[The methodology of remote monitoring of patients with urinary stone disease: development and primary approbation].

INTRODUCTION: Urolithiasis is a clinically and socially significant disease that requires long-term follow-up in order to prevent stone recurrence. Currently, telemedicine consultations in the "patient-doctor" format are actively used in urology, however, the methodology, technological base and assessment of the efficiency of remote monitoring of the patient's health status are virtually not developed. AIM: To provide basics for the methodology of remote monitoring of patients with urolithiasis for detailed comprehensive examination and comprehensive metaphylaxis of recurrent stone formation. MATERIALS AND METHODS: A comprehensive clinical examination was carried out on the basis of the Institute of Urology and Human Reproductive Health, the National Medical Research Center on Urology and the Institute of Digital Medicine of FGAOU VO I.M. Sechenov First Moscow State Medical University during the period from 1st February to 1st December 2020. A total of 30 patients with urolithiasis were included in the study. Remote monitoring of health status was carried out using a portable analyzer "ETTA AMP-01" on dipstick. Data transmission was performed through a mobile application, which is part of the "NetHealth" information system (www.nethealth.ru). The values and frequency of urine tests performed by the patient independently, as well as patient satisfaction and adherence to the monitoring technology were evaluated. Analytical, clinical, sociological and statistical research methods were used. RESULTS: By systematizing published data and our own clinical experience, we have developed a model for remote monitoring of the health status of patients with urinary stone disease, which included a system of indications and contraindications, a program and an order of the monitoring, as well as a basic technological solution (medical devices and a hardware-software complex). In this study, median duration of remote monitoring was 168 days. According to the questionnaire, general positive assessment and desire to continue telemonitoring was seen in 100.0% of cases, while 86.7% of patients positively evaluated the technical accessibility and reliability of the system and 93.3% considered the quality and availability of medical care as high. CONCLUSION: A methodology for remote monitoring of patients with urolithiasis has been developed with the aim of preventing recurrent stone formation. There was a high adherence of patients to remote monitoring with a tendency to decrease in values after 4 and 6 months. During these periods, it is necessary to carry out routine consultations by the physician who appointed remote monitoring in order to continue the follow-up program. There was a high satisfaction of patients with remote monitoring, and they pointed out the quality and availability of urological care owing to telemedicine technologies.

[A complicated case of calcium urolithiasis in a carrier of SLC7A9 gene mutation responsible for cystinuria].

The article describes a clinical case of kidney stone disease (KSD) in a child of 4 y.o. with calcium urolithiasis. Analysis of chemical content of the kidney stones revealed their calcium-oxalate composition. According to the results of clinical exome sequencing the patient found to be a heterozygous carrier of a pathogenic variant c.695A>G (p.Tyr232Cys) in the gene SLC7A9, attributable for an autosomal recessive form of cystinuria type B. Because of the uroliths calcium composition the patient was also genotyped for SNPs in 15 genes involved in calcium metabolism. Polymorphisms associated with increased risk of calcium urolithiasis were found in 8 of 15 tested genes. The findings could explain clinical features of the patient.

[Molecular and genetic technologies for the diagnosis of monogenic forms of urinary stone disease: clinical cases].

Kidney stone disease (KSD) is an actual problem of modern health care. By now, more than 80 monogenic forms of urolithiasis have been described. To diagnose such forms of KSD different molecular genetic technologies are used. In the current article 5 clinical cases of KSD among the patients aged 1-9 years old are presented. All of them underwent comprehensive instrumental, clinical, laboratory and molecular genetic investigations. DNA analysis was carried out by Next Generation Sequencing method (NGS) (target NGS-panels and Whole Exome Sequencing). In all cases the molecular genetic cause of the disease was found - idiopathic infantile hypercalcemia type 1 (gene CYP24A1 - 3 cases) and cystinuria (gene SLC7A9 - 2 case). Several unknown genetic variants were found in CYP24A1 (c.1379G>T, c.1156A>T, c.1286T>C) and SLC7A9 (c.920T>A). The importance of genetic testing and the role of genetic counseling for patients with KSD were shown.

