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1.
J Nutr Sci Vitaminol (Tokyo) ; 70(3): 237-247, 2024.
Article in English | MEDLINE | ID: mdl-38945889

ABSTRACT

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by osteocytes in response to dietary phosphate intake. An increase in FGF23 level is an indicator of excess phosphate intake relative to the residual nephron number. Therefore, avoiding excessive phosphate intake and inhibiting the elevation of serum FGF23 levels are important to preserve the number of functional nephrons. This randomized crossover trial aimed to determine the potential differences in the impacts on serum FGF23 levels between plant protein and animal protein-based meals in individuals with normal renal function. Nine young men were administered plant (no animal protein) or animal protein-based meals (70% of their protein was from animal sources) with the same phosphate content. The test meals consisted of breakfast, lunch, and dinner. Blood samples were collected in the morning, after overnight fasting, and before and after eating the test meals (for two consecutive days at the same hour each day). Furthermore, a 24-h urine sample was obtained on the day the test meal was consumed. No significant interactions were found among serum phosphate, calcium, and 1,25-dihydroxyvitamin D levels. However, after eating plant protein-based meals, serum FGF23 levels decreased and serum intact parathyroid hormone levels increased (interaction, p<0.05). Additionally, urine 24-h phosphate excretion tended to be lower in individuals consuming plant protein-based meals than in those consuming animal protein-based meals (p=0.06). In individuals with normal renal function, plant protein-based meals may prevent an increase in serum FGF23 levels and kidney damage caused by phosphate loading.


Subject(s)
Cross-Over Studies , Fibroblast Growth Factor-23 , Fibroblast Growth Factors , Meals , Parathyroid Hormone , Phosphates , Humans , Male , Fibroblast Growth Factors/blood , Young Adult , Parathyroid Hormone/blood , Phosphates/blood , Adult , Dietary Proteins/administration & dosage , Dietary Proteins/pharmacology , Calcium/blood , Calcium/urine , Vitamin D/blood , Vitamin D/administration & dosage , Vitamin D/analogs & derivatives
2.
Urolithiasis ; 52(1): 94, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896256

ABSTRACT

Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10- 5. A total of 132 SNPs reached a threshold of P < 5 × 10- 8 using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Kidney Calculi , Polymorphism, Single Nucleotide , Humans , Female , Male , Kidney Calculi/genetics , Kidney Calculi/urine , Middle Aged , Taiwan/epidemiology , Adult , Multifactorial Inheritance , Calcium/urine , Calcium/blood , Calcium/metabolism , Aged , Case-Control Studies , Genetic Loci , Gene Frequency , Genetic Risk Score
3.
Sci Rep ; 14(1): 12001, 2024 05 25.
Article in English | MEDLINE | ID: mdl-38796538

ABSTRACT

The current study aimed to establish an experimental model in vitro and in vivo of urinary crystal deposition on the surface of ureteral stents, to evaluate the ability to prevent crystal adhesion. Non-treated ureteral stents were placed in artificial urine under various conditions in vitro. In vivo, ethylene glycol and hydroxyproline were administered orally to rats and pigs, and urinary crystals and urinary Ca were investigated by Inductively Coupled Plasma-Optical Emission Spectrometer. in vitro, during the 3- and 4-week immersion periods, more crystals adhered to the ureteral stent in artificial urine model 1 than the other artificial urine models (p < 0.01). Comparing the presence or absence of urea in the composition of the artificial urine, the artificial urine without urea showed less variability in pH change and more crystal adhesion (p < 0.05). Starting the experiment at pH 6.3 resulted in the highest amount of crystal adhesion to the ureteral stent (p < 0.05). In vivo, urinary crystals and urinary Ca increased in rat and pig experimental models. This experimental model in vitro and in vivo can be used to evaluate the ability to prevent crystal adhesion and deposition in the development of new ureteral stents to reduce ureteral stent-related side effects in patients.


