Comparison of metabolic parameters between pure-uric acid and mixed-uric acid kidney stone formers.

PURPOSE: We seek to compare clinical and 24-h urine parameters between pure-uric acid (UA) and UA-CaOx stone formers in our practice and explore how any differences in metabolic profiles could suggest different prevention strategies between the two groups. METHODS: We retrospectively reviewed patients with either pure- or mixed-UA nephrolithiasis from 2020 to 2023 at a tertiary care center. We included patients with a 24-h urine collection and a stone analysis detecting any amount of UA. Patients were organized into two cohorts: (1) those with 100% UA stones and (2) < 100% UA stones. Differences in demographic characteristics were compared between pure-UA and UA-CaOx stone formers. Twenty-four hour urine metabolic parameters as well as metabolic abnormalities were compared between the pure-uric acid and mixed-uric acid groups. RESULTS: We identified 33 pure-UA patients and 33 mixed-UA patients. Patient demographics were similar between the groups (Table 1). Pure- and mixed-UA patients had a similar incidence of metabolic syndrome, diabetes, history of stones, and stone burden. Table 1 Demographic and baseline characteristics among pure- and mixed-uric acid stone formers Pure-uric acid stones (n = 33) Mixed-uric acid stones (n = 33) p-value Median age [IQR] 63.00 [58.00-72.50] 63.00 [53.50-68.00] 0.339 Median BMI [IQR] 28.79 [25.81-33.07] 27.96 [25.81-29.55] 0.534 Gender, n (%) 1.000  Male 21 (63.6) 21 (63.6)  Female 12 (36.4) 12 (36.4) Metabolic syndrome, n (%) 17 (51.5) 16 (48.5) 0.806 Diabetes, n (%) 13 (39.4) 12 (36.4) 0.800 History of stones, n (%) 23 (69.7) 22 (66.7) 0.792 Median total stone burden, mm [IQR] 12.00 [6.00-26.50] 13.00 [7.05-20.00] 0.995 Median serum uric acid, mg/dL [IQR] 6.20 [4.80-7.15] 5.90 [4.98-6.89] 0.582 IQR Interquartile range BMI Body Mass Index n number We found the pure-UA cohort to have 24-h lower urine volume (1.53 vs. 1.96 L/day, p = 0.045) and citrate levels (286 vs. 457 mg/day, p = 0.036). UA-CaOx stone formers had higher urinary calcium levels (144 vs. 68 mg/day, p = 0.003), higher urinary oxalate levels (38 vs. 30 mg/day, p = 0.017), and higher median urinary calcium oxalate super-saturation (3.97 vs. 3.06, p = 0.047). CONCLUSIONS: Pure-UA kidney stone formers have different urinary metabolic parameters when compared with UA-CaOx stone formers, thus requiring different and tailored medical management.

The synergistic effect of multiple organic macromolecules on the formation of calcium oxalate raphides of Musa spp.

Needle-like calcium oxalate crystals called raphides are unique structures in the plant kingdom. Multiple biomacromolecules work together in the regulatory and transportation pathways to form raphides; however, the mechanism by which this occurs remains unknown. Using banana (Musa spp.), this study combined in vivo methods including confocal microscopy, transmission electron microscopy, and Q Exactive mass spectrometry to identify the main biomolecules, such as vesicles, together with the compositions of lipids and proteins in the crystal chamber, which is the membrane compartment that surrounds each raphide during its formation. Simulations of the vesicle transportation process and the synthesis of elongated calcium oxalate crystals in vitro were then conducted, and the results suggested that the vesicles carrying amorphous calcium oxalate and proteins embedded in raphides are transported along actin filaments. These vesicles subsequently fuse with the crystal chamber, utilizing the proteins embedded in the raphides as a template for the final formation of the structure. Our findings contribute to the fundamental understanding of the regulation of the diverse biomacromolecules that are crucial for raphide formation. Moreover, the implications of these findings extend to other fields such as materials science, and particularly the synthesis of functionalized materials.

Efficacy of Bisphosphonate for Urolithiasis Complicated by Osteogenesis Imperfecta.

