Nephrogenic (renal) hypertension - Information Overview

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

Of the large number of patients suffering from arterial hypertension, a third have it of a nephrogenic nature, i.e. caused by a disease of the kidneys and their vessels.

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

Epidemiology

Nephrogenic hypertension is one of the leading secondary or symptomatic arterial hypertensions and occurs in 5-16% of patients. It leads to complications that cause a decrease or loss of working capacity and death of patients.

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

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

Causes 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), renal arteriovenous fistula, calcification, aneurysm, thrombosis or embolism of the renal artery, renal artery hypoplasia, developmental anomalies of the aorta and renal artery (renal artery atresia and hypoplasia), stenosis, thrombosis of the veins, renal vascular trauma, horseshoe-shaped, dystopic and pathologically mobile 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 renovascular hypertension), nephroptosis, thrombosis of the renal artery or its large branches, nonspecific aortoarteritis (pulseless disease, Takayasu's disease) with damage to the renal artery, nodular periarteritis, renal artery aneurysm, arteriovenous fistula (usually as a result of trauma), compression of the renal artery from the outside (tumor, kidney cyst, adhesions, hematoma).

Vasorenal hypertension in 99% of cases is determined by two diseases: atherosclerotic lesions of the renal artery (60-70%) and its fibromuscular dysplasia (30-40%). Other causes are extremely rare and together account for no more than 1% of cases.

Thrombosis and embolism, being occlusive forms of renal artery damage, often lead to arterial hypertension. Finally, vasorenal hypertension can develop as a result of compression of the main renal arteries by a tumor, cyst, adhesions, organized hematoma, etc.

Parenchymatous renal arterial hypertension may occur in the context of acute and chronic glomerulonephritis, chronic pyelonephritis, obstructive nephropathy, polycystic kidney disease, simple renal cysts, including multiple, diabetic nephropathy, hydronephrosis, congenital renal hypoplasia, renal trauma, renin-secreting tumors, renopriv conditions, primary sodium retention (Liddle, Gordon syndromes), systemic connective tissue diseases (systemic lupus erythematosus, systemic scleroderma), and renal tuberculosis. Much less frequently (about 20%), renal hypertension is detected in kidney diseases with tubular and interstitial lesions (renal amyloidosis, interstitial drug-induced nephritis, tubulopathy).

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

Pathogenesis

At the end of the 19th century, Tigerstedt and Bergman (1898), experimenting with extracts from the renal cortex, discovered renin, a hormone that played a huge role in the study of arterial hypertension.

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

A number of factors influence the synthesis of renin by the JGA of the kidneys. Stimulation of sympathetic neurohumoral activity leads to increased renin production independent of renal blood flow and glomerular filtration. This effect is mediated by the action on 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 be changed under the influence of sympathetic activity. Sodium loading inhibits, and depletion of its reserves stimulates, the expression of the renin gene and the secretion of renin. A decrease in perfusion pressure stimulates, and an increase in it suppresses, the secretion of renin. At the same time, many other factors influence renin secretion, in particular angiotensin II, an active product of renin metabolism, an enzyme with a powerful hypertensive effect. Angiotensin II suppresses renin secretion by a feedback mechanism.

It is currently known that renin synthesized in the kidneys, under the influence of the liver enzyme angiotensinogen, combines with a1-globulin in the blood, forming the polypeptide angiotensin, which has a vasopressor effect. Angiotensin exists in two forms: inactive angiotensin I and angiotensin II, which has a powerful vasopressor effect. The first form is transformed into the second under the influence of angiotensin-converting enzyme (ACE). It belongs to zinc-containing metalloproteases. Most of the ACE is associated with cell membranes. It exists in two forms: endothelial and testicular. ACE is widespread in most tissues of the body. Unlike renin, ACE has no specificity and is able to affect many substrates. One of these substrates is bradykinin, a substance with depressor properties and related to the kallikrenne-kinin system. A decrease in ACE activity causes a decrease in the production of angiotensin II and simultaneously increases the sensitivity of blood vessels to bradykinin, leading to a decrease in blood pressure.

Angiotensin II has a hypertensive effect both directly, by influencing the tone of arterioles, and by stimulating the secretion of aldosterone. The hypertensive effect 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 arterioles increases, which leads to their swelling, increased tone and increased sensitivity to pressor effects. The interactions of renin, angiotensin and aldosterone, characterized by both positive and negative feedback, are called the renin-angiotensin-aldosterone system.

It has been established that kidney tissue is capable of producing substances with direct or indirect depressant properties. The depressant action of the kallikrein-kinin system and the vasodilatory action of prostacyclin, which simultaneously stimulates renin secretion, have been discovered. There is a close relationship between the pressor and depressor substances produced by the kidneys.

