Normative data on the Bonn Risk Index for calcium oxalate crystallization in healthy children.
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ABSTRACT:
SUBMITTER: Porowski T
PROVIDER: S-EPMC1805047 | biostudies-other | 2007 Apr
REPOSITORIES: biostudies-other
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Project description:An indole-reacted calcium oxalate crystallization index (iCOCI) test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals. We conducted the prospective cohort study in accordance with the STARD guideline to evaluate the accuracy of urinary iCOCI test (index test) for diagnosing urolithiasis. A total of 281 participants were recruited for the study. Levels of urinary iCOCI were determined in the pre-diagnostic 24-h urine samples. Positive urinary iCOCI (? 0.6 COM eqv., g/L) was accounted for 51% (144/281), and the rest of 49% (137/281) were negative. Non-contrast CT imaging (reference standard) was subsequently performed for the definite diagnosis of urolithiasis to divide the participants into two groups, non-stone subjects (NSS, n?=?122) and stone-forming subjects (SFS, n?=?159). It should be noted that only subjects who currently had urinary stone at the time of study were classified as SFS. Urinary iCOCI levels in the SFS were significantly higher than the NSS. ROC analysis revealed an area under curve (AUC) of 0.893 (95% CI: 0.855-0.932) in separating NSS from all SFS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LH+) and negative likelihood ratio (LH-) of urinary iCOCI test for diagnosis of all urolithiasis were 87%, 80%, 84%, 84%, 83%, 4.44 and 0.16, respectively. Of 159 SFS, 38 were confirmed to have CaOx stones. Among these 38 CaOx SFS, only 2 had negative urinary iCOCI test. The AUC of urinary iCOCI test for separating CaOx SFS from NSS was markedly high (0.946, 95% CI: 0.914-0.978). Sensitivity, specificity, PPV, NPV, accuracy, LH+ and LH- of urinary iCOCI test for diagnosing CaOx urolithiasis were 95%, 86%, 68%, 98%, 88%, 6.80 and 0.06, respectively. Conclusion, we clinically validated that an innovative non-invasive urinary iCOCI test was highly accurate to diagnose urolithiasis, especially CaOx stone. With its high sensitivity and NPV, urinary iCOCI test is clinically intended to use as a screening test for CaOx urolithiasis. LH- of 0.06 indicates that negative result of urinary iCOCI test is highly accurate to rule out the CaOx stone formation. It is noted that urinary iCOCI level is expressed as arbitrary unit, and it is not directly related to the actual physiological level of urinary oxalate.
| S-EPMC7239845 | biostudies-literature
Project description:Calcium oxalate (CaOx) crystal-induced nephropathies comprise a range of kidney disorders, for which there are no efficient pharmacological treatments. Although CaOx crystallization inhibitors have been suggested as a therapeutic modality already decades ago, limited progress has been made in the discovery of potent molecules with efficacy in animal disease models. Herein, an image-based machine learning approach to systematically screen chemically modified myo-inositol hexakisphosphate (IP6) analogues is utilized, which enables the identification of a highly active divalent inositol phosphate molecule. To date, this is the first molecule shown to completely inhibit the crystallization process in the nanomolar range, reduce crystal-cell interactions, thereby preventing CaOx-induced transcriptomic changes, and decrease renal CaOx deposition and kidney injury in a mouse model of hyperoxaluria. In conclusion, IP6 analogues based on such a scaffold may represent a new treatment option for CaOx nephropathies.
| S-EPMC7175250 | biostudies-literature
Project description:Crystal growth rates have been extensively studied in calcium oxalate monohydrate (COM) crystallization, because COM crystals are the principal component in most kidney stones. Constant composition methods are useful for studying growth rates, but fail to differentiate concurrent nucleation and aggregation events. A constant composition method coupled with particle size determinations that addresses this deficiency was previously published for a calcium phosphate system, and this method was extended to COM crystallization in this report. A seeded constant composition experiment was combined with particle size determination and a separate near-equilibrium aggregation experiment to separate effects of growth rate, nucleation, and aggregation in COM crystal formation and to test the effects of various inhibitors relevant to stone formation. With no inhibitors present, apparent COM growth rates were heavily influenced by secondary nucleation at low seed crystal additions, but growth-related aggregation increased at higher seed crystal densities. Among small molecule inhibitors, citrate demonstrated growth rate inhibition but enhanced growth-related aggregation, while magnesium did not affect COM crystallization. Polyanions (polyaspartate, polyglutamate, or osteopontin) showed strong growth rate inhibition, but large differences in nucleation and aggregation were observed. Polycations (polyarginine) did not affect COM crystal growth or aggregation. Mixtures of polyanions and polycations produced a complicated set of growth rate, nucleation, and aggregation behaviors. These experiments demonstrated the power of combining particle size determinations with constant composition experiments to fully characterize COM crystallization and to obtain detailed knowledge of inhibitor properties that will be critical to understanding kidney stone formation.
