Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1. METHODS: For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox). We compared values among 3 groups: homozygous G170R, heterozygous G170R, and non-G170R AGXT variants both before and after initiating pyridoxine (B6). RESULTS: Of 403 patients with PH1 in the registry, 83 met the inclusion criteria. Uox:cr decreased rapidly over the first 5 years of life. Both before and after B6 initiation, patients with non-G170R had the highest Uox:cr, 24-h Uox, and Pox. Patients with heterozygous G170R had similar Uox:cr to homozygous G170R prior to B6. Patients with homozygous G170R had the lowest 24-h Uox and Uox:cr after B6. Urinary oxalate excretion and Pox tend to decrease over time during childhood. eGFR over time was not different among groups. CONCLUSIONS: Children with PH1 under 5 years old have relatively higher urinary oxalate excretion which may put them at greater risk for nephrocalcinosis and kidney failure than older PH1 patients. Those with homozygous G170R variants may have milder disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

Rare variants in the sodium-dependent phosphate transporter gene SLC34A3 explain missing heritability of urinary stone disease.

Urinary stone disease (USD) is a major health burden affecting over 10% of the United Kingdom population. While stone disease is associated with lifestyle, genetic factors also strongly contribute. Common genetic variants at multiple loci from genome-wide association studies account for 5% of the estimated 45% heritability of the disorder. Here, we investigated the extent to which rare genetic variation contributes to the unexplained heritability of USD. Among participants of the United Kingdom 100,000-genome project, 374 unrelated individuals were identified and assigned diagnostic codes indicative of USD. Whole genome gene-based rare variant testing and polygenic risk scoring against a control population of 24,930 ancestry-matched controls was performed. We observed (and replicated in an independent dataset) exome-wide significant enrichment of monoallelic rare, predicted damaging variants in the SLC34A3 gene for a sodium-dependent phosphate transporter that were present in 5% cases compared with 1.6% of controls. This gene was previously associated with autosomal recessive disease. The effect on USD risk of having a qualifying SLC34A3 variant was greater than that of a standard deviation increase in polygenic risk derived from GWAS. Addition of the rare qualifying variants in SLC34A3 to a linear model including polygenic score increased the liability-adjusted heritability from 5.1% to 14.2% in the discovery cohort. We conclude that rare variants in SLC34A3 represent an important genetic risk factor for USD, with effect size intermediate between the fully penetrant rare variants linked with Mendelian disorders and common variants associated with USD. Thus, our findings explain some of the heritability unexplained by prior common variant genome-wide association studies.

Patient compliance to dietary recommendations: tips and tricks to improve compliance rates.

Urinary stone disease continues to be a public health problem with growing incidence and recurrences. Recurrence is nearly detected in 50% of the patients within 5 years after the first episode. However, stone recurrence rates can be reduced to a certain extent. The American Urological Association (AUA) and the European Urological Association (EAU) guidelines advice dietary, fluid intake, and medical treatment to prevent or minimize stone recurrence. However, studies have shown that compliance to dietary and fluid intake recommendations is low. Beside this, nutritional evaluation of the patients is sufficient. Using food frequency questionnaires (FFQs), 24 h recall methods (short, individual-oriented, and easily applicable) or mobile apps can be used. In addition, cooperation with registered dietitians (RD) and planning tailored dietary programmes may have positive effect on compliance. Providers who give dietary advices should improve their knowledge about the topic and communication skills to create a patient-provider trust relationship. Simplifying the advices (shorter lists, applicable advices), spending more time, and giving education until being sure for patients' understanding with regular remindings may improve adherence. Moreover, patients increased awareness and knowledge about dietary advices are beneficial. Smart devices for fluid uptake or urine pH monitoring, mobile apps or web-based portals, and telemedicine applications can be used to maintain the compliance on dietary advices. Compliance with dietary modifications and fluid intake recommendations can be well achieved by individualized evaluation/close follow-up and the elimination of the problems limiting the patient compliance.

Stone diet and dietary change: understanding determinants for dietary change behaviour in patients following urinary stones.