A 44-year-old man with osteogenesis imperfecta presented with left renal colic. Non-contrast computed tomography revealed a stone (10×9 mm) in the left upper ureter. Ureteroscopic lithotripsy was performed twice and stone-free status was achieved. An analysis of the stone revealed a mixed composition including calcium oxalate and calcium phosphate. Postoperatively, we administered bisphosphonates to prevent recurrence of urolithiasis, as 24-hour urine collection revealed marked hypercalciuria. Eighteen months after surgery, the urinary calcium levels had normalized, and there was no recurrence of urolithiasis. Osteogenesis imperfecta can be complicated by urolithiasis, but bisphosphonates may be useful in preventing recurrence of this disease.

A novel in vivo model of ureteral fibrosis induced by calcium oxalate beads in C57BL/6J mice.

The global incidence of ureteroliths in humans is increasing, particularly posing a problem in developed countries. The most common stone type is calcium oxalate, which is associated with a high recurrence rate. In veterinary medicine, stones are the most common cause of ureteral obstruction in cats, accounting for 72-87% of cases. In cats, stones cause irreversible ureteral damage, necessitating stone treatment as well as ureteral therapy. However, the mechanisms underlying the ureteral damage caused by stones remain unclear. Therefore, this study aimed to create a mouse model suitable for studying the ureteral fibrosis caused by oxalate stones by artificially embedding calcium oxalate in the ureter. Pathological tissue analysis was used to compare normal ureters without ligation and ureters with sham or oxalate bead implantation. The ureters of the sham and oxalate bead groups showed granulation tissue formation, transitional epithelium exfoliation, and densely packed connective tissue in the proprietary and muscle layer regions. Particularly in the oxalate bead group, infiltration of degenerated neutrophils, presence of foreign body giant cells, and hyperplasia of the transitional epithelium were observed. The proportion of fibrosis was higher in the oxalate group than in the sham group. Overall, this mouse model created using oxalate bead implantation has the potential to efficiently induce ureteral obstruction. This mouse model is expected to be used for elucidating the molecular mechanisms of ureteral fibrosis and evaluating therapeutic drugs in future.

Patient compliance for metabolic evaluation and medical treatment (CoMET) in calcium-oxalate stone patients: prospective study by EULIS eCORE study group.

PURPOSE: In this study, we aimed to identify the compliance rates of calcium-oxalate stone patients for metabolic evaluation, diet and medical treatment and also determine the factors that are associated with poor compliance rates. METHODS: This study was conducted by the EULIS eCORE working group prospectively. In the initial visit, demographic and stone-related characteristics were recorded. Patients were suggested metabolic evaluation, dietary advices and medical treatment. Follow-up visit was performed after 3 months and compliance rates were recorded. Logistic regression analysis was performed to determine factors associated with poor compliance to metabolic evaluation, diet and medical treatment. RESULTS: Data of 346 patients from nine centers were analyzed. Compliance rates were 71.7%, 65.3%, and 63.7% for metabolic evaluation, diet, and medical treatment, respectively. In multivariate analysis, level of education (p = 0.003), history of emergency department visit (p = 0.04), number of stone surgeries (p = 0.03), patient care in dedicated stone clinic (p = 0.03), and history of shock wave lithotripsy (p = 0.005) were detected as independent predictors of compliance to metabolic analysis. Level of education (p < 0.001) and history of emergency department visit (p = 0.01) were detected as independent predictors of patient compliance to diet. Number of stone episodes (p = 0.03), family history of stones (p = 0.02), and polypharmacy (p < 0.001) were detected as independent predictors of patient compliance to medical treatment. CONCLUSIONS: Patient compliance to metabolic evaluation, diet, and medical therapy is important for successful management of urolithiasis. Dietary advices and medications should be personalized by taking in to account the factors associated with poor compliance.

Detection and characterization of urinary stones using material-specific images derived from contrast-enhanced dual-energy CT urography.

