction angiography. Patients suffering from diseases accompanied by increased bleeding, in the period of preparation for the study, conduct specific hemostatic therapy. Angiography also should not be performed against a background of high hypertension, since the probability of a hematoma at the femoral artery puncture site increases many times.

Absolute contraindications are decompensation of chronic renal failure (the possibility of developing acute renal failure). Terminal stage of renal failure and extremely severe general condition of the patient.

Complications of angiography. There are easy and severe complications of angiography. Minor complications include small hematomas in the arterial puncture area, headache, nausea, vomiting, short-term fever, chills, short spasm of the arteries, etc. Most of these complications are caused by the action of iodide compounds used as RVB. With the introduction of less toxic RVC into clinical practice, the frequency of these complications has significantly decreased.

Severe complications of angiography:

• acute violation of cerebral or coronary circulation:
• acute renal failure;
• severe arterial hypertension;
• massive thromboembolism;
• damage to the intima of the artery leading to the dissection of its wall;
• perforation of the artery wall, accompanied by bleeding, the formation of pulsating hematoma and arteriovenous anastomosis;
• separation of the catheter or conductor.

A serious complication can be the cause of the patient's death.

The general drawback of the described methods of examining the patient is the indirect nature of information on the lesions of the renal arteries with vasorenal hypertension. The only method that determines the structural changes in the kidneys in vivo is the morphological examination of the kidney biopsy. However, kidney biopsy is unsafe because of the risk of internal bleeding. In addition, in some cases there are medical contraindications to its conduct.

Indications for consultation by other specialists

All persons with a suspicion of the vasorenal nature of hypertension are advised of a nephrologist, and in his absence - a cardiologist. Consultation of the nephrologist is especially indicated for patients with suspected bilateral lesions of the renal arteries, renal artery disease of a single or only functioning kidney, chronic renal failure. All patients are advised by an ophthalmologist to determine the condition of the fundus and identify ophthalmological signs of the malignancy of hypertension. At the stage of determining the tactics of treatment - a consultation of a urologist or a vascular surgeon and an anesthesiologist.

Differential diagnosis

Vasorenal hypertension has to differentiate with all other chronic symptomatic hypertension, less often with hypertensive disease.

Renoparenchymatous arterial hypertension. Carrying out a radioisotope study confirming the symmetry of kidney damage allows resolutely to exclude vasorenal hypertension. Further defeat of renal vessels is determined or rejected by Doppler ultrasound. The last stages of differential diagnosis are isotope studies with captopril and angiography.

Primary hyperaldosteronism. Usually the condition of these patients is determined not so much by hypertension as by hypokalemia, and the severity of the condition does not depend on the amount of adrenal involvement. Typical are complaints of muscle weakness, and unstable in time and sometimes extreme severity, there may be swelling, and from diuretics (loop and thiazide) their condition worsens. Hypotensive therapy is difficult to select. There may be rhythm disturbances (with corresponding changes on the electrocardiogram) and polyuria as a result of hypokalemic nephropathy. The raised level of a renin, revealed against a canceling of therapy, allows to exclude unequivocally primary hyperaldosteronism.

Syndrome and Ithenko-Cushing's disease. With these diseases, patients have a characteristic appearance, skin dystrophy, bone damage and steroid diabetes. A delay in sodium and a low renin can be detected. The diagnosis is confirmed by the definition of an elevated level of corticosteroids in the blood.

Renal tumor that produces renin. The origin of hypertension in these patients is the same as with the vasorenal form, but there are no changes in the main renal arteries.

Pheochromocytoma and other tumors that produce catecholamines. In about half of cases, the disease manifests itself as typical catecholamine crises with corresponding complaints and no signs of kidney damage. The crisis can be stopped by the intravenous administration of the alpha-blocker of phentolamine, but in view of the rarity of such patients and the extremely narrow spectrum of the use of phentolamine, sodium nitroprusside is usually used. Diagnosis by pheochromocytoma should not be based on information about the effectiveness of any drugs.