BACKGROUND: Dietary habit is one of the most important methods to prevent and treat urinary stones. However, only limited evidence of the experiences of dietary management among urinary stone patients in Malaysia is available. This study aimed to explore participants' current dietary practices after the diagnosis of urinary stones and to identify the factors that facilitate their dietary changes. METHODS: A qualitative study with purposive sampling was conducted using face-to-face semistructured interviews. A total of 20 participants from a tertiary general hospital in Kuantan, Malaysia, were recruited in this study. Data were analysed using framework analysis. RESULTS: Two themes emerged from the analysis. The first theme explained the changes in the dietary practice of the participants postdiagnosis. The second theme revealed that the participants' dietary changes were greatly influenced by personal factors and external support from professionals, family and peers. CONCLUSIONS: Urinary stone patients highlighted the fear of complications, self-determination and knowledge of nutrition as the main drivers of their dietary change postdiagnosis. Emphasising proper nutritional care by assessing and evaluating dietary self-management among patients can facilitate effective self-care in stone prevention management.

[Obstructive uropathia in pregnant women: results of treatment depending on the etiopatogenetic factor of development].

Actuality. The development of renal colic in pregnant women is one of the most common reasons for visiting a hospital that is not associated with obstetric pathology. Given the pharmacological and diagnostic limitations during gestation, the problem of expanding the renal cavitary system in pregnant women, as well as the choice of treatment tactics, remains a difficult clinical task. MATERIALS AND METHODS: The study group included 537 patients with obstructive uropathy with a gestation period of 5 to 36 weeks, who were hospitalized from January 2018 to January 2022 at the GBUZ GKB named after. S.S. Yudina DZM. Depending on the etiopathogenetic obstructive uropathy, the patients were divided into 3 groups: group I - 201 (37.4%) patients with gestational pyelonephritis (the presence of a systemic inflammatory response syndrome) and expansion of the renal cavitary system without confirming the diagnosis of urolithiasis; group II - 216 (40.2%) patients with renal colic (presence of pain without signs of a systemic inflammatory reaction) and enlargement of the renal cavitary system not associated with urolithiasis; group III - 120 (22.4%) pregnant women with an expansion of the cavitary system of the kidney caused by urolithiasis, both with and without signs of a systemic inflammatory reaction. Age, body mass index and previous number of pregnancies in all groups did not differ. The mean age of the patients in the three groups was 26.1 years, with a mean gestational age of 20.8 weeks. In 433 (80.6%) patients, pain was observed in the lumbar region on the right, in 83 (15.5%) - on the left, the bilateral nature of the process - in 21 (3.9%) patients. RESULTS: In group I, despite ongoing conservative therapy, 129 (64.2%) pregnant women received an internal ureteral stent. After 2-4 weeks of follow-up, the ureteral stent was removed in all patients. As a result, a short-term drainage method (up to 4 weeks) was effective in 90.1% of pregnant women, and in 13 (9.9%) patients, it was necessary to re-insert the stent, followed by a routine replacement of the drain every month. Considering the pain syndrome among patients of group II, drainage was performed in 80 (37%) pregnant women. Routine stent replacement was required in 2 (2.3%) patients. In group III, the location of the calculus in the pyelocaliceal system was in 28 (23.3%) patients, in the ureter - in 92 (76.7%) patients. Independent passage of the calculus was noted in 8 (6.7%) pregnant women, ureteroscopy without prior stenting was performed in 31 (25.8%) pregnant women with ureteral calculus. The remaining 81 (67.5%) pregnant women underwent stent placement at the first stage. When the stone was localized in the ureter, 32 (22.7%) patients underwent contact laser ureterolithotripsy and 21 (17.5%) patients underwent ureterolithoextraction. When a stone was located in the kidney, 28 (23.3%) pregnant women underwent pyelocalicolithotripsy. Achievement of the stone-free status was observed in 92.8%. CONCLUSION: Obstructive uropathy in pregnant women requires identification of the cause and a multidisciplinary approach. Long-term drainage of the urinary tract should be avoided and short-term drainage should be preferred. Surgical treatment of urolithiasis, regardless of gestational age, is an effective and safe method.

An empirical study on hospital-based prevention of recurrent urinary stone disease in Germany.

