Search

Background: Phthalates, ubiquitous in plastics and softening agents, are pervasive in our daily environment. Growing concerns have emerged regarding their potential impact on renal health, particularly due to their propensity to induce oxidative stress. However, the relationship between phthalate exposure and urolithiasis remains poorly understood. This research seeks to explore the connection between phthalate exposure, oxidative stress, and the risk of urolithiasis., Methods: A case-control study involving 285 patients diagnosed with calcium urolithiasis and 594 healthy controls was conducted. Participants completed structured questionnaires and provided urine samples for measuring 10 phthalate metabolites, biomarkers of oxidative stress (malondialdehyde [MDA]) and early renal injury (N-acetyl-beta-D-glucosaminidase [NAG] and albumin/creatinine ratio [ACR]). For subsequent analyses, we utilized distinct categories: the sum of high-molecular-weight phthalate metabolites (∑HMWm), the sum of low-molecular-weight phthalate metabolites (∑LMWm), and the daily intake of di-2-ethylhexyl phthalate (DEHP)(DI_DEHP_5)., Results: Stone patients exhibited significantly elevated urinary biomarkers of oxidative stress (MDA) and early renal injury (NAG and ACR), along with higher levels of 9 out of 10 assessed phthalate metabolites compared to normal controls. Within the study population, significant positive associations were found between almost all individual phthalate metabolites and urinary biomarkers of oxidative stress (MDA) as well as early renal injury (NAG and ACR). Logistic regression further confirmed that elevated phthalate levels, including ∑HMWm, ∑LMWm, and DI_DEHP_5, were uniformly associated with an increased risk of oxidative stress, early renal injury, and urolithiasis after adjusting for confounding factors., Conclusions: Our study uncovers a novel association between phthalate exposure and the risk of urolithiasis, underscoring the heightened risk of kidney injury posed by such exposure. Considering the widespread presence of phthalates, regulatory measures and public health interventions are crucial to mitigate phthalate-related nephrotoxicity, while further large-scale longitudinal research is imperative to validate our initial findings and elucidate the underlying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Urolithiasis is a prevalent urological ailment characterized by increasing prevalence and recurrence rates, resulting in substantial social and economic burden. While men exhibit an incidence rate nearly twice that of women, this gender disparity is gradually diminishing. Nevertheless, the mechanisms underlying this condition remain incompletely elucidated. The identification of the urinary microbiome (urobiome) has provided a fresh perspective on urolithiasis. This study aimed to analyze the urobiome of unilateral stone formers in the renal pelvis and evaluate the variations in microbial diversity and community composition between males and females., Methods: Renal pelvis urine samples were obtained from a cohort of 21 male and 9 female patients and subsequently subjected to taxonomic and functional analysis using 2bRAD sequencing for Microbiome (2bRAD-M). The collected samples were categorized into four distinct groups, namely the stone side of males (SM), stone side of females (SF), non-stone side of males (NSM), and non-stone side of females (NSF)., Results: Through the application of beta diversity analysis, dissimilarity was observed between NSM and NSF. Additionally, NSF exhibited a higher abundance of microbial populations, and a total of 29 distinct species were identified as differentially present between NSM and NSF using LEfSe. Lactobacillus iners, Atopobium deltae, Lawsonella clevelandensis, and Meyerozyma guilliermondii exhibited enrichment in the SF group compared to the SM group. Furthermore, we identified distinct species that differed between the SM and NSM groups, as well as the SF and NSF groups. Besides, we conducted COG annotation and KEGG pathway predictions, revealing significant differences in urobiome function across the different groups., Conclusion: Variations in microbial community composition and predicted functions were observed among the various groups. Future research could potentially leverage the urobiome to personalize urolithiasis treatment based on individual microbial characteristics, taking into account gender-specific differences., (© 2024. The Author(s).)

The purpose of our work was to assess the possibility of predicting the risks of postoperative complications in patients with urolithiasis in a urological hospital., Materials and Methods: We performed a retrospective comparative study. We analyzed the medical records of patients in the department of urology of hospital clinics of Siberian State Medical University from November 2022 to May 2023. A total of 48 records of patients who had a verified diagnosis of urolithiasis were selected. Inclusion criteria were the presence of stones in the kidney or ureter and surgical intervention during the current hospitalization. Exclusion criteria included bladder stones. All patients underwent surgery for urolithiasis. The laboratory range of studies included a general urine test before surgery, bacteriological examination of urine for microflora and sensitivity to antibacterial drugs before surgery, as well as bacteriological examination of stone obtained intraoperatively. Risk factors for antibiotic resistance were also assessed., Results: Of the 48 patients included in the study, urine and stone cultures did not reveal microflora growth in 26 (54.2%) patients. In the remaining 22 patients, we received different results: 1. only positive urine culture in 9 (18.8%) patients 2. only positive stone culture in 5 (10.4%) people 3. combination of positive bacteriological examination of urine and stone in 8 (16.7%) patients. Looking separately at 22 patients who had a positive urine or stone culture, or a combination of both, we noted that the combination of a positive urine culture with a positive stone culture and the combination of a positive urine culture with a negative stone culture were not significantly different and occurred in 36.4% and 40 .9% of cases, respectively, i.e. with a positive urine culture, there is an equal probability of about 40% of both an infected stone and a sterile one, while with a negative urine culture, an infected stone can occur in 22.7% of cases. In the early postoperative period, infectious complications were recorded in 3 (6.25%) patients. Complications were observed in 2 patients on the 4th day after surgery, and in one patient on the 2nd day. All three cases were postoperative pyelonephritis., Conclusions: Our small study demonstrated the importance of culture in planning surgical treatment for urolithiasis. And further study of bacteriological studies of urine before surgery, urine obtained from the renal pelvis intraoperatively, and stones represents new directions for creating algorithms for monitoring patients with urolithiasis, predicting complications in the postoperative period, as well as local protocols for perioperative antibiotic prophylaxis and antibacterial therapy for patients with urolithiasis.

Background: Ammonium chloride is the most common urine acidifier used for urolithiasis treatment and prevention in goats., Aim: The objective of this study was to determine a guideline for ammonium chloride administration to acidify urine in goats., Methods: A three-period, three-treatment crossover study was conducted in three groups, with 10 female goats in each group. Three dosages of ammonium chloride were used (250, 350, or 450 mg/kg). In each experimental period, ammonium chloride was orally administered for three consecutive days or until the urine pH dropped below 6.5. Urine samples were collected to measure the pH before each administration and 1 day after the last administration. The Cox proportional hazards model was conducted to identify factors associated with the success rate in reducing the urine pH below 6.5 at a time., Results: The dosage of ammonium chloride and period of administration were significantly associated with the success rate ( p < 0.001). The success rates during a unit of time for goats receiving 350 mg/kg and 450 mg/kg were greater than that of goats receiving 250 mg/kg. The second and third periods of ammonium chloride administration provided higher success rates during a unit of time compared to the first period. The success rate was also associated with the pretreatment urine pH ( p = 0.044). There was a higher success rate for goats with a lower pretreatment urine pH., Conclusion: The recommended ammonium chloride dosage was 350 mg/kg. Periodic use can be considered to achieve better outcomes. The pretreatment urine pH should be measured to anticipate the clinical response., Competing Interests: The authors declare that there is no conflict of interest.