In half of the remaining cases, hypertension is relatively labile with some vegetative component. The extreme variability of the clinical picture of the disease dictates when examining patients with suspected symptomatic arterial hypertension to include an analysis of the excretion of metabolic products of catecholamines with urine, which can be performed against the background of therapy.

Coarctation of the aorta. Usually patients of young age, despite having hypertension, with good health and provoking distrust with excellent physical endurance, have well developed muscles of the upper extremities and hypotrophy of the muscles (especially the calf) legs. High blood pressure is detected only in the arteries of the upper limbs. Coarse systolic murmur, which is determined during normal auscultation of the heart and large vessels, is also heard between the scapulae.

Hypertensive disease is a disease that begins slowly at a young age and, as a rule, proceeds benignly. Clearly visible dependence of high blood pressure on physical and emotional loads, fluid intake, characterized by hypertensive crises. The detection of asymmetry of nephropathy decisively contradicts even the most malignant course of hypertensive disease.

Thyrotoxicosis. Outwardly, these patients appear to be the complete opposite of patients with vasorenal hypertension. With vasorenal hypertension, the patient, regardless of age, does not look like a seriously ill patient, he is adequate, sometimes slightly stunted, may have memory impairment due to encephalopathy from prolonged severe hypertension. In severe thyrotoxicosis, patients (mostly young women) give the impression of deeply unhealthy physically or mentally persons. Their actions, judgments and speech are too fast and unproductive, thoughts are difficult to formulate. When examining attracts attention is not so much hypertension, as a strong, nothing inexplicable, even at rest, tachycardia and a tendency to heart rhythm disturbances (in severe cases, there may be constant atrial fibrillation). For vasorenal hypertension, heart rhythm disturbances are extremely uncharacteristic, and left ventricular hypertrophy is characteristic. The diagnosis of primary thyrotoxicosis is confirmed by the detection of a high level of thyroxine and an extremely low level of thyroid-stimulating hormone.

Erythremia. Elderly people usually suffer from erythremia. Their complexion is red, but there is no edema, almost always high blood pressure, which they suffer worse than people of their age with hypertension. Typical complaints are various pain localizations (in the hands, feet, head, heart, sometimes even in the bones and spleen), skin itch, because of which patients sleep poorly at night. In the general analysis of blood, the excess activity of all three sprouts of the bone marrow is revealed, which is never the case with symptomatic erythrocytosis. Vasorenal hypertension contradicts pain in the bones, especially worse with percussion (a sign of bone marrow proliferation), an increase in the spleen and pain in it. Identification of changes in isotopic kidney examination does not necessarily reject the diagnosis of erythremia, because due to inadequate disinhibition of the platelet germ and the resulting thrombocytosis, the disease can be complicated by thrombosis of any vessel, including the kidney.

Treatment of the nephrogenic (renal) hypertension

Treatment of nephrogenic hypertension consists in the following: improvement of well-being, adequate control of arterial pressure, slowing of progression of chronic renal failure, prolongation of life, including without dialysis.

Indications for hospitalization with nephrogenic hypertension

The newly discovered nephrogenic hypertension or suspicion of it is an indication for hospitalization in a hospital to clarify the causative nature of the disease.

In outpatient settings, preoperative preparation for surgery for the vasorenal genesis of hypertension is possible, as well as management of patients who have a parenchymal form of the disease or the severity of the condition, operative treatment for vasorenal hypertension is contraindicated.

Non-pharmacological treatment of nephrogenic hypertension

The role of non-drug treatment is low. Patients with nephrogenic hypertension are usually restricted to consumption of salt and fluid intake, although the effect of these recommendations is questionable. They are rather necessary for the prevention of hypervolemia, which is possible with excessive use of salt and liquid.

The need for active treatment tactics for patients with lesions of the renal arteries is universally recognized, since surgical treatment is aimed not only at eliminating hypertensive syndrome, but also at preserving kidney function. The life expectancy of patients with vasorenal hypertension who underwent surgery is significantly greater than in patients who for one reason or another did not undergo surgery. In the period of preparation for the operation, with its insufficient effectiveness or when it is impossible to perform it, it is necessary to treat patients with vasorenal hypertension with medication.