PURPOSE: Urinary stone disease is a common disease with a prevalence of 4.7% in Germany. The incidence increased over the last decades, and recurrence rates are up to 50% in the first 5 years after diagnosis. Adequate preventive measures can avoid up to 46% of stone recurrences. These numbers outline the importance of prevention. Especially among high-risk stone formers, specific diagnostics and measures are required. Published data indicate the divergence between the importance of prevention and its implementation in everyday clinical practice. This is the first survey among German urological departments highlighting medical care concerning the prevention of recurrent urinary stone disease, identifying challenges and providing recommendations for improvements. METHODS: Two hundred and seventy urological hospital departments in Germany were anonymously surveyed about measurements to prevent recurrent stone disease. The questionnaire comprised 23 items dealing with diagnostics, counselling, knowledge among doctors concerning preventive measures and difficulties in preventing recurrent urinary stone disease. RESULTS: Sixty-three urological departments (23.8%) answered the survey. The majority perform stone analysis at first and repeat events. Most patients with urinary stone disease receive general advice on preventive measures during their hospitalization. General recommendations focus on fluid intake and lifestyle changes. However, specific diets are infrequently recommended by inpatient urologists. Diagnostics to identify high-risk stone formers are mostly insufficient, and guideline-compliant urine tests are uncommon. CONCLUSION: The quality of secondary prevention needs to improve considerably. The focus should be put on identifying high-risk stone formers and offering those patients specific counselling. Furthermore, general advice on dietary recommendations should be extended.

Quality of life impact and recovery after ureteroscopy and stent insertion: insights from daily surveys in STENTS.

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains. METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30. RESULTS: The median age was 44 years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5 mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2 days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability. CONCLUSIONS: This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients' experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS.

A nationwide registry for recurrent urolithiasis in the upper urinary tract - The RECUR study protocol.

BACKGROUND: Urinary stone disease is a widespread disease with tremendous impact on those affected and on societies around the globe. Nevertheless, clinical and health care research in this area seem to lag far behind cardiovascular diseases or cancer. This may be due to the lack of an immediate deadly threat from the disease and therefore less public and professional interest. However, the patients suffer from recurring, sometimes intense pain and often must be treated in hospital. Long-term morbidity includes doubled rates of chronic kidney disease and arterial hypertension after at least one stone-related event. Observational studies, more specifically, registries and other electronic data sets have been proposed as a means of filling critical gaps in evidence. We propose a nationwide digital and fully automated registry as part of the German Ministry for Education and Research (BMBF) call for the "establishment of model registries". METHODS: RECUR builds on the technical infrastructure of Germany's Medical Informatics Initiative. Local data integration centres (DIC) of participating medical universities will collect pseudonymized and harmonized data from respective hospital information systems. In addition to their clinical data, participants will provide patient reported outcomes using a mobile patient app. Scientific data exploration includes queries and analysis of federated data from DICs of eleven participating sites. All primary patient data will remain at the participating sites at all times. With comprehensive data from this longitudinal registry, we will be able to describe the disease burden, to determine and validate risk factors, and to evaluate treatments. Implementation and operation of the RECUR registry will be funded by the BMBF for five years. Subsequently, the registry is to be continued by the German Society of Urology without significant costs for study personnel. DISCUSSION: The proposed registry will substantially improve the structural and procedural framework for patients with recurrent urolithiasis. This includes advanced diagnostic algorithms and treatment pathways. The registry will help us identify those patients who will most benefit from specific interventions to prevent recurrences. The RECUR study protocol and the registry's technical architecture including full digitalization and automation of almost all registry-associated proceedings can be transferred to future registries. TRIAL REGISTRATION: This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923 , date of registration January, 11th 2022.

[Functional state of kidneys and cardiovascular risk in patients with urolithiasis in an outpatient setting].

AIM: To analyze the functional state of the kidneys and vascular stiffness in patients with urinary stone disease in an outpatient setting. MATERIAL AND METHODS: A total of 110 patients with urinary stone disease aged 17-72 years were included in the study. The stone size was 2,67 (1,90-3,49) mm. A clinical examination included evaluation of vascular stiffness, serum level of creatinine, cystatin C, calcium, phosphorus, sodium, magnesium, uric acid and total cholesterol. The glomerular filtration rate (eGFR) was calculated based on the formulas CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) and MDRD (Modification of Diet in Renal Disease) and Hoek's equations using creatinine and cystatin C, respectively. RESULTS: Most often, urinary stone disease was associated with arterial hypertension (75%), a sedentary lifestyle (66.3%), hypercholesterolemia (53.6%), obesity (47.2%), hyperuricemia (44.5%) and smoking (40.9%). The median and interquartile range of eGFR according to CKD-EPI, MDRD and Hoek's equations was 100.00 (78.00;113.00) ml/min, 96.00 (71.00;106.00) ml/min and 77.65 (61.50; 93.60) ml/min, respectively. The normal GFR was significantly more often detected by the formula CKD-EPI (66.3%) in comparison with the Hoek's equations (52.7%), p<0.05. A decrease in mild GFR was found in 21 (19.0%) patients according to CKD-EPI and 33 (30.0%) according to Hoek's equations (p<0.05). In the subgroup of patients with a mild to moderate decrease in GFR according to the Hoek's equations, stiffness index and resistive index were significantly higher than in the similar subgroup of patients with decrease of GFR measured using the CKD-EPI formula (p<0.05). A negative correlation between GFR calculated using three formulas and Augmentation Index was established. CONCLUSIONS: In patients with urinary stone disease, potential cardiovascular risk factors are very common. The study of serum cystatin C level with calculation of GFR according to Hoek's equations in individuals with urolithiasis allows to evaluate total renal nitrogen excretion, as well as the level of the cardiovascular risk in the early stages of the disease.

