The effectiveness of using the citrate mixture "Blemaren" for uric acid nephrolithiasis

Pharmacological properties of the drug Blemaren

A drug used to dissolve urinary stones. As a result of establishing the optimal urine pH value when taking the drug, favorable conditions are created to stop the growth and dissolution of uric acid and mixed stones. Reduces the secretion of calcium ions by stimulating the excretion of endogenous citrate, eliminating the conditions for the formation of stones containing calcium and making up the majority of all stones in urolithiasis. As a result of the metabolism of citrate (a salt of a strong alkali and a weak acid), alkalization (neutralization) of urine occurs. In this case, the citrate residue is oxidized to form CO2 or bicarbonate. Excess alkali, which is formed as a result of the hydrolysis of citrates, is excreted by the kidneys and causes an increase in urine pH. With oral administration of alkaline citrates (Blemaren citrate complex), dose-dependent neutralization or alkalinization of urine can be achieved. As a result, the degree of dissociation increases, and at the same time, the dissolution of uric acid or cystine. Litholysis of uric acid stones is confirmed by x-ray. Serum bicarbonate concentration is a regulating factor for citrate secretion by renal tubular cells. With an excess of alkalis and an increase in intracellular pH in the cells of the renal tubules, the tubular metabolism of citrates slows down, reverse resorption decreases and citrate excretion increases. Changes in renal calcium transport as a result of alkalization lead to a significant decrease in urinary calcium excretion. Alkalinization of urine, increased excretion of citrate and decreased excretion of calcium cause a decrease in the amount of calcium oxalate in the urine, since citrate forms a chemical compound with calcium in a weak alkaline environment. In addition, the citrate ion should be considered as the most important physiological inhibitor of the crystallization of calcium oxalate (as well as calcium phosphate) and the aggregation of these crystals. Regarding the solubility of cytostatic agents that are excreted by the kidneys, there are similar patterns. It can be assumed that there is a correlation between the aggressiveness of metabolites (for example, cytotoxic drugs such as cyclophosphamide) and the concentration of hydrogen ions in the urine, as well as the pH-dependent solubility of the cytostatic drug or its metabolites in urine (for example, methotrexate). When taking potassium sodium hydrogen citrate as an adjuvant agent as part of cytostatic therapy, the urine pH should be at least 7.0 in order to sufficiently reduce urotoxicity or nephrotoxic reactions that are caused by chemotherapy. In skin porphyria tarda there is a deficiency of uroporphyrinogen decarboxylase, which promotes the conversion of uroporphyrinogen to coproporphyrinogen. By means of metabolic alkalization, it is necessary to prevent the reverse diffusion of coproporphyrin in the renal tubules to increase the clearance of coproporphyrin. Due to increased excretion of coproporphyrin, there is an increase in the synthesis of coproporphyrinogen from uroporphyrinogen, and along with this, a decrease in the level of uroporphyrin. The bioavailability of the drug components is close to 100%. Citrate is metabolized almost completely, only 1.5–2% is excreted unchanged in the urine. When taking 4 effervescent tablets of Blemaren, 38 mmol of citrate enters the body, which corresponds to 2% of the amount of citrate that is metabolized daily in the body. After a one-day use of the drug Blemaren, the administered amount of sodium and potassium is excreted from the body by the kidneys over 24–48 hours. With prolonged use of the drug, the daily excretion of potassium and sodium corresponds to the daily intake. When using the drug, there are no changes in the gas composition or electrolyte balance of the blood.

The prevalence of nephrolithiasis in developed countries is up to 5%. Most urinary stones are composed of calcium oxalate (60%), calcium phosphate (20%), uric acid (10%), cystine (3%), tripelphosphate (7%). There are several reasons for the formation of stones. This is low diuresis, increased excretion of calcium in the urine - hypercalciuria. Hyperuricosuria, an elevated serum uric acid level, is found in approximately 10% of patients with calcium oxalate stones. The causes of hyperuricosuria may be gout, consumption of foods rich in purines, hemoblastosis, alcohol abuse, or taking uricosuric drugs. With hyperuricosuria, crystals or colloidal particles of uric acid form, promoting the formation of calcium stones.