Subject(s)
Stents , Animals , Rats , Swine , Male , Hydrogen-Ion Concentration , Calcium/urine , Crystallization , Ureter , Ethylene Glycol/chemistry , Hydroxyproline/urine , Urine/chemistry , Rats, Sprague-Dawley
4.
Am J Physiol Renal Physiol ; 327(1): F77-F90, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38721663

ABSTRACT

Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca2+) and magnesium (Mg2+) are essential for cellular function, and their deficiency can lead to impaired fetal growth. A key contributor to the homeostasis of these ions is the kidney, which in a pregnant rat undergoes major changes in morphology, hemodynamics, and molecular structure. The goal of this study is to unravel the functional implications of these pregnancy-induced changes in renal handling of Ca2+ and Mg2+, two cations that are essential in a healthy pregnancy. To achieve that goal, we developed computational models of electrolyte and water transport along the nephrons of a rat in mid and late pregnancy. Model simulations reveal a substantial increase in the reabsorption of Mg2+ along the proximal tubules and thick ascending limbs. In contrast, the reabsorption of Ca2+ is increased in the proximal tubules but decreased in the thick ascending limbs, due to the lower transepithelial concentration gradient of Ca2+ along the latter. Despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of Ca2+ and Mg2+ in pregnancy. Furthermore, we conducted simulations of hypocalcemia and hypomagnesemia. We found that hypocalcemia lowers Ca2+ excretion substantially more than Mg2+ excretion, with this effect being more pronounced in virgin rats than in pregnant ones. Conversely, hypomagnesemia reduces the excretion of Mg2+ and Ca2+ to more similar degrees. These differences can be explained by the greater sensitivity of the calcium-sensing receptor (CaSR) to Ca2+ compared with Mg2+.NEW & NOTEWORTHY A growing fetus' demands of minerals, notably calcium and magnesium, necessitate adaptations in pregnancy. In particular, the kidney undergoes major changes in morphology, hemodynamics, and molecular structure. This computational modeling study provides insights into how these pregnancy-induced renal adaptation impact calcium and magnesium transport along different nephron segments. Model simulations indicate that, despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of calcium and magnesium in pregnancy.


Subject(s)
Calcium , Glomerular Filtration Rate , Kidney , Magnesium , Female , Pregnancy , Animals , Magnesium/metabolism , Magnesium/urine , Calcium/metabolism , Calcium/urine , Kidney/metabolism , Rats , Computer Simulation , Renal Reabsorption , Models, Biological
5.
Vet J ; 305: 106146, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38788995

ABSTRACT

The pathogenesis of increased serum phosphate concentration and proteinuria in dogs with spontaneous hyperadrenocorticism (HAC) is unclear. A potential link between proteinuria and calcium/phosphate metabolism has never been studied in dogs with HAC. The aims of the study were: (1) To evaluate calcium/phosphate metabolism in dogs with spontaneous HAC and compare to healthy dogs as well as to dogs with non-HAC illness; (2) to look for associations between markers of calcium/phosphate metabolism and biomarkers of kidney disease in dogs with HAC. Fifty-four dogs were included in the study, classified as HAC (n=27), non-HAC disease (n=17), and healthy (n=10). Serum calcium, phosphate, 25(OH)Vitamin D, 1,25(OH)2Vitamin D, plasma intact parathyroid hormone concentration (iPTH), FGF23, and urinary fractional excretion of calcium and phosphate were evaluated in all dogs at diagnosis and compared between each group. The correlation between these variables and urine protein-to-creatinine ratio (UPC) and urinary N-acetylglucosaminidase-to-creatinine ratio (uNAG/C) was evaluated in the HAC group. Medians [range] of serum phosphate concentration, urinary fractional excretion of calcium (FE(Ca)), and iPTH were significantly higher in dogs with HAC than in dogs with non-HAC illness (P<0.01) and healthy dogs (P<0.01). Increased 1,25(OH)2Vitamin D/25(OH)Vitamin D was also observed (P<0.001). In HAC group, UPC was significantly negatively correlated with 25(OH)Vitamin D (r(s): -0.54; P<0.01). Urinary NAG/C was significantly positively correlated with serum phosphate (r(s): 0.46; P=0.019). Increased serum phosphate, urinary excretion of calcium, and hyperparathyroidism were observed in dogs with HAC. Vitamin D metabolism may be shifted towards increased 1-alpha hydroxylation.