The tactics of a physician in the pharmacological treatment of vasorenal hypertension

Surgical treatment of patients with vasorenal hypertension does not always lead to a decrease or normalization of blood pressure. Moreover, in many patients with stenosis of the renal arteries, especially atherosclerotic origin, the increase in arterial pressure is due to hypertensive disease. That is why the final diagnosis of vasorenal hypertension is relatively often necessary to establish ex juvantibui, focusing on the results of surgical treatment.

The heavier arterial hypertension occurs in patients with atherosclerosis or fibromuscular dysplasia, the greater the likelihood of its vasorenal genesis. Operative treatment gives good results in young patients with fibromuscular dysplasia of the renal arteries. The efficiency of the operation on the renal arteries is lower in patients with atherosclerotic stenosis, since many of these patients are in advanced age and suffer from hypertension.

Possible variants of the course of the disease, determining the choice of treatment tactics:

• true vasorenal hypertension, in which the stenosis of the renal arteries is the only cause of arterial hypertension;
• hypertensive disease in which atherosclerotic or fibromuscular lesions of the renal arteries are not involved in the genesis of arterial hypertension;
• hypertensive disease, which is "layered" vasorenal hypertension.

The purpose of drug treatment of such patients is to keep blood pressure under control, to take measures to minimize the damage to target organs, to avoid undesirable side effects of the drugs used. Modern antihypertensive drugs allow you to monitor the patient's blood pressure with vasorenal hypertension and during the preparation for surgery.

Indications for drug therapy of patients with nephrogenic (renal) arterial hypertension, including vasorenal genesis:

• old age,
• severe atherosclerosis;
• doubtful angiographic signs of hemodynamically significant stenosis of the renal arteries;
• high risk of surgery;
• impossibility of surgical treatment due to technical difficulties;
• refusal of the patient from invasive methods of treatment.

Medicamentous treatment of nephrogenic hypertension

Medicinal antihypertensive therapy of nephrogenic hypertension should be conducted more aggressively, achieving strict control of blood pressure at the target level, although this is difficult to achieve. However, treatment should not rapidly reduce blood pressure, especially with vasorenal hypertension, regardless of the intended drug or a combination thereof, as this leads to a reduction in GFR on the affected side.

Usually for the treatment of nephrogenic hypertension, and primarily its parenchymal form, various combinations of the following groups of drugs are used: beta-adrenoblockers, calcium antagonists, ACE inhibitors, diuretics, peripheral vasodilators.

In patients with tachycardia, which is not characteristic for vasorenal hypertension, beta-blockers are prescribed: nebivolol, betaxolol, bisoprolol, labetalol, propranolol, pindolol, atenolol, which require strict control in chronic renal failure.

In patients with bradycardia or normal heart rate, beta-blockers are not shown and the first-line drugs are calcium antagonists: amlodipine, felodipine (prolonged forms), felodipine, verapamil, diltiazem, prolonged dosage forms of nifedipine.

ACE inhibitors are given the role of second-line and sometimes first-line drugs: trandolapril, ramipril, perindopril, fosinopril. Enalapril may be prescribed, but the dose of the drug is likely to be close to the maximum.

With the vasorenal genesis of hypertension, which in the vast majority of observations is highly prenic, the purpose of ACE inhibitors has its own characteristics. You can not sharply reduce blood pressure, as this can lead to a pronounced deficit of filtration in the affected kidney, including by decreasing the tone of the efferent arterioles, which increases the deficit of filtration due to a decrease in the filtration pressure gradient. Therefore, in connection with the danger of acute renal failure or exacerbation of chronic renal failure, ACE inhibitors are contraindicated in bilateral renal artery lesions or in lesions of the artery of a single kidney.

When carrying out the pharmacological test, the strength of the bond with the enzyme is not important; A drug with the shortest action and rapid onset of the effect is needed. These properties among ACE inhibitors are captopril.