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

Kidney function may be normal, but more often it slowly but progressively declines, reaching 85-90% deficit with the development of chronic renal failure.

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

Symptoms nephrogenic (renal) hypertension

Symptoms of nephrogenic hypertension are caused by impaired renal tissue perfusion due to a disease or pathological condition that leads to a sharp restriction of renal blood flow. In this case, the kidneys can simultaneously be the cause of 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 in nephroptosis is usually orthostatic in nature and is caused by a kink or tension in the renal artery.

If nephrogenic (renal) arterial hypertension is suspected, the diagnostic algorithm is complex and consists of several stages, which end with clarification of its cause (vasorenal or parenchymatous), determination of the functional significance of the detected lesions of the renal artery in vasorenal hypertension, since this fundamentally affects the choice of treatment tactics. For a urologist, this practically comes down to confirming or excluding 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) together with a therapist (cardiologist), during which the issue of the possibility of surgical treatment of the disease in order to reduce or stabilize blood pressure is decided. In the absence of data for vasorenal hypertension or if the patient's condition does not allow radical surgical treatment for vasorenal hypertension, he is transferred to the supervision and treatment of a therapist (cardiologist).

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

Physical examination findings are of greater preliminary value in detecting renovascular hypertension than history, but the absence of such objective findings does not exclude the diagnosis of renovascular hypertension. The detection of vascular bruits or other manifestations of systemic vascular disease suggests the presence of renovascular hypertension but does not establish the diagnosis. Typical symptoms of nephrogenic hypertension include sudden and rapid increase in blood pressure, resistance of hypertension to potent combination therapy, or “unexplained” loss of blood pressure control. Renal artery stenosis is more common among patients with systemic, and especially atherosclerotic, arterial disease. In addition, percussion may reveal marked left ventricular hypertrophy due to prolonged severe hypertension.

Vasorenal hypertension does not necessarily have to have, but is very characteristic of, a symptom when the patient has very high blood pressure against the background of a normal heart rate, or even bradycardia.

Clinical and biochemical blood tests are performed (the latter involves determining the content of urea, creatinine and electrolytes in the blood), general urine analysis, Zimnitsky urine analysis, Kakovsky-Addis test and bacteriological urine analysis. Fundus examination is mandatory. A test with a single dose of captopril is performed.

Instrumental methods used at this stage include ultrasound of the kidneys, dynamic nephroscintography with I-hippuran. At the second stage, angiography is performed to detect lesions of the renal arteries (traditional aortography, selective angiography of the renal arteries, or digital subtraction angiography).

At the third stage, in order to clarify the nature of arterial hypertension, determine the functional significance of renal artery lesions and optimize intraoperative tactics, central hemodynamics are examined, a radioimmunological study of the renin level in the blood obtained from the renal veins and inferior vena cava is performed, as well as a pharmacoradiological test with captopril.

Forms

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

Vasorenal hypertension is a symptomatic arterial hypertension that occurs as a result of ischemia of the renal parenchyma against the background of damage to the main renal arterial vessels. Less commonly, vasorenal hypertension is called fibromuscular dysplasia of the renal arteries and arteriovenous malformation, vasorenal hypertension is divided into two forms: congenital and acquired.

Almost all diffuse kidney diseases, in which hypertension is associated with damage to the glomeruli and small arterial vessels within the organ, can occur with parenchymatous renal arterial hypertension.

[ 31 ], [ 32 ]

Diagnostics nephrogenic (renal) hypertension

Diagnosis of nephrogenic hypertension includes the following stages:

[ 33 ], [ 34 ], [ 35 ]

Determination of renin levels in peripheral blood

It has been established that a decrease in sodium intake and excretion leads to an increase in the renin level. In humans, the plasma renin level fluctuates sharply during the day, and therefore its single measurement is uninformative. In addition, almost all antihypertensive drugs have a significant effect on the blood renin level. Therefore, they must be discontinued at least 2 weeks before the study, which is dangerous for patients with severe hypertension.

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

Single-use captopril test

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

[ 40 ], [ 41 ]

Complete blood count

Rarely, erythrocytosis may occur due to excessive production of erythropoietin by the affected kidney.

In this case, isolated stimulation of the red germ of the bone marrow is observed: reticulocytosis, an excessively large number of erythrocytes, an excessively high, but corresponding to erythrocytosis, level of hemoglobin, although each individual erythrocyte or reticulocyte is completely normal.

General urine analysis

Minor proteinuria (up to 1 g/day), erythrocyturia, and, less commonly, minor leukocyturia are possible.