Subject(s)
Adrenocortical Hyperfunction , Biomarkers , Calcium , Dog Diseases , Phosphates , Animals , Dogs , Dog Diseases/urine , Dog Diseases/metabolism , Dog Diseases/blood , Biomarkers/blood , Biomarkers/urine , Male , Phosphates/blood , Phosphates/urine , Phosphates/metabolism , Female , Calcium/urine , Calcium/blood , Calcium/metabolism , Adrenocortical Hyperfunction/veterinary , Adrenocortical Hyperfunction/urine , Adrenocortical Hyperfunction/blood , Kidney Diseases/veterinary , Kidney Diseases/metabolism , Kidney Diseases/urine , Parathyroid Hormone/blood , Vitamin D/blood , Vitamin D/analogs & derivatives , Proteinuria/veterinary , Proteinuria/urine , Fibroblast Growth Factor-23
6.
J Bone Miner Res ; 39(3): 315-325, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38477773

ABSTRACT

Environmental factors and genetic variation individually impact bone. However, it is not clear how these factors interact to influence peak bone mass accrual. Here we tested whether genetically programmed high bone formation driven by missense mutations in the Lrp5 gene (Lrp5A214V) altered the sensitivity of mice to an environment of inadequate dietary calcium (Ca) intake. Weanling male Lrp5A214V mice and wildtype littermates (control) were fed AIN-93G diets with 0.125%, 0.25%, 0.5% (reference, basal), or 1% Ca from weaning until 12 weeks of age (ie, during bone growth). Urinary Ca, serum Ca, Ca regulatory hormones (PTH, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)), bone parameters (µCT, ash), and renal/intestinal gene expression were analyzed. As expected, low dietary Ca intake negatively impacted bones and Lrp5A214V mice had higher bone mass and ash content. Although bones of Lrp5A214V mice have more matrix to mineralize, their bones were not more susceptible to low dietary Ca intake. In control mice, low dietary Ca intake exerted expected effects on serum Ca (decreased), PTH (increased), and 1,25(OH)2D3 (increased) as well as their downstream actions (ie, reducing urinary Ca, increasing markers of intestinal Ca absorption). In contrast, Lrp5A214V mice had elevated serum Ca with a normal PTH response but a blunted 1,25(OH)2D3 response to low dietary Ca that was reflected in the renal 1,25(OH)2D3 producing/degrading enzymes, Cyp27b1 and Cyp24a1. Despite elevated serum Ca in Lrp5A214V mice, urinary Ca was not elevated. Despite an abnormal serum 1,25(OH)2D3 response to low dietary Ca, intestinal markers of Ca absorption (Trpv6, S100g mRNA) were elevated in Lrp5A214V mice and responded to low Ca intake. Collectively, our data indicate that the Lrp5A214V mutation induces changes in Ca homeostasis that permit mice to retain more Ca and support their high bone mass phenotype.


Optimizing peak bone mass (PBM) is critical for strong bones and osteoporosis prevention. Both genetics and dietary factors like calcium (Ca) contribute to PBM. The goal of this research study was to determine how dietary Ca intake and genetics interact with each other to impact bone mass. Lowering dietary Ca in control mice causes hormonal changes that increase intestinal Ca absorption and reduce urinary Ca loss to protect bone; but this process fails when dietary Ca becomes too low. However, mice with genetically programmed high bone mass could maintain high bone mass even when challenged with Ca deficient diets. This protection is because the high bone mass mice maintain higher serum Ca, have altered production and utilization of Ca-regulating hormones, and have increased molecular indicators of intestinal Ca absorption and kidney Ca retention. Our findings are important because they demonstrate how a genetic program that increases bone formation can drive improved efficiency of Ca utilization to accommodate the increased need for Ca deposition into bone. We believe that our preclinical study provides important proof-of-principle support for the concept of personalized recommendations for bone health management.


Subject(s)
Calcium, Dietary , Low Density Lipoprotein Receptor-Related Protein-5 , Animals , Male , Low Density Lipoprotein Receptor-Related Protein-5/metabolism , Low Density Lipoprotein Receptor-Related Protein-5/genetics , Calcium, Dietary/pharmacology , Calcium, Dietary/metabolism , Mice , Vitamin D/metabolism , Vitamin D/pharmacology , Vitamin D/administration & dosage , Parathyroid Hormone/blood , Parathyroid Hormone/metabolism , Bone and Bones/metabolism , Bone and Bones/drug effects , Bone Density/drug effects , Calcium/metabolism , Calcium/urine , Calcitriol/blood , Calcitriol/pharmacology , Calcitriol/metabolism , Organ Size/drug effects
7.
J Hum Nutr Diet ; 37(3): 762-771, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38534044

ABSTRACT

BACKGROