Radioisotope diagnostics of urological diseases

Modern medical disciplines are impossible without interaction with related specialties, especially diagnostic ones. Successful treatment and its prognosis largely depend on the quality and accuracy of diagnostic studies. Medical radiology is one of the most important disciplines, which has occupied a strong place in the diagnostics of various diseases and lesions of internal organs since the second half of the twentieth century.

Medical radiology is the science of using ionizing radiation to detect and treat human diseases. It is divided into diagnostic and therapeutic.

The high information content of the results obtained, combined with the simplicity of execution and non-traumatic nature of the study, are not the only advantages of diagnostic radiology. Obtaining not only additional information about the functional and structural state of the genitourinary system, but also original diagnostic information puts the methods of radioisotope indication in one of the main places in the complex of modern urological examination.

The use of radioactive tracers in clinical practice began in the 1940s, when a strict pattern of radioactive iodine distribution was established for various pathological conditions of the thyroid gland. At the same time, diagnostic tests were developed that contained radioactive iron to determine erythrocytes in various blood diseases, radioactive phosphorus to study malignant growth, and radioactive sodium to study general and local blood flow in cardiovascular diseases. Since the mid-1950s, when industrial production of various radioactive nuclides in sufficient quantities became possible and reliable, easy-to-use radiometric devices appeared, radioisotope research methods were introduced into clinical practice in urology. Since then, radioactive research methods have gained a strong place in the diagnosis of various diseases and lesions of internal organs and have formed an independent discipline called nuclear medicine. At the same time, the essence of nuclear medicine was formed and certain traditions of using specific research methods were established, which formed four main groups.

• Radiography (renography, cardiography, hepatography).
• Organ scanning.
• Clinical radiometry (study of the volume of various elements using the whole body counting method).
• Laboratory radiometry (study of radiopharmaceutical concentrations in biological environments of the body).

In the 70s of the last century, new methods of radioisotope research began to develop rapidly - scintigraphy and radioimmunological methods in vitro. They became the main ones and make up about 80% of the total volume of radioisotope diagnostics in modern clinical practice. To conduct a functional radioisotope study, radiopharmaceuticals and radiometric equipment are needed.

Radiopharmaceuticals

Radiopharmaceuticals are chemical compounds containing a specific radionuclide in their molecule, permitted for administration to humans for diagnostic or therapeutic purposes. Administration of radiopharmaceuticals to patients is carried out only in accordance with the "Radiation Safety Standards".

The biological behavior of radiopharmaceuticals or the so-called tropism - the time of accumulation, passage and excretion from the examined organ - is determined by their chemical nature. In modern urological practice, several radiopharmaceuticals are used to assess the functional state of the kidneys in studies of tubular secretion and glomerular filtration. In the first case, sodium salt of orthoiodine hippuronic acid - sodium iodine hippurate - is used. Despite the relative radiotoxicity of sodium iodine hippurate, the optimal diagnostic indicators of its transfer in the system of labeled tubules allow it to be widely used in radioisotope renography and dynamic nephroscintigraphy. Glomerulotropic drugs pentatech 99mTc are successfully used to determine glomerular filtration. In recent years, due to the synthesis of new labeled compounds - technemag and sodium iodine hippurate, it has become possible to reduce the radiation load on the patient, which is especially important when examining young children.

Technetium-labeled colloidal solutions are used in diagnostics of the state of the skeletal system (osteoscintigraphy), lymphatic system (indirect radioactive lymphography), and vascular bed (indirect radioisotope angio- and venography).

Methods of radioisotope diagnostics

Radioisotope diagnostic methods used in urology are divided into static and dynamic. Statistical methods include:

• static nephroscintigraphy;
• hepatography:
• lymphoscintigraphy;
• osteoscintigraphy.

The first two methods are not often used at present, since ultrasound diagnostic methods are not inferior in information content to radioisotope static methods of examining the kidneys or liver.

Indirect lymphoscintigraphy is used to detect lymph node damage by a metastatic process and to assess its prevalence. Low trauma for the patient and simplicity of the method allow it to be performed on an outpatient basis.