Prevention of Urinary Stones With Hydration (PUSH): Design and Rationale of a Clinical Trial.

RATIONALE & OBJECTIVE: Although maintaining high fluid intake is an effective low-risk intervention for the secondary prevention of urinary stone disease, many patients with stones do not increase their fluid intake. STUDY DESIGN: We describe the rationale and design of the Prevention of Urinary Stones With Hydration (PUSH) Study, a randomized trial of a multicomponent behavioral intervention program to increase and maintain high fluid intake. Participants are randomly assigned (1:1 ratio) to the intervention or control arm. The target sample size is 1,642 participants. SETTING & PARTICIPANTS: Adults and adolescents 12 years and older with a symptomatic stone history and low urine volume are eligible. Exclusion criteria include infectious or monogenic causes of urinary stone disease and comorbid conditions precluding increased fluid intake. INTERVENTIONS: All participants receive usual care and a smart water bottle with smartphone application. Participants in the intervention arm receive a fluid intake prescription and an adaptive program of behavioral interventions, including financial incentives, structured problem solving, and other automated adherence interventions. Control arm participants receive guideline-based fluid instructions. OUTCOMES: The primary end point is recurrence of a symptomatic stone during 24 months of follow-up. Secondary end points include changes in radiographic stone burden, 24-hour urine output, and urinary symptoms. LIMITATIONS: Periodic 24-hour urine volumes may not fully reflect daily behavior. CONCLUSIONS: With its highly novel features, the PUSH Study will address an important health care problem. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03244189.

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers.

BACKGROUNDS: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs). METHODS: Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. RESULTS: Urine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies. CONCLUSIONS: Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

[Bilateral simultaneous retrograde intrarenal surgery].

Bilateral nephrolithiasis is one of the most prevalent and severe form of urinary stone disease, that is usually linked with endocrinological disorders. These patients are quite often treated in our clinic. A clinical case of patient with bilateral nephrolithiasis who undergone to bilateral simultaneous retrograde intrarenal surgery is presented.

[Adjustment of urine PH as effective tool for successful metaphylaxis of urinary stone disease. phytotherapy].

Urinary stone disease constitutes significant burden for healthcare system worldwide. Metaphylaxis after removal or spontaneous passage of urinary stone may be an effective measure for the prevention of recurrent stone episodes. An adjustment of urine pH, based on the type of urinary stone plays a key role in the metaphylaxis of urolithiasis. The use of combined preparations based on herbal plants, which has antioxidant, anti-inflammatory, antimicrobial activity and diuretic effect, and also affects pH level of urine without impairment of the body microbiome, is very promising for the metaphylaxis of urinary stone disease.

[Possibilities of using dietary supplements with antioxidant properties in urinary stone disease].

INTRODUCTION: Dietary supplements are successfully used in many fields of medicine, including urology. In particular, urologists often prescribe dietary supplements for patients with urolithiasis. AIM: to study an influence of dietary supplements Nefradoz on the metabolism of the main stone-forming substances and inhibitors of stone formation in patients with urolithiasis. INTRODUCTION: Dietary supplements are successfully used in many fields of medicine, including urology. In particular, urologists often prescribe dietary supplements for patients with urolithiasis. AIM: to study an influence of dietary supplements Nefradoz on the metabolism of the main stone-forming substances and inhibitors of stone formation in patients with urolithiasis. MATERIALS AND METHODS: A total of 60 patients with urinary stone diseases were included in a single-center prospective randomized study. All patients were divided into 2 groups of 30 people, depending on the treatment. In the main group, patients followed standard diet, received general recommendations and dietary supplements Nefradoz for 28-30 days, 1 capsule (150 mg) 2 times a day with meals. In the control group, patients received only general recommendations and followed standard diet therapy for 28-30 days. The blood biochemical profile and 24-hour urine analysis were evaluated, as well as a urinalysis was performed on daily basis. RESULTS: In patients receiving Nefradoz, urinary uric acid excretion increased by 0.9 mmol/day. It must be emphasized that an increase in uric acid excretion did not exceed the upper normal limit. A tendency towards an increase in urine excretion of sodium (by 54 mmol / day), magnesium (by 1 mmol / day) and citrates (by 0.6 mmol / day) was also found. The analysis of urinalysis showed that in the main group, urine specific gravity was lower than in the control group. Higher urine pH in the main group compared to the control group was also shown. The severity of hematuria with the use of Nefradoz was almost two times lower than in patients who did not receive dietary supplement. CONCLUSION: Considering our data on the ability of dietary supplement Nefradoz to increase the concentration of main inhibitors of stone formation (magnesium and citrates), Nefradoz can be recommended for patients with urinary stone diseases, especially with concomitant hypomagnesuria and hypocitraturia.