[Dual-energy computed tomography in the diagnostics of urolithiasis].

THE AIM: To assess the diagnostic performance of dual-energy computed tomography (DECT) in the evaluation of the composition of urinary stones "in vivo". MATERIALS AND METHODS: A total of 91 patients aged from 20 to 70 years old (mean 42.7) with urinary stone disease were examined at Sechenov University, including 68 men (75%) and 23 women (25%). Prior to surgery, all patients underwent DECT (Canon, Japan) in order to predict the chemical composition of urinary stones in vivo. Extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS) was performed in 53 (58.2%), 18 (19.7%) and 20 (22.1%) patients, respectively. Postoperatively, all stones or stone fragments (n=91; 100%) were examined using a comprehensive physical and chemical analysis (X-ray phase analysis, electron microscopy, infrared spectroscopy). RESULTS: In 6 patients (6.6%) staghorn stones were diagnosed, while in 15 (16.5%), 17 (18.7%), 22 (24.2%) and 31 (34.1%) stones were located in ureteropelvic junction, pelvis and ureter, respectively, including 24 patients with lower ureteric stones (26.4%). Prediction of the stone composition in vivo was carried out on the basis of the one indicator, the dual energy ratio (DER). The threshold values of DER for different types of stones were taken from the literature. All stones were divided into 4 groups according to the DECT results: vevellite stones (n=40, 43.9%), Ca-containing stones without vevellite (n=34, 37.3%), uric acid stones (n=10, 10.9%) and struvite stones (n=7, 7.9%). Thus, when comparing the results of DECT and physical and chemical analysis, in the first group four stones were incorrectly assigned by DECT to the group of Ca-containing stones without vevellite and three stones were incorrectly assigned to the group of struvite stones; in the second group four stones were incorrectly assigned to the group of vevellite stones; in the third group one stone was incorrectly assigned to the group of struvite stones; in the fourth group one stone was incorrectly assigned to the group of vevellite stones and one stone in the group of uric acid stones. In order to increase the diagnostic efficiency of DECT, we performed a comprehensive analysis of five specific DECT indicators (stone density at 135 kV, Z eff of the stone, DER, DEI, DED) using discriminant analysis. Thus, the sensitivity, specificity and overall accuracy of DECT with the use of just one indicator (DER) were 83.3%, 89.8%, 86.8% for vevellite, 88.2%, 92.9%, 91.2% for Ca-containing stones without vevellite, 90%, 98.8%, 97.8% for uric acid stones and 60%, 95.3%, 93.4% for struvite stones, respectively. When using discriminant analysis with five specific DECT indicators, higher values of sensitivity, specificity and overall accuracy were seen: 95.2%, 89.8%, 92.3% for a vevellite, 85,3%, 96,4%, 92,3% for Ca-containing stones without a vevellite and 100%, 100% and 100% for both uric acid and struvite stones, respectively. CONCLUSIONS: Dual-energy computed tomography is a highly informative method which allows to perform preoperatively the reliable assessment of the chemical composition. DECT in patients with urinary stone disease allows to optimize the treatment strategy and carry out preventive measures on individual basis, taking into account the stone type.

[Clinical value of CT-perfusion in patients with ureteric stones].

