Metabolomics analysis of the serum from children with urolithiasis using UPLC-MS.

Pediatric urolithiasis is a common urologic disease with high morbidity and recurrence rates. Recent studies have shown that metabolic dysfunction plays a vital role in the pathogenesis of urolithiasis, especially in children, but the specific mechanism is still unclear. Metabolomics is an ideal technology for exploring the mechanism of metabolic disorders in urolithiasis. In the present study, a serum metabolomics based on ultra-performance liquid chromatography mass spectrometry was performed. A total of 50 children subjects were recruited for the study, including 30 patients with kidney stones and 20 normal controls (NCs). Principal component analysis and orthogonal partial least-squares determinant analysis were carried, and 40 metabolites were found to be significantly altered in patients with kidney stones, mainly involving retinol metabolism, steroid hormone biosynthesis, and porphyrin and chlorophyll metabolism. The kidney stone group appeared to have a lower serum level of bilirubin, but a relative higher level of retinal, all-transretinoic acid, progesterone, and prostaglandin E2 compared with those of the NC group. All the findings suggest that patients with urolithiasis have several metabolic characteristics, which are related to stone formation or compensation. These metabolites and pathways are very likely associated with development of kidney stones and should be considered as potential novel targets for treatment and prevention.

Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats.

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)-regular diet with a FR < 3%; F10 (n = 6)-regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)-60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.

Effect of Fat-Soluble Vitamins A, D, E and K on Vitamin Status and Metabolic Profile in Patients with Fat Malabsorption with and without Urolithiasis.

Patients with intestinal fat malabsorption and urolithiasis are particularly at risk of acquiring fat-soluble vitamin deficiencies. The aim of the study was to evaluate the vitamin status and metabolic profile before and after the supplementation of fat-soluble vitamins A, D, E and K (ADEK) in 51 patients with fat malabsorption due to different intestinal diseases both with and without urolithiasis. Anthropometric, clinical, blood and 24-h urinary parameters and dietary intake were assessed at baseline and after ADEK supplementation for two weeks. At baseline, serum aspartate aminotransferase (AST) activity was higher in stone formers (SF; n = 10) than in non-stone formers (NSF; n = 41) but decreased significantly in SF patients after supplementation. Plasma vitamin D and E concentrations increased significantly and to a similar extent in both groups during intervention. While plasma vitamin D concentrations did not differ between the groups, vitamin E concentrations were significantly lower in the SF group than the NSF group before and after ADEK supplementation. Although vitamin D concentration increased significantly in both groups, urinary calcium excretion was not affected by ADEK supplementation. The decline in plasma AST activity in patients with urolithiasis might be attributed to the supplementation of ADEK. Patients with fat malabsorption may benefit from the supplementation of fat-soluble vitamins ADEK.

The Increased Risk of Complicated Ureteral Stones in the Era of COVID-19 Pandemic.

Background: Ureteral stone disease may be an emergent condition if the appropriate management is not performed in a timely manner. As the coronavirus disease 2019 (COVID-19) continues to spread globally, isolation and restriction orders taken by the governments have become the cores to control the pandemic. In this study, we, therefore, aimed to investigate the ureteral stone presentations in a high-volume university hospital during the COVID-19 restriction order period. Materials and Methods: The data of 149 patients who were hospitalized due to ureteral stone both during the COVID-19 pandemic restriction period and the corresponding period (non-COVID-19) of the previous year were collected and analyzed retrospectively. Unpaired Student's t-test was used to compare continuous variables. The categorical data were assessed using Chi-square and Fisher's exact tests. Results: Of 149 patients, 35 were hospitalized in the COVID-19 restrictions period. While the mean age and the stone characteristics of the two groups did not differ significantly, serum creatinine levels (1.9 ± 1.85 vs 1.15 ± 0.64) and the white blood cell counts (12.45 ± 6.54 vs 8.21 ± 4.15) at hospital admission were significantly higher in the COVID-19 restrictions group (p = 0.034 and p = 0.005, respectively). According to the priority classification recommendations of the European Urology Guidelines Office Rapid Reaction Group for urolithiasis applicable during the COVID-19 pandemic, a significant difference was observed between the two periods (X2 = 9.907, p = 0.019). In particular, the rate of emergency cases was found more than threefold in the COVID-19 period. Although there was no significant difference in terms of the grade of hydronephrosis at hospital admission between the two groups, the rates of grade 3 and 4 hydronephrosis were higher in the COVID-period group (1.8- and 3.3-fold, respectively). Conclusion: The rate of complicated ureteral stone disease significantly increased during the COVID-19 restrictions period. Urologists should prioritize the patients most in need of urgent care during COVID-19-like biosocial crisis.