Drugs of central action in the treatment of patients with nephrogenic hypertension are preparations of deep reserve, but sometimes due to the peculiarities of their action, they become drugs of choice. Important is the main feature of these drugs - the possibility of their appointment with high hypertension without concomitant tachycardia. They also do not reduce renal blood flow with a decrease in systemic blood pressure and increase the effect of other antihypertensive drugs. Clonidine is not suitable for permanent admission, since it has withdrawal symptoms and causes tachyphylaxis, but is the drug of choice when it is necessary to quickly and safely reduce blood pressure.

Among the imidazoline receptor agonists on the market, rilmenidine has some advantage due to a longer half-life.

When identifying secondary hyperaldosteronism, spironolactone should be prescribed.

Diuretics with vasorenal hypertension are preparations of deep reserve.

This is due to the fact that the cause of vasorenal hypertension is not in fluid retention, and the appointment of diuretics for the sake of their diuretic effect does not make much sense. In addition, the hypotensive effect of diuretics due to increased release of sodium, with vasorenal hypertension is questionable, as increasing the excretion of sodium by a conventionally healthy kidney leads to an increase in the release of renin.

Angiotensin II receptor antagonists are very similar in their effects to ACE inhibitors, but there are differences in the mechanisms of action that determine the indications for their use. In this regard, if the effect of ACE inhibitors is insufficient, it is necessary to use antagonists of angiotensin II receptors: telmisartan, candesartan, irbesartan, valsartan. The second indication for the appointment of receptor antagonists for angiotensin II is determined by the propensity of ACE inhibitors to provoke a cough. In these situations, it is advisable to change the ACE inhibitor to an angiotensin II receptor antagonist. In view of the fact that all preparations of this group, in comparison with ACE inhibitors, have less effect on the tone of the blood-bearing arterioles and thereby lessen the gradient of the filtration pressure, they can be prescribed for bilateral renal artery lesions and for lesions of the single-kidney artery under the control of creatinine and potassium levels in blood.

Alfa-adrenoblockers with nephrogenic hypertension are usually not prescribed, but an elderly man with nephrogenic hypertension against atherosclerosis and concomitant adenoma of the prostate can additionally be assigned to the main scheme of an alpha-blocker of a prolonged action.

In extreme cases, you can appoint hydralazine - a peripheral vasodilator, nitrates (peripheral vasodilators) and ganglion blockers. Nitrates and ganglion blockers in order to reduce pressure can only be used in a hospital.

It should be taken into account that when considering drugs, only the fact of nephrogenic hypertension was taken into account, however, in the conditions of chronic renal failure or cardiac complications, the therapy scheme significantly changes.

The effectiveness of beta-adrenergic receptor blockers and especially ACE inhibitors is explained by their specific effect on the "renin-angiotensin-aldosterone" system. Plays a leading role in the pathogenesis of nephrogenic hypertension. Blockade of beta adrenergic receptors, suppressing the release of renin, consistently inhibits the synthesis of angiotensin I and angiotensin II, the main substances that cause vasoconstriction. In addition, beta-adrenoblockers contribute to lowering blood pressure, reducing cardiac output, inhibiting the central nervous system. Reducing peripheral vascular resistance and increasing the sensitivity threshold of baroreceptors to catecholamines and stress. In the treatment of patients with a high degree of probability of nephrogenic hypertension, blockers of slow calcium channels are effective enough. They have a direct vasodilating effect on the peripheral arterioles. The advantage of this group of drugs for the treatment of vasorenal hypertension is their more favorable effect on the functional state of the kidneys than in ACE inhibitors.

Complications and side effects of drug treatment for vasorenal hypertension

In the treatment of vasorenal hypertension, a number of inherent undesirable functional and organic disorders, such as hypo- and hyperkalemia, acute renal failure, are important. Reduction of renal perfusion, acute edema of the lungs and ischemic contraction of the kidney on the side of stenosis of the renal arteries.