INTRODUCTION: Urinary stone disease is one of the most significant urologic diseases, since its prevalence increases annually, which makes it necessary to study and improve effective preventive measures, diagnostic methods and to implement new treatment interventions. AIM: to study changes in blood flow in the renal cortex and medulla in patients with ureteral stones using CT perfusion. MATERIALS AND METHODS: From 2017 to 2019, a total of 53 patients with upper ureteric stones were evaluated at the Russian-Japanese Center for Imaging and the Institute of Urology and Reproductive Health of the FGAOU VO I.M. Sechenov First Moscow State Medical University. Preoperatively, all patients underwent CT perfusion. The study was performed on a Toshiba Aquilion One 640 in volume mode with a slice thickness of 0.5 mm. In this study, blood flow changes were evaluated depending on the degree of dilatation of collecting system. RESULTS: In patients without dilatation of the collecting system, the average values of cortical and medullary blood flow and blood volume were within normal values. In patients with a dilatation of collecting system, there were significant differences cortical and medullary blood flow between the affected renal unit and contralateral side (27% and 34%, respectively). A decrease in cortical and medullar perfusion by 55% and 58%, respectively, in patients with the dilatation of calyxes was more pronounced in comparison with a decrease in perfusion in patients with the dilatation of only the ureter and pelvis. CONCLUSION: CT perfusion performed on the 640-slice CT scan allows an objective assessment of changes in renal blood flow in patients with ureteric stones.

[Genetic aspects of primary hyperoxaluria: diagnostics and treatment].

Primary hyperoxaluria is a group of inherited metabolic diseases characterized by increased formation of calcium-oxalate stones in kidneys with development of nephrolithiasis and chronic kidney disease. The article summarizes the modern information on the diagnostics and treatment of the disorder depending on genotype of the patient (AGXT, GRHPR, HOGA1 genes). The evaluation of the molecular genetic aetiology of the kidney stone disease contributes to the personalized treatment and prevention of the pathology in the patients and their relatives.

[Inluence of osteoporosis and its causative factors on the prevention of recurrence of urinary stone disease].

INTRODUCTION: The aim of postoperative examination, treatment and follow-up of patients with urinary stone disease is a prevention of recurrence. A choice of method of prevention is based on the results of postoperative examination with consideration of etiological factors of urinary stone disease. An analysis of influence of osteoporosis and its causative factors on the recurrence of urinary stone disease is presented in the article. AIM: to clarify the influence of osteoporosis and its causative factors on excretion of calcium, uric acid and recurrence of urinary stone disease. MATERIALS AND METHODS: A total of 86 patients after surgical treatment of urinary stone disease were included in the study. A physicochemical analysis of stones and their fragments, excretion of calcium and uric acid were done postoperatively. The risk factors for osteoporosis were identified using specific questionnaire. Bone mineral density (BMD) was assessed by X-ray densitometry. After X-ray phasic analysis of the stones and studying of the daily excretion of calcium and uric acid, 10 and 7 patients were prescribed to thiazide diuretics and allopurinol, respectively. In 69 patients (80.2%) there were no indications to the treatment and all of them were included in control surveillance group. RESULTS: Calcium oxalate stones were predominated in patients who were under surveillance (=0,0254). A prevalence of risk factors for osteoporosis was similar in all groups (=0,2156), as well as rate of decrease in BMD (=0,64). In patients taking thiazide diuretics, a significant decrease in daily calcium excretion was found (=0,0054) without significant changes in excretion of uric acid and diuresis volume. Among patients receiving allopurinol there was a significant decrease in daily uric acid excretion (=0,021), without significant changes in excretion of calcium and diuresis volume. There were no significant changes of these values in the control group. A recurrence of urinary stone disease in treatment group was detected in 4 patients with a decrease of BMD after 381+/-61 days, while in control group there were 5 recurrences in patients with decreased BMD and I recurrence in patient with normal BMD after 836+/-64 days. CONCLUSION: Treatment aimed at prevention of recurrence of urinary stone disease allows to correct detected metabolic disturbances. However, such factor as the decrease in BMD can influence on the rate and frequency of recurrence of urinary stone disease. A clarifying of risk factors for osteoporosis and diagnosis of osteoporosis allow to give reliable recommendations for its treatment and to decrease risk of recurrence of urinary stone disease.

[Clinical value of herbal terpenes after extracorporeal shock-wave therapy].