Preliminary analysis of serum electrolytes and body mass index in patients with and without urolithiasis.

OBJECTIVES: To compare body mass index (BMI); serum parameters; and urine parameters between patients with and without urolithiasis. METHODS: Data from 1164 patients admitted to our Department of Urology from January 2011 to July 2013 were retrospectively reviewed; 714 patients (age, 5-87 years; male:female ratio, 1.8:1) exhibited urolithiasis, and 450 patients (age, 12-94 years; male:female ratio, 3.8:1) did not. Blood and urine were collected from patients the morning after hospital admission. Serum and urine parameters were checked by an automatic biochemistry analyzer. Statistical analysis included the Mann-Whitney U test and binary logistic regression. RESULTS: Serum sodium, potassium, chloride, calcium, phosphorus, and carbon dioxide combining power significantly differed between groups. In male patients, serum sodium, calcium, and phosphorus levels were higher in the urolithiasis group, whereas serum potassium and urine pH levels were lower. In female patients, serum sodium was higher in the urolithiasis group. BMI was higher in the urolithiasis group in all patients, male and female. Respective ß-values of serum sodium and BMI in male patients were 0.077 and 0.084; in female patients, these values were 0.119 and 0.102. CONCLUSIONS: Changes in serum sodium and BMI may be involved in the pathogenesis and treatment of urolithiasis.

[Application of serum amino acid profile in urolithiasis based on gas chromatography-mass spectrometry].

An overall workflow based on gas chromatography-mass spectrometry (GC-MS) was established for the analysis of the serum amino acid profile between urolithiasis patients (n=80, age (46.82±13.39) years) and healthy controls (n=37, age (43.46±12.79) years). The raw data from GC-MS analysis were processed by multivariate statistical methods to build the model. Following this, student's t-test and logistic regression were performed and receiver operator characteristic (ROC) curve was plotted to identify the potential biomarkers. Good linearities were observed for the target amino acids, with correlation coefficients (R2) greater than 0.9985. The limits of detection (LODs) were 0.1-4.0 µmol/L. The results indicated a significant discrimination between the urolithiasis and control groups. Five significantly differentially expressed amino acids (variable importance in projection (VIP)>1 and p<0.05) were found to provide the scientific evidence for the early diagnosis of urolithiasis, while the sensitivity of the integrated five differential amino acids was up to 97.3%. In particular, the area under the curve (AUC) of serine reached 0.819, which suggested a great clinical screening value.

[Specific features of the immune status and blebbing of the plasmatic membrane of lymphocytes patients with urolithiasis complicated by the pyelonephritis].

INTRODUCTION: According to the epidemiological studies, prevalence of urolithiasis is nearly 10% worldwide. The course of the disease is often complicated by the development of pyelonephritis, the pathogenesis of which is rather multifactorial. Along with urinary tract obstruction, increasing virulence of microorganisms and immune insufficiency in patients also plays a major role. AIM: To define specific features of immune insufficiency in patients who develop pyelonephritis as a complication of urolithiasis. MATERIALS AND METHODS: A total of 150 patients with urolithiasis complicated by pyelonephritis were prospectively enrolled into our study in order to develop a novel method. All patients were divided into two clinical groups. Group I consisted of 75 patients with urolithiasis complicated by serous pyelonephritis and Group II included 75 patients with urolithiasis complicated by purulent pyelonephritis. In all patients an evaluation of the immune status with a determination of CD3, CD4, CD8, CD16, CD19 level and phagocyte activity of immune system was carried out. The state of lymphocytes plasmatic membrane was evaluated by phase contrast microscopy. RESULTS: It is established that development of pyelonephritis in patients with urolithiasis is accompanied by a lymphopenia, the decrease in relative contents T-helpers, natural killers, as well as a decrease in the immuno-regulatory index and an increase in indicators of terminal and total lymphocytes blebbing. The most pronounced changes were noted in purulent pyelonephritis, where suppressed immune status was confirmed by the high level of lymphocyte with terminal blebbing state.