Low urine pH is the cause of urate stones. In an acidic environment, uric acid is in an undissociated form and easily crystallizes, forming urate or mixed stones or promoting the formation of calcium stones. With renal distal tubular acidosis, secondary oxaluria, hypokalemia, heavy physical activity, increased consumption of animal protein and excess sodium, hypocitraturia is observed. Citrate forms soluble complexes with calcium, reducing the saturation of urine with calcium salts. Decreased urinary citrate excretion is another cause of stone formation in the urinary system. Hypocitraturia is the only disorder for 10% of patients with urolithiasis, and for 50% of patients it is combined with other causes of stone formation. When examining patients with nephrolithiasis, urine pH and its dynamics are clarified. At a pH of more than 7.2, tripel phosphate stones are formed, and at a pH of less than 5.5, urate stones are formed. An inverse relationship has been shown between high fluid intake and the formation of kidney stones. A general recommendation for patients who develop urinary stones may be to maintain a high urine output (at least 2 liters) by drinking significant volumes of fluids.

Adequate patient education regarding fluid intake and diet appears to be more important since treatment outcome will be largely determined by patient compliance. The ideal drug should prevent the formation of calcium stones, not cause side effects, and allow for simple dosage regimens. These aspects are especially important for achieving a sufficiently good degree of adherence to treatment. Low citrate excretion is one of the well-studied and common disorders in the calcium type of stone formation. Citrate plays an important role given the possibility of forming complexes with calcium. Moreover, citrate inhibits the growth and aggregation of these crystals. Administration of alkaline salt results in increased pH and increased citrate excretion. Taking drugs that create conditions for the dissolution of stones can be an effective first-line therapy [11]. This treatment method is used in addition to external shock wave lithotripsy (ESWL), percutaneous lithotripsy, urethrolithotripsy, or open surgery to facilitate removal of small residual fragments.

The clinical effectiveness of extracorporeal lithotripsy is related to the physicochemical characteristics of the stone [12, 14, 17, 18]. One of the significant prognostic factors is the structural density of the stone, determined by spiral X-ray computed tomography (CT density) [8, 13].

Research conducted at the Urology Clinic of the First Moscow State Medical University named after. THEM. Sechenov, in order to identify the dependence of the frequency of DLT on the structural density, showed that when the structural density is more than 800–1000 on the Hounsfield scale (HU), the frequency (2–3) of repeated DLT sessions increases and there is a need to use high-energy disintegration modes [13]. In view of this, preoperative drug preparation for DLT means the need to use drugs that change the structure, density and size (volume) of the stone [13]. Achieving this clinical result is possible with citrate therapy: potassium-sodium citrate preparations (Blemaren), potassium citrate and potassium-magnesium citrate.

The importance of citrate therapy is especially increasing after DLT of calyx stones, in particular, in patients with recurrent and residual stones of the lower calyx. According to a randomized study (110 patients), conducted in patients with complete passage of stones after radiotherapy and treatment with potassium citrate, after 12 months there were no recurrent stones, and in the control group the latter occurred in 28.1% of cases [9]. Similar results were observed in the group of patients with residual stones. When treated with potassium citrate, the period of remission was significantly higher compared to the group in which patients did not receive treatment (44.5 and 12.5%, respectively). According to the authors, potassium citrate therapy is important in the preventive treatment of calcium oxalate urolithiasis after radiotherapy of lower calyx stones.

The combined use of EBRT and chemolysis is the most minimally invasive method of treating patients with staghorn stones who are not candidates for percutaneous nephrolithotripsy. Crushing the stone leads to an increase in its surface, which increases the efficiency of chemolysis. Taking drugs intended for chemolysis is effective only for uric acid stones.