BACKGROUND: Rowatinex is a combined drug based on plant terpenes which provides diuretic, anti-inflammatory and antispasmodic effect. A use of herbal preparation Rowatinex in patients with urinary stone disease after extracorporeal shock-wave therapy (ESWL) is analyzed in the article. AIM: To clarify the efficiency of the drug Rowatinex in patients with urinary stone disease after ESWL. MATERIALS AND METHODS: All patients were divided into two groups depending on therapy administered after ESWL. In main group (n=150) patients received Rowatinex, while in control group (n=70), antispasmodics were administered. Spontaneous passage of fragments was observed in 104 patients in main group (69.3%) and 30 patients in control group (42.9%). RESULTS: When studying the effect of therapy on the changes of complete blood count, biochemical panel and daily excretion of some substances (magnesium, uric acid, calcium, etc) there were no significant differences between main group and control group. All values were normal. It was estimated that increase in diuresis during use of Rowatinex contributes to effective and rapid passage of stone fragments. In addition, there was a decrease in leukocyturia in both groups. CONCLUSION: Drug Rowatinex allows to reduce the time to spontaneous passage of fragments after ESWL, intensity of pain syndrome and leukocyturia as well as to increase in daily diuresis. This is not accompanied by the development of complications and side effects which allows to administer Rowatinex for a long time as part of complex medical expulsive therapy and use it for recurrence prevention of urinary stone disease. Effect of Rowatinex didnt depend on the stone composition.

[Clinical value of Canephron N after surgical treatment of urinary stone disease].

BACKGROUND: The drug Canephron N is a combination of extracts of centaury, lovage and rosemary. Moderate antispasmoic, anti-inflammatory, antioxidant, diuretic and antimicrobial effects are of great interest for urological practice. The optimal combination of components that were made of herbal medicine allows to use their synergistic effect for prevention of recurrence of urinary stone disease. The experience of using the drug Canephron in clinical practice is of great interest. AIM: to clarify the clinical efficiency of Canephron N in patients with urinary stone disease after surgical treatment and to evaluate the changes in diuresis and calcium excretion. MATERIALS AND METHODS: The results of using the drug Canephron after surgical treatment of urinary stone disease are provided. The changes in diuresis and calcium excretion in 75 patients undergone surgical treatment of urinary stone disease were studied. Patients after ureteroscopy, percutaneous nephrolithotomy and extracorporeal shock-wave lithotripsy were prescribed treatment to prevent stone formation including herbal drug Canephron N. RESULTS: At baseline, there was negative correlation between 24-hours diuresis and calcium excretion in all groups. During follow-up, a positive correlation between 24-hours diuresis and calcium excretion was found in patients receiving Canephron N and other types of treatment. The average follow-up was 390 days. During this period, recurrence was noted in 1 patient receiving Canephron, 4 patients in patients who took other drugs and in 5 patients who didnt receive any treatment. CONCLUSION: Risk factors of stone formation persist after surgical treatment of urinary stone disease. This is reflected in a negative correlation between 24-hour diuresis and calcium excretion. During treatment, a positive correlation between diuresis and calcium excretion was noted in patients with urinary stone disease. The use of drugs that affect stone formation as well as herbal medicine Canephron N allow to obtain comparable ratio of diuresis and calcium excretion.

[Genetic aspects of primary hyperoxaluria: epidemiology, ethiology, pathogenesis, and clinical signs of the disorder].

Primary hyperoxaluria is a group of rare inherited diseases characterized by impaired oxalate metabolism with the early manifestation of urolithiasis and the development of the chronic kidney disease. The mutations in the AGXT, GRHPR, HOGA1 genes are attributable for different types of primary hyperoxaluria leading to the dysfunction of specific enzymes involved in the oxalate metabolism. The article summary the current data on the epidemiology, genetic and biochemical aspects of pathogenesis of the primary hyperoxaluria types 1-3. The variety of clinical signs and disease severity depend on the type of hyperoxaluria.

[Modern radiology diagnostics methods for assessment of renal perfusion in patients with urinary stone disease].