Urokinase alteration and its correlation with disease severity and oxidative/nitrosative stress in buffalo calves with obstructive urolithiasis.

The present study was aimed to understand the development of bovine urolithiasis through measuring oxidative/nitrosative, cortisol and urokinase status and their relationship with disease severity. The cases of buffalo calves with obstructive urolithiasis were selected based on clinical signs, ultrasonography and laboratory examination of blood and urine (creatinine, urea nitrogen). Total 35 urolithiatic buffalo calves (urolithiatic controls) and 6 healthy calves (healthy controls) were used for study. Further, calves of urolithiatic control were sub-divided into two groups based on disease severity: mild (n = 10) and severe (n = 25) form. Oxidative/nitrosative stress were evaluated based on serum malondialdehyde (MDA), glutathione-S-transferase (GST), nitric oxide (NO) parameters. Serum cortisol was evaluated to measure stress hormone status. Serum and urine urokinase were measured and its relationship with disease severity and oxidative/nitrosative stress were established. Obstructive urolithiasis resulted in significant (p < .05) increase in biochemical parameters (creatinine, urea nitrogen), oxidant/antioxidant imbalance (increased MDA, and increased GST), nitrosative stress (increased nitric oxide), upregulated stress hormone (cortisol) in serum and elevated urokinase in serum and urine (p < .05) as compared to healthy controls. In non-parametric Kendall rank correlation (p < .01), a positive correlation was established between urokinase level and disease severity (urolithiasis). It is concluded that in bovine obstructive urolithiasis, increased oxidative/nitrosative stress, cortisol and urokinase play a significant role. The urokinase can help to understand pathophysiology of bovine urolithiasis because of having positive correlation with disease severity (urolithiasis) and stress markers.

The association between a non-invasive hepatic fibrosis score and urolithiasis among non-alcoholic fatty liver disease (NAFLD) patients in China: a cross-sectional study.

OBJECTIVE: Mounting data now support a strong link between the presence of non-alcoholic fatty liver disease (NAFLD) and an increased risk of urolithiasis. However, little is known on the association between hepatic fibrosis and the risk of urolithiasis among NAFLD patients. Therefore, this study aimed to investigate the prevalence of urolithiasis among NAFLD patients and determine whether the Fibrosis-4 (FIB-4) score, a surrogate marker of hepatic fibrosis, is associated with urolithiasis among NAFLD patients. DESIGN: Cross-sectional studies. SETTING: China. METHODS: A total of 2058 adult patients with NAFLD were included in this study. Logistic regression analysis was used to detect the association between FIB-4 score and urolithiasis. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of FIB-4 score for the detection of urolithiasis among NAFLD patients. RESULTS: 200 (9.7%) individuals had ultrasonography-diagnosed urolithiasis among 2058 NAFLD patients. FIB-4 score (OR=1.58; 95% CI 1.06 to 2.31), age (OR=1.11; 95% CI 1.08 to 1.13), obesity (OR=3.16; 95% CI 2.29 to 4.39) and hyperuricemia (OR=3.79; 95% CI 2.67 to 5.36) were independent factors associated with urolithiasis among NAFLD patients. Moreover, a novel algorithm including multiple variables (FIB-4 score, age, obesity and hyperuricemia) showed an area under a ROC curve of 0.813 (95% CI 0.795 to 0.829) for identifying urolithiasis among NAFLD patients. The optimal cut-off value of > -2.23 for the multivariate model provides a sensitivity of 76% and a specificity of 74% for predicting urolithiasis among NAFLD patients. CONCLUSION: Urolithiasis among NAFLD patients is associated with FIB-4 score. Further, a novel algorithm based on FIB-4 score could serve as a useful tool for identifying individuals with a higher risk of urolithiasis among NAFLD patients, although prospective cohort studies are still needed in the future.