The elderly patient's age, diabetes mellitus and azotemia are often accompanied by hyperkalemia, which, when treated with slow calcium channel blockers and ACE inhibitors, can reach a dangerous degree. Often observed the emergence of acute renal failure in the treatment of ACE inhibitors in patients with bilateral renal artery stenosis or with severe stenosis of a single kidney. Attacks of pulmonary edema in patients with unilateral or bilateral stenosis of the renal artery are described.

[47], [48], [49]

Operative treatment of vasorenal hypertension

Operative treatment with vasorenal hypertension reduces to the correction of vascular lesions underlying it. There are two approaches to this task:

• various ways of expanding the stenotic artery by means of devices mounted at the end of the catheter inserted into it (a balloon, a hydraulic injector, a laser waveguide, etc.);
• different variants of operations on open kidney vessels, conducted in situ or extracorporally.

The first option, available not only to surgeons, but also to specialists in the field of angiography, was called in our country the x-ray endovascular dilatation or percutaneous transluminal angioplasty.

The term "X-ray endovascular dilatation" more corresponds to the content of the intervention, which includes not only angioplasty, but also other types of X-ray surgery of the renal arteries: transluminal, mechanical, laser or hydraulic atherectomy. To the same field of operative treatment of vasorenal hypertension is the X-ray endovascular occlusion of the arterial arteriovenous fistula or the fistulas themselves.

X-ray endovascular balloon dilatation

The first X-ray endovascular dilatation in stenosis of the renal arteries was described by A. Grntzig et al. (1978). In the future CJ Tegtmeyer and TA. Sos simplified and improved the technique of this procedure. The essence of the method consists in the introduction into the artery of a catheter with a double lumen, at the distal end of which is strengthened an elastic, but hardly extensible balloon of a certain diameter. The balloon through the artery is injected into the stenotic area, after which the liquid is injected into it under high pressure. In this case, the balloon is spread several times, reaching the established diameter, and expanding the artery, crushing a plaque or other formation, narrowing the artery.

Technical failures include the immediate development of restenosis after successful dilatation of the renal artery. This may be due to the presence of a tissue flap functioning as a valve, or by entering the renal artery of atheromatous detritus from a plaque located in the aorta in the immediate vicinity of the site of the renal artery.

If there is no possibility to perform X-ray endovascular dilatation due to technical difficulties, use medicamentous therapy, stent installation, renal artery bypass grafting, atherectomy, including laser energy. Sometimes, with a good function of the contralateral kidney, nephrectomy or embolization of the artery is performed.

Serious complications of X-ray endovascular dilatation:

• perforation of the renal artery by a conductor or catheter complicated by bleeding:
• exfoliation of the intima;
• formation of an intramural or retroperitoneal hematoma;
• arterial thrombosis;
• microembolism of the distal parts of the vascular bed of the kidney with detritus from the damaged plaque;
• a sharp drop in blood pressure due to inhibition of renin production in combination with the abolition of preoperative antihypertensive therapy:
• exacerbation of chronic renal failure.

Percutaneous transluminal angioplasty achieves efficacy in fibromuscular hyperplasia in 90% of patients and in atherosclerotic renovascular hypertension in 35% of patients.

Super selective embolization of the segmental renal artery with arteriovenous fistula of renal vessels

In the absence of efficacy of drug treatment of arterial hypertension, one must resort to operations that previously boiled down to kidney resection or even nephrectomy. The successes achieved in the field of X-ray endovascular surgery, and, in particular, the method of endovascular hemostasis, allow us to reduce local blood flow with the help of endovascular occlusion, thereby relieving the patient from hematuria and arterial hypertension.

X-ray endovascular occlusion of the cavernous sinus fistula was first performed in 1931 by Jahren. In the last two decades, interest in the X-ray endovascular occlusion method has been increasing, due to the improvement of angiographic equipment and instruments, the creation of new embolic materials and devices. The only method for diagnosis of intrarenal arteriovenous fistulas is angiography using selective and superselective methods.