| S-EPMC4573792 | biostudies-literature
Project description:BackgroundMusculoskeletal ultrasound is a well accessible technique to assess disease activity in children with juvenile idiopathic arthritis. Knowledge of reference values of joint structures is indispensable to differentiate between physiological and pathological finding. The aim of this study was to assess the structural sonographic features of joints and tendons in healthy children from several age groups (0.2-18 year), and develop a set of normative data.MethodsGreyscale ultrasound was performed in 500 healthy children (age 0.2-18 years) according to a predefined scanning protocol (Additional file 1) including the shoulder, elbow, wrist, second metacarpophalangeal joint, hip, knee, ankle, and first metatarsophalangeal joint). Demographic data and values of cartilage thickness, tendon diameters, and the degree of capsular distention measured by bone-capsular distance (BCD) were collected. Differences according to the sex were assessed by unpaired t-test. Single and multiple regression analyses were performed between the ultrasound outcomes and covariates such as age, height, weight and body mass index. Growth charts and tables were developed with respect to age. Nonparametric quantile regression was applied using the R-packages quantreg and quantregGrowth.ResultsA total of 195 male and 305 female volunteers were included between the age of 0 and 18 years (mean age 8.9; range: 0.2-17.9 years). Cartilage diminished markedly as children aged, and cartilage of the boys was significantly thicker compared to the girls in all joints (p < 0.001). In addition, cartilage became thinner as children's height and weight increased (beta regression coefficients between - 0.27 and - 0.01, p < 0.0001). Capsular distention (i.e., BCD > 0 mm) was uncommon in the ankle, wrist and MCP2 (resp. in 3, 6, and 3% of cases). It was more common in the suprapatellar and parapatellar knee, MTP1 and posterior recess of the elbow (resp. in 34, 32, 46, and 39% of cases). In the hip, some capsular distention was always present. Age was found to be the best predictor for BCD (beta regression coefficients between 0.05 and 0.13, p < 0.0001). Height was, in addition to age, a good predictor of tendon diameter (beta regression coefficients between 0.03 and 0.14, p < 0.0001). Growth curves and tables for each variable were developed.ConclusionsReference values of sonographic cartilage thickness, BCD and diameters of tendons at several joints were established from 500 healthy children, aged between 0.2 and 18 years. Growth charts and tables were developed to distinguish normal findings from pathology in children with complaints suspicious of arthritis.
| S-EPMC10508001 | biostudies-literature
Project description:Calcineurin inhibitors (CNIs) are widely used in organ transplantation to suppress immunity and prevent allograft rejection. However, some transplant patients receiving CNIs have hypocitraturia, hyperoxaluria and kidney stone with unclear mechanism. We hypothesized that CNIs suppress activities of urinary calcineurin, which may serve as the stone inhibitor. This study aimed to investigate effects of calcineurin B (CNB) on calcium oxalate monohydrate (COM) stone formation. Sequence and structural analyses revealed that CNB contained four EF-hand (Ca2+-binding) domains, which are known to regulate Ca2+ homeostasis and likely to affect COM crystals. Various crystal assays revealed that CNB dramatically inhibited COM crystallization, crystal growth and crystal aggregation. At an equal amount, degrees of its inhibition against crystallization and crystal growth were slightly inferior to total urinary proteins (TUPs) from healthy subjects that are known to strongly inhibit COM stone formation. Surprisingly, its inhibitory effect against crystal aggregation was slightly superior to TUPs. While TUPs dramatically inhibited crystal-cell adhesion, CNB had no effect on this process. Ca2+-affinity assay revealed that CNB strongly bound Ca2+ at a comparable degree as of TUPs. These findings indicate that CNB serves as a novel inhibitor of COM crystallization, growth and aggregation via its high Ca2+-affinity property.
| S-EPMC10427926 | biostudies-literature
Project description:Objectives: Early identification of children at risk of atherosclerosis is of paramount importance for implementing primary preventive measures addressing vascular health. Carotid intima-media thickness (cIMT) is a non-invasive biomarker of atherosclerosis. Semiautomatic radiofrequency-based software-guided technique quality intima-media thickness (RF-QIMT) was used to determine cIMT normative values in a healthy cohort of Caucasian children aged 6 to 18 years. Study design: In a cross-sectional study, data on age, chronic illness, medication use, and pubertal status was acquired by a questioner. Anthropometric and blood pressure measurements were performed by standardized methods and trained medical personnel. cIMT of the right common carotid artery far wall (1 centimeter proximal to bifurcation) was determined using a multifrequency (3-13 MHz) electronic linear array transducer SL1543, a portable ultrasound device (MyLab Gamma Esaote, Genoa, Italy), and RF-QIMT software. A systematic review of the published normal cIMT in children was done using PRISMA methodology, and identified normative values were compared to those obtained in the presented study. Results: 1137 non-obese normotensive children (males: n = 512; mean age 12.04 ± 3.52 years, females: n = 625, mean age 12.98 ± 3.83 years) were included. Gender-, age-, and height-specific mean cIMT percentile tables, percentile charts, and LMS tables for the RF-QIMT method were provided. They were comparable to the previously published data on mean cIMT gained by other validated ultrasound imaging techniques. cIMT increased with age, height, hip circumference, and BMI and was higher in males. Conclusions: Gender-, age-, and height-specific normative cIMT values, using the semiautomatic software-guided RF-QIMT technique, in children aged 6 to 18 years were developed and validated in respect to the previously published pediatric normative cIMT data. It is suggested that the investigated method could be used for the estimation of atherosclerotic risk in children, especially in epidemiological studies.