The severity of NAFLD is associated with the risk of urolithiasis.

BACKGROUND AND AIMS: Population-based studies suggest a strong association between the presence of nonalcoholic fatty liver disease (NAFLD) and an increased risk of urolithiasis. However, the available information on the association of the severity of NAFLD with urolithiasis is limited. We hypothesised a link between the severity of NAFLD and the risk of urolithiasis. METHODS: We recruited 1527 adult patients with NAFLD who completed a comprehensive health checkup. The severity of NAFLD was measured with AST to platelet ratio (APRI score). Logistic regression analysis was used to detect the association of APRI score with the risk of urolithiasis among NAFLD patients. ROC analysis was used to assess the diagnostic value of APRI score for identifying urolithiasis among NAFLD patients. RESULTS: Multivariate analysis showed three independent risk factors for urolithiasis: obesity (OR 2.06 95%CI 1.35-3.13), APRI score (OR 1.29 95%CI 1.05-1.59), and serum uric acid (OR 1.07 95%CI 1.05-1.09), suggesting an independent association between the noninvasive staging of liver fibrosis and the risk of urolithiasis in NAFLD patients. A three-variable model (obesity, APRI score, and serum uric acid) with an AUROC of 0.73 (95% CI 0.70-0.75) was significant in identifying urolithiasis. CONCLUSIONS: The severity of NAFLD is associated with the risk of urolithiasis among NAFLD patients. Moreover, a three-variable model (obesity, APRI score, serum uric acid) could serve as a useful tool for identifying individuals at high risk for urolithiasis in these patients.

Association between blood lipid profile and urolithiasis: A systematic review and meta-analysis of observational studies.

The objective of this study was to pool individual studies regarding the association of blood lipid profiles with urolithiasis to carry out a systematic review and meta-analysis. We searched MEDLINE, PubMed, Embase and Cochrane Library to identify the relevant studies up to November 2017. Studies that met all inclusion criteria were chosen, and a pooled analysis of the odds ratio between urolithiasis and dyslipidemia traits was calculated. A total of 11 observational studies (seven cross-sectional, three cohort, one case-control) with a total of 282 479 participants were examined. The overall pooled analysis of eight studies showed that high triglyceride was associated with increased estimated risk of urolithiasis (odds ratio 1.287, 95% CI 1.073-1.544; P = 0.007). Estimates of the total effect size were consistent in the sensitivity analysis. No evidence of publication bias was detected. The overall pooled analysis of nine studies showed low high-density lipoprotein was weakly associated with increased estimated risk of urolithiasis (odds ratio 1.171, 95% CI 1.010-1.358; P = 0.032). The sensitivity analysis showed conflicting results. No evidence of publication bias was detected. Three studies on the association between any dyslipidemia traits and urolithiasis showed a significant association (odds ratio 1.309, 95% CI 1.202-1.425; P < 0.001). The present meta-analysis showed that patients with higher triglyceride and lower high-density lipoprotein had an increased estimated risk of urolithiasis. A triglyceride-urolithiasis association was found to be more coherent and consistent compared with the high-density lipoprotein-urolithiasis association. Although somewhat contradictory results have been found, the meta-analysis is encouraging for evaluating urolithiasis as a systemic disorder. Further well-designed prospective randomized controlled or cohort studies are necessary to better elucidate the causal association of dyslipidemia and urolithiasis.

Heavy Metal Components in Blood and Urinary Stones of Urolithiasis Patients.

Lifestyle, food intake, and exposure to chemicals are potential risk factors for the development of calcium urolithiasis. Pb, Cd, and Hg have been proved to cause renal illness, and urinary tract stones might be caused by exposure to metals. Therefore, this study aimed to measure the concentration of metals in urinary tract stones and blood simultaneously in urolithiasis patients. Moreover, we intended to determine whether urinary tract stones can be regarded as a biomarker of exposure or an effect marker in a population with environmental exposure to metals. Thirty-five urolithiasis patients (case) and 34 healthy inhabitants (control) were recruited in this study. The contents of Pb, Cd, Cr, Cu, Ni, As, Zn, and Hg were determined in urinary stones and blood in the case and control groups. The most abundant metals were Zn and Cu in blood and Zn and Ni in urinary stones. Significantly higher levels of Zn, Ni, and As were found in calcium phosphate stones than in calcium oxalate or uric acid stones. The majority of metals were not present at consistent levels in both blood and urinary stones, except for Zn. Urinary stones might be explained as providing another metabolic pathway for metal contamination. Moreover, as the metals with the highest content in urinary stones were Ni and Zn, and Ni content was very much higher than in other countries, contamination by Ni should be further taken into consideration if there is any serious contamination in Taiwan.