Bone scintigraphy is used to diagnose metastases of malignant tumors of the genitourinary system. High sensitivity of the method (over 90%), the probability of false positive results not exceeding 5-6%, and the ability to detect osteoblastic metastases 6-8 months earlier than X-ray make radioisotope bone scintigraphy a popular method. The principle of the method is based on the active absorption of a number of radiopharmaceuticals by metastatic foci of the skeleton. Radiopharmaceuticals are concentrated in structures in the process of bone formation (osteoblasts). When conducting bone scintigraphy, phosphorus-containing radiopharmaceuticals are used. The level of accumulation of which in different parts of the skeleton is determined by the amount of blood flow, the state of microcirculation, the degree of mineralization and osteoblastic activity. Uneven distribution of radiopharmaceuticals, going beyond the usual anatomical and physiological features of its inclusion, is the main sign of pathological changes in the skeletal system.

A variation of the study is the so-called three-phase osteoscintigraphy, which involves obtaining a series of images and assessing the amount of radioactivity in the affected area in the first 10-30 seconds (blood flow), 1-2 minutes (perfusion) and after 2-3 hours (accumulation). However, low specificity leads to false-positive results, especially in elderly patients with osteodystrophic age-related changes.

Dynamic methods include:

• radioisotope renography;
• dynamic nephroscintigraphy.

To obtain information about the functional and anatomical state of the kidneys using special radiopharmaceuticals that actively participate in the physiological processes of the body during the redistribution period, dynamic methods of radioisotope diagnostics are carried out.

Radioisotope renography has been introduced into clinical practice since 1956. The study is a method of primary screening of patients with suspected genitourinary disease. However, it reliably reveals separate dysfunctions of each kidney only if the difference between them exceeds 15% and if the study is carried out under correct technical conditions. The method is based on the study of the process of active tubular secretion of a labeled drug by the kidneys and its excretion through the upper urinary tract into the bladder. The technique involves intravenous administration of radiopharmaceuticals and continuous recording for 15-20 minutes of the level of radioactivity above the kidneys using radiocirculator (renograph) sensors. The resulting curve - renogram - consists of three sections:

• vascular, reflecting the distribution of radiopharmaceuticals in the vascular bed of the kidney:
• secretory, the process of selective and active accumulation of radiopharmaceuticals in renal structures:
• evacuation, representing the process of removing radiopharmaceuticals from the kidneys into the bladder.

To determine true physiological parameters, the patient is in a sitting position during the examination.

However, radioisotope renography has certain disadvantages.

• The placement of the detector over the kidney area during renography is performed approximately in accordance with known anatomical landmarks, which in some patients (those suffering from nephroptosis, having a dystopic kidney, etc.) may lead to incorrect centering and obtaining inaccurate data.
• When recording the dynamics of the passage of radiopharmaceuticals through the kidney, it is not possible to clearly distinguish the contribution of the secretory and excretory stages to the renogram, and therefore the division of the renogram into generally accepted segments is conditional.
• Registration of radiation over the kidney area includes not only the drug directly passing through the kidney, but also the radiopharmaceutical located in the soft tissues preceding and underlying the organ, which also introduces a certain error into the results of the study.
• The clearance curve obtained during registration over the heart area does not provide clear information about the true purification of the body from the radiopharmaceutical, since a significant portion of the drug is distributed in the intercellular space, causing the formation of the so-called hippuran space (especially in patients with chronic renal failure).
• A study of the rate of accumulation of radiopharmaceuticals in the urinary bladder, usually performed without appropriate calibration of the detector according to the value of the activity introduced into the phantom, gives only an approximate idea of the total function of the kidneys.

The principle of the dynamic nephroscintigraphy method is based on the study of the functional state of the kidneys by recording the active accumulation of labeled compounds by the renal parenchyma and their removal through the VMP. The study is performed on modern single- or multi-detector gamma cameras with the ability to select areas of interest. Subsequently, computer visualization of the organ is performed to assess the anatomical state and plot curves with the calculation of the functional state.

The method consists of intravenous administration of tubutropic or glomerulotropic radiopharmaceuticals and continuous recording of radioactivity for 15-20 minutes over the kidney area. The information is recorded in the memory of a specialized computer and displayed on the screen, reproducing the step-by-step passage of the radiopharmaceutical through the organ. The dynamics of the passage of the radiopharmaceutical after special computer processing can be reproduced in the form of computer renograms with segments - vascular, secretory and evacuation, and also calculated in terms of separate regional renal clearances. Only with the help of dynamic nephroscintigraphy is it possible to study the functional activity of various areas of the renal parenchyma.

The method of dynamic nephroscintigraphy has a number of undeniable advantages compared to radioisotope renography.

• The performance of dynamic nephroscintigrams is not associated with errors caused by incorrect centering of detectors, since the field of vision of the gamma camera crystal, with rare exceptions, includes the entire area of possible location of the kidneys.
• During scintigraphy, it is possible to register the drug in the area of perirenal tissues, corresponding in shape to each kidney, which allows one to take into account the contribution of hippuran radiation located in the pre- and underlying tissues and to correct the scintigraphic curve.
• With dynamic scintigraphy, it is possible, along with general information about the transport of radiopharmaceuticals through the kidney, to obtain data on the separate secretory and excretory functions and differentiate the level of ureteral obstruction.
• Nephroscintigraphy makes it possible to obtain an image of the kidneys sufficient for assessing their anatomical and topographic state, in particular for assessing the kidneys by segments.
• Renographic curves are free from the error caused by imprecise channel calibration that occurs with standard renographs, allowing for a more accurate quantitative analysis of the functional status of each kidney.

The listed advantages of dynamic nephroscintigraphy, compared to renography, allow for increased reliability and sensitivity of the study, and a reliable assessment of the function of each kidney is achieved with a difference of 5%.

In specialized urological hospitals equipped with modern equipment, radioisotope renography can be used only in clinical situations not associated with the possibility of severe kidney damage, when an in-depth study of its functional and topographic-anatomical state is required. Urological diseases in which it is possible to limit oneself to isotope renography as an additional examination method include chronic pyelonephritis (without kidney shrinkage), urolithiasis (without significant impairment of the excretory function of the kidneys according to excretory urography), stage 1 hydronephrosis, as well as a number of other diseases in which no anomalies in the development or location of the kidneys have been identified.

Absolute indications for dynamic scintigraphy:

• significant impairment of renal excretory function (according to excretory urography)
• all anomalies of the development of the upper urinary tract
• changes in the anatomical and topographic location of the kidneys
• hydronephrosis stages 2 and 3
• hypertension
• large single and multiple kidney cysts, as well as examination of children and patients after kidney transplantation.

Dynamic nephroscintigraphy helps clinicians to solve a number of questions about the nature of the disease course, the prevalence of renal tissue damage, diagnosis clarification, prognosis, and evaluation of therapy results. features of the pathological process. Even in the absence of other clinical and laboratory manifestations of renal failure, dynamic nephroscintigraphy is able to detect partial disorders of the functional state of the secretory and evacuation functions of the kidneys. It is most important for determining the localization of the disease side, as well as the level of renal tissue damage - tubular secretion disorders or glomerular filtration.