Biochemical blood test. In the absence of severe chronic renal failure, changes may not be detected, and in patients with concomitant diseases, changes characteristic of these diseases are detected (in patients with widespread atherosclerosis - high levels of low and very low density lipoproteins, cholesterol, etc.).

Reberg test - for all patients with long-term and severe hypertension of any origin, including suspected nephrogenic, to detect chronic renal failure.

Daily protein excretion is studied when differential diagnosis with primary glomerular lesions is necessary.

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

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

Instrumental methods for diagnosing nephrogenic hypertension

The task of instrumental methods of research is to find damage to the renal vessels and prove the asymmetric nature of nephropathy. If the kidney damage is symmetrical, then this usually indicates parenchymatous renal hypertension due to various 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 research 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 during an angiographic study to assess the structural and functional state of the kidneys. Against the background of obvious decompensation of chronic renal failure, the introduction of RCA is contraindicated due to their nephrotoxicity (risk of a sharp exacerbation of chronic renal failure). In addition, the study against such a background is uninformative.

It is necessary to refrain from excretory urography in cases of excessively high hypertension and to perform it only after at least a temporary reduction in blood pressure with any short-acting drug (for example, clonidine).

The first image is taken immediately after the contrast is introduced, the second - after 3-5 minutes, then decisions are made based on the results obtained in the first images.

Characteristic features include delayed contrasting of the kidney on the affected side, renal asymmetry, delayed release of contrast agent on the affected side on early radiographs, early and persistent nephrogram, hyperconcentration of contrast agent on late urograms on the affected side, and in severe nephrosclerosis, the affected kidney may not be contrasted at all.

Ultrasound examination of the kidneys and renal arteries

Ultrasound assessment of kidney size is not sensitive enough. Even with severe renal artery stenosis, kidney size remains normal. In addition, ultrasound determination of kidney size is highly dependent on the method used. Therefore, comparative kidney size has proven useless for screening renal artery stenosis in renovascular hypertension.

Ultrasound Doppler and duplex scanning (a combination of ultrasound scanning and Doppler) are more effective methods for assessing the renal arteries. Arterial stenosis affects the nature of intravascular blood flow, increasing its velocity in the affected area and creating turbulence in the area of poststenotic dilation. Since duplex ultrasound provides information on blood flow, it is more important in detecting hemodynamic disturbances in the renal arteries than in detecting renal artery stenosis.

Thus, ultrasound and Doppler ultrasound can reveal signs of impaired blood flow in the affected renal artery, signs of nephrosclerosis on the affected side and possible compensatory hypertrophy of the opposite kidney.

Intravascular ultrasound imaging of the renal arteries is a standard method for studying their anatomical features in the clinic. In most cases, it allows for the detection of vasorenal hypertension and differential diagnosis between its two main causes - atherosclerosis and fibromuscular dysplasia. However, due to the invasive nature of the method, it cannot be considered suitable for screening purposes.

Radioisotope renal scintigraphy

Methods of radioisotope diagnostics of nephrogenic (renal) hypertension determine the secretory function of the proximal tubules, urodynamics of the upper urinary tract, as well as topographic-anatomical, functional and structural features of the kidneys. For this purpose, dynamic nephroscintigraphy is used with a drug, the transport of which is carried out mainly by secretion in the proximal tubules of the kidneys - 131 I-hippuran.

Renography or dynamic nephroscintigraphy can reveal asymmetry of renographic curves or kidney images. 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 may not be significant asymmetry. Then you cannot do without a captopril test. To do this, the patient's blood pressure is reduced with captopril (usually 25-50 mg at a time), then an isotope study is repeated. Asymmetry of the curves or images should appear or increase (a drop in filtration on the affected side of more than 10% of the initial level is considered significant). This procedure proves two facts:

• hypertension is vasorenal, since there is a significant drop in filtration on the affected side in response to a drop in systemic arterial pressure;
• hypertension is high-renin, which is typical for the described syndrome and will further help in prescribing a treatment regimen.

However, renovascular hypertension is not always high-renin; sometimes it occurs with normal renin levels.

Since the main task of isotope research methods is to confirm or refute the symmetry of nephropathy, it is pointless and economically inappropriate to perform them in the case of a single kidney, when all questions related to kidney function are resolved by nephrological laboratory tests.

Computer tomography and magnetic resonance imaging (CT) allow to assess the condition of the abdominal vessels, primarily the aorta and its branches, and to detect renal vascular diseases. The use of intravenous administration of RCA in minimal quantities visualizes the vessel walls. CT data correlate well with the results of angiography. The most reliable in terms of identifying the causes of vasorenal hypertension is MSCT, which has now practically replaced renal arteriography, which is performed for the same purpose. In some cases, MRI can be an alternative to angiography.

Angiography in the diagnosis of renal artery lesions

The most reliable method of examining the renal arteries for diagnosing vasorenal hypertension is X-ray contrast study. Angiography determines the nature, extent and localization of damage to the renal vessels.

Intravital X-ray examination of human blood vessels with the introduction of a contrast agent was first performed by Sicard and Forestier in 1923. In the late 1920s and early 1930s, aortoarteriography, thanks to the work of Dos Santos et al., gradually entered clinical practice, but did not become widely used in the diagnosis of arterial system diseases. The cautious attitude towards aortography at that time was explained by the high toxicity of the contrast agents used and severe reactions to their introduction, as well as the risk of complications caused by puncture of the aorta and arteries. In addition, the diagnosis of many diseases of the arterial system, including lesions of the arterial system of the kidneys, was of purely academic interest at that time, since most patients with vasorenal hypertension underwent nephrectomy.

A new stage in the development of angiography dates back to the second half of the 1930s. This was facilitated by the synthesis of relatively low-toxic RCAs and the first successful radical operations on the aorta and large arteries. In the late 1940s - early 1950s, aortography became increasingly widespread 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 percutaneous aortic catheterization technique he had developed. This technique, using a special conductor, replaces the needle in the aorta with a polyethylene catheter. N.A. Lopatkin, the first Russian researcher, performed renal angiography in 1955.

An important role in the evolution of the aortoarteriography method is played by the creation of powerful X-ray units for angiography with electron-optical amplification and a television observation system, as well as the use of triiodide organic RCA. Progress in electronics and computer technology in the late 70s leads to the creation of a fundamentally new method of X-ray contrast examination of vessels - digital (or digital) subtraction angiography.

Further improvement of the method is possible due to the combination of X-ray and electronic computing technology, using simultaneously the principle of enhancing the image of vessels and subtraction (subtraction) of the image of soft tissues and bones. The essence of the method is that computer processing of the X-ray image suppresses its background, i.e. eliminates the image of soft tissues and bones and simultaneously enhances the contrast of the vessels. This visualizes arteries and veins well. Nevertheless, the doctor should remember about the possibility of a technical error in identifying some forms of damage to the renal arteries and, if there are other compelling arguments in favor of the diagnosis of vasorenal hypertension, continue the research.

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

Indications for angiography:

• high stable or malignant arterial hypertension resistant to combination antihypertensive therapy;
• high blood pressure caused by other diseases;
• parenchymal kidney diseases (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, periarteritis nodosa, arteritis of the aorta and its branches);
• diseases characterized by the development of thrombosis and embolism of arteries;
• decreased secretory function of the kidney according to dynamic nephroscintigraphy data.

The presence of signs of renal artery stenosis, identified at the stages of the previous examination, serves as an additional criterion for the appropriateness of angiography. Angiography is indicated for patients potentially subject to renal vascular reconstruction, and allows one to determine the shape, volume and localization of renal vascular lesions. In this case, during the study, blood can be taken separately from each kidney for subsequent determination of the renin level, which increases the reliability of the analysis.

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

Contraindications to renal angiography are few and mostly not absolute. Thus, if the patient is intolerant to iodine preparations, non-iodine contrast agents may be used. Patients with renal failure, if there are clear indications for angiographic examination, undergo arterial digital subtraction angiography instead of traditional angiography. Patients suffering from diseases accompanied by increased bleeding undergo specific hemostatic therapy during the preparation for the examination. Angiography should also not be performed against the background of high hypertension, since the likelihood of a hematoma at the site of puncture of the femoral artery increases many times over.

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

Complications of angiography. There are mild and severe complications of angiography. Mild complications include small hematomas in the area of arterial puncture, headache, nausea, vomiting, short-term increase in body temperature, chills, short-term spasm of the arteries, etc. Most of these complications are caused by the action of iodine compounds used as RCA. With the introduction of less toxic RCA into clinical practice, the frequency of these complications has significantly decreased.

Severe complications of angiography:

• acute cerebrovascular or coronary circulatory disorder:
• acute renal failure;
• severe arterial hypertension;
• massive thromboembolism;
• damage to the intima of the artery, leading to dissection of its wall;
• perforation of the arterial wall, accompanied by bleeding, formation of a pulsating hematoma and arteriovenous anastomosis;
• catheter or guidewire detachment.

A severe complication can cause the death of the patient.

The general disadvantage of the described methods of examining a patient is the indirect nature of information about damage to the renal arteries in vasorenal hypertension. The only method that determines structural changes in the kidneys during life is a morphological study of kidney biopsies. However, kidney biopsy is unsafe due to the risk of internal bleeding. In addition, in some cases there are medical contraindications to its implementation.

Indications for consultation with other specialists

All patients with suspected vasorenal hypertension should consult a nephrologist, and if there is no nephrologist, a cardiologist. A nephrologist consultation is especially indicated for patients with suspected bilateral renal artery disease, renal artery disease of the only or only functioning kidney, and chronic renal failure. All patients should consult an ophthalmologist to determine the condition of the fundus and identify ophthalmological signs of malignancy of hypertension. At the stage of determining treatment tactics, a consultation with a urologist or vascular surgeon and anesthesiologist is recommended.

Differential diagnosis

Vasorenal hypertension must be differentiated from all other chronic symptomatic hypertensions, and less often from hypertension.

Renoparenchymatous arterial hypertension. Performing a radioisotope study confirming the symmetry of kidney damage allows to decisively exclude vasorenal hypertension. Then, the damage to the renal vessels is determined or rejected by Doppler ultrasound. The last stages of differential diagnostics are isotope study 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 extent of adrenal damage. Complaints of muscle weakness are typical, and it is inconstant in time and sometimes of extreme severity, there may be edema, and diuretics (loop and thiazide) worsen their condition. Hypotensive therapy is difficult to select. Rhythm disturbances (with corresponding changes in the electrocardiogram) and polyuria as a result of hypokalemic nephropathy are possible. An increased level of renin, detected against the background of therapy discontinuation, allows us to clearly exclude primary hyperaldosteronism.

Cushing's syndrome and disease. These diseases present with a characteristic appearance, skin dystrophy, bone lesions, and steroid diabetes. Sodium retention and low renin may be present. The diagnosis is confirmed by detecting elevated levels of corticosteroids in the blood.

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

Pheochromocytoma and other catecholamine-producing tumors. In about half of the cases, the disease manifests itself with typical catecholamine crises with corresponding complaints and no signs of kidney damage. The crisis can be stopped by intravenous administration of the alpha-blocker phentolamine, but due to the rarity of such patients and the extremely narrow spectrum of phentolamine use, sodium nitroprusside is usually used. The diagnosis of 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 that when examining patients with suspected symptomatic arterial hypertension, an analysis of the excretion of catecholamine metabolism products in the urine should be included, which can be performed during therapy.

Coarctation of the aorta. Usually young patients, despite high hypertension, with good health and distrustfully excellent physical endurance, have well-developed muscles of the upper limbs and muscle hypotrophy (especially in the calves) of the legs. High blood pressure is detected only in the arteries of the upper limbs. A rough systolic murmur, determined by routine auscultation of the heart and large vessels, is also heard between the shoulder blades.

Hypertension is a disease that begins slowly at a young age and, as a rule, proceeds benignly. The dependence of high blood pressure on physical and emotional stress, fluid intake is clearly visible, hypertensive crises are characteristic. The detection of nephropathy asymmetry decisively contradicts even the most malignant course of hypertension.

Thyrotoxicosis. Outwardly, these patients look the complete opposite of patients with vasorenal hypertension. With vasorenal hypertension, the patient, regardless of age, does not look like a seriously ill person, he is adequate, sometimes slightly inhibited, and may have memory impairment due to encephalopathy from prolonged severe hypertension. With severe thyrotoxicosis, patients (usually young women) give the impression of being deeply unhealthy physically or mentally. Their actions, judgments, and speech are too fast and unproductive, and thoughts are difficult to formulate. During examination, it is not so much hypertension that attracts attention, as strong, inexplicable tachycardia, even at rest, and a tendency to heart rhythm disturbances (in severe cases, constant atrial fibrillation may occur). Heart rhythm disturbances are extremely uncharacteristic for vasorenal hypertension, and left ventricular hypertrophy is typical. The diagnosis of primary thyrotoxicosis is confirmed by the detection of high levels of thyroxine and extremely low levels of thyroid-stimulating hormone.

Erythremia. Usually elderly people suffer from erythremia. Their complexion is red, but there is no edema, almost always high blood pressure, which they tolerate worse than people of their age with hypertension. Complaints of pain of various localizations (in the hands, feet, head, heart, sometimes even in the bones and spleen), skin itching, due to which patients sleep poorly at night, are typical. A general blood test reveals excessive activity of all three bone marrow sprouts, which never happens with symptomatic erythrocytosis. Vasorenal hypertension is contradicted by pain in the bones, especially increasing with percussion (a sign of bone marrow proliferation), an enlarged spleen and pain in it. The detection of changes in isotope examination of the kidneys does not necessarily reject the diagnosis of erythremia, since due to inadequate disinhibition of the platelet germ and the resulting thrombocytosis, the disease can be complicated by thrombosis of any vessel, including the renal one.

Treatment nephrogenic (renal) hypertension

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

Indications for hospitalization in nephrogenic hypertension

Newly diagnosed nephrogenic hypertension or suspicion of it is an indication for hospitalization to clarify the causal nature of the disease.