Sporadic primary hyperparathyroidism and stone disease: a comprehensive metabolic evaluation before and after parathyroidectomy.

OBJECTIVES: To characterize the stone risk and the impact of parathyroidectomy on the metabolic profile of patients with primary hyperparathyroidism (PHPT) and urolithiasis. PATIENTS AND METHODS: We analysed the prospectively collected charts of patients treated at our stone clinic between January 2001 and January 2016 searching for patients with PHPT and urolithiasis. Imaging evaluation of the kidneys, bones and parathyroid glands was assessed. We analysed the demographic data, serum and urinary variables before and after parathyroidectomy. We used a paired t-test, Fisher's test, Spearman's test and anova in the statistical analysis. RESULTS: A total of 51 patients were included. The mean patient age was 57.1 ± 12.1 years and 82.4% were women. Before parathyroidectomy, mean calcium and parathyroid hormone (PTH) levels were 11.2 ± 1.0 mg/dL and 331 ± 584 pg/dL, respectively. Hypercalcaemia was present in 84.3% of patients. All eight patients with normal calcium levels had elevated PTH levels. Only two patients did not have PTH above the normal range, although both had elevated calcium levels. The most common urinary disorders were low urinary volume (64.7%), hypercalciuria (60.8%), high urinary pH (41.2%) and hypocitraturia (31.4%). After parathyroidectomy, the number of patients with hypercalcaemia (n = 4; 7.8%), elevated PTH (n = 17; 33.3%) and hypophosphataemia (n = 3; 5.9%) significantly decreased (P < 0.001). The number of urinary abnormalities decreased and there was a reduction in urinary calcium (P < 0.001), pH (P = 0.001) and citrate levels (P = 0.003). CONCLUSION: Individuals with PHPT and nephrolithiasis frequently have elevated baseline PTH and calcium levels. Low volume, hypercalciuria, high urinary pH, and hypocitraturia are the most frequent urinary disorders. Parathyroidectomy is effective in normalizing serum calcium and PTH levels, although other urinary metabolic may persist. Patients should be monitored for the need for citrate supplementation.

Perineal urethrostomy to treat obstructive urolithiasis in a captive hand-raised steenbok (Raphicerus campestris).

The steenbok (Raphicerus campestris) is a small antelope of the family Bovidae native to the African continent. Urolithiasis, the formation of urinary calculi in the urinary tract, can be caused by a variety of factors such as diet, dehydration, infection and anatomical predisposition. Urolithiasis, with uroliths identified as magnesium calcium phosphate carbonate in composition, was diagnosed in a hand-reared 5-month-old steenbok. Perineal urethrostomy was performed as a component of the broad treatment regime that included fluid therapy, antibiotic and anti-inflammatory treatment. However, the animal died 4 days later as a result of systemic hypoxia and energy depletion because of stress and cachexia. The challenges of post-surgical treatment, the importance of positive energy balance in small ruminants under stressful circumstances, as well as the role of diet of hand-reared antelope in predisposition to urolith formation are highlighted.

PREVALENCE AND PREDICTORS OF PRIMARY HYPERPARATHYROIDISM AMONG PATIENTS WITH UROLITHIASIS.