The high effectiveness of citrate therapy in the prevention of recurrent calcium oxalate stone formation has been noted by a number of authors [1, 2, 10, 15, 16]. Carrying out citrate therapy after radiotherapy helps to reduce the incidence of recurrent and residual calcium oxalate stone formation by 2 times [3]. The effectiveness of preventive citrate therapy (potassium-magnesium citrate) for calcium oxalate stones is 85% [5]. Prevention with citrate preparations is most effective for stones made of uric acid (100%), calcium oxalate (86.7%) [16], as well as for combined stones of calcium oxalate and phosphate (96.7%). The authors emphasize the relevance of preventing calcium oxalate stone formation using citrate in hypercalciuria with hyperuricosuria, in the presence of calcium oxalate dihydrate (veddelite) in the stone and the risk of recurrent stone formation in a single kidney.

The fundamental advantage of the drug Blemaren (Esparma GmbH, Germany) over other citrate drugs is the predominance of citric acid over its salt, while a significant part of the buffering function is performed by potassium hydrogen carbonate. The reduced sodium content in the drug promotes accelerated dissolution of uric acid in the renal tubules and prevents their further crystallization. The limited amount of potassium in the drug makes it possible to expand the indications for its use in cases where the potassium content in the body is of clinical significance [19, 20]. Oral administration of Blemaren provides a dose-dependent shift in urine pH from acidic to neutral or alkaline, without changing the acid-base balance of the blood; a daily dose of potassium-sodium citrate of 66–110 mmol has no effect on the level of potassium, sodium, oxygen, carbon dioxide and hydrogen carbonate in the blood. Citrate binds calcium ions along its entire path - from the gastrointestinal tract, where it reduces calcium absorption, to the urinary tract, where this effect is most active due to the highest concentration of citrate. In addition, by stabilizing solutions, citrate prevents crystallization processes in the urine. The complex effect of citrate on the physicochemical state of urine leads to an increase in the solubility of urates, calcifications and, first of all, oxalates, complex magnesium-ammonium phosphates and some other salts, helping to inhibit stone formation and dissolve already formed stones, thereby increasing the inhibitory activity of urine [1, 2, 4, 6, 7, 15]. The dose of Blemaren is set individually depending on the achieved urine acidity, which must be maintained at the optimal level for each type of stone. Urine pH is monitored using indicator paper before each dose of the drug. For urate, calcium-oxalate or mixed urate-oxalate stones, the pH should be maintained within 6.2–6.8 during the day. Average daily doses range from 6–18 g, evenly distributed throughout the day in 2–3 doses.

Treatment is based on alkalinization of urine by taking citrate mixtures or sodium bicarbonate. The destruction of calcium oxalate stones using potassium sodium citrate is based on the binding of the calcium citrate ion to the ion and its transition to a soluble compound. Based on the data obtained, we believe that the action of Blemaren in vitro leads to a decrease in the hardness of calcium oxalate stones (from 1400 to 900 Нu), possibly due to an increase in their “porosity”.

During dynamic monitoring of litholytic citrate therapy with Blemaren in vivo using spiral X-ray computed tomography with densitometry for 3–6 weeks, we also noted a decrease in the characteristics of mixed stones (size, volume, structure, density). Changes in stone characteristics during citrate therapy are presented on plain radiographs and densitometric histograms (Fig. 1). In this clinical observation, citrate therapy reduced the average structural density of a kidney stone by 254 HU, which made it possible to fragment the stone in one DLT session.

We analyzed the results of clinical use of the drug Blemaren in the form of a water-soluble effervescent tablet in 30 patients aged 33 to 62 years in 2000–2001. The distribution of stone density according to computed tomography data is presented in Fig. 2.