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 μg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01-1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 μg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02-1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Case Series Summary: Four confirmed cases of xanthinuria in cats, and one suspected case based on pedigree analysis, were identified. Clinical presentations varied and included haematuria, pollakiuria, dysuria, and urethral and ureteral obstruction. All cats had upper urinary tract uroliths. Diagnosis was obtained through infrared mass spectrometry of uroliths or urine. Clinical signs commenced at 3-8 months of age and reduced in all cats in the medium to long term after the introduction of a protein-restricted diet. Four cats were castrated males and one was a spayed female. Cases consisted of four Munchkin pedigree cats and one unrelated domestic shorthair cat. All four affected Munchkin pedigree cats were related, with three cases full siblings and the fourth case a half-sibling. No connection to the Munchkin pedigree could be established for the domestic shorthair cat. A candidate causative genetic variant ( XDH p.A681V) proposed for this cat was excluded in the Munchkin family., Relevance and Novel Information: All affected cats presented diagnostic challenges and routine urinalysis was insufficient to obtain a diagnosis. Cases of feline xanthinuria may be underdiagnosed due to situations where uroliths cannot be retrieved for analysis and there is an inability to make a diagnosis using crystal morphology alone on routine urinalysis. Metabolic screening of urine may provide an effective mechanism to confirm xanthinuria in suspected cases where uroliths are inaccessible or absent. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs and urethral obstruction developing secondary to xanthine urolithiasis. A protein-restricted diet appears to reduce clinical signs as part of long-term management., Plain Language Summary: Four closely related Munchkin cats and one domestic shorthair cat were found with a suspected genetic disease causing high levels of xanthine in their urine. The case series looks at similarities and differences in their clinical signs, as well as difficulties experienced in obtaining a correct diagnosis. All cats had upper urinary tract stones and required metabolic testing of the stones or urine to diagnose. All cats were young when their clinical signs started and were on a high-protein diet. Four cats were desexed males and one was a desexed female. A genetic variant that may have caused the disease in the domestic shorthair cat was ruled out in the Munchkin family. Cases of high xanthine levels in feline urine may be underdiagnosed as the stones may not be accessed for testing. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs. A protein-restricted diet appears to reduce clinical signs as part of long-term management., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study describes the primary characteristics of the selected kidney stones surgically removed from the patients at the Mersin University Hospital in the southern Turkey and interprets their formation via petrographic, geochemical, XRD, SEM-EDX, and ICP-MS/OES analyses. The analytical results revealed that the kidney stones are composed of the minerals whewellite, struvite, hydroxyapatite, and uric acid alone or in different combinations. The samples occur in staghorn, bean-shaped composite, and individual rounded particle shapes, which are controlled by the shape of the nucleus and the site of stone formation. The cross-section of the samples shows concentric growth layers due to variations in saturation, characterizing the metastable phase. Kidney stone formation includes two main stages: (i) nucleation and (ii) aggregation and/or growth. Nucleation was either Randall plaque of hydroxyapatite in tissue on the surface of the papilla or a coating of whewellite on the plaque, or crystallization as free particles in the urine. Subsequently, aggregation or growth occurs by precipitation of stone-forming materials around the plaque or coating carried into the urine, or around the nucleus formed in situ in the urine. Urinary supersaturation is the main driving force of crystallization processes; and is controlled by many factors including bacterially induced supersaturation., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

It is well known that the coexisting metal ions could significantly influence the atomic spectroscopy (AS) analysis. In this work, a cation-modulated mercury ions (Hg 2+ ) strategy via chemical vapor generation (CVG) was developed for oxalate assay due to the phenomenon that the Ag  +  can significantly reduce the Hg 2+ signal. The regulation effect was studied in depth via experimental investigations. Since Ag  +  can be reduced to silver nanoparticles (Ag NPs) by reductant SnCl 2 , the decrease of the Hg 2+ signal is attributed to the formation of a silver-mercury (Ag-Hg) amalgam. Due to the oxalate can react with Ag  +  to generate Ag 2 C 2 O 4 , which can reduce the generation of Ag-Hg amalgam, a portable and low-power point discharge chemical vapor generation atomic emission spectrometry (PD-CVG-AES) system was constructed to quantify the content of oxalate via monitoring the signal of Hg 2+ . Under optimal conditions, the limit of detection (LOD) was as low as 40 nM in the range of 0.1-10 μM for oxalate assay, while exhibiting good specificity. This method was applied to quantitative oxalate in 50 clinical urine samples of urinary stones patients. The levels of oxalate detected in clinical samples were consistent with clinical imaging results, which is promising for point-of-care testing in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Urolithiasis is a common disease of the urinary system. Its recurrence rate is high and may increase medical expenses. Urine stones are composed of urine crystals and other impurities. We discovered the existence of autofluorescence in some of the urine crystals, especially in urolithiasis patients. The fluorescent molecule existed in urine crystals was verified and identified. We have applied micro-Raman and fluorescence microscopy to classify the urine crystals, used confocal laser scanning microscopy (CLSM) to examine the 3D images and spectra of autofluorescence in crystals, used Fourier-transform infrared spectroscopy (FTIR) and mass spectrometry (MS) to identify the type of fluorophore in the autofluorescent urine crystals in urine. Riboflavin was identified as one of the major fluorophores in these autofluorescent urine crystals. The prevalence rates of the autofluorescent crystals in urolithiasis patients and subjects without the history of urolithiasis were to gather statistics. We observed that 80% of urolithiasis patients had autofluorescent crystals. Contrastingly, such crystals existed in only 7% of subjects without the history of urolithiasis. The presence of autofluorescent urine crystals may be linked to a sign of urolithiasis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We performed a cross-sectional study on 25 children (17 boys) with urolithiasis with normal glomerular functions at a tertiary care teaching hospital between March, 2018 to March, 2019. Dietary assessment showed that caloric intake was below recommended dietary allowance (RDA) in 68% patients while the median protein intake was 34.3% more. The fluid intake was below the recommended standards in 56%, and 48% of the children had urine output below 1.5 mL/kg/hour. The urinary sodium was elevated in 96% of the children, urinary potassium was low in 40%, and hypercalciuria was seen in 28%. While metabolic causes predominate in childhood urolithiasis, other factors like dietary changes, liberal fluid and low sodium intake are advised for prevention of recurrences as they have a contributory role too.