OBJECTIVE: Urolithiasis may be the only presenting manifestation of primary hyperparathyroidism (PHPT), and early detection of PHPT in such patients may prevent future urolithiasis and other PHPT complications. This study was performed to study the prevalence and predictors of PHPT in patients presenting with urolithiasis. METHODS: Consecutive patients presenting with urolithiasis were evaluated for clinical and biochemical manifestations of PHPT with serum and urine calcium (Ca), serum intact parathyroid hormone and 25 (OH) vitamin D. We then compared the clinical and biochemical characteristics of PHPT patients presenting with urolithiasis (group A) and without (group B). RESULTS: During the 3-year study period, 381 patients with urolithiasis were seen with a mean age of 38.5 ± 13.9 years. Nineteen of the 381 (5%) patients had histologically proven PHPT (group A). Four patients in group A (21%) and 8 in group B (2%) had nephrocalcinosis (P<.0001), multiple stones (≥3), calcific pancreatitis, and neuropsychiatric manifestations were more common in group A (P<.0001). Presence of multiple or bilateral stones, and recurrent stone episodes predicted PHPT (odds ratio [OR]: 3.06, confidence interval [CI]: 0.87, 0.7). CONCLUSION: One out of every 20 patients with urolithiasis had PHPT, which is higher than the prevalence of PHPT in general population. The presence of nephrocalcinosis and multiple, bilateral, and recurrent stone disease increased the risk of PHPT among stone formers. ABBREVIATIONS: Ca = calcium; CI = confidence interval; iPTH = intact parathyroid hormone; nPHPT = normocalcemic PHPT; OR = odds ratio; PHPT = primary hyperparathyroidism.

Metabolic Work-up of Patients with Urolithiasis: Indications and Diagnostic Algorithm.

CONTEXT: The incidence of urinary tract stone disease is increasing and the risk of recurrent stone formation is high. Appropriate therapeutic procedures with the aim of counteracting the progress of stone formation are highly desirable. Metabolic work-up is considered essential as a base for optimal design and follow-up of effective recurrence prevention. OBJECTIVE: To scrutinize the current literature with regard to principles of metabolic work-up for this heterogeneous group of patients. EVIDENCE ACQUISITION: Relevant articles in PubMed, guideline documents, consensus reports, and the Cochrane Library published during the past 20 yr were consulted. EVIDENCE SYNTHESIS: Grades of recommendation were used according to the principles applied in the European Association of Urology and American Urological Association guidelines. Medical efforts to prevent recurrent stone formation should be part of the care of patients with urinary tract stone disease (grade of recommendation A). A careful medical history and imaging together with analysis of stone composition, blood, and urine provide the basis for appropriate measures, but the treatment has to be individualized (grade of recommendation D). Whenever possible, stone analysis should be carried out at least once for every patient or each time when a long time has elapsed between two stone episodes because the risk factors explaining stone formation may have changed (clinical principle). The medical history, including information on dietary and drinking habits as well as lifestyle, is necessary for appropriate advice (grade of recommendation C). The medical history, together with imaging and stone composition, is used to estimate the severity of the disease (clinical principle). Identification of specific medical conditions should be supported by blood and/or urine analysis (grade of recommendation B). Pharmacological agents associated with an increased risk of stone formation should be identified (grade of recommendation C). Patients who have formed noncalcium stones should always be given recurrence preventive treatment. Analysis of urine composition for these patients is optional, but might be of value in the follow-up to support decisions on appropriate dosage regimens (grade of recommendation C). For patients with idiopathic calcium stone disease information from 24-h urine samples should be used, although the number of samples to be taken is debated (grade of recommendation C). Information from 24-h urine analysis should be used for selective dietary and drinking advice as well as for selection of the most appropriate pharmacological agent (grade of recommendation B). The treatment effects on the risk of stone formation can be followed by estimates of supersaturation based on urine composition (grade of recommendation C). CONCLUSIONS: It is clear that the metabolic work-up of patients with urinary tract stone disease should be individualized according to stone type and severity of the disease, and that the different therapeutic approaches are closely associated with the availability of therapeutic tools and motivation by the patient. PATIENT SUMMARY: Effective prevention of recurrent stone formation is determined by several factors such as the current and previous stone episodes and surgical procedures, stone composition, medical history, dietary and drinking habits, lifestyle, and ongoing pharmacological therapy. Analysis of blood and urine is an important part of the metabolic evaluation, but how extensive the risk evaluation should be is determined by the type of stone and the severity of the disease.

Emergency Ureteral Stone Treatment Score Predicts Outcomes of Ureteroscopic Intervention in Acute Obstructive Uropathy Secondary to Urolithiasis.