In 13 (43.3%) patients, the stone density before treatment was from 700 to 1000 HU, and in 17 (56.7%) the density was from 1001 to 1500 HU. The dynamics of stone density according to computed tomography data are presented in Fig. 3. After using Blemaren, 26 (86.7%) showed a decrease in stone density, and 4 (13.3%) had an increase. The change in stone size depending on the change in density is shown in Fig. 4. There was a significant predominance of the number of patients with a decrease in the size of the stone against the background of a decrease in its density (p = 0.176). Thus, litholytic citrate therapy reduced the average density in 26 (86.7%).

However, in 4 (13.3%) patients the average density increased. Moreover, in 2 (6.67%) patients, an increase in the density of the stone along with an increase in size was noted. The analysis showed that the reasons for the negative result (increase in stone volume and density) of citrate therapy in 4 (13.3%) patients are as follows:

• Use of the drug when phases predominate in the composition of the stone (more than 50%) with a density of more than 800 HU.
• Inability to stabilize urine pH within 6.2–6.8.

Thus, carrying out citrate therapy with Blemaren before extracorporeal lithotripsy allows:

• reduce the structural density of the stone;
• change the macro- and microstructure of the stone;
• by stabilizing the pH of urine, change crystallization processes.

Clinical assessment of the results of citrate therapy allowed us to detail the indications for prescribing citrate drugs before extracorporeal lithotripsy:

• mixed stones (X-ray heterogeneous, pH<6);
• the average density according to computed tomography is more than 800–1000 НU;
• the volume of structures (voxels) of stone with a density of up to 800 НU is more than 45–50%.

A prerequisite for citrate therapy in preparation for DLT should be complex anti-inflammatory and antibacterial therapy, because the effect of “bacterial hypocitraturia” is possible due to the ability of bacteria to metabolize urine citrate [1, 2]. Repeated DLT sessions were performed in 4 (13.3%) patients with an average stone density of more than 1100 Nu due to partial disintegration of the stone or the formation of an extended “stone path”.

Thus, carrying out citrate therapy with Blemaren for mixed (X-ray heterogeneous) stones before ELT increases the effectiveness of external nephrolithotripsy and reduces the frequency of repeat sessions. The duration of citrate therapy in preparation for radiotherapy should be at least three weeks. When planning chemolysis, the pH level should be adjusted to 7.0–7.2. For urinary tract obstruction due to uric acid stones, oral chemolysis is prescribed in combination with urinary tract drainage. The dosage of the drug is determined by the pH level of the urine. For the purpose of prevention, the optimal pH level is 6.2–6.8. When carrying out chemolysis – 7.0–7.2.

Indications for use of the drug Blemaren

Litholysis of urate stones in the urinary tract and prevention of their primary and re-formation; litholysis of mixed urate-oxalate stones; prevention of calcium oxalate stones (prevention of re-formation of stones and growth of residual fragments); alkalinization of urine during cytostatic therapy during the use of uricosuric drugs, during the treatment of patients with cystine stones, as well as in renal tubular acidosis with phosphate lithiasis; as an adjuvant in the treatment of hyperuricemia with xanthine oxidase inhibitors (for example, gout); as an adjuvant in combination symptomatic treatment of skin porphyria tarda.

Blémarin

Now you don’t know how to live further with this diagnosis, what you can eat, how much to drink, and how to generally behave so that the stone does not cause problems... We will help you and tell you about diet, lifestyle and some methods of treating urolithiasis.

Today it has been proven that there are stones that can be completely dissolved or stopped growing, regardless of size and location in the urinary system. Modern medications, such as citrate mixtures, when used correctly, can avoid traumatic operations to remove kidney stones. With this treatment, a chemical effect on kidney stones is carried out by changing the pH of urine in order to dissolve them and the process of stone formation itself is blocked, since with a new changed pH of urine, salts of oxalic and uric acid do not precipitate.