OBJECTIVE: To determine the accuracy of material-specific images derived from contrast-enhanced dual-energy CT urography (DECTU) in detecting and measuring urinary stones in comparison with that of unenhanced images and its utility in calcified stone differentiation. METHODS: 105 patients with 202 urinary stones (121 had confirmed composition by infrared spectroscopy) underwent triphasic (unenhanced, portal venous (VP) and excretory phase (EP)) DECTU. Material-specific images were derived in VP and EP with calcium-water, calcium-iodine and CaOxalate_Dihydrate (COD)-Hydroxyapatite (HAP) as basis material pairs. Stone number and size were recorded on unenhanced images and VP and EP material-specific images, where stone densities were also measured. Material densities of calcified stones (pure calcium oxalate [pCaO, n = 34], mixed calcium oxalate [mCaO, n = 14], mixed carbonate phosphate [mCaP, n = 70]) were compared and thresholds for differentiating these stones were determined using receiver operating characteristic analysis. RESULTS: All 202 urinary stones were detected on the unenhanced, calcium (water) and calcium (iodine) images in VP. While the detection rate was significantly decreased to 58 and 64% using calcium (water) and calcium (iodine) images in EP, respectively (all p < 0.001). Stone sizes measured on calcium (iodine) images in VP was similar to that of unenhanced images (10.6 vs 10.7 mm, p > 0.05). Significant differences in material densities were found among pCaO, mCaO and mCaP on COD(HAP) images with AUC of 0.72-0.74 for differentiating these stones. CONCLUSION: Material-specific images in VP derived from DECTU allow reliably detecting and measuring urinary tract stones in comparison with unenhanced images and can identify calcified stones with moderate diagnostic performance to provide potential 33% dose reduction. ADVANCES IN KNOWLEDGE: Material-specific images, especially the calcium (iodine) images in VP allow for reliable detection of urinary stones.Stone size measurement should be performed on the calcium (iodine) images in VP.Material density measurements on COD-HAP (VP) material decomposition images can be used to differentiate among pure calcium oxalate, mixed calcium oxalate and mixed carbonate phosphate stones with AUC of 0.72-0.74.

Pediatric Age-Related Distribution of Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate in Urinary Tract Stones: Metabolic, Gender, and Ethnic Correlates.

Introduction: Previous studies of pediatric urolithiasis have suggested possible associations between the relative proportions of calcium oxalate dihydrate (COD) and calcium oxalate monohydrate (COM) stones with age, gender, and ethnicity. This study aimed to investigate the composition and distribution of calcium oxalate (CaOx) stones according to these clinical factors and the metabolic correlates of the different subtypes in pediatric stone formers (PSFs). Patients and Methods: We retrospectively reviewed the database of all first-time stone formers between 2014 and 2019. Infrared spectrometry was used to determine stone composition. Stones were categorized by their highest relative component and reported as a percentage of occurrences in the cohort as a whole and by patient gender, age (divided into three age groups: 1-5, 6-12, and 13-18 years), and ethnicity. Clinical and metabolic correlates were analyzed. Results: Of 2479 consecutive stones submitted to our chemical stone laboratory, 220 first-time PSFs were identified. COD stones were the predominant subtype in the youngest group, and COM stones in the oldest group (odds ratio 0.39, 95% confidence interval: 0.18-0.86, p = 0.036). In the intermediate-age group (6-12 years), COM stones were more prevalent in Arab boys, and COD stones in girls of either ethnicity. COD stones were associated with hypercalciuria (p < 0.0001), and COM stones with hyperoxaluria (p = 0.0024). Hypercalciuria and hypocitraturia were the most prevalent abnormalities at ages 1 to 5 and 13 to 18 years, respectively. Conclusions: Analysis of CaOx stone subtypes and their metabolic correlates in stone formers has significant clinical relevance, specifically in children. In the present study, COD stones and hypercalciuria were more common in younger children, and COM stones and hypocitraturia in adolescents. These findings suggest unique complex interactions driving stone formations in children that may guide a more practical, limited, and cost-effective approach to metabolic evaluations, choice of treatment, and preventive measures, particularly in first-time CaOx PSFs.

The relationship between patients' kidney stone type and demographics in Israel: analysis of 10 K patients.

PURPOSE: To analyze urinary stone composition in Israel and assess the effects of key demographic parameters (gender, age, socioeconomic status, ethnicity, medical history and geographic region) on stone composition. METHODS: A retrospective review was conducted of stone analysis of 10,633 patients from an HMO Israeli database analyzed by a central laboratory from 2014 to 2019 and subjected to Fourier-transform infrared spectroscopy. Associations between stone composition and different demographic parameters were determined using the Chi-square test. RESULTS: Calcium oxalate (CaOx) monohydrate accounted for 51.9% of the stones. Of the total sample, 5776 stones had one single component (54%), whereas 4857 (46%) had mixed components. Men had a higher frequency of CaOx stones (89.6% vs. 85.6%), whereas women had a higher frequency of calcium phosphate, infection, and cystine stones (27.2%, 17.7%, and 0.9% vs. 17.2%, 7.5%, and 0.5%, respectively). Cystine stones were more abundant in Arabs (1.2% vs. 0.5% in the Jewish population). Lower socioeconomic status was associated with a higher prevalence of calcium phosphate, uric acid, and infection stones and a lower prevalence of CaOx stones. Uric acid stones were associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity (28.3%, 24.9%, 25.7%, and 22.6% vs. 9.6%, 8.4%, 12.3%, and 10.3%, respectively). CONCLUSIONS: Stone types were highly influenced by patients' demographics. COM was the most common stone component in either pure or complex form. UA stone prevalence was found to increase with age and was associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity.