[An influence of herbal plant based on the combination of natural terpenes, vitamin and essential oil on the spontaneous stone passage after extracorporeal shock-wave lithotripsy].

INTRODUCTION: There are more than 20 drugs, that are widely used as medical expulsive therapy after extracorporeal shock wave lithotripsy (ESWL). Herbal plants are actively used along with the drug therapy in order to improve the efficiency of the treatment. PURPOSE OF THE STUDY: to evaluate the efficiency of the drug "Renotinex" in patients with kidney stones, as medical expulsive therapy. MATERIALS AND METHODS: A total of 41 patients with kidney stones who undergone ESWL were included in the study. Patients were divided into two groups of 21 patients. In the main group, patients received the dietary supplement "Renotinex" 2 capsules 2 times a day for 1 month, along with standard medical expulsive therapy (NSAIDs [Diclofenac suppositories 50 mg in case of pain] + alpha blockers [Tamsulosin 0.4 mg in the morning for 1 month). The efficiency of treatment was evaluated after 2 and 4 weeks by means of ultrasound and x-ray. A presence and mean size of the stone and dilatation of the collecting system were assessed. In addition, complete blood count (hemoglobin, level of red blood cells and white blood cells), as well as urinalysis (microhematuria and leukocyturia) were performed. For statistical analysis, Student's criterion and the Fishers method were used. RESULTS: After 2 weeks of treatment, a decrease in the hemoglobin level, number of leukocytes and erythrocytes in urine, as well as a significant decrease in pelvis size and the average size of the urinary stone were seen in the main group. In the control group, there was also a slight decrease in the hemoglobin and a significant increase in the grade of leukocyturia and microhematuria. After 4 weeks, significant intergroup differences were documented in the level of microhematuria, pelvis size and the presence of stone in the collecting system, as confirmed by ultrasound and X-ray study. Stone-free rate in the main group was 47.6%, compared to 20% in the control group. CONCLUSION: Medical expulsive therapy in combination with dietary supplements "Renotinex" after ESWL is more efficient than standard medical expulsive therapy (NSAIDs and -blockers) as monotherapy.

[Characteristics and efficiency of extracorporeal shock wave lithotripsy in children using ultrasound guidance].

INTRODUCTION: The aim of the study was to retrospectively evaluate the efficiency of extracorporeal shock wave lithotripsy (ESWL) with ultrasound guidance and the results of treatment of children with urolithiasis, of different age groups depending on the stone location and size. MATERIALS AND METHODS: A total of 135 children and adolescents, aged from 1 to 18 years treated by ESWL at IZMIRLIAN Medical Center from 2005 to 2016 were enrolled in this study. Number, size and location of stones were evaluated. A total of 153 ESWL sessions were performed, including two sessions in 9 cases, three sessions in 1 case, and four sessions in 2 cases. Intra- and posttreatment stone fragmentation rate, number of ESWL sessions, shock-wave pulses per session, stone-free rate, and number of ancillary procedures depending on the stone location and size as well as radiation exposure were evaluated. Follow-up observation was performed after 14, 30 and 90 days. RESULTS: In most cases, there was a good stone fragmentation after ESWL. From 200 to 3000 low-energy pulses with a frequency 1-2 Hz and power of 30-50 units on Modulith SLK scale were delivered. Number of shock-wave pulses up to 1000, 2000 and 3000 was sufficient in 18.3%, 51.9% and 26.8% cases, respectively. SFR in children aged 1-5 years was 95.2%, compared to 100%, 100% and 83.7% in patients in the 6-10, 11-15 and 16-18 year age groups, respectively. Complete stone clearance was achieved in patients of 1-5 and 6-10 years after two weeks. In only one patient in the 11- to 15-year age group, all fragments passed after two weeks, while in 4 adolescents in the 16- 18-year age group SFR was achieved after more than 3 months. In addition, in other 3 patients in this age group ESWL was unsuccessful. CONCLUSION: Our results suggest high efficiency of ESWL under ultrasound guidance in children and adolescents. Absence of X-ray exposure, minimal complication rate, non-invasiveness and high efficiency allow to consider ESWL as a method of choice for the treatment of urolithiasis in children and adolescents.

