Metabolic syndrome and the risk of calcium stones

Sakhaee et al in this issue have investigated whether the risk of the common calcium nephrolithiasis is associated with the metabolic syndrome (MS). This question is interesting since it deals with a more general problem on whether calcium nephrolithiasis is a ‘systemic disorder' and entails a cardiovascular ris

“Trust my morphology”, the key message from a kidney stone

International audienceThe Consensus Conference Group recently published an article in Urolithiasis highlighting the importance of urine and stone analysis in the metabolic evaluation of kidney stone formers (KSF) [1]. Indeed, each kidney stone contains the imprints of the conditions which created them during their 'lifetime in the kidney'. The morpho-constitutional classification method (MCC) established by Prof Michel Daudon correlates the morphological characteristics of stones with specific metabolic disorders [2]. Briefly, it distinguishes 7 types and 21 subtypes according to the crystalline composition and shape, color and structure of stones identified using an optical stereomicroscope (Table 1). This very specific method is easy to learn and provides the opportunity to quickly identify highly recurrent diseases, sometimes serious in their clinical consequences. Indeed, subtypes Ic, Ie, IIId, IVa2 and

Case study on the pathophysiology of Fabry disease: abnormalities of cellular membranes can be reversed by substrate reduction in vitro

It is still not entirely clear how α-galactosidase A (GAA) deficiency translates into clinical symptoms of Fabry disease (FD). The present communication investigates the effects of the mutation N215S in FD on the trafficking and processing of lysosomal GAA and their potential association with alterations in the membrane lipid composition. Abnormalities in lipid rafts (LRs) were observed in fibroblasts isolated from a male patient with FD bearing the mutation N215S. Interestingly, LR analysis revealed that the distribution of cholesterol and flotillin-2 are distinctly altered in the Fabry fibroblasts when compared with that of the wild-type cells. Furthermore, increased levels of glycolipid globotriaosylceramide 3 (Gb3) and sphingomyelin (SM) were observed in non-raft membrane fractions of Fabry cells. Substrate reduction with N-butyldeoxynojirimycin (NB-DNJ) in vitro was capable of reversing these abnormalities in this patient. These data led to the hypothesis that alterations of LRs may contribute to the pathophysiology of Morbus Fabry. Furthermore, it may be suggested that substrate reduction therapy with NB-DNJ might be a promising approach for the treatment of GAA deficiency at least for the selected patients

Quantitative Measurements of the Depth of Enamel Demineralization before and after Bleach: An In Vitro Study

Objective. This study is aimed at determining two main points. First, if the Canary System™ (CS), initially used to assess caries, can measure a decalcification depth of bleached enamel quantitatively, and second, whether or not whitening has a harmful effect on enamel. This device can be considered a useful tool in the clinical assessment of the progression of demineralization after bleaching. Materials and Methods. This study collected sixty human premolars that are in a good state recently extracted for orthodontic reason. To properly disinfect and preserve the premolars, they were stored in a saline solution and later in distilled water for a period of two weeks to allow the premolars to rehydrate. Later, 24 hours before the experiment, the premolars were introduced into a solution of artificial saliva to acquire back their minerals. The mineral content of the teeth was measured by the Canary System™ before bleaching. The teeth were bleached with 30% hydrogen peroxide (fläsh HP 30%), 30 min per week and for 3 consecutive weeks to simulate the conditions of strong bleaching in the clinic. The extent of demineralized enamel was measured by the Canary System™ at three points on the enamel surface of each tooth. The data were averaged for each application of the bleaching product. The demineralization extent of the teeth was measured by the Canary System™ before and after bleaching. The significance level was set at 0.05, and SPSS version 26 was used. The data were analyzed by using Wilcoxon’s and Student’s tests. Results. Mineral loss occurred after the first bleaching session; the Canary System™ detected a decalcification in the first bleaching session ( μm) compared to the other sessions (), while no significant change was detected between the second and the third sessions (). Conclusion. Based on the findings of the present study, under in vitro conditions, it was possible to measure the demineralization extent of bleached enamel with the Canary System™

Variability in urinary oxalate measurements between six international laboratories

Background. Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement. Methods. Urine samples from 24-h urine collection covering a broad range of oxalate concentrations were aliquoted and sent, in duplicates, to six blinded international laboratories for oxalate, sodium and creatinine measurement. In a second set of experiments, ten pairs of native urine and urine spiked with 10 mg/L of oxalate were sent for oxalate measurement. Three laboratories used a commercially available oxalate oxidase kit, two laboratories used a high-performance liquid chromatography (HPLC)-based method and one laboratory used both methods. Results. Intra-laboratory reliability for oxalate measurement expressed as intraclass correlation coefficient (ICC) varied between 0.808 [95% confidence interval (CI): 0.427-0.948] and 0.998 (95% CI: 0.994-1.000), with lower values for HPLC-based methods. Acidification of urine samples prior to analysis led to significantly higher oxalate concentrations. ICC for inter-laboratory reliability varied between 0.745 (95% CI: 0.468-0.890) and 0.986 (95% CI: 0.967-0.995). Recovery of the 10 mg/L oxalate-spiked samples varied between 8.7 ± 2.3 and 10.7 ± 0.5 mg/L. Overall, HPLC-based methods showed more variability compared to the oxalate oxidase kit-based methods. Conclusions. Significant variability was noted in the quantification of urinary oxalate concentration by different laboratories, which may partially explain the differences of hyperoxaluria prevalence reported in the literature. Our data stress the need for a standardization of the method of oxalate measuremen

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

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains. METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30. RESULTS: The median age was 44 years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5 mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2 days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability. CONCLUSIONS: This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients\u27 experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS

Variability in urinary oxalate measurements between six international laboratories

Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement

Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid rafts to gain its full functionality