Blemaren is recognized as the “gold standard” for the treatment of urolithiasis. Oral administration of Blemaren provides a dose-dependent change in urine pH from acidic, in which salts of uric and oxalic acids precipitate, to neutral or alkaline, when salts do not precipitate, while the acid-base balance of the blood does not change. The dose of Blemaren is selected individually depending on the initial indicators of urine acidity. To dissolve stones, prevent their growth or prevent recurrent stone formation, the urine pH must be maintained for a long time and constantly at the optimal level for each type of stone. Urine pH is monitored before each dose of the drug 3 times a day using indicator paper, which is included with the package. Blemaren can completely dissolve urate (urate) stones, regardless of their size, stop the growth of oxalate (calcium-oxalate) stones and mixed urate-oxalate stones (with an oxalate content of less than 25%). Blemaren is also used in the treatment of cystine stones.

The duration of therapy aimed at dissolving stones is individual and ranges from 4 weeks to 6 months. Prevention of re-formation of stones removed by surgery or lithotripsy or citrate litholysis is carried out according to an individual schedule. It is also necessary to adhere to the diet recommended for the corresponding metabolic disorders discovered during the examination of the stone.

Modern drug litholytic therapy significantly expands the possibilities for complex treatment and prevention of re-formation of certain types of stones in the urinary tract.

Use of the drug Blemaren

The average daily dose is determined individually and can be 6–18 g of active substance (2–6 effervescent tablets per day). Effervescent tablets are taken after dissolving in water or fruit juice. The daily dose is divided into 3 equal parts, which are taken throughout the day (for example, at 8.00, 14.00, 21.00). Monitoring the effectiveness of the drug is carried out by determining the pH of fresh urine 3 times a day before the next dose of the drug. To do this, use standard indicator strips included in each package. The indicator zone of the test strip should be briefly immersed in urine, then removed and after 2 minutes, compare the resulting color of the test strip with the color scale applied to the set of indicator strips, and record the determined pH values ​​in the control calendar. The dose of the drug is considered correctly selected if the pH values ​​determined 3 times a day are within the recommended limits for each pathology. To dissolve urate stones, urine pH should be between 6.2–6.8. If the daily profile of pH values ​​is below 6.2, the dose should be increased, and if it is above 6.8, the dose should be reduced. To dissolve urate-oxalate stones and prevent the re-formation of calcium-oxalate stones, urine pH must be maintained for a certain time at a level of 6.8 to 7.4. Blemaren is used before external nephrolithotripsy for mixed (X-ray heterogeneous) stones to enhance its effectiveness, reduce the structural density of the stone and reduce the frequency of repeated sessions. The duration of therapy to prepare for extracorporeal lithotripsy should be at least 3 weeks. To alkalinize the urine in patients with cystine stones, the urine pH should be between 7.5 and 8.5. This requires the use of the drug at a higher dose. When carrying out cytostatic therapy, urine pH should not be lower than 7.0, and when treating late porphyria of the skin - 7.2–7.5. With uricosuric therapy, as with litholysis of urate stones, the pH should be 6.2–6.8. pH values ​​that can be determined using standard test strips are in the range of 5.4–7.4. If it is necessary to control urine pH in patients with cystine stones or with late porphyria of the skin, special indicator strips are used to determine pH in the range of 7.2–9.7 (prescribed additionally by a doctor). For litholysis of stones (depending on their size and composition), the duration of treatment usually ranges from 4 weeks to 6 months. To prevent relapses of nephrolithiasis, the drug is prescribed in courses, the duration and number of which are determined individually for each patient.

The effectiveness of using the citrate mixture "Blemaren" for uric acid nephrolithiasis

I.A. Aboyan, V.A. Sknar, S.V. Pavlov Municipal budgetary healthcare institution “Clinical Diagnostic, Rostov-on-Don”, Russia

Urolithiasis (UCD) has a high medical and social significance, which is due to a fairly high incidence, reaching 10% in the world, its annual growth in many countries and the defeat of the most able-bodied part of the population [1].