Background: Recommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions., Material and Methods: We collected urine samples from ten healthy volunteers and prepared aliquots to be stored either at room temperature or 4 °C. Some aliquots were preserved using hydrochloric acid prior to storage, some thereafter, some using the BD Urine preservation tube and some were not preserved at all. Storage duration was 0, 24, 48 or 72 h. In all samples calcium, magnesium, phosphorus, creatinine, oxalate, citrate and uric acid were measured and compared to the according reference sample., Results: We could not find any significant deviation for any of the analytes and preanalytical treatment conditions compared to the associated reference sample., Conclusion: Preservation of 24 h urine for the metabolic evaluation in stone formers might not be necessary for sample storage up to 72 h., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Individuals with urinary stone disease (USD) exhibit dysbiosis in the urinary tract and the loss of Lactobacillus that promote urinary tract health. However, the microbial metabolic functions that differentiate individuals with USD from healthy individuals are unknown. The objective of the current study was to determine the microbial functions across prokaryotic, viral, fungal, and protozoan domains that are associated with calcium oxalate (CaOx) stone formers through comparative shotgun metagenomics of midstream, voided urine samples for a small number of patients (n = 5 CaOx stone formers, n = 5 healthy controls). Results revealed that CaOx stone formers had reduced levels of genes associated with oxalate metabolism, as well as transmembrane transport, proteolysis, and oxidation-reduction processes. From 17 draft genomes extracted from the data and > 42,000 full length reference genomes, genes enriched in the Control group mapped overwhelming to Lactobacillus crispatus and those associated with CaOx mapped to Pseudomonas aeruginosa and Burkholderia sp. The microbial functions that differentiated the clinical cohorts are associated with known mechanisms of stone formation. While the prokaryotes most differentiated the CaOx and Control groups, a diverse, trans-domain microbiome was apparent. While our sample numbers were small, results corroborate previous studies and suggest specific microbial metabolic pathways in the urinary tract that modulate stone formation. Future studies that target these metabolic pathways as well as the influence of viruses, fungi, and protozoa on urinary tract physiology is warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The potential of Alhagi maurorum (Boiss.) aqueous extract (AME), used in traditional medicine for treatment or prevention of urolithiasis, to dissolve calcium oxalate stones in vitro was evaluated. In order to determine the litholytic potential of the extract, Calcium oxalate urinary stones were incubated during 12 weeks under continuous shaking in the presence of AME, Rowanix or NaCl 9 g/mL solution were used as controls. After the incubation period, the residual weight of the treated calculi was determined and the rate of dissolution was calculated. The medium pH variation was measured and changes in the calcium oxalate crystals at the stone surface were assessed using a scanning electron microscope (SEM). The results showed a significant dissolution effect for the extract on the kidney calculi during the experimentation period. At the end of the experiment, the percentages of calculi weight decrease were 41.23, 4.97 and 55.67% for the extract, NaCl solution and Rowanix, respectively. Gas Chromatography analysis revealed mainly the presence of the following phyto-compounds: Cyclopropenone, 2,3-diphenyl; 1-Nonadecanol; methyl-alpha-D-mannopyranoside; cis-9-Hexadecenal. These compounds unarguably play crucial roles in the health care system especially in cancer treatment and many other diseases including urolithiasis. The urinary stone dissolution, independent of medium pH, could be attributed to formation of complexes between the phytochemical compounds in the extract and the calculi.

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.

Background: Urolithiasis is a multi-etiological disease resulting from a combination of environmental and genetic factors. One of the most challenging aspects of this disease is its high recurrence rate. For most patients, an in-depth metabolic evaluation may reveal the presence of urinary stones. The fact that different urinary stone-related compounds (USRCs) are measured by different methods renders the metabolic evaluation of urolithiasis quite tedious and complex., Methods: A three-channel ion chromatograph (IC) that automatically measures the concentration of common metabolic indicators of urolithiasis in urine (i.e., oxalate, citrate, uric acid, calcium, and magnesium) was developed to improve the efficiency. To validate its precision and specificity, standard curves were prepared using working solution of these indicators. 100 standard solutions of these indicators were measured with our new IC and three other ICs as the control instruments; analyte concentrations in 100 24-h urine samples from volunteers and 135 calculi patients were also measured., Results: All analytes had good linear relationships in concentration ranges of 0-10 mg/L. The precision experiments in the standard and urine samples showed that the measurement errors of the newly developed IC were all less than 5%. In urine, the recovery rate ranged from 99.6 to 100.4%, the coefficient of variation ranged from 1.39 to 2.99%, and the results matched between our newly developed IC and the control ICs. The results of the efficiency test showed that we can finish the analysis at the average number of 14 people per day with the new IC. While the average number in the control group is 3.85/day (p = 0.000)., Conclusions: Overall, this multi-channel system significantly improves the efficiency of metabolic evaluation while retaining accuracy and precision., (© 2021. The Author(s).)

We analyzed children with urolithiasis with age- and gender-matched healthy children. Calcium (mmol/mmol creatinine) and the calcium/citrate ratio (mol/mmol) are the only variables that differentiate children before puberty from healthy children (ROC analysis confirmed only calcium/citrate as a significant variable with cut-off value > 0.84). Peri-pubertal children are distinguished from age- and gender-matched healthy children by the following variables: citrate (mmol/mol creatinine), calcium/citrate (mol/mmol), oxalate/glycosaminoglycans (mmol/g), oxalate/citrate ratios (mmol/mmol) and oxalate/(citrate × glycosaminoglycans) (mol oxalate × mol creatinine)/(mol citrate × g glycosaminoglycans). All variables were confirmed by ROC analysis with cut-off values ≤ 327.87, >1.02, >11.24, >0.12 and >0.03, respectively. These results indicate a different risk of urinary stones development before puberty vs. pubertal/postpubertal children and increasing importance (deficiency) of citrate and glycosaminoglycans in such children. J48 classifier confirmed the importance of the oxalate/(citrate × glycosaminoglycans) and the calcium/citrate ratios (Ox/Cit × GAG 0.22 and Cit/GAG 0.612) with the practically applicable classification tree for distinguishing between pubertal/postpubertal children with urolithiasis with age- and gender-matched healthy children.

Purpose: To evaluate the impact of extensive surgery on urine profile, serum exams and stone composition of complicated IBD patients., Methods: Patients with IBD and a history of total proctocolectomy (TPC) with fecal diversion (end ileostomy or ileal pouch anal anastomosis-IPAA) were selected. Only patients with at least one complete 24-h urine profile were included. A case-control study was performed selecting patients with kidney stone disease in a random way who had also at least on complete 24-h urine profile. Case and controls were matched for age, gender, and body mass index (BMI). Groups were compared to urine profile, serum exams and stone composition., Results: Sixty-eight patients were enrolled in this study, 34 patients with IBD who underwent TPC and had diagnosis of kidney stones and 34 matched patients with only kidney stones. IBD patients had a significantly lower urine volume, urine citrate and urine sodium. Regarding serum exams, only serum bicarbonate was statistically significant lower. In both groups, calcium oxalate stone was the most common., Conclusion: Patients with IBD with TPC and kidney stones have a low urine volume and low urine citrate as main risk factors for kidney stone formation. As seen in the general population, calcium oxalate is the most common stone composition.