Hydroalcoholic Extract of Ziziphus Jujuba Leaf to Prevent Ethylene Glycol and Ammonium Chloride-Induced Kidney Stones in Male Rat: Is it Effective?

PURPOSE: This study aimed to evaluate the effect of Ziziphus jujuba (Z. jujuba) leaf hydroalcoholic extract on the prevention/treatment of kidney stones. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control, Sham (kidney stone induction (KSI) by ethylene glycol 1% + ammonium chloride 0.25% through drinking water for 28 days), Prevention groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) through gavage for 28 days), and Treatment groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) from the 15th day). On the 29th day, the rats' 24-hour urine was assessed, the animals were weighed, and blood samples were taken. Finally, after nephrectomy and weighing the kidneys, tissue sections were prepared to examine the number of calcium oxalate crystals and tissue changes. RESULTS: The results indicated a significant increase in kidney weight and index, tissue changes, and the number of calcium oxalate crystals in the Sham group compared to the control; using Z. jujuba leaf considerably reduced them in experimental groups compared to the Sham. Body weight decreased in the Sham and experimental groups (except the prevention 2 group) compared to the control, while this observed reduction was lower in all experimental groups compared to the Sham. The mean urinary calcium, uric acid, creatinine, and serum creatinine in Sham and experimental groups (except the prevention 2 group) indicated a substantial increase compared to the control and decreased significantly in all experimental groups compared to the Sham. CONCLUSION: Hydroalcoholic extract of Z. jujuba leaf is effective in the reduction of calcium oxalate crystals forming, and its most effective dose was 500mg/kg.

Visualisation of calcium oxalate crystal macropatterns in plant leaves using an improved fast preparation method.

Leaves of the majority of plants contain calcium oxalate (CaOx) crystals or druses which often occur in spectacular distribution patterns. Numerous studies on CaOx in plant tissues across many different plant groups have been published, since it can be visualised readily under a light microscope (LM). However, there is surprisingly limited knowledge on the actual, precise distribution of CaOx in the leaves of quite ordinary plants such as common native and exotic trees. Traditional sample preparation for the documentation of the distribution of CaOx crystals in a given sample - including overall distribution - requires time-consuming clearing procedures. Here we present a refined fast preparation method to visualise the overall CaOx complement in a sample: The plant material is ashed and the ash viewed under the polarising microscope. This is a rapid method which overcomes many shortcomings of other methods and permits the visualisation of the entire CaOx content in most leaf samples. Pros and cons in comparison with the conventional clearing technique are discussed. Further aspects for CaOx investigations by micro-CT and scanning electron microscopy are discussed.

Use of scanning electron microscopy and energy dispersive X-ray for urine analysis: A preliminary investigation.

Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) are powerful tools to study the ultrastructure of numerous specimens and to determine their elemental composition, respectively. However, results have not yet been reported on their application to urine samples in routine clinical laboratory practice. Herein we investigate urine sediment by using SEM and EDX to detect and identify different urine components. A total of 206 urine samples from patients with and without urinary tract infections were analyzed using SEM and EDX. Microorganisms, crystals, epithelial cells, leukocytes, and erythrocytes were targeted in urine sediment samples. The identification of urine components was based on their morphology, size, contrast, and elemental composition. SEM-analysis allowed us to identify and classify microorganisms in urine sediments into the categories of gram-negative bacilli, cluster cocci, chain cocci, gram-negative bacilli, gram-positive bacilli, and yeasts. In addition, various types of epithelial cells such as renal, transitional, and squamous epithelial cells were found. Furthermore, leukocytes and erythrocytes were well identified, with the detection of various morphological forms of erythrocytes, such as dysmorphic and isomorphic erythrocytes. Using SEM-EDX analysis, calcium oxalate was the most frequently-identified crystal (92.0%), with prominent peaks of C, O, and Ca elements, followed by struvite (6%), with peaks of Mg, P, O, and N. These preliminary data suggest that the two complementary SEM-EDX analyses can be used to detect and identify microorganisms and crystals in urine samples. Further studies are still needed to apply SEM-EDX to urine sediment analysis. SEM-EDX analyses provided comparative results with the routine results, with accurate identification, high resolution and deep focus compared to the routine urinalysis SEM-analysis allowed us to identify and classify microorganisms in urine sediments into the categories of gram-negative bacilli, cluster cocci, chain cocci, gram-negative bacilli, gram-positive bacilli and yeasts. SEM-EDX analysis enabled the accurate identification of crystals based on both morphology and elemental composition.