In the Russian Federation in 2012, the incidence of urolithiasis was 550.5 people per 100 thousand population, and its increase over the period from 2002 to 2012 exceeded 25% [2]. The prevalence of uric acid stones worldwide varies from 5 to 40% and varies geographically, so in North America it ranges from 5 to 10%, and in Israel it is 40% [3-5].

In the structure of the incidence of urolithiasis, there is an increase in the frequency of uric acid nephrolithiasis to 20-30%, which may be due to an increase in people's life expectancy, physical inactivity leading to impaired purine metabolism, and increased consumption of protein foods and alcohol.

The ratio of uric acid stones according to the results of a study of the composition of uroliths in recent years was 11.9-30.5% [7-10].

Numerous studies indicate the high efficiency of litholysis of uric acid stones using citrate mixtures (Blémaren and others) [11-17].

According to the recommendations of the European Association of Urology, the method of choice for non-invasive surgical treatment of stones up to 2 cm can be external shock wave lithotripsy (ESW) [11,18].

Most authors indicate that the effectiveness of this procedure depends on the size and density of the stone [6,14,17,19], along with some negative assessments of such a correlation [21].

In recent years, increasing attention has been paid to the effect of citrate drugs on stone density and the results of a subsequent course of extracorporeal lithotripsy (ESLT). Most studies have noted an increase in efficiency and a reduction in the duration of a course of DLT as a result of the use of citrates [14,16,19, 21].

The purpose of the study is to study the effectiveness of litholysis and the dynamics of the density of uric acid and mixed stones during therapy using citrate mixtures.

MATERIALS AND METHODS

We conducted a study of a group of 30 patients (14 women and 16 men aged 27-64 years) with uric acid nephrolithiasis. The size of the stones ranged from 8 mm to 22 mm, there were no signs of obstructive uropathy. Multislice computed tomography (MSCT) of the kidneys was performed on Siemens Somatom Difinition AS 64 and AS 40 devices in all patients before the start of therapy, after 3 months and after the end of the 6-month course of treatment (if a stone was present after 3 months according to MSCT).

The diagnosis of uric acid (urate) nephrolithiasis was established if the patient had a low stone density (138-600 NU) on MSCT of the kidneys; X-ray negative stones on plain urography or when performing a topographic image before MSCT of the kidneys, the results of X-ray phase analysis (XRF) of urinary stones that had passed earlier or were obtained as a result of lithotripsy, lithoextraction or surgical treatment before the current course of treatment, the presence of hyperuricemia and/or hyperuricuria. All patients received the Blemaren citrate mixture 3 times a day, in an individual pH-dependent dose from 0.5 tablets to 1.5 - 2 tablets 3 times a day during the course of litholysis (3-6 months).

In the presence of hyperuricemia and/or hyperuricuria, allopurinol 100–200 mg per day was also prescribed during the course of litholysis, usually in one dose. Some patients were recommended to take allopurinol twice a day if they had complaints of discomfort in the stomach with a single dose of the drug. In this case, the daily dose of allopurinol depended on the degree of hyperuricemia and/or hyperuricuria and was the minimum necessary to normalize the level of uric acid in the blood and/or urine.

RESULTS AND DISCUSSION

Complete dissolution of stones occurred in 22 patients (73.3%). In 6 cases (20%) there was a decrease in the size of the stone (Table 1). Of these, in three patients the stones decreased in size and passed naturally. The three remaining patients with a decrease in stone size underwent EBRT of stones. We noted greater efficiency in dissolving calculi when their size is less than 1 cm.

Table 1. Results of litholysis of uric acid stones using Blemaren

As for two cases of lack of effect from the course of litholysis, in one case DLT was successfully performed. The density of this stone after the course of litholysis decreased slightly (by 6 HU units). Analysis of stone fragments showed a combination of uric acid dihydrate and apatite in a ratio of 70% and 30%. The second patient underwent laser nephrolithotripsy. XRF of this calculus revealed the presence of uricite and insoluble sodium urate in a ratio of 60%:40%. The density of the stone in this case also decreased slightly - by 3 units. HU.