In outpatient settings, preoperative preparation for surgery for vasorenal genesis of hypertension is possible, as well as management of patients in whom a parenchymatous form of the disease is detected or, due to the severity of the condition, surgical treatment for vasorenal hypertension is contraindicated.

Non-drug treatment of nephrogenic hypertension

The role of non-drug treatment is small. Patients with nephrogenic hypertension are usually limited in the use of table salt and fluid intake, although the effect of these recommendations is questionable. They are rather needed to prevent hypervolemia, which is possible with excessive consumption of salt and fluid.

The need for active treatment tactics for patients with renal artery lesions is generally recognized, since surgical treatment is aimed not only at eliminating the hypertensive syndrome, but also at preserving kidney function. The life expectancy of patients with vasorenal hypertension who have undergone surgery is significantly longer than that of patients who, for one reason or another, have not undergone surgery. During the period of preparation for surgery, if it is insufficiently effective or if it cannot be performed, patients with vasorenal hypertension must undergo drug treatment.

Physician's tactics in drug treatment of vasorenal hypertension

Surgical treatment of patients with vasorenal hypertension does not always lead to a decrease or normalization of arterial pressure. Moreover, in many patients with renal artery stenosis, especially of atherosclerotic genesis, the increase in arterial pressure is caused by hypertension. That is why the final diagnosis of vasorenal hypertension relatively often has to be established ex juvantibui, based on the results of surgical treatment.

The more severe the arterial hypertension in patients with atherosclerosis or fibromuscular dysplasia, the greater the probability of its vasorenal genesis. Surgical treatment gives good results in young patients with fibromuscular dysplasia of the renal arteries. The effectiveness of surgery on the renal arteries is lower in patients with atherosclerotic stenosis, since many of these patients are elderly and suffer from hypertension.

Possible variants of the course of the disease that determine the choice of treatment tactics:

• true vasorenal hypertension, in which renal artery stenosis is the sole cause of arterial hypertension;
• hypertension in which atherosclerotic or fibromuscular lesions of the renal arteries are not involved in the genesis of arterial hypertension;
• hypertension, on which vasorenal hypertension is “superimposed”.

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

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

• old age,
• severe atherosclerosis;
• questionable angiographic signs of hemodynamically significant renal artery stenosis;
• high risk of surgery;
• impossibility of surgical treatment due to technical difficulties;
• patient's refusal of invasive treatment methods.

Drug treatment of nephrogenic hypertension

Antihypertensive drug therapy for nephrogenic hypertension should be more aggressive, achieving tight control of blood pressure at the target level, although this is difficult to achieve. However, treatment should not rapidly reduce blood pressure, especially in renovascular hypertension, regardless of the drug or combination of drugs prescribed, as this leads to a decrease in SCF on the affected side.

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

In patients with tachycardia, which is not typical 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 indicated and calcium antagonists are the first-line drugs: amlodipine, felodipine (extended forms), felodipine, verapamil, diltiazem, extended-release forms of nifedipine.

ACE inhibitors are assigned the role of second-line drugs, and sometimes first-line drugs: trandolapril, ramipril, perindopril, fosinopril. It is quite possible to prescribe enalapril, but the doses of the drug will most likely be close to the maximum.

In the case of vasorenal hypertension, which in the vast majority of cases is high-renin, the use of ACE inhibitors has its own characteristics. Blood pressure should not be reduced sharply, as this may lead to a pronounced filtration deficit in the affected kidney, including due to a decrease in the tone of the efferent arterioles, which increases the filtration deficit by reducing the filtration pressure gradient. Therefore, due to the risk of acute renal failure or exacerbation of chronic renal failure, ACE inhibitors are contraindicated in case of bilateral renal artery disease or in case of disease of the artery of a single kidney.

When conducting a pharmacological test, the strength of the bond with the enzyme is not important; a drug with the shortest action and rapid onset of effect is needed. Among ACE inhibitors, captopril has these properties.

Centrally acting drugs are deep reserve drugs in the treatment of patients with nephrogenic hypertension, but sometimes, due to the peculiarities of their action, they become drugs of choice. The main feature of these drugs is important - the possibility of their administration in high hypertension without concomitant tachycardia. They also do not reduce renal blood flow when systemic arterial pressure decreases and enhance the effect of other antihypertensive drugs. Clonidine is not suitable for continuous use, as it has a withdrawal syndrome and causes tachyphylaxis, but is a drug of choice when it is necessary to quickly and safely reduce arterial pressure.

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

If secondary hyperaldosteronism is detected, spironolactone should be prescribed.

Diuretics for vasorenal hypertension are deep reserve drugs.