Protein network analysis and functional enrichment via computational biotechnology unravel molecular and pathogenic mechanisms of kidney stone disease.

Mass spectrometry-based proteomics has been extensively applied to current biomedical research. From such large-scale identification of proteins, several computational tools have been developed for determining protein-protein interactions (PPI) network and functional significance of the identified proteins and their complex. Analyses of PPI network and functional enrichment have been widely applied to various fields of biomedical research. Herein, we summarize commonly used tools for PPI network analysis and functional enrichment in kidney stone research and discuss their applications to kidney stone disease (KSD). Such computational approach has been used mainly to investigate PPI networks and functional significance of the proteins derived from urine of patients with kidney stone (stone formers), stone matrix, Randall's plaque, renal papilla, renal tubular cells, mitochondria and immune cells. The data obtained from computational biotechnology leads to experimental validation and investigations that offer new knowledge on kidney stone formation processes. Moreover, the computational approach may also lead to defining new therapeutic targets and preventive strategies for better outcome in KSD management.

Analysis of the Components of 236 Cases of Urinary Stones in Xinjiang Uyghur Children.

INTRODUCTION: The aim of the study is to explore the relationship between clinical characteristics and urinary calculus in Xinjiang Uyghur children, and to provide clinical basis for the prevention as well as treatment of urinary stone. MATERIALS AND METHODS: In total, 236 urinary tract stone samples were collected from pediatric patients from February 2017 to April 2019, and those samples were analyzed by infrared spectroscopy. Stone compositions were compared with demographic data. RESULTS: Among the 236 cases, 166 cases were boys (70.34%) and 70 cases were girls (29.66%), with a male-to-female ratio of 2.37:1. A total of 21 kinds of calculi were detected, including 107 cases with six kinds of simple calculi and 129 cases with 15 kinds of mixed calculi. In this study, magnesium ammonium phosphate hexahydrate was only found in boys, and the difference was statistically significant (6.6 vs. 0.0%, p = 0.037). There were statistical differences in the age distribution of children with ammonium hydrogen urate, calcium oxalate, and other stone components (p < 0.05), while there were no statistical differences in the age distribution of children with apatite carbonate, magnesium ammonium phosphate hexahydrate, and anhydrous uric acid. The results showed that there was a significant difference in the localization of calculi between male and female children (upper urinary tract stones: 78.9 vs. 98.6%, p < 0.001). CONCLUSION: Uyghur pediatric patients with urolithiasis were young and the majority of stones was mixed, The main components of calculi were ammonium hydrogen urate, calcium oxalate and apatite carbonate, and there are differences in the localization of calculi between genders.

Performance of threshold-based stone segmentation and radiomics for determining the composition of kidney stones from single-energy CT.