Indications for X-ray endovascular occlusion of the leading artery are arteriovenous fistulas, complicated by hematuria, arterial hypertension, resulting from:

• traumatic kidney damage;
• congenital vascular anomalies;
• iatrogenic complications: percutaneous renal biopsy or endoscopic percutaneous renal surgery.

Contraindications to X-ray endovascular dilatation are only the extremely serious condition of the patient or intolerance of the RVC.

Open surgical interventions for nephrogenic hypertension

The main indication for the surgical treatment of vasorenal hypertension is high blood pressure.

The functional state of the kidneys is usually considered from the point of view of the risk of intervention, since in the majority of patients with vasorenal hypertension the total renal function does not go beyond the limits of the physiological norm. Violation of the total renal function is most often observed in patients with bilateral lesions of the renal arteries, as well as with severe stenosis or occlusion of one of the arteries and violation of the function of the contralateral kidney.

The first successful reconstructive surgery on the renal arteries for the treatment of vasorenal hypertension was performed in the 50s of the last century. Direct reconstructive operations (transaortal endarterectomy, resection of the renal artery with reimplantation into the aorta or end-to-end anastomosis, splenorenal arterial anastomosis, and transplant operations) were widely used.

For aortorenal anastomosis, use a segment of vena saphena or a synthetic prosthesis. Anastomosis is imposed between the infrarenal aorta and the renal artery distal to the stenosis. This operation is applicable, to a greater extent, in patients with fibromuscular hyperplasia, but may be effective in patients with atherosclerotic plaques.

Thromboendarterectomy is performed by arteriotomy. To prevent narrowing of the artery at the site of dissection, a patch from the venous flap is usually applied.

With severe atherosclerosis of the aorta, surgeons use alternative surgical techniques. For example, the creation of splenorenal anastomosis during surgery on the vessels of the left kidney. Sometimes forced to perform autotransplantation of the kidney.

One of the methods for correcting vasorenal hypertension is still nephrectomy. Surgical intervention can relieve hypertension of 50% of patients and reduce the dosage of antihypertensive drugs used in the remaining 40% of patients. An increase in life expectancy, effective control of arterial hypertension, protection of kidney function testify to the aggressive therapy of patients with renovascular hypertension.

Further management of nephrogenic hypertension

Regardless of whether surgical treatment was performed or not, further management of the patient is reduced to keeping the blood pressure level.

If the patient has undergone reconstructive surgery on renal vessels, acetylsalicylic acid is necessarily included in the regimen for the prevention of renal artery thrombosis. Side effects on the gastrointestinal tract are usually preventable by the appointment of special medicinal forms - effervescent tablets, buffer tablets, etc.

More pronounced antiagregatsionny effect have blockers ADP-receptor platelets - ticlopidine and clopidogrel. Clopidogrel has advantages due to dose-dependent and irreversible action, the possibility of use in monotherapy (due to the additional action on thrombin and collagen), rapid effect. Ticlopidine should be used in combination with acetylsalicylic acid, since its angiagregant effect is achieved after about 7 days. Unfortunately, the high value of modern highly effective antiplatelet agents is hampered by their high cost.

Information for Patient

It is necessary to train the patient to independently control the level of arterial pressure. It is good, when the patient takes medications meaningfully, and not mechanically. In this situation, he is quite able to independently produce a minor correction of the therapy scheme.

Forecast

Survival of patients directly depends on how much it is possible to correct blood pressure. With the rapid elimination of the cause of hypertension, the prognosis is much better. The hypotensive effect of reconstructive surgery for vasorenal hypertension is about 99%, but only in 35% of patients can be completely removed antihypertensive drugs. In 20% of operated patients, there is a significant positive dynamics of the functional parameters of the affected kidney.

The probability of a radical resolution of the situation with conservative treatment is not possible, but high-grade antihypertensive therapy with modern drugs leads to a reduction in blood pressure in 95% of patients (without taking into account the degree of correction, persistence of effect, cost of treatment, etc.). Among untreated patients with the unfolded clinical picture of malignant vasorenal hypertension, the annual survival rate does not exceed 20%.

[50]