| S-EPMC7732599 | biostudies-literature
Project description:BACKGROUND:Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. METHODS:A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24?h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and eGFR. RESULTS:Mean (±SD) age at first visit was 19.5?±?16.6?years with an estimated glomerular filtration rate (eGFR) of 68.4?±?21.0?ml/min/1.73m2. After adjustment for age, sex, and eGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher eGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. CONCLUSION:In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.
| S-EPMC7161151 | biostudies-literature
Project description:BackgroundThe purpose of this cross-sectional study involving healthy emmetropic four-year-old Caucasian children was to provide a macular perfusion normative database acquired with optical coherence tomography angiography (OCTA). One eye of each examinee underwent OCTA imaging. The following parameters were analyzed using AngioTool Image J software: vessels area (VA), vessels density (VD), total number of junctions (TNJ), junctions density (JD), total vessel length (TVL), average vessel length (AVL), total number of endpoints (TNEP), lacunarity (L), vessel diameter index (VDI), tortuosity (T) and foveal avascular zone (FAZ). Average central macular thickness (CMT) and average central macular volume (CMV) were measured.ResultSixty-two eyes of 62 children of average age 50.4 ± 3.8 months were examined. VA, VD, and T increased from the inner towards the outer layers of the retina. The intermediate capillary plexus had the highest JD and TNEP and narrowest FAZ. Retinal sexual differentiation was supported with higher values of the retinal VA, VDI and TNEP, and chorioretinal VA, VDI and L in males. The choriocapillaris presented with the highest VD, AVL, and T and the lowest L and TNEP.ConclusionThe study provides the first detailed normative database of the macular vascular network in the youngest uniform cohort of emmetropic four-year-old children.
| S-EPMC8491392 | biostudies-literature
Project description:PURPOSE:Thymus grows after birth, reaches maximal size after the first few years and involutes by puberty. Because of the postnatal developmental and involutional duration, we aimed toinvestigate normal stiffness values of mediastinal thymus by shear wave elastography (SWE) in different age groups of children and discuss imaging findings of thymus. METHODS:We prospectively examined 146 children (90 girls, 56 boys) who underwent a thyroid or neck ultrasound examination. All subjects underwent ultrasound and SWE evaluation of mediastinal thymus by parasternal and suprasternal approach. We subdivided the subjects based on the ages as 0 to 2 months (group 1), >2 to 6 months (group 2); >6 months to 2 years (group 3), >2 to 5 years (group 4), >5 to 8 years (group 5), and greater than 8 years old (group 6).We investigated differences of mean shear wave elasticity (kPa) and shear wave velocity (m/sec) values among age groups and the association of SWE values with age, body mass index (BMI), height, and weight of the patients. RESULTS:Medians and ranges of age, height, weight, and BMI were 24 (2-84) months, 85 (55-120) cm, 12(4.55-22) kg, 15.37 (13.92-17.51) kg/m2, 11 (2.64-23.15) cc, respectively. Mean shear wave elasticity of thymus when all participants were included was 6.76±1.04 kPa. Differences of mean elasticity values among age groups and also gender groups were not statistically significant. There were highly significant negative correlations among age (r:0.3), height (r:0.26), weight (r:0.3) with elasticity and also velocity values (p<0.001). The thymus elasticity is negatively correlated with age. CONCLUSION:Quantitative evaluation of the thymus by SWE provides normative stiffness values based on age and gender groups. The thymus elasticity decreases with increased age, height and weight.
| S-EPMC7051269 | biostudies-literature
Project description:The removal of kidney stones can lead to small residual fragments remaining in the human body. Residual stone fragments can act as seeds for kidney stone crystallization and may necessitate another intervention. Therefore, it is important to create a consistent model with a particle size comparable to the range of kidney stone fragments. Thus, the size-determining parameters such as supersaturation ratio, energy input, and pH value are examined. The batch crystallizations were performed with supersaturation ratios between 5.07 and 6.12. The compositions of the dried samples were analyzed with Raman spectroscopy, infrared spectroscopy, and X-ray diffraction (XRD). The samples were identified as calcium oxalate monohydrate with spectroscopic analysis, while calcium oxalate dihydrate being the most prominent crystalline species at all supersaturation ratios for the investigated conditions. The aggregate size, obtained with analytical centrifugation, varied between 2.9 and 4.3 μm, while the crystallite domain size, obtained from XRD, varied from 40 to 61 nm. Our results indicate that particle sizes increase with increasing supersaturation, energy input, and pH. All syntheses yield a high particle heterogeneity and represent an ideal basis for reference materials of small kidney stone fragments. These results will help better understand and control the crystallization of calcium oxalate and the aggregation of such pseudopolymorphs.
| S-EPMC8515601 | biostudies-literature