Urinary stone disease is the current issue for healthcare system worldwide. High prevalence of urinary stone disease (at least 5% of the population of developed countries) determines clinical significance of the studying of its etiology and pathogenesis, improving of diagnostic methods and novel treatment technologies. The development of endoscopic devices, creation of new eswl machines and improvement of endourology interventions under X-ray guidance allowed to solve the problem of surgical treatment. Therefore, one of the actual issue is the choice of X-ray method for predicting and evaluating of treatment efficiency in patients with urinary stone disease. The changes of renal blood flow depend on urodynamic disturbances, stone location and size, the duration of disease, complications, patients age. Therefore, for comprehensive studying of renal function the hemodynamics evaluation is needed. In this review the advantages, drawbacks and perspective on developing of different radiologic methods for renal hemodynamic assessment are given.

[Characteristic features of urinary calcium excretion and osteoporosis risk factors in patients with urolithiasis].

RELEVANCE: The prevalence of urolithiasis and osteoporosis (OP) indicates that these diseases may be found concurrently in the same patient. The detection of risk factors for OP and disorders of calcium metabolism in patients with urolithiasis is of interest in the context of primary stone formation and metaphylaxis. AIM: To identify risk factors for osteoporosis and disorders of calcium metabolism in patients with urolithiasis. MATERIALS AND METHODS: Osteoporosis risk factors were studied in 45 urolithiasis patients undergoing surgical treatment. Patients were asked to fill out the osteoporosis risk factor questionnaire, and urinary calcium excretion was measured in 24-h collections. RESULTS: Risk factors for osteoporosis were detected in 20 (44.4%) urolithiasis patients. Patients with osteoporosis risk factors identified by the questionnaire were statistically significantly older (p=0.032). Osteoporosis risk factors were found in 20% of patients with newly diagnosed urolithiasis and 24.4% of patients with recurrent urolithiasis. The study patients showed increased urinary calcium excretion and decreased diuresis. The negative correlation between urinary calcium excretion and 24-h diuresis was greater in patients who had than in those who did not have osteoporosis. CONCLUSION: An increase in urinary calcium excretion and a decrease in diuresis can be a predisposing factor for the recurrence of urolithiasis. In patients with risk factors for osteoporosis, it can provide a rationale for administering drugs aimed at preventing stone formation (thiazide diuretics).

[Clinical implications of dual-energy computed tomography in the diagnosis and treatment of urolithiasis].

Urolithiasis (urolithiasis) is one of the most common urologic diseases with an estimated prevalence of no less than 3% in the population, usually affecting active working-age patients of 30-50 years. Taking into account major public health and economic significance of this problem, there is the need for the development of effective modern diagnostic techniques. Rapid medical-technological advances of the past two decades have led to the wide spread use of minimally invasive surgery the management of urolithiasis. Nevertheless, surgical intervention only removes the result of a long pathological process and does not change its course. Thus, there is a need for a detailed understanding of the etiology, epidemiology, and pathogenesis of urolithiasis. Diagnostic imaging plays a key role in the diagnosis of urolithiasis. Multislice spiral computed tomography (MSCT) is the gold standard for the diagnosis of urolithiasis. It provides information about the size, location, and density of the calculus. Over the past decade, the use of dual-energy computed tomography (DECT) in urological practice has been widely discussed in the international and domestic literature. One of the main advantages of DECT is the ability to determine the chemical composition of urinary stones. Previous studies have reported a high diagnostic value of the method, including the ability to predict treatment outcomes. However, the shortcomings of the method and the absence of standardized examination protocols leave a wide field for further research. This article reviews major distinctive features of using DECT in the diagnosis of urolithiasis.

[Genetic factors for monogenic forms of calcium urolithiasis].

