scholarly journals Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiqing Zhang ◽  
Sanjay Kumar ◽  
Muthuvel Jayachandran ◽  
Loren P. Herrera Hernandez ◽  
Stanley Wang ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Calcium Oxalate ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Kidney Stone ◽  
Fibroblast Growth Factor 23 ◽  
Pathogenic Mechanisms ◽  
Phosphorus Excretion ◽  
Stone Formers ◽  
Calcium Phosphorus

Abstract Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs). Methods Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. Results Urine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies. Conclusions Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

2020 ◽  
Author(s):  
Jiqing Zhang ◽  
Sanjay Kumar ◽  
Muthuvel Jayachandran ◽  
Stanley Wang ◽  
Elena M. Wilson ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Kidney Stone ◽  
Fibroblast Growth Factor 23 ◽  
Pathogenic Mechanisms ◽  
Calcium Stone ◽  
Phosphorus Excretion ◽  
Stone Formers ◽  
Calcium Phosphorus

Abstract Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium stone formers (CSFs) compared to non-stone formers (NSFs). Methods Incident CSFs (n = 24) and age- and sex- matched NSFs (n = 21) were studied. Clinical data were abstracted and biobanked cell-free urine samples were used to quantify specific urinary EV populations. EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23)); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. Results The urine pH of CSFs was lower than NSFs (P < 0.05), whereas urine excretion of calcium, phosphorus, and calcium oxalate and uric acid supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive ) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion whereas excretion of EVs expressing FGF23 correlated negatively (P < 0.05) with both urinary calcium and phosphorus excretion. Conclusions Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation were different between CSFs and NSFs. Thus, further validation of these and other populations of urinary EVs could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

scholarly journals Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers

2020 ◽  
Author(s):  
Daniel G Fuster ◽  
Gaétan A Morard ◽  
Lisa Schneider ◽  
Cedric Mattmann ◽  
David Lüthi ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Kidney Stone ◽  
Urinary Calcium ◽  
Sex Hormone ◽  
Urinary Oxalate ◽  
Oxalate Excretion ◽  
Stone Formers ◽  
17Β Estradiol ◽  
Urinary Citrate ◽  
Urinary Oxalate Excretion

Abstract Background Sex-specific differences in nephrolithiasis with respect to both distribution of prevalence and stone composition are widely described and may be influenced by sex hormones. Methods We conducted a cross-sectional analysis of the relationship between 24-hour urinary sex hormone metabolites measured by gas chromatography–mass spectrometry with urinary calcium, oxalate and citrate excretion in a cohort of 628 kidney stone formers from a tertiary care hospital in Switzerland, taking demographic characteristics, kidney function and dietary factors into account. Results We observed a positive association of urinary calcium with urinary testosterone and 17β-estradiol. Positive associations of urinary calcium with dehydroepiandrosterone, 5α-DH-testosterone, etiocholanolone, androsterone, and estriol were modified by net gastrointestinal alkali absorption or urinary sulfate excretion. As the only sex hormone, dehydroepiandrosterone was inversely associated with urinary oxalate excretion in adjusted analyses. Urinary citrate correlated positively with urinary testosterone. Associations of urinary citrate with urinary androsterone, 17β-estradiol and estriol were modified by urinary sulfate or sodium, or by sex. Conclusions Urinary androgens and estrogens are significantly associated with urinary calcium and citrate excretion, and associations are in part modified by diet. Our data furthermore reveal dehydroepiandrosterone as a novel factor associated with urinary oxalate excretion in humans.

scholarly journals Distinguishing Characteristics of Idiopathic Calcium Oxalate Kidney Stone Formers with Low Amounts of Randall's Plaque

2014 ◽  
Vol 9 (10) ◽  
pp. 1757-1763 ◽  
Author(s):  
Xiangling Wang ◽  
Amy E. Krambeck ◽  
James C. Williams ◽  
Xiaojing Tang ◽  
Andrew D. Rule ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Kidney Stone ◽  
Randall’S Plaque ◽  
Stone Formers ◽  
Randall's Plaque

A Method for Discrimination Between Calcium Oxalate Kidney Stone Formers and Normals