Aim: The objectives of this study were to evaluate the impact of preoperative urine culture and the infected nature of stones on the occurrence of postoperative urinary sepsis., Material and Methods: A prospective monocentric study included 29 patients operated on for urolithiasis between January and June 2018., Results: Postoperative urinary sepsis was observed in 4 patients (14%). Urinary colonization rate on preoperative CBU exam was 27.6% (8 of 29) while the rate of colonized stones was 31% (9 of 29). The occurrence of urinary sepsis was observed in 37.5% (3 of 8) of patients with urinary colonization, compared to 44.4% of patients with colonized stones (4 of 9). By comparing the bacteriological results observed during sepsis, the germs isolated in postoperative urine were the same found in the culture of stones. The chemical nature of the colonized stones was mainly calcium oxalate (monohydrate, dihydrate) P=0.02. There was a statistically significant correlation between the preoperative urine culture, the bacteriological culture of stones and the postoperative urinary sepsis (P=0.05, P=0.005) respectively., Conclusion: Our study demonstrated a strong association between the bacteriological culture of stones and postoperative urinary sepsis superior to preoperative urine culture. It makes it possible to anticipate the occurrence of sepsis in patients requiring many endoscopic treatments. However, several multicentric prospective series may prove necessary to validate these results., Level of Evidence: 3., (Copyright © 2020. Published by Elsevier Masson SAS.)

The aim of our study is to explore the relationship between genotype and phenotype in Chinese PH1 patients and determine the putative mutation hotspot regions. This was a retrospective study regarding 13 Chinese PH1 patients. And all sporadic published researches of Chinese PH1 populations were searched and enrolled based on the inclusive standard. All patients presented with multiple urolithiasis or nephrolithiasis. Urinary oxalate values demonstrated an obvious and extensive variability, ranging from 1.01 to 3.85 mmol/1.73 m 2 . Molecular diagnosis showed that 13 mutant types were detected. Infantile form patient (pt.) 10 and five patients (pts. 5, 7, 8, 9, 12) carrying c.815&#95;816insGA or c.33&#95;34insC demonstrated a worse prognosis, of whom pt. 5 progressed into ESRD 4 years later and died of chronic kidney failure. Based on the integrated Chinese mutation data, two variants (c.815&#95;816insGA and c.33&#95;34insC) were determined as the most common mutations. Besides, c.1049G>A was initially identified in a Chinese patient. Conclusions: heterogeneity between genotype and phenotype was observed and described in Chinese PH1 patients. c.815&#95;816insGA and c.33&#95;34insC which were recognized as AGXT mutation hotspot regions in China implied a poor prognosis. And c.1049G>A was not determined as the race-specific mutation of Pakistani.

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl β-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 μg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 μg/kg&#95;bw/day and the US FDA's 63 μg/kg&#95;bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To identify how demographic factors, stone-associated medical comorbidities, and treatment predict compliance with 24-hour urine collection., Materials and Methods: A retrospective medical record review of patients treated for urolithiasis between August 2014 and March 2017 was performed. Patient demographics, medical characteristics, stone factors, type of treatment, and compliance data were included for patients requested to submit a collection. Variables that were statistically significant on bivariate analysis were then used to formulate a model predicting submission of a 24-hour urine sample., Results: Of the 303 patients who met inclusion criteria, 183 (60.4%) submitted an initial 24-hour urine collection. On bivariate analysis, patients older than 50 were more likely to submit a 24-hour urine collection (71.4% vs 51.5%; P <.001), patients with a metabolic predisposition for stones were more likely to submit a 24-hour urine collection (70.6% vs 53.1%; P <.003), and patients who did not have surgery were more likely to submit a 24-hour urine collection (97.9% vs 53.5%; P <.001). Our 3-variable prediction model found that not undergoing surgery was a strong predictor of 24-hour urine collection., Conclusions: We suspect that patients perceive surgery as a more definitive treatment for kidney stones than conservative management. Patient education on the natural history and role of metabolic management in the prevention of nephrolithiasis is essential in improving compliance with 24-hour urine collection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Milk of calcium is a viscous colloidal suspension of calcium salts that forms in dilated cysts or cavities. We present, for the first time in literature, a toddler with isolated milk of calcium and treated with a conservative approach. A boy with a history of one urinary tract infection and recurrent fever without vesicoureteral reflux showed at the age of 14 months a left obstructive staghorn stone. Because of absent function of the left kidney at mercapto acetyl tri glycine scintigraphy, a JJ stent was positioned with a leak of whitish material immediately after the stent positioning. Renal scintigraphy performed 1 month later revealed a partial resumption in renal function (18%). When he was 18 months old, the child suffered episodes of acute pain with inconsolable crying, unresponsive to paracetamol administration. Ultrasound assessment revealed left pelvic dilation (anterior-posterior diameter of 18 mm), suspended echogenic debris in the bladder, and dilated left distal ureter with particulate matter. These episodes of acute pain were followed by expulsion of numerous soft formations and emission of greenish urine. Both urine culture at the admission and culture on the greenish urines were sterile. After the expulsion of the soft formations, pain episodes stopped. The diagnosis of milk of calcium stone was made. With this case, we highlight a condition that can be easily diagnosed (if known) because the morphology of the expelled material is pathognomonic. Diagnosing it could avoid unnecessary treatments (ie, extracorporeal shockwave lithotripsy) and support a conservative approach (ie, stent positioning)., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

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 β-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.

Background: Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are thought to present with a less severe phenotype than PH1 and PH2 patients. However, the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aims of this study were to report HOGA1 mutations of PH3 in Chinese children, and to analyze the genotype and clinical characteristics of these PH3 patients., Methods: Genetic analysis (targeted gene panel-based and/or whole-exome sequencing) of HOGA1 was performed in 52 patients with a high suspicion of PH3, and DNA was obtained from the patient and both the parents. The clinical, biochemical, and genetic data of these 12 patients identified with HOGA1 mutations were subsequently retrospectively reviewed., Results: These 12 patients were identified with HOGA1 mutation. The median onset of clinical symptoms was 18.25 (range 5-38) months. In total, 14 different mutations were identified including 9 novel mutations in these 12 patients with PH3. All of these 12 patients initially presented with urolithiasis, and 3 patients among them comorbid urinary tract infection (UTI) as another initial symptom. Ten patients experienced hyperoxaluria (average oxalate 0.77 mmol/1.73 m 2 /24h). In contrast, urine calcium excretion was normal in 8 patients and 2 patients with hypercalciuria (urine calcium > 4 mg/kg/24 h). At the time of diagnosis, estimated GFR was 155.6 ml/min per 1.73 m 2 , and at last follow-up time (17.3 months later from diagnosis on average), estimated GFR was 157.5 ml/min per 1.73 m 2 . To date, none of the patients has impaired renal function based on and progressed to ESRD., Conclusions: We found that PH3 was significantly diagnosed in our urolithiasis patients during childhood. Nine novel HOGA1 mutations were identified in association with PH3, which provide a first-line investigation in Chinese PH3 patients. The eGFR was normal in all children with PH3. This finding is in contrast to the early impairment of renal function in PH1 and PH2.