PURPOSE: Knowledge of kidney stone composition can help in patient management; urine composition analysis and dual-energy CT are frequently used to assess stone type. We assessed if threshold-based stone segmentation and radiomics can determine the composition of kidney stones from single-energy, non-contrast abdomen-pelvis CT. METHODS: With IRB approval, we identified 218 consecutive patients (mean age 64 ± 13 years; male:female 138:80) with the presence of kidney stones on non-contrast, abdomen-pelvis CT and surgical or biochemical proof of their stone composition. CT examinations were performed on one of the seven multidetector-row scanners from four vendors (GE, Philips, Siemens, Toshiba). Deidentified CT images were processed with a radiomics prototype (Frontier, Siemens Healthineers) to segment the entire kidney volumes with an AI-based organ segmentation tool. We applied a threshold of 130 HU to isolate stones in the segmented kidneys and to estimate radiomics over the segmented stone volume. A coinvestigator verified kidney stone segmentation and adjusted the volume of interest to include the entire stone volume when necessary. We applied multiple logistic regression tests with precision recall plots to obtain area under the curve (AUC) using a built-in R statistical program. RESULTS: The threshold-based stone segmentation successfully isolated kidney stones (uric acid: n = 102 patients, calcium oxalate/phosphate: n = 116 patients) in all patients. Radiomics differentiated between calcium and uric acid stones with an AUC of 0.78 (p < 0.01, 95% CI 0.73-0.83), 0.79 sensitivity, and 0.90 specificity regardless of CT vendors (GE CT: AUC = 0.82, p < 0.01, 95% CI 0.740-0896; Siemens CT: AUC = 0.77, 95% CI 0.700-0.846, p < 0.01). CONCLUSION: Automated threshold-based stone segmentation and radiomics can differentiate between calcium oxalate/phosphate and urate stones from non-contrast, single-energy abdomen CT.

Machine learning based multi-label classification of single or mixed-composition urinary stones in in vivo spectral CT.

BACKGROUND: Urinary stones comprise both single and mixed compositions. Knowledge of the stone composition helps the urologists choose appropriate medical interventions for patients. The parameters from the spectral computerized tomography (CT) analysis have potential values for identification of the urinary stone compositions. PURPOSE: The present study aims to identify the compositions of urinary stones in vivo using parameters from spectral CT and machine learning, based on multi-label classification modeling. METHODS: This retrospective study collected 252 urinary stone samples with single/mixed compositions (including carbapatite [CP], calcium oxalate monohydrate [COM], calcium oxalate dehydrate [COD], uric acid [UA], and struvite [STR]), which were confirmed by ex vivo infrared spectroscopy. Parameters were extracted from an energy spectrum analysis (ESA) of the spectral CT, including the effective atomic number (Zeff ), Zeff histogram, CT values at a given x-ray energy level, and material densities. These ESA parameters were utilized for composition analysis via a multi-label classification fusion framework, where 250 multi-label models were built and the classification decisions from the top performance models were integrated by a multi-criterion weighted fusion (MCWF) approach in order to reach a consensus prediction. An example-based metric A c c e x a m $Ac{c_{exam}}$ and label-based metric A c c l a b e l $Ac{c_{label}}$ were used for global and label-wise accuracy evaluations, respectively. The top-ranked parameters associated with discriminating the stone composition were also identified. RESULTS: The multi-label classification fusion framework achieved an overall A c c e x a m $Ac{c_{exam}}$ of 81.2%, with A c c l a b e l $Ac{c_{label}}$ of 86.7% (CP), 90.6% (COM), 80.6% (COD), 95.0% (UA), and 94.4% (STR) for each composition on the independent testing cohort 1, and A c c e x a m $Ac{c_{exam}}$ of 76.4% with A c c l a b e l $Ac{c_{label}}$ of 80.5% (CP), 88.7% (COM), 74.9% (COD), 94.4% (UA), and 98.5% (STR) on the independent testing cohort 2. CONCLUSION: The parameters extracted from the ESA on spectral CT can be utilized to characterize single or mixed stone compositions via multi-label classification modeling. The generalization capability of the proposed methodology still requires further verification.

Aspergillus niger pneumonia as superinfection in a patient with pulmonary tuberculosis.

We report a patient with severe cavitary pulmonary tuberculosis and Aspergillus niger superinfection, whose only comorbidity was untreated diabetes mellitus. A. niger pneumonia was proven by PCR, sequencing and culture of pleural and respiratory secretions. The patient was successfully treated with a four-drug antituberculous regimen, liposomal amphotericin B (up to 5 mg/kg/d) and pleuro-pneumonectomy. Histology of the resected lung revealed destroyed lung tissue with inflammatory cells and fungal conidia. There were large deposits of polarising material, which was found to be calcium oxalate. There was also nodular caseating necrosis bordered by epitheloid cells and connective tissue. Thus, all diagnostic criteria for invasive A. niger infection were met. Several local risk factors, such as extensive lung damage and tissue acidification, may have favoured superinfection by A. niger. This case highlights the diagnostic value of calcium oxalate crystals in lung tissue and the need for combined antimicrobial and surgical treatment in extensive invasive aspergillosis caused by A. niger.