In the implementation of the excretory function of the body, an important place belongs to the secretion of peritubular fluid into the lumen of the tubule of a number of organic compounds. Tubular secretion is an active transport, in the implementation of which a certain number of carrier proteins participate, ensuring the capture of organic substances and their transport through the cell of the proximal tubule to the apical membrane. The appearance of any inhibitors of the secretory process in the blood reduces the number of carrier proteins, and the process of tubular secretion slows down. The process of glomerular filtration is passive and occurs under the influence of pressure created by the work of the heart. Glomerular filtration in each nephron is determined by the magnitude of the effective filtration pressure and the state of glomerular permeability. And it, in turn, depends on the total area of the capillary surface through which filtration occurs, and the hydraulic permeability of each section of the capillary. The glomerular filtration rate (GFR) is not a constant value. It is subject to the influence of the circadian rhythm and can be 30% higher during the day than at night. On the other hand, the kidney has the ability to regulate the constancy of glomerular filtration, and only with severe damage to the glomeruli do irreversible processes occur. From a physiological point of view, secretion and filtration are two different processes. That is why dynamic studies with various drugs reflect each of them. In addition, in the initial stages of most urological diseases, the function of the tubular apparatus is affected. Therefore, the most informative method of determination will be dynamic nephroscintigraphy with tubulotropic drugs.

Analysis of a large number of results of a combined examination of urological patients made it possible to develop the so-called general functional classification of kidney and uterine urinary tract lesions, based on the main non-specific variants of changes in the system of paired organs.

By appearance:

• one-sided and two-sided;
• acute and chronic.

By the form of predominant damage:

• renal circulation
• tubular apparatus
• glomerular apparatus
• Urodynamics of the VMP
• combined disturbances of all renal parameters.

By stages:

• initial;
• intermediate;
• final.

In case of unilateral damage, the contralateral healthy kidney takes on the main functional load. In case of bilateral damage, other organs, in particular the liver, are involved in the body cleansing process. Three forms of pathological changes are distinguished in patients with chronic organic renal disorders. The first is characterized by complete intrarenal compensation of the cleansing function. The second is characterized by a decrease in the cleansing capacity of various parts of the nephrons. The third is accompanied by a sharp decrease in all renal parameters. It is noteworthy that the second and third forms are equally observed in adults and children. This fact is explained by morphological studies, which in the first case indicate significant sclerotic and atrophic processes in the organ parenchyma, and in the second - a combination of ureteral obstruction with congenital disorders of renal tissue differentiation. In the initial stages of development of pathological changes in the kidneys, their own compensation mechanisms are included within the organ - parenchyma perfusion increases or the reserve capacity of the nephrons is mobilized. The decrease in the cleansing capacity of the tubular apparatus is compensated by increased glomerular filtration. In the intermediate stage, compensation of renal function is achieved by the work of the contralateral kidney. In the final stage of the lesion, mechanisms of the extrarenal factor of cleansing the body are activated.

In each specific group of patients, along with these non-specific signs, specific forms of impairment of functional renal parameters can be identified. Impaired urodynamics of the upper urinary tract are the leading link in the pathogenesis of many urological diseases and a target for diagnostic and therapeutic measures. The problem of the relationship between chronic impairment of urodynamics of the upper urinary tract and the functional state of the kidneys, as well as predicting the functional results of surgical treatment is always very relevant. In this regard, radioisotope diagnostic methods that allow non-invasive and relatively simple quantitative assessment of the degree of damage to each kidney individually are widely used in diagnosing the functional state. To determine the degree of functional and organic changes in the renal circulatory system, as well as to identify the functional reserves of the affected kidney, radioisotope pharmacological tests are used with drugs that reduce peripheral vascular resistance and significantly increase renal blood circulation. These include drugs of the theophylline group, xanthinol nicotinate (theonikol), pentoxifylline (trental).

Functional indicators of the kidneys are compared before and after the administration of the drug. There are three types of non-specific reactions to the pharmacotest of pathologically altered kidneys - positive, partially positive and negative.

In case of obstructive disorders in the urinary system, pharmacotests are used with diuretics - drugs that block the process of water reabsorption in the distal tubules of the nephron and do not affect the central and peripheral hemodynamics, but only increase the outflow of urine. This group of drugs includes aminophylline (euphyllin). In patients with urolithiasis, three main forms of functional disorders are distinguished.