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay., Methods: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (r s )., Results: The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (r s  = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls., Conclusions: High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The SFBC working group aimed to deal with biological tests outside the french nomenclature that may be useful in the context of urinary exploration of metabolism. This section will be divides into three parts: 1) nutritional assessment using urinary urea; 2) metabolic assessment of urolithiasis; 3) exploration of tubulopathies. National and international recommendations support the evaluation of nutritional status from urea measurements in urine and dialysate with the following indications: primary metabolic evaluation of urolithiasis patients, monitoring of protein intake in chronic renal failure stage 3 or stage 5D with residual diuresis. For the management of the urolithiasis disease, biomedical tests recommended by the national and international guidelines are the measurement of the urinary density using refractometry in the primary metabolic evaluation as well as the determination of oxalemia in the diagnosis (patients with GFR< 30 mL/min/1.73 m 2 ) and follow-up (patients with GFR< 60 mL/min/1.73 m 2 ) of primary hyperoxaluria. The determination of the bicarbonaturia is retained for the in depth exploration of urolithiasis and tubular acidosis. The measure of chlore in urine is used to evaluate the volume status during metabolic alkalosis and to calculate the urinary anionic gap during metabolic acidosis.

Our purpose was to study the relationship of adherence to the Mediterranean diet (MedDiet) with urinary factors that favor the formation of renal calcium and uric acid stones in overweight and obese participants who had metabolic syndrome. This cross-sectional study examined 267 participants. A well-known MedDiet score (range 0-9) was calculated for each patient, and patients were then categorized has having low (≤3), medium (4-5), or high (≥6) adherence to the MedDiet. Baseline characteristics and urinary parameters were also analyzed. High calcium salt urinary crystallization risk (CaUCR) and high uric acid urinary crystallization risk (UrUCR) were calculated from urinary parameters using pre-defined criteria. More than half of patients with MedDiet scores ≤3 had high UrUCR (55.4%) and high CaUCR (53.8%). In contrast, fewer patients with high adherence (≥6) to the MedDiet had high UrUCR (41.2%) and high CaUCR (29.4%). Relative to those with low adherence, individuals with high adherence had a prevalence ratio (PR) of 0.77 for a high UrUCR (95% CI: 0.46-1.12; p for trend: 0.069) and a PR of 0.51 for a high CaUCR (95% CI: 0.26-0.87; p for trend: 0.012) after adjusting for age, sex, body mass index, type 2 diabetes, and total energy intake. Our findings indicate that greater adherence to the MedDiet was associated with a reduced CaUCR and a reduced UrUCR. This suggests that adequate dietary management using the MedDiet patterns may prevent or reduce the incidence and recurrence of calcium salt and uric acid renal stones., Competing Interests: The authors declare no conflict of interest.

Purpose: Hypercalciuria is one of the risk factors for calcium kidney stone formation (the most common type of urinary stones). Although vitamin D deficiency is prevalent among urolithiasis patients, the effect of vitamin D supplementation on urine calcium in these patients is still unclear., Materials and Methods: In this retrospective study, medical and laboratory tests records of 26 patients with recurrent calcium kidney stones and vitamin D deficiency treated with 50000IU vitamin D per week for 8-12 weeks were analyzed. The changes in 24-hour urine calcium (24-h Ca), serum 25-hydroxyvitamin D (25 (OH) D), serum parathormone (PTH), other 24-hour urine metabolites and calculated relative supersaturations of calcium oxalate (CaOxSS), calcium phosphate (CaPSS) and uric acid (UASS) were assessed. Moreover, correlations between changes in 24-h Ca and other aforementioned variables were assessed., Results: Serum 25 (OH) D and 24-h Ca increased after vitamin D supplementation, while serum PTH decreased (p < 0.001, for all analyses). The levels of 24-hour urine sodium and urea increased significantly (p = 0.005 and p = 0.031, respectively). The levels of CaOxSS and CaPSS increased, but the changes were not significant (p = 0.177, and p = 0.218, respectively). There were no correlations between the changes in 24-h Ca and serum 25 (OH) D or PTH., Conclusions: The result of current study suggests that although urine Ca increased in vitamin D supplemented patients, this increase was not associated with the increase in serum vitamin D and may be due to other factors such as dietary factors. Further randomized clinical trials considering other factors associated with urine Ca are warranted., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: There are abnormalities in vitamin D metabolism in people with calcium nephrolithiasis, but limited data are available on vitamin D status in dogs with calcium oxalate (CaOx) urolithiasis., Objective: To compare serum concentrations of vitamin D metabolites in dogs with and without hypercalciuric CaOx urolithiasis., Animals: Thirty-eight dogs with (n = 19) and without (n = 19) a history of CaOx urolithiasis and hypercalciuria., Methods: Retrospective cross-sectional study. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH) 2 D], and 24,25-dihydroxyvitamin D [24,25(OH) 2 D] were measured. The ratios of 25(OH)D/24,25(OH) 2 D and 1,25(OH) 2 D/25(OH)D were compared between cases and controls., Results: There were no significant differences between cases and controls when comparing 25(OH)D, 24,25(OH) 2 D, 1,25(OH) 2 D, or 1,25(OH) 2 D/25(OH)D. Cases had higher 25(OH)D/24,25(OH) 2 D (median = 1.40, range = 0.98-1.58) compared to controls (median = 1.16, range = 0.92-2.75; P = .01). There was overlap in the ranges for 25(OH)D/24,25(OH) 2 D between cases and controls, but 6 cases (32%) had ratios above the control dog range. There was a moderate positive correlation between the ratio of 25(OH)D/24,25(OH) 2 D and urinary calcium-to-creatinine ratios (r = 0.40, 95% confidence interval = 0.10-0.64; P = .01)., Conclusions and Clinical Importance: These data suggest that decreased conversion of 25(OH)D to 24,25(OH) 2 D occurs in a subset of dogs with CaOx urolithiasis. Abnormalities in vitamin D metabolism might contribute to stone risk in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: Considering the predictive role of the relatively low urinary citrate for stone formation, especially in hypercalciuric patients, this study is aimed at comparing urine calcium to citrate (Ca/Cit) ratio in 3 groups of children, including patients with idiopathic hypercalciuria with and without renal stone as well as the healthy children., Methods: This study was carried out on 96 children (2 to 12 years old) referred to a pediatric nephrology clinic in the city of Ahvaz, Southwest Iran. All the children underwent renal ultrasonography, urinalysis, and measurement of random nonfasting urine Ca, Cr, and citrate. Those with secondary hypercalciuria, urinary tract malformations, and/or functional abnormalities of the gastrointestinal tract were excluded from the study., Results: The mean Ca/Cit. ratio (mg/mg) in the three groups, including children with hypercalciuric with and without renal stones and the healthy children (control group), was 0.44 ± 0.14, 0.39 ± 0.13, and 0.19 ± 0.08, respectively, which showed a significant difference (P < .001). There was also a significant difference in Ca/Cit ratio between the first and the control group by Tukey's range test (P < .001). Mean urinary Ca/Cit ratio in those with a positive family history of urolithiasis within three groups was 0.42 ± 0.17 and in those with a negative family history was 0.32 ± 0.16 (P = .013). Mean Ca/Cit. ratio (mg/mg) of 0.25 showed a sensitivity of 90.6% (confidence interval: 75.7-96.7%) and a specificity of 81.2% (confidence interval: 64.7-91.1%) to differentiate between the renal stone group and the control group., Conclusion: High Ca/Cit ratio can predict stones formation in hypercalciuric patients, especially in those with a positive family history of urolithiasis. The present study found the cutoff level of 0.25 for Ca/Cit. ratio as the highest prognostic value for renal stone formation., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females., Methods: The 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133μmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women., Results: A total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19-84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion., Conclusions: Postmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women., Competing Interests: The authors have declared that no competing interests exist.