1982 ◽  
Vol 128 (3) ◽  
pp. 645-649 ◽  
Author(s):  
Sara Sarig ◽  
Nissim Garti ◽  
Reuven Azoury ◽  
Yohann Wax ◽  
Saul Perlberg
Keyword(s):  
Calcium Oxalate ◽  
Kidney Stone ◽  
Stone Formers

scholarly journals Association between aortic calcification and the presence of kidney stones: calcium oxalate calculi in focus

2021 ◽  
Author(s):  
Bo Li ◽  
Yin Tang ◽  
Liang Zhou ◽  
Xi Jin ◽  
Yu Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Calcium Oxalate ◽  
Kidney Stone ◽  
Renal Calculi ◽  
Aortic Calcification ◽  
Smoking History ◽  
Multivariable Model ◽  
Stone Formers ◽  
The Relationship ◽  
Calcium Oxalate Calculi

Abstract Purpose The current research is aimed at analyzing the relationship between kidney stone (KS) and abdominal aortic calcification (AAC) and the relationship between KS components and AAC. Methods This is a retrospective, case–control study. Kidney stone formers (KSFs) were treated at the Department of Urology, West China Hospital, Sichuan University for urological calculus disease from January 2014 to January 2020. Matched non-stone formers (non-SFs) were drawn from the same hospital for routine health examination from January 2018 to February 2019. Research-related information was collected and reviewed retrospectively from the hospital’s computerized records. AAC were evaluated using available results of computed tomography imaging and abdominal vascular ultrasound. The relationships of AAC between KSFs and non-SFs were compared. The composition of renal calculi was analyzed by Fourier-transform infrared spectrophotometer. KSFs were divided into AAC groups and non-AAC based on AAC. The relationship of the composition of renal calculi between AAC and non-AAC were compared. The independent-sample t test, the chi-squared test and binary logistics regression were performed. Results Altogether, 4516 people were included, with 1027 KSFs and 3489 non-SFs. There were no significant differences in the laboratory parameters between KSFs and non-SFs. The association between the presence of AAC and KS was significant in multivariable model 2 [adjusting hypertension, diabetes mellitus, fasting blood glucose, uric acid, serum triglyceride (TG), serum calcium, and urine pH] (OR 5.756, 95% CI 4.616–7.177, p < 0.001). The result of KSFs showed that calcium oxalate calculi (CaOx) was significantly associated with AAC in multivariable model 3 (adjusting age, hypertension, diabetes mellitus, drinking history, smoking history, and TG) (OR 1.351, 95% CI 1.002–1.822, p = 0.048). Conclusions The current study pioneered the revelation of the relationship between CaOx and AAC. Through an elimination of the confounding factors, the study demonstrated that KS and AAC were connected.

MO119COMPUTER-DERIVED SOFTWARE IN CLINICAL PRACTICE: RESULTS FROM A SHORT-TERM FOLLOW-UP ACCORDING TO KIDNEY STONE COMPOSITION IN KIDNEY STONE FORMERS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Tamara Cunha ◽  
Adrian Rodriguez ◽  
Pietro Manuel Ferraro
Keyword(s):  
Uric Acid ◽  
Calcium Oxalate ◽  
Kidney Stone ◽  
Urine Collection ◽  
Stone Composition ◽  
Regular Treatment ◽  
Stone Formers ◽  
Before And After ◽  
Over Time

Abstract Background and Aims Urinary supersaturation (SS) contributes to stone formation, and its assessment in stone formers may be helpful in clinical practice. Several computer programs are available for SS calculation, including EQUIL2, JESS and Lithorisk1. The aim of this study was to evaluate changes in SS in 24-hour urine in patients with known stone composition before and after about three months of regular treatment. Method Patients who submitted their stone/s for composition analysis and had provided an adequate 24-hour urine collection (creatinine 15-20 mg/kg/24-hour) before and around 90 days under regular treatment were included. Stone composition was defined using morphoconstitutional and infrared spectroscopy. The treatment was initiated in accordance with specific guidelines, and included dietary advices and medications2. SS for calcium oxalate (CaOx), calcium phosphate (CaP) and uric acid (UA) using EQUIL2, JESS and Lithorisk were calculated at baseline and after about 90 days on treatment. Continuous variables were reported as means (SD) while categorical variables were reported as frequencies and percentages. Baseline and follow-up SS urine values were compared using the Wilcoxon signed-rank test. 3D graphs were plotted using mean SS values of CaOx, CaP and UA obtained from each program before and after treatment, dividing the stones into 4 groups1: calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), calcium phosphate (CaP), and uric acid (UA). Ethical Committee approval was obtained. Results 105 patients (61 men, 58%) were followed and provided 24h urine collection. Of these, 101 (96%) were recurrent patients. The mean (SD) follow-up was 94 (14) days. 48 (46%) of all calculi were made of CaOx, either COM or COD, 36 (34%) of UA, and 21 (20%) of CaP. A significant reduction in SS values during treatment was observed in patients with COM (p&lt;0.05) , COD (p&lt;0.001), and UA stones (p&lt;0.001) with all programs. The reduction in SS values over time in patients with CaP stones was not significant (Table 1). Figure 1 shows 3D plots with SS before and after treatment into 4 groups of stone formers. Conclusion EQUIL2, JESS and Lithorisk are suitable software currently used for clinical and research purposes. SS values calculated by EQUIL2, JESS and Lithorisk during follow-up showed a significant reduction among COM, COD and UA stone formers. CaP stone formers did not show significant changes in SS over time.