[Multimodal approach to the treatment of staghorn stones in modern clinic].

This lecture is dedicated to increasing stone free rate (SFR) in patients with staghorn renal stones by using a multimodal approach. Percutaneous nephrolithotomy (PCNL) is the "gold standard" for the treatment of this group of patients. Depending on a stone size and complexity, SFR for PCNL varies from 55 to 98%. Due to low SFR, which is a main criterion for the effective procedure, various approaches currently are being suggested. In this lecture, we highlighted the following approaches: multi-access PCNL, a use of a ureteroscope in case of antegrade stone migration, a use of flexible instruments, ureterorenoscopy in combination with PCNL. Various lithotripsy techniques are briefly described. The advantage of ultrasound-guided puncture of the kidney is also discussed.

[Interdisciplinary approach for prevention of recurrent urinary stone disease].

Urolithiasis is a multifactorial metabolic disease caused by the interaction of genetic, environmental factors and is directly related to lifestyle. Multiple factors influencing the initiation of stone formation and the growth of urinary crystals are presented in the article. Based on the available data, an involvement of various specialists, including urologists, geneticists, physician office laboratory, radiation diagnostics specialists, nutritionists, endocrinologists, immunologists, physiotherapy and balneotherapy specialists, general practitioner, is necessary for effective treatment of patients with kidney stones.

[The use of herbal supplement Renotinex based on terpenes for the complex treatment of patients with urinary stone disease].

AIM: to evaluate the efficiency of dietary supplements Renotinex for the complex treatment of patients with urinary stone disease who undergone to extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: a total of 60 patients with uncomplicated form of the urinary stone disease with the first stone episode (of size up to 1 cm) were evaluated. Patients were divided into two groups of 30 people and treated by ESWL. In the first group, patients additionally received Renotinex. In the second group, standard complex therapy (antispasmodics, analgesics, non-steroidal anti-inflammatory drugs) was prescribed. The urinary level of 2-microglobulin and serum level of tocopherol were considered as markers of damage and inflammation. Pain intensity was assessed using visual analogue scale. Follow-up studies were carried out on the 1st, 7th and 14th day of therapy. Duration of treatment and follow-up was 1 month. The average number of ESWL sessions was 2.6 in both groups. RESULTS: according to the study, it was established that components of Renotinex had antiseptic, antispasmodic, anti-inflammatory effects on the genitourinary system, enhancing renal blood flow and decreasing the permeability of the kidney capillaries. In addition, Renotinex has diuretic effect and nephroprotective effect, and improves renal function, alleviating aggressive therapeutic influence of ESWL. Antioxidant and nephroprotective effect are among the main mechanisms of action of Renotinex. CONCLUSION: In patients who received Renotinex as dietary supplements fragments after ESWL pass twice as fast, while in patients who did not receive Renotinex, there was more pronounced damage to the kidney parenchyma diagnosed by urine level of 2-microglobulin. The serum concentration of vitamin E increases, while taking Renotinex, which may prevent the peroxidation of polyunsaturated lipids in cell membranes and enhances the nephroprotective effect of Renotinex.

Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls.

Randall's plaque (RP; subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (<5% papillary surface area) and high (≥5% papillary surface area) percentages of RP and a group of nonstone formers. RPs were quantitated via videotaping and image processing in consecutive CSFs undergoing percutaneous surgery for stone removal. Urinary EVs derived from cells of different nephron segments of CSFs (n = 64) and nonstone formers (n = 40) were quantified in biobanked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared with nonstone former controls (P < 0.05) but did not differ statistically between CSFs with low and high RPs. The number of EVs associated with osteopontin did not differ between any groups. Thus, EVs carrying MCP-1 and NGAL may directly or indirectly contribute to stone pathogenesis as evidenced by the lower of these populations of EVs in stone formers compared with nonstone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.