In the study group, we studied the relationship between the effectiveness of treatment, stone density before and after treatment and the degree of reduction in stone density depending on the composition of stones according to X-ray phase analysis. The density and composition of stones from patients who had complete stone dissolution after 3 months are presented in Table 2.

Table 2. Initial density and composition of stones in patients who had complete stone dissolution after 3 months.

The initial composition of stones and the degree of reduction in the density of stones in patients who had complete stone dissolution after 6 months are presented in Table 3.

Table 3. Composition of stones and the degree of reduction in the density of stones in patients who had complete stone dissolution after 6 months.

The density, the degree of its reduction and the composition of the stones of patients in whom partial dissolution of the stones was noted are presented in Table 4.

Table 4. Density, degree of density reduction and composition of stones from patients with partial dissolution of stones

The density, the degree of its reduction and the composition of the stones of patients in whom stone dissolution was not noted are presented in Table 5. These patients are characterized by a relatively high density of stones and a low degree of reduction in the density of stones.

Table 5. Density, degree of density reduction and composition of stones from patients in whom stone dissolution was not noted

As can be seen from tables 2-5, the best results were observed with litholysis of monophasic uric acid stones. As the density of stones increases, the proportion of patients with successful litholysis decreases and the duration of the dissolution process lengthens.

Table 6 shows the dynamics of stone density during litholysis in patients receiving the Blemaren citrate mixture for 6 months (complete dissolution, partial dissolution and no dissolution).

Table 6. Dynamics of stone density during litholysis in patients receiving the citrate drug Blemaren for 6 months (complete dissolution, partial dissolution and no dissolution)

As can be seen from the table, during the treatment the density of stones decreased significantly, by an average of 89 units. НU (31.6%).

During the study, we noted a decrease in the level of stone density during therapy with the citrate drug Blemaren in all patients, while the stone density according to MSCT in all patients with successful litholysis was less than 500 NU.

Figure 1 shows the relationship between the average density of stones and the results of litholysis (the degree and timing of stone dissolution).

Rice. 1. Relationship between the average density of stones and the results of litholysis

Our study also revealed a directly proportional relationship between the average degree of reduction in stone density during treatment and the results of litholysis, that is, the degree and timing of stone dissolution (Fig. 2).

Rice. 2. Average degree of reduction in the density of calculi during litholysis

CONCLUSIONS

Litholysis of uric acid stones using a citrate mixture (Blemaren) is a highly effective non-traumatic method of treating patients.

During treatment, a significant decrease in the density of uric acid and mixed stones was noted

The noted decrease in density turned out to be more pronounced when performing litholysis of monophasic (single-component) uric acid stones.

In addition, we noted that this type of treatment turned out to be highly effective when the stone density according to MSCT data is less than P 500 NU.

LITERATURE

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The article was published in the journal “Experimental and Clinical Urology” No. 2 2021, pp. 44-49

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Journal "Experimental and Clinical Urology" Issue No. 2, 2018

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Special instructions for the use of the drug Blemaren

When dissolving urate stones, prolonged excessive alkalization of urine (pH 7.8) should not be allowed, given the possible appearance of a sediment of phosphate salts on the surface of the stone, which may prevent its further dissolution. The drug can be used for compensated renal failure, which is not accompanied by potassium retention in the body. Before use, it is necessary to determine the level of electrolytes in the blood serum and check renal function. If renal tubular acidosis is suspected, a COR study should be performed. Patients with heart failure should take into account that 1 effervescent tablet or measuring spoon of the drug contains 380 mg or 9.7 mmol of potassium, which can affect the action of cardiac glycosides (an increase in the extracellular concentration of potassium reduces the effectiveness of glycosides, and a decrease increases the arrhythmogenic effect). For patients with uric acid metabolism disorders, it is recommended to combine the drug with allopurinol. Persons who follow a sodium-restricted diet should take into account that 1 effervescent tablet of Blemaren contains 220 mg or 9.7 mmol of sodium. During therapy with Blemaren, it is recommended to follow a low-protein diet, limiting the consumption of foods rich in purines (meat, sausages, offal, sardines). Every day you need to drink 2-3 liters of fluid in the form of tea, fruit juice or alkaline mineral water in order to reduce the risk of stone formation by producing a sufficient amount of urine. The drug does not contain carbohydrates and can be used to treat patients with diabetes. Changes in color of unused test strips do not affect pH results. When using the drug in accordance with the instructions, no negative effects were observed during pregnancy and lactation.