The first occurs in patients with kidney or ureter stones and is characterized by a distinct decrease in the intrarenal transit of the labeled drug in combination with a moderate slowdown in the process of excretion from the kidney. The second type is characterized by a significant decrease in the cleansing capacity of the tubular apparatus with a sharp slowdown in the process of excretion. The third type is detected in patients with coral stones and is manifested by a violation of the transit of the drug through the vascular bed of the kidney in combination with a predominant violation of the function of the tubular or glomerular apparatus. When a radiopharmacological test with euphyllin is administered to patients in the presence of reserve capacities, positive dynamics of the functional state of the kidney are noted. In the absence of reserve capacities, the deficiency of purification does not change compared to the original. This test is characterized by two types of nonspecific reactions: positive and no reaction.

In case of renal artery damage and vasorenal origin of arterial hypertension (AH), a typical functional symptom complex is observed - a distinct decrease in blood flow and clearance rates on the affected side in combination with an increase in the time of intrarenal drug transport. Only the degree of these changes varies. Such functional semiotics is extremely important for the clinical picture of the disease, especially at the stage of screening examination of patients with arterial hypertension. For differential diagnosis in such patients, it is necessary to conduct a radiopharmacological test with captopril (capoten). Comparison of load and control studies clearly records the reserve capacity of the renal vascular bed and renal parenchyma and facilitates the diagnosis of vasorenal and nephrogenic origin of arterial hypertension.

Modern capabilities of dynamic nephroscintigraphy allow quantitative assessment of the severity of disorders of not only the secretory, but also the evacuation function of the upper urinary tract in patients with obstructive uropathies. A close relationship has been confirmed between the severity of the violation of urine passage through the upper urinary tract and the degree of impairment of the functional state of the kidneys. Both during the period of formation of urodynamic disorders and after surgical restoration of urine passage through the upper urinary tract, the degree of preservation of the evacuation function as a whole determines the severity of renal dysfunction. The most informative indicator is the deficiency of blood purification from hippuran. The filtration function of the kidney is not directly related to the state of urodynamics.

The secretory function of the renal tubules is impaired in proportion to the degree of hemodynamic disorders and is restored only partially depending on the severity of the initial disorders. In case of impaired urodynamics of the upper urinary tract, a reliable correlation was found between the degree of impaired urine passage and the decrease in renal tubular function. However, the severity of the initial renal function deficiency does not affect the effectiveness of the reconstructive operation, and the degree of impaired evacuation function in the preoperative period is of significant importance for the postoperative period. If the cause of severe urodynamic impairment lies not so much in the mechanical occlusion of the lumen of the upper urinary tract, but in the changes that occurred in the wall of the pelvis and ureter, leading to a significant loss of contractile activity, then the elimination of obstruction cannot lead to the desired therapeutic effect. On the other hand, with adequate improvement of urodynamics, the operation gives a positive result even with an initially significant deficiency in purification.

The results of dynamic nephroscintigraphy in patients with vesicoureteral reflux are presented by two forms of functional disorders. In the first case, there is a slight decrease in the cleansing function of the renal tubular apparatus with the preservation of normal values of other functional indicators. The second form is distinguished mainly by a violation of the process of excretion from the kidney.

Problems of physiology and pathophysiology of hormones are mainly the object of research of endocrinologists. Hormones produced by kidneys and renal effects of other hormones are of increasing interest to urologists and nephrologists. Interest in tissue regulators (tissue hormones), such as prostaglandins and histamines produced by kidneys, is growing. Kidneys play a major role in catabolism and excretion of renal and extrarenal hormones and thus participate in regulation of hormonal status of the whole organism.

At the end of the 20th century, a highly effective method for determining hormone levels in biological fluids was developed and implemented - radioimmunoassay. It involves competition between labeled and unlabeled analogues of the substance being studied for a limited number of binding sites in a specific receptor system until chemical equilibrium is achieved for all components of the reaction mixture. Antibodies are used as a specific receptor system, and antigens labeled with a radioactive isotope are used as a labeled analogue. The label does not change the specific immunological specificity and reactivity of the antigen. Depending on the percentage ratio of labeled and unlabeled antigens in the solution, two "antigen-antibody" complexes are formed. Due to its specificity, high sensitivity, accuracy and simplicity of analysis, the radioimmunoassay method has replaced many biochemical methods for determining the concentration of hormones, tumor antigens, enzymes, immunoglobulins, tissue and placental polypeptides, etc. in biological fluids.