This is because the cause of vasorenal hypertension is not fluid retention, and prescribing diuretics for their diuretic effect does not make much sense. In addition, the hypotensive effect of diuretics, due to increased sodium excretion, is questionable in vasorenal hypertension, since increased sodium excretion by a conditionally healthy kidney leads to increased renin release.

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 resort to prescribing angiotensin II receptor antagonists: telmisartan, candesartan, irbesartan, valsartan. The second indication for prescribing angiotensin II receptor antagonists is determined by the tendency of ACE inhibitors to provoke cough. In these situations, it is advisable to change the ACE inhibitor to an angiotensin II receptor antagonist. Since all drugs in this group, compared to ACE inhibitors, have less effect on the tone of blood-delivering arterioles and thus reduce the filtration pressure gradient less, they can be prescribed for bilateral renal artery lesions and for lesions of the artery of a single kidney under the control of creatinine and potassium levels in the blood.

Alpha-blockers are usually not prescribed for nephrogenic hypertension, but an elderly man with nephrogenic hypertension due to atherosclerosis and concomitant prostate adenoma may be additionally prescribed a long-acting alpha-blocker to the main regimen.

In extreme cases, hydralazine, a peripheral vasodilator, nitrates (peripheral vasodilators) and ganglion blockers can be prescribed. Nitrates and ganglion blockers can only be used in a hospital setting to reduce blood pressure.

It is necessary to take into account that when considering the drugs, only the fact of nephrogenic hypertension was taken into account, however, in conditions of chronic renal failure or cardiac complications, the treatment regimen changes significantly.

The effectiveness of beta-adrenergic receptor blockers and especially ACE inhibitors is explained by their specific action on the renin-angiotensin-aldosterone system, which plays a leading role in the pathogenesis of nephrogenic hypertension. The blockade of beta-adrenergic receptors, suppressing the release of renin, consistently inhibits the synthesis of angiotensin I and angiotensin II - the main substances causing vasoconstriction. In addition, beta-blockers help to reduce blood pressure, reducing cardiac output, depressing the central nervous system, reducing peripheral vascular resistance and increasing the sensitivity threshold of baroreceptors to the effects of catecholamines and stress. In the treatment of patients with a high probability of nephrogenic hypertension, slow calcium channel blockers are quite effective. They have a direct vasodilating effect on peripheral arterioles. The advantage of drugs of this group for the treatment of vasorenal hypertension is their more favorable effect on the functional state of the kidneys than that of ACE inhibitors.

Complications and side effects of drug treatment of vasorenal hypertension

In the treatment of vasorenal hypertension, a number of undesirable functional and organic disorders are important, such as hypo- and hyperkalemia, acute renal failure, decreased renal perfusion, acute pulmonary edema and ischemic shrinkage of the kidney on the side of renal artery stenosis.

Old age of the patient, diabetes mellitus and azotemia are often accompanied by hyperkalemia, which can reach a dangerous degree when treated with calcium channel blockers and ACE inhibitors. Acute renal failure is often observed when treating patients with bilateral renal artery stenosis or severe stenosis of a single kidney with ACE inhibitors. Attacks of pulmonary edema have been described in patients with unilateral or bilateral renal artery stenosis.

[ 47 ], [ 48 ], [ 49 ]

Surgical treatment of vasorenal hypertension

Surgical treatment for vasorenal hypertension is reduced to correction of the underlying vascular lesions. There are two approaches to solving this problem:

• various methods of expanding a stenotic artery using devices mounted at the end of a catheter inserted into it (a balloon, a hydraulic nozzle, a laser waveguide, etc.);
• various types of operations on open renal vessels, performed in situ or extracorporeally.

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

The term "X-ray endovascular dilation" is more consistent with the content of the intervention, which includes not only angioplasty, but also other types of X-ray surgical dilation of the renal arteries: transluminal, mechanical, laser or hydraulic atherectomy. X-ray endovascular occlusion of the afferent artery of arteriovenous fistulas or the fistulas themselves also belongs to this area of surgical treatment of vasorenal hypertension.

X-ray endovascular balloon dilation

X-ray endovascular dilation of renal artery stenosis was first described by A. Grntzig et al. (1978). Subsequently, C. J. Tegtmeyer and T. A. Sos simplified and improved the technique of this procedure. The essence of the method consists of inserting a double-lumen catheter into the artery, at the distal end of which an elastic but difficult-to-stretch balloon of a certain diameter is fixed. The balloon is inserted through the artery into the stenotic area, after which fluid is pumped into it under high pressure. In this case, the balloon is straightened several times, reaching the established diameter, and the artery is expanded, crushing the plaque or other formation narrowing the artery.