Instructions for use BLEMAREN tab. fizzy

Serum electrolytes and renal function may need to be checked prior to use. If renal tubular acidosis is suspected, the acid-base balance should also be checked.

In the presence of diseases that can contribute to the formation of uric acid stones (for example, parathyroid adenoma, malignant neoplasms accompanied by the formation of uric acid stones), etiotropic therapy must first be carried out.

Caution should be exercised when prescribing Blemaren effervescent tablets to patients who have been prescribed a salt-free diet, especially to patients with severe arterial hypertension. It is important to note that 1 effervescent tablet contains 220 mg of sodium ions / 9.7 mmol of sodium (corresponding to 0.57 g of table salt).

During treatment, urine and blood parameters should be regularly monitored. Particular attention should be paid to the acid-base balance.

To maintain and maintain the effect of the drug, patients should be advised to reduce salt intake during treatment.

A daily intake of 2-3 liters of fluid in the form of tea, juice or alkaline mineral water is necessary to form a sufficient amount of urine, which in turn reduces the risk of stone formation.

Patients with severe functional liver failure should be prescribed Blemaren with extreme caution.

One effervescent tablet contains 9.7 mmol (380 mg) of potassium, which must be taken into account when treating patients with renal failure and those on a potassium-controlled diet.

One effervescent tablet contains 9.7 mmol (220 mg) sodium, which must be taken into account when treating patients on a sodium-controlled (salt-free) diet.

Blemaren is safe when prescribed to patients with diabetes (0.02 carbohydrates/per tablet).

The drug contains lactose monohydrate. In this regard, the drug is not recommended for patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Influence on reaction speed when driving vehicles and working with other mechanisms

Blemaren does not affect the reaction rate when driving vehicles or operating other mechanisms.

Preclinical safety data

Acute toxicity

Acute toxicity studies in rats and mice following oral administration showed an LD50 value of 5000 mg/kg body weight.

Chronic toxicity

Chronic toxicity studies in rats and dogs showed no evidence of specific toxic reactions at doses up to max. 3000 mg/kg when taken orally.

Oncogenic and mutagenic potential

No oncogenic or mutagenic effects were detected at therapeutic doses.

Reproductive toxicity

In a reproductive toxicity study in rats and rabbits, no embryotoxic potential was observed up to the maximum tested dose of 2000 mg/kg PO.

Fertility studies in the pre- and postpartum period have not been conducted.

No special studies have been conducted in pregnant and lactating women. However, existing experience with the use of this class of substances indicates that there are no possible risks during use.

Preclinical safety data based on standard acute toxicity, repeated dose toxicity, genotoxicity and carcinogenic potential studies do not indicate any risk to human health.

Interactions of the drug Blemaren

Simultaneous use of drugs containing citrate and aluminum may cause an increase in aluminum resorption, so it is recommended to maintain a 2-hour pause between doses of such drugs. The drug enhances the therapeutic effect of allopurinol. Aldosterone antagonists, potassium-sparing diuretics, ACE inhibitors, as well as non-narcotic analgesics and NSAIDs may reduce potassium excretion, which should be taken into account when prescribing Blemaren simultaneously. With long-term use of Blemaren, accumulation of quinidine in the body is possible if it is taken simultaneously, as well as a decrease in the effectiveness of nitrofurantoin, salicylates and lithium preparations.