To study the impact of body mass index (BMI) on quantitative 24-h urine chemistries in stone forming patients and to explore how overweight and obesity contribute to urolithiasis. A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science was performed in July 2017 and updated in October 2017 to detect relevant studies. After that, we screened all the relevant articles in accordance with the predetermined inclusion and exclusion criteria. Data of eligible studies were extracted, and then, a meta-analysis was conducted via RevMan 5.3 software. Nine studies, involving 5965 stone forming patients who underwent 24-h urine collection for chemistry analysis, were included in our analysis. BMI was used to clarify the body size. BMI ≥ 25 kg/m 2 group, including overweight and obesity patients, erected more calcium (WMD 34.44 mg; 95% CI 11.33-57.55; p = 0.003), oxalate (WMD 3.44 mg; 95% CI 1.40-5.49; p = 0.001), urate (WMD 97.71 mg; 95% CI 63.05-132.38; p < 0.00001), and sodium (WMD 26.64 mg; 95% CI 18.23-35.05; p < 0.00001) in 24 h than BMI < 25 kg/m 2 group. However, the BMI < 25 kg/m 2 group showed higher pH of urine (WMD 0.12; 95% CI 0.04-0.20; p = 0.004). There was no significant difference in 24-h urine volume (WMD - 29.30 ml; 95% CI - 122.03 to - 63.42; p = 0.54), citrate (WMD - 34.03 mg; 95% CI - 72.88 to 4.82; p = 0.09), magnesium (WMD - 4.50 mg; 95% CI - 10.48 to 1.48; p = 0.14), phosphate (WMD - 89.38 mg; 95% CI - 219.23 to 40.47; p = 0.18), and creatinine (WMD - 191.98 mg; 95% CI - 395.35 to 11.38; p = 0.06) between the two groups. All the results kept the same tendency when gender was taken in consideration. Sensitivity analysis generated similar results. The current evidence suggested that patients with BMI ≥ 25 kg/m 2 erected more promotions but not inhibitors of urolithiasis than those with BMI < 25 kg/m 2 , which increased the risk of urolithiasis in overweight and obesity individuals.

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.

Purpose: In the emergency setting, flank pain commonly leads to a noncontrast CT despite a significant percentage of patients having alternative diagnoses, often difficult to characterize without contrast. We investigated the combined utility of urinalysis and history of urolithiasis in identifying patients who are unlikely to have urolithiasis and may benefit from a contrast-enhanced study., Methods: Retrospective review of 350 patients from May 2013 to May 2016 was performed for patients in the emergency department with renal colic that underwent noncontrast CT and urinalysis testing., Results: Urolithiasis was present in 282 of the 350 patients reviewed (81%), of which 175 (62%) had an obstructing calculus. RBC-positive urinalysis was present in 231 patients with calculi on CT (sensitivity 82%). Patient history of urolithiasis plus urinalysis had a sensitivity of 94% for detecting calculi. Thirty-five patients (10%) had alternative diagnoses, 33 of which were in patients without obstructing calculi. Sixty-seven patients underwent noncontrast CT despite no history of urolithiasis and a negative urinalysis, 10 of which (15%) had alternative diagnoses. Only three cases in this subset (4%) had nonobstructing 1-2-mm calculi, potentially missed with contrast. In this subset, the projected proportion of optimally characterized cases with intravenous contrast is 96%, compared to 85% without contrast (p = .03)., Discussion: Given the high combined sensitivity of urinalysis and patient history (94%), this simple analysis can confidently direct clinicians to a contrast-enhanced CT in "rule-out" cases of flank pain in patients with a negative history and negative urinalysis, particularly given that 15% of these patients had alternative diagnoses.

Purpose: The aim of the study was assessment of four selected macromolecules level: osteopontin, calgranulin, uromodulin and bikunin in fresh morning urine sample in children with nephrolithiasis in the course of idiopathic hypercalciuria., Materials and Methods: The study included 90 subjects aged from 12 months to 18 years. The study group comprised 57 subjects- children with urinary tract lithiasis in the course of idiopathic hypercalciuria and the control group - 33 healthy children with no history of urolithiasis. Determinations of osteopontin, calgranulin, uromodulin and bikunin levels in the first morning urine were performed., Results: The study group had a significantly decreased osteopontin excretion and significantly increased bikuninexcretion, and increased, however statistically nonsignificant, calgranulin excretion in comparison with the control group. Uromodulin excretion did not differ between groups. In both groups a statistically significant positive correlation was observed between uromodulin and bikunin levels., Conclusion: Children with urinary tract lithiasis in the course of idiopathic hypercalciuria reveal a different distribution of the study proteins than a healthy population.

Objective: To identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria., Methods: The formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3-MX); 40 mg/L for 7-methylxanthine (7-MX), 1-methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. Scanning electron microscopy was used to examine the morphology of the crystals formed when inhibitory effects were observed., Results: Only 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization., Conclusion: Two of the inhibitors identified here-7-MX and 3-MX-are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36% as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo., Competing Interests: I have read the journal's policy and the authors (FG, AC-B and AR) of this manuscript have the following competing interests: Those authors declare that they are the inventors of a pending patent based on some aspects of this work. It is a national (Spanish) patent, which has not been yet licensed. (Patent name: Inhibitors of the crystallization of xanthine. Patent number: P201830385). Those authors confirm that this patent does not alter their adherence to all PLOS ONE policies on sharing data and materials.