Technical failures include immediate restenosis after successful renal artery dilation. This may be due to the presence of a flap of tissue functioning as a valve or to the entry of atheromatous debris into the renal artery from a plaque located in the aorta in close proximity to the origin of the renal artery.

If it is not possible to perform X-ray endovascular dilation due to technical difficulties, drug therapy, stent placement, renal artery bypass grafting, atherectomy, including laser energy, are used. Sometimes, with good function of the contralateral kidney, nephrectomy or artery embolization is performed.

Serious complications of X-ray endovascular dilation:

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

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

Superselective embolization of segmental renal artery in arteriovenous fistula of renal vessels

In the absence of effective drug treatment of arterial hypertension, it is necessary to resort to operations, which previously were limited to resection of the kidney or even nephrectomy. Advances in the field of X-ray endovascular surgery, and, in particular, the method of endovascular hemostasis, make it possible to reduce local blood flow with the help of endovascular occlusion, thereby relieving the patient of hematuria and arterial hypertension.

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

Indications for X-ray endovascular occlusion of the afferent artery are arteriovenous fistulas complicated by hematuria, arterial hypertension, arising as a result of:

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

Contraindications to X-ray endovascular dilation are only an extremely severe condition of the patient or intolerance to X-ray endovascular dilation.

Open surgical interventions for nephrogenic hypertension

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

Renal function is usually considered in terms of the risk of intervention, since the total renal function in most patients with renovascular hypertension is within the physiological norm. Impaired total renal function is most often observed in patients with bilateral renal artery disease, as well as in cases of severe stenosis or occlusion of one of the arteries and impaired function of the contralateral kidney.

The first successful reconstructive surgeries on the renal arteries for the treatment of vasorenal hypertension were performed in the 1950s. Direct reconstructive surgeries (transaortic endarterectomy, renal artery resection with reimplantation into the aorta or end-to-end anastomosis, splenorenal arterial anastomosis, and surgeries using transplants) became widespread.

Aortorenal anastomosis is performed using a section of vena saphena or a synthetic prosthesis. The anastomosis is performed between the infrarenal aorta and the renal artery distal to the stenosis. This procedure is more applicable to patients with fibromuscular hyperplasia, but can also be effective in patients with atherosclerotic plaques.

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

In case of severe atherosclerosis of the aorta, surgeons use alternative surgical techniques. For example, creating a splenorenal anastomosis during surgery on the vessels of the left kidney. Sometimes they are forced to perform autotransplantation of the kidney.

One of the methods of correction of vasorenal hypertension is still nephrectomy. Surgical intervention can relieve hypertension in 50% of patients and reduce the dosage of antihypertensive drugs used in the remaining 40% of patients. Increased life expectancy, effective control of arterial hypertension, protection of renal function indicate in favor of aggressive therapy of patients with renovascular hypertension.

Further management in nephrogenic hypertension

Regardless of whether surgery was performed or not, further management of the patient is limited to maintaining blood pressure levels.

If the patient has undergone reconstructive surgery on the renal vessels, acetylsalicylic acid is necessarily included in the treatment regimen to prevent renal artery thrombosis. Side effects on the gastrointestinal tract are usually prevented by prescribing special dosage forms - effervescent tablets, buffer tablets, etc.

A more pronounced antiaggregatory effect is possessed by platelet ADP receptor blockers - ticlopidine and clopidogrel. Clopidogrel has advantages due to its dose-dependent and irreversible action, the possibility of use in monotherapy (due to additional action on thrombin and collagen), and rapid achievement of the effect. Ticlopidine should be used in combination with acetylsalicylic acid, since its angioaggregatory effect is achieved in about 7 days. Unfortunately, the widespread use of modern highly effective antiaggregants is hindered by their high cost.

Information for the patient

It is necessary to teach the patient to independently control the level of arterial pressure. It is good when the patient takes the drugs consciously, and not mechanically. In this situation, he is quite capable of independently making minor corrections to the therapy regimen.

Forecast

The survival rate of patients directly depends on how well the arterial pressure can be corrected. With surgical elimination of the cause of hypertension, the prognosis is significantly better. The hypotensive effect of restorative operations for vasorenal hypertension is about 99%, but only 35% of patients can completely stop taking hypotensive drugs. 20% of operated patients show significant positive dynamics of the functional indices of the affected kidney.

The probability of a radical resolution of the situation with conservative treatment is impossible, but full-fledged hypotensive therapy with modern drugs leads to a decrease in blood pressure in 95% of patients (without taking into account the degree of correction, durability of the effect, cost of treatment, etc.). Among untreated patients with a detailed clinical picture of malignant vasorenal hypertension, the annual survival rate does not exceed 20%.

[ 50 ]