The article presents pooled results of domestic and international studies investigating genetic aspects of urolithiasis associated with impaired calcium metabolism. The review highlights the importance of early and accurate diagnosis of hereditary diseases associated with kidney stone formation. Of more than 80 currently known monogenic forms of urolithiasis, the authors provide the list of the most significant forms. Using such molecular genetic methods as NGS (next generation sequencing) allows accurate detection of the genetic cause of the disease, develop an individual approach the patients management and timely prevention of the disease among the relatives of the proband.

[Genetic aspects of urolithiasis].

The article presents summarized results of domestic and international studies of the genetic aspects of urolithiasis. The presented evidence suggests the importance of early and accurate molecular genetic diagnostics of hereditary diseases associated with stone formation for timely treatment and prevention for patients' relatives. Also provided are examples of using molecular genetic diagnostics in urologist's practice for monogenic and multifactorial diseases associated with stone formation. Taken together, these results show that using modern post-genomic technologies for assessing the risk of hereditary predisposition to urolithiasis is justified.

[Plant-derived terpenes in treating patients with urolithiasis].

Numerous metabolic abnormalities intrinsic to urolithiasis require drug therapy. At the same time, despite the constant expansion of synthetic drugs, plant-derived medications play a large role in the treatment and prevention of the disease. AIM: To evaluate the effect of a plant-derived preparation Rowatinex in patients with urolithiasis after extracorporeal shock wave lithotripsy (ESWL) and analyze the changes in blood and urine parameters in patients receiving the preparation. MATERIALS AND METHODS: Depending on the type of post-ESWL treatment, patients were divided into two groups. After ESWL, patients of group A (n=107) and group B (n=50) were administered Rowatinex and antispasmodic drugs, respectively. RESULTS AND DISCUSSION: Clearance of stone fragments after ESWL within 1-5 days was achieved in 76 (71.1%) patients of group A and in 20 (40.4%) of group B. Analysis of the effect of the therapy on blood count, biochemistry tests and 24h excretion (magnesium, uric acid, calcium, etc.) did not reveal significant differences between group A group B and reference values. Increased diuresis caused by antispasmodic effects of Rowatinex resulted in the complete clearance of stone fragments. Urinalysis in patients of the two groups showed decreased leukocyturia. Furthermore, stabilization of urine pH within the 6.2-6.8 was noted in group A, which is important and necessary in metaphylaxis of recurrent stone formation. CONCLUSIONS: Administration of Rowatinex increases the percentage of stone fragment clearance after ESWL and reduces pain intensity. Rowatinex reduces leukocyturia, increases 24h diuresis and stabilizes the pH of urine. Increasing and stabilizing urine pH in patients with calcium oxalate and urate stones reduces the risk of recurrence after ESWL. No complications associated with Rowatinex were reported, allowing long-term administration of the preparation in the complex lithokinetic therapy and for metaphylaxis of recurrent stone formation.

[Clinical implications of shear wave ultrasound elastography for evaluation of urinary stones].

INTRODUCTION: Currently, extracorporeal shock wave lithotripsy (ESWL) is a minimally invasive treatment for patients with urolithiasis. With advancing medical technology, elastography has evolved as a method for measuring the elasticity of tissues. AIM: To investigate the elasticity of urinary stones for assessing their physical and chemical composition. MATERIALS AND METHODS: The elasticity of urinary stones was determined before ESWL in 30 urolithiasis patients (18 men and 12 women, aged 25-65 years) using shear wave ultrasound elastography (SWUE). In 40%, 23.3% and 20% of patients, urinary stones were located in the renal pelvis, the middle calyceal group and the lower calyceal group, respectively. RESULTS: Elastography is a method of determining the elasticity of urinary stones, measured in kPa. Mean elasticity (Emean) of calcium oxalate monohydrate stones, uric acid stones and mixed urinary stones was 39.8, 14.6 and 26.3-29.8 kPa, respectively. Urinary stones smaller than 5 mm did not differ in the color spectrum. Excess body mass index (BMI) also reduced the informative value of the method. CONCLUSIONS: The findings of SWUE are comparable with the results of computer densitometry and physical and chemical composition of the investigated urinary stones.