The incidence of urinary tract stones in infancy has been increasing in Turkey. Risk factors and vitamin D receptor (VDR) gene polymorphisms were investigated in infants aged < 1 year who had stones. Forty infants with urinary tract stones and 80 infants without stones, aged < 1 year were enrolled in this study. Detailed surveys were taken of all infants, metabolic parameters and ApaI and FokI VDR gene polymorphisms were investigated. Infants with stones tended to be more commonly fed formula and multivitamins (vitamins A, C, D) (p < 0.05). Positive family history came into prominence in the stony group (p < 0.05). There were no significant differences in ApaI and FokI VDR gene polymorphisms between the groups with stones and the control groups. However, CA genotype of ApaI polymorphism was associated with family history and C allele of ApaI was related with family history and hypercalciuria (p < 0.05). Hypercalciuria emerged as an underlying metabolic abnormality in the etiology of stones, and was observed at a rate of 38%. Infants who are given formula and multivitamins for vitamin D supplementation are at increased risk for the formation of urinary tract stones. VDR gene polymorphisms cause the formation of urinary tract stones and affect calcium (Ca) metabolism.

The study of the crystalluria is the search and the identification for crystals in urines. This multi-parametric study brings a precious help in the diagnosis and/or the follow-up of acquired or congenital lithiasis. The lack of the internal urinary quality control (IQC) makes the accreditation of this analysis, according to the NF EN ISO 15189 standard, particularly delicate. After a presentation of the three steps (pre-analytical, analytical and post-analytical) performed in the laboratory, the authors present some insights in order to mitigate the lack of the urinary IQC. These insights, particularly concern by the "misappropriation" of IQC, the elaboration of an "in house" IQC as well as by the evaluation of the external evaluation of the quality. Thanks to the implementation of these tools, it becomes easier to prove that the laboratory of medical biology masters the qualification, the authorization and the continuous preservation of the skills of the operators performing the study of the crystalluria.

Background: Urinary tract infection (UTI) is very common in patients with urolithiasis, which makes the treatment of urolithiasis complicated, even dangerous. The objective of this study was to determine the risk factors for UTI in patients with urolithiasis., Methods: Eight hundred six patients with urolithiasis were retrospectively evaluated in the fourth affiliated hospital of China Medical University. All patients admitted to the study were divided into either a UTI infection group or a non-infection group. Sex, age, smoking, stone shape, alcohol consumption, position of stones, and presence of obstruction were used as exposure factors for the cross-sectional study., Results: One hundred seventy-eight patients (22.0%) had UTI. Through a urine culture test, gram-negative bacilli were the most common pathogen, followed by gram-positive bacilli and fungi., Conclusions: Sex, age, obstruction, stone shape, and multiple sites of stones could be considered the independent factors for UTI in patients with urolithiasis; smoking and drinking had no statistically significant correlation with the condition. Gram-negative bacilli are the most common pathogen in UTI 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).

Background: Various genetic and environmental factors are involved in urolithiasis. The 2 most common metabolic abnormalities are the increase in urinary calcium and low urinary citrate excretion. The ratio calculated between the concentrations of both substances is a good risk marker for the formation of calcium stones., Objectives: To determine whether the risk of urinary calcium stone formation changes throughout the day in the same patient., Methods: We studied 56 children (23V, 33M) to check if they had prelithiasis. Calcium, citrate, and creatinine concentrations were determined in two urine samples collected one before dinner and the other in the morning. It was collected if they had ultrasound stones and if there was a history of urolithiasis in first and/or second degree relatives., Results: In 25 patients (44.6%), renal ultrasound was positive for lithiasis (stones [n=9] and microlithiasis [n=16]). Forty of the 56 families (71.4%) had a history of urolithiasis. The percentage of abnormal urinary calcium (28.6%) concentrations and an abnormal calcium/citrate ratio (69.6%) was higher in the first urine of the day. The calcium/citrate ratio was the only studied parameter that was related to a family history of urolithiasis. There were no differences in urinary parameters between patients with and without ultrasound-confirmed kidney stones., Conclusions: Urinary concentrations of calcium and the calcium/citrate ratio vary throughout the day. Urine produced at night has a higher risk of urinary calcium stone formation., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The formation of urinary stone, urolithiasis, is one the oldest known disease affecting human throughout different civilizations and times. The exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding. A single theory cannot explain its formation; therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall's plaque theory. In addition, various factors and components are identified that play an important role in the formation of these urinary calculi. In this review, composition of kidney stones, its prevalence/incidence, explanation of pathophysiological mechanisms and role of various factors; urinary pH, uric acid, parathyroid hormone, citrate, oxalate, calcium and macromolecules; osteopontin, matrix Gla protein, kidney injury molecules, urinary prothrombin fragment-1, Tamm-Horsfall protein, inter-α-inhibitors, have been discussed in detail.

BACKGROUND Urine solute supersaturation leads to the formation of urinary tract caliceal stones. Many parameters can be involved in the supersaturation of solutes in urine, such as pH. Uric acid has pKa ≤5.5, and it is solubilized at pH ≥5.5. The objective of the study was to evaluate the effects of potassium citrate and lemonade supplementation in pediatric patients with urolithiasis. MATERIAL AND METHODS A total of 126 children who had lower ureteral stones calculi and fragments with severe colic pain participated in this cross-over study. Children drank lemonade (2 mEq/kg/day citrate) in 3 divided doses for 5 days. After a 15-day washout period, children drank 2 mEq/kg/day of potassium citrate in 3 divided doses for 5 days. On the sixth of the day of individual intervention, a 24-h urine sample was collected and evaluated for pH, urine volume, citrate level, uric acid level, magnesium, phosphorus, potassium, and sodium. Urinary parameters for 1-day urine collection measurements after each supplementation were compared with baseline using the Mann-Whitney test following Tukey post hoc test at 95% confidence level. RESULTS Potassium citrate supplementation resulted in reduction of sodium concentration (p=0.0337; q=3.76) and increased pH of urine (p=0.0118; q=4.389). However, urine volume, citrate level, and uric acid level, as well as elemental magnesium, phosphorus, and potassium, remained unchanged after 5 days of supplementation with potassium citrate or lemonade. CONCLUSIONS Potassium citrate supplementation is an effective therapy for preventing pediatric urolithiasis, with acceptable adverse effects.

Hyperuricosuric calcium urolithiasis is a condition of mixed calcium oxalate stones characterized by hyperuricosuria either in isolation or in conjunction with other risk factors for calcium oxalate stones such as hypercalciuria, hyperoxaluria, and hypocitraturia. There are three proposed physicochemical models of pathogenesis where urate in its crystalline phase via heterogeneous nucleation, in its colloidal phase via removal of crystallization inhibitors, and in solution via precipitation crystallization, can all increase propensity to calcium oxalate precipitation. Regardless of the model, the phenomenologic observation of urate increasing calcium oxalate precipitation appears solid. Another supporting factor are retrospective data analysis and prospective trials showing uric acid lowering reduces stones events in hyperuricosuric calcium stone formers. Due to the heterogeneity of pathogenesis of calcium oxalate stones in the unselected stone-formers, association cannot be demonstrated between uric acid excretion rate and risk of kidney stone the general population. In calcium oxalate stoners with isolated hyperuricosuria or hyperuricosuria in combination with other calcium stone risks where treatment of these traditional risks fails to reduce stone formation, urate acid lowering should be cautiously attempted. More refinement of pathogenic models and prospective controlled trials in phenotypically defined subgroups of subjects with calcium oxalate urolithiasis will be informative.