ICD and coral nephrolithiasis is a polyetiological disease. Disruption of calcium-phosphorus metabolism in the body with a certain frequency leads to the formation of kidney stones. Parathyroid hormone produced by the parathyroid glands has a huge impact on maintaining calcium homeostasis in the body. Parathyroid hormone is metabolized in the liver and kidneys and affects the functional structures of the kidney - reduces the reabsorption of inorganic phosphates in the proximal tubules. It has an active effect on oxidation-reduction processes in the cells of the renal tubules, stimulates the synthesis of the active metabolite of vitamin D, which is the main regulator of calcium absorption in the intestine. With hyperfunction of the parathyroid glands, the concentration of parathyroid hormone in the blood increases significantly. Nephrolithiasis is the most common clinical sign of primary hyperparathyroidism (in 5-10% of patients with ICD). Determination of the concentration of parathyroid hormone and calcitonin in the blood is the most accurate method for diagnosing hyperparathyroidism. Since immediately after entering the blood, the parathyroid hormone molecule disintegrates into two fragments with different biochemical activity and half-life, then for a reliable determination of the level of plasma concentration of its active fragment, it is necessary to take blood for research in the immediate vicinity of the place of its secretion - from the veins of the thyroid gland. This also allows you to determine the location of the parathyroid gland with increased functional activity. For differential diagnosis of primary and secondary hyperparathyroidism, the concentration gradient of parathyroid hormone and calcitonin is determined. The biological effect of the latter is to enhance the excretion of calcium, phosphorus, sodium and potassium by the kidneys and inhibit resorptive processes in bone tissue. In primary hyperparathyroidism, the concentration of parathyroid hormone in the blood increases, and calcitonin remains within normal values or slightly below normal. In secondary hyperparathyroidism, the concentrations of both parathyroid hormone and calcitonin in the blood increase.

In a comprehensive examination of patients with arterial hypertension, radioimmunological determinations of renin, aldosterone, and adrenocorticotropic hormone in blood plasma are mandatory. Under ischemic conditions, renal tissue secretes renin, which belongs to the group of proteolytic enzymes, which, when interacting with angiotensinogen, forms a pressor polypeptide - angiotensin. Blood samples for determining renin concentration by the radioimmunological method are taken directly from the renal veins and the inferior vena cava before and after orthostatic loading, which allows for reliable detection of asymmetry in renin secretion.

No less significant is the role of the adrenal glands, which produce aldosterone in response to increasing stimulation by angiotensin. With prolonged vasorenal hypertension (VRH), secondary aldosteronism develops, which is based on water-electrolyte disturbances, consisting of water retention in the body, increased excretion of potassium in the urine, swelling of the walls of arterioles, increased sensitivity to various pressor agents and an increase in total peripheral resistance. The most powerful stimulator of aldosterone secretion is adrenocorticotropic hormone, which also increases the secretion of corticosteroids, in particular cortisol. Increased concentration of cortisol in the blood increases diuresis, has hypokalemic and hypernatremic effects. Therefore, patients with VRH need a thorough radioimmunological study of the concentration of the above substances in the blood.

The hypothalamus, pituitary gland and male sex glands form a single structural and functional complex, in the interaction of which there are both direct and feedback connections. The need to determine the concentration of the corresponding hormones in the blood of patients with sexual dysfunction and fertility is obvious. Radioimmunological analysis in this area is the most accurate method at present.

The use of radioisotope diagnostic methods in urology is appropriate and promising. The capabilities of nuclear medicine for obtaining an objective assessment of the anatomical and functional changes occurring in the organs of the genitourinary system are quite multifaceted. However, as diagnostic equipment is modernized and new radiopharmaceutical preparations are released, the capabilities of radioisotope methods will improve, and diagnostics will improve with them.

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