scholarly journals Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease

2020 ◽  
Vol 31 (6) ◽  
pp. 1358-1369 ◽  
Author(s):  
Michelle R. Denburg ◽  
Kristen Koepsell ◽  
Jung-Jin Lee ◽  
Jeffrey Gerber ◽  
Kyle Bittinger ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Kidney Stones ◽  
Gut Microbiome ◽  
Early Onset ◽  
Kidney Stone ◽  
Stone Disease ◽  
Metagenomic Sequencing ◽  
Kidney Stone Disease ◽  
Stone Formers ◽  
Age Related

BackgroundThe relationship between the composition and function of gut microbial communities and early-onset calcium oxalate kidney stone disease is unknown.MethodsWe conducted a case-control study of 88 individuals aged 4–18 years, which included 44 individuals with kidney stones containing ≥50% calcium oxalate and 44 controls matched for age, sex, and race. Shotgun metagenomic sequencing and untargeted metabolomics were performed on stool samples.ResultsParticipants who were kidney stone formers had a significantly less diverse gut microbiome compared with controls. Among bacterial taxa with a prevalence >0.1%, 31 taxa were less abundant among individuals with nephrolithiasis. These included seven taxa that produce butyrate and three taxa that degrade oxalate. The lower abundance of these bacteria was reflected in decreased abundance of the gene encoding butyryl-coA dehydrogenase (P=0.02). The relative abundance of these bacteria was correlated with the levels of 18 fecal metabolites, and levels of these metabolites differed in individuals with kidney stones compared with controls. The oxalate-degrading bacterial taxa identified as decreased in those who were kidney stone formers were components of a larger abundance correlation network that included Eggerthella lenta and several Lactobacillus species. The microbial (α) diversity was associated with age of stone onset, first decreasing and then increasing with age. For the individuals who were stone formers, we found the lowest α diversity among individuals who first formed stones at age 9–14 years, whereas controls displayed no age-related differences in diversity.ConclusionsLoss of gut bacteria, particularly loss of those that produce butyrate and degrade oxalate, associates with perturbations of the metabolome that may be upstream determinants of early-onset calcium oxalate kidney stone disease.

scholarly journals Garcinia cambogia extract removes calcium oxalate kidney stones in both genetic and non-genetic Drosophila models of nephrolithiasis

2018 ◽  
Author(s):  
Qiuxia Fan ◽  
Xiaoming Feng ◽  
Xizhen Hong ◽  
Siqiao Gong ◽  
Jianwei Tian ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Kidney Stones ◽  
Kidney Stone ◽  
Ex Vivo ◽  
Malpighian Tubules ◽  
High Rate ◽  
Garcinia Cambogia ◽  
Stone Formers ◽  
Effective Medication ◽  
Drosophila Models

ABSTRACTKidney stone formers with family history have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication available for treatment. Here, we show that Garcinia cambogia extract (GCE) efficiently removes calcium oxalate kidney stones from Malpighian tubules in both genetic and non-genetic Drosophila models of nephrolithiasis, and hydroxycitrate -a major component of GCE, directly dissolves calcium oxalate stones in Drosophila Malpighian tubules ex vivo. Our study discovers a potential novel therapeutic strategy for the clinical treatment of nephrolithiasis and suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.

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