The study aimed to investigate the changes in the concentration of bikunin, osteopontin, and nephrocalcin, depending on the changes in the renal stone-forming activity in patients with recurrent urolithiasis., Materials and Methods: The study comprised 152 patients with recurrent calcium oxalate stones at various localizations. Patients of the study group (n=78) were administered complex preventive treatment (water load, Blamaren, thiazide diuretics, oral calcium supplementation) aimed at reducing the activity of urolithiasis. Patients of the control group (n=74) received no treatment. The studied parameters included concentrations of urine bikunin, osteopontin, and nephrocalcin in using ELISA. The follow-up period was six months., Results: By the end of the follow-up, the bikunin concentration in the control group was significantly higher than in the study group (7.0+/-0.81 mg/ml vs. 3.28+/-0.86 mg/ml, respectively, p<0.05) while osteopontin level was significantly lower (2.4+/-0.39 mg/ml vs. 3.4+/-0.36 mg/ml, p<0.05). The nephrocalcin concentrations during the follow-up period did not change significantly (p>0.05). The presence of hypercalciuria did not lead to significant changes in the concentration of stone formation inhibitors., Discussion: The increase in bikunin concentration in control patients is associated with an increase in the expression of this stone formation inhibitor due to the rise in the urolithiasis activity. Reduction in the osteopontin concentration in patients with high urolithiasis activity is a consequence of osteopontin being a constituent of calcium oxalate stones., Conclusion: In patients with calcium oxalate urolithiasis, testing for urine concentrations of bikunin and osteopontin as potential markers can be used to estimate the risk of stone recurrence.

Background: To investigate relationships among urinary biomarkers [kidney injury molecule-1 (KIM-1), N-acetyl-β-glucosaminidase (NAG)], neutrophil gelatinase-associated lipocalin (NGAL) levels and renal tubular injury in childhood urolithiasis., Methods: Seventy children [36 girls, mean age: 7.3 ± 5.0 years (0.5-18.2)] with urolithiasis/microlithiasis and 42 controls [18 girls, mean age: 8.5 ± 3.8 years (0.9-16.2)] were included in this multicenter, controlled, prospective cohort study. Patients were evaluated three times in 6-month intervals (0, 6 and 12th months). Anthropometric data, urinary symptoms, family history and diagnostic studies were recorded. Urine samples were analyzed for metabolic risk factors (urinary calcium, uric acid, oxalate, citrate, cystine, magnesium, and creatinine excretion), and the urinary KIM-1, NAG, and NGAL levels were measured., Results: Stones were mostly located in the upper urinary system (82.9%), and six patients (8.6%) had hydronephrosis. Thirty patients (42.9%) had several metabolic risk factors, and the most common metabolic risk factor was hypocitraturia (22.9%). Urinary KIM-1/Cr, NAG/Cr and NGAL/Cr ratios were not significantly different between patients and controls. Furthermore, no significant changes in their excretion were shown during follow-up. Notably, the urinary KIM-1/Cr, NAG/Cr, and NGAL/Cr levels were significantly higher in children under 2 years of age (p = 0.011, p = 0.006, and 0.015, respectively). NAG/Cr and NGAL/Cr ratios were significantly increased in patients with hydronephrosis (n = 6, p = 0.031 and 0.023, respectively)., Conclusions: The results of this study suggest that none of the aforementioned urinary biomarkers (KIM-1, NAG and NGAL levels) may be useful for the early detection and/or follow-up of renal tubular injury and/or dysfunction in childhood urolithiasis.

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., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Numerous studies have reported an association between stress and urolithiasis. Although urinary risk factors have been measured in several of these, compelling evidence of a causal relationship has not been established. A shortcoming is that alterations in single urinary parameters rather than ratios and quotients, which provide a more synergistic risk evaluation, have been measured. Recently, we speculated about a possible association between chronic stress and stone recurrence. This presents an intriguing dichotomy of whether stress causes stones or vice versa, or whether they are linked in a self-propagating stress-stones-stress-recurrence cycle. We investigated the latter hypothesis in a retrospective case-control designed study in which we calculated urinary ratios and quotients which are regarded as diagnostic indicators of stone risk. These included Ca/Cr, Ox/Cr, Mg/Cr, Cit/Cr, urate/Cr and citrate-magnesium-calcium ratios, activity product quotient for calcium oxalate (CaOx) and relative supersaturation of CaOx, brushite and uric acid. Overnight urinary data from 128 participants comprising 31 first time (FS), 33 recurrent (RS) CaOx stone formers and 64 controls were used. All subjects had been previously assessed for chronic stress dimensions, as well as for stress caused by their stone episodes per se. Conditional and unconditional logistic regression (with a Bonferroni correction for multiple tests) and simple linear regression were used to analyse various components of the data. Although RS had more stressful life events, with greater intensity of perception than FS, there were no significant differences between the groups regarding any of the urinary risk factors. No significant association between stressful life events and any of the urinary ratios or quotients was observed. A direct causal link between stress and stone recurrence was not indicated. We believe that future studies should shift their focus from traditional urinary risk factors to other stone-forming mechanisms. However, we recognize that there is an inherent problem in attempting to solve the stress-stones dichotomy as it would be impossible to disentangle alterations in risk factors which arise from lifestyle stress and those arising from stone episodes themselves.

Environmental low-dose melamine exposure has been associated with urolithiasis risk in adults, but it is unclear if this exposure can cause early renal damage. This cross-sectional study investigated the association of this exposure and early renal damage in patients with calcium urolithiasis. We recruited patients diagnosed with upper urinary tract calcium urolithiasis from three hospitals in southwestern Taiwan between November 2010 and January 2015. All patients completed a structured questionnaire and provided one-spot urine samples for the measurement of melamine level and markers of early renal injury, including N-acetyl b-d-glucosaminidase (NAG), β2-microglobulin (β2-MG), and microalbumin. We used urinary melamine levels as an indicator of environmental melamine exposure. A total of 309 patients (mean age of 54.7 ± 12.8 years) were studied. Median urinary melamine level (μg/mmol Cr) was 1.26 (interquartile range 0.48-3.29). A significant and positive correlation was found between urinary melamine concentration and urinary NAG levels (Spearman correlation coefficient, r = 0.157, p = 0.006, n = 309). With urinary melamine levels categorized into quartiles, multivariate regression results showed the same relationship, particularly in those with first stone episode. In this group, patients with the highest quartile of urinary melamine concentration had a 3.95-fold risk (95% confidence interval = 1.43-10.94) of high NAG levels (dichotomized by median), compared to the lowest quartile after adjustment. No association was found between urinary melamine concentration and urinary microalbumin levels. In conclusion, urinary melamine is significantly associated with urinary marker of early renal tubular injury, NAG, in urolithiasis patients, especially ones with first stone episode., (Copyright © 2017. Published by Elsevier Ltd.)