The SLC6A19 gene mutation in a young man with hyperglycinuria and nephrolithiasis: a case report and literature review.

BACKGROUND: Hyperglycinuria is a rare disorder, with few reported cases, caused by either a defect in glycine metabolism or a disturbance in renal glycine reabsorption. Genetic findings of hyperglycinuria are rare and have not previously been reported in Chinese young men. CASE PRESENTATION: A 24-year-old man presented with a compliant of bilateral lumbago for 1 month. Abdominal computed tomography revealed bilateral kidney stones and right upper ureteral dilatation. The 24-h urine analysis showed high urine oxalate levels of 63 mg/day. Analysis of amino acids in urine revealed that his urinary glycine levels were abnormally high (2.38 µmol/mg creatinine). Whole-exome sequencing detected the SLC6A19 variant c.1278 C > T p. (Cys426). Flexible ureteroscopy with holmium laser lithotripsy was conducted twice to remove his bilateral nephrolithiasis. Postoperative stone biochemical composition analysis revealed that the stones were composed of approximately 70% calcium oxalate monohydrate and 30% calcium oxalate dihydrate. The patient was subsequently diagnosed with hyperglycinuria. Three months after the stone surgery, ultrasonography revealed one nodule under the right thyroid lobe during a health checkup. His serum parathyroid hormone (PTH) levels increased to 392.3 pg/mL. Resection of the right parathyroid nodule was performed, and the histopathological examination confirmed right parathyroid adenoma. During the 2-year follow-up period, nephrolithiasis did not relapse, and serum PTH, calcium, and phosphorus levels were normal. CONCLUSION: The SLC6A19 gene may have been significant in the development of hyperglycinuria in a Chinese young man. Further evaluation for the possibility of a glycine excretion disorder could be considered when encountering nephrolithiasis.

Differential identification of urine crystals with morphologic characteristics and solubility test.

BACKGROUND: Urinary crystals are the most diverse forms of urine sediments. Reference images for typical urinary crystals are common, however, but images for interpreting atypical urinary crystals are very rare. The authors reviewed various forms and solubility tests of urine crystals to interpret atypical crystals found in clinical specimens. METHODS: We reviewed textbooks on urinary crystals and articles published in PubMed. Some atypical crystals were confirmed using a solubility test. RESULTS: The classification, shape, chemical structure, and solubility of the crystals were summarized. In the solubility test, some crystals showed different results; therefore, a new solubility test was proposed based on the literature review. We presented various types of calcium oxalates. CONCLUSIONS: These review articles will be helpful in the examination of atypical crystals found in clinical specimens. The solubility test requires additional studies to discriminate the inconsistent results between the authors.

Diuretic and Antiurolithic Effect of Garcinia humilis (Vahl) C.D. Adams Leaves, a Medicinal Plant Native to South American Countries.

This study evaluated the diuretic and antiurolithic effect of methanolic extract (MEGHL), dichloromethane (DCM), and ethyl acetate (EtA) fractions obtained from the leaves of Garcinia humilis, a medicinal plant known as achachairu and native to South American countries such as Bolivia, Peru, and Brazil. For the analysis of diuretic effect, the female rats received the treatment with MEGHL (3, 10, and 30 mg/kg), DCM (1, 3 and 10 mg/kg), EtA (1, 3, and 10 mg/kg), hydrochlorothiazide (HCTZ; 10 mg/kg), or vehicle (VEH) after an overload of saline solution. At the end 8 h of the experiment, the urinary parameters were measured. Additionally, the antiurolithic effect was analyzed, in which sodium oxalate was added in synthetic urine in the presence or absence of MEGHL, DCM, and EtA in different concentrations (0.1, 0.3, and 1 mg/mL). MEGHL, DCM, and EtA were able to promote 8-h diuresis in rats. MEGHL treatment at dose 30 mg/kg was accompanied by increased urinary Na+ , K+ and Cl- excretion. Moreover, the DCM and EtA fractions treatment increased K+ and Cl- excretion in the urine, although it does not cause any change in Na+ elimination. All the preparations were able to exert an antiurolithic effect in vitro, decreasing the number of calcium oxalate crystals of the monohydrate and dihydrate types. Taking together, the results presented herein showed that the preparations of G. humilis leaves are promising strategies to induce diuresis and antiurolithic effects.