INTRODUCTION: Immediate ureteroscopic treatment for patients presenting to the emergency room with symptomatic ureterolithiasis is more commonly being utilized. Recent reports demonstrate good efficacy for emergency ureteroscopy (URS); however, preoperative predictors of treatment success have not been described. In this study, we report our multicenter experience with emergency URS and identify predictors of successful treatment. We also describe the Emergency Ureteral Stone Treatment (EUST) score, which integrates these predictors and stratifies patients into those that are likely and unlikely to have successful treatment. MATERIALS AND METHODS: Laboratory and radiographic data for all patients who underwent emergency URS for acute symptomatic ureterolithiasis from 2010 to 2015 were reviewed. Statistical difference among parameters for patients who were stone free (SF) and not SF was assessed with the Student's t-test. Cutoff values for significant predictors were determined using sensitivity and specificity analysis. The EUST score was determined based on the number of cutoffs a patient was below. RESULTS: Two hundred two of 247 patients (81.8%) were SF. Two complications (ureteral perforation) occurred. Stone size, duration of symptoms before presentation, and serum white blood count at presentation did not affect SF rates. 95.5% of the treatment failures were attributed to a tight ureter preventing stone access. Patients who received alpha blockers before treatment were more likely to be SF (98.0% vs 55.5%, p < 0.01). Periureteral density (PUD) was lower in SF patients (2.8 HU vs 19.6 HU, p < 0.01), whereas the increase in serum creatinine from baseline (ΔCr) was greater in non-SF patients (0.44 mg/dL vs 0.20 mg/dL, p < 0.01). EUST score of 0, 1, and 2 correlated with SF rates of 20.6%, 81.9%, and 99.2%, respectively. CONCLUSIONS: Combined consideration of PUD and ΔCr with the EUST score can assist in selecting optimal candidates for immediate ureteroscopic management. Administration of alpha blockers before surgery may improve success rates by providing preoperative ureteral dilation.

Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats.

Urolithiasis is a painful disorder in which stones are formed in the kidney, bladder or urethra. There are no proper therapeutic treatments available for kidney stones and people suffering from larger stones have to undergo surgery which has many side effects. A natural remedy with therapeutic effects that can dissipate and remove even the larger stones would eliminate the need of a surgery and the risks associated with it. The flowers of Phlogacanthus thyrsiformis used in culinary recipes in the north eastern India are also widely used as a folklore medicine for the treatment of kidney stones and liver disorders. The aim of this study was to evaluate the prophylactic and therapeutic activity of the aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles against struvite urinary stones and calcium oxalate kidney stones. A kidney stone inhibition study was carried out on struvite stones grown in gel medium and calcium oxalate stones in rat models using an aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles. The aqueous extract of P. thyrsiformis flowers and their biofabricated silver nanoparticles, obtained by a green synthetic method, were used to treat struvite urinary stones in vitro and calcium oxalate kidney stones in vivo. Struvite stones were grown in tubes by gel diffusion technique and were treated with varying concentrations of the extract and its nanoparticles. The size of the struvite stones was monitored for 96h using a travelling microscope. Calcium oxalate stones were induced in male Wistar rats by feeding ethylene glycol-ammonium chloride mixture for 14days. Both, prophylactic and therapeutic activities were evaluated by analyzing the urine, serum and histopathological parameters of the rats. The qualitative screening of water extract unveiled the presence of flavonoids as a major constituent. Both, the extract and the nanoparticles effectively reduced the size of struvite stones in vitro and eliminated calcium oxalate stones in Wistar rats in vivo. The potent therapeutic activity of both extract and silver nanoparticles was observed as compared to preventive activity. Anti-urolithiatic potency can be attributed to the presence of flavonoids.

Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis.

Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)2D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31-16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07-18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, -1.04-2.80; p = 0.37 and WMD, -0.63 ng/mL; 95% CI, -2.72-1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)2D (WMD, 9.41 pg/mL; 95% CI, 0.15-18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, -0.20-5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99-9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14-7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)2D level (WMD, 6.85 pg/mL; 95% CI, -5.00-18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, -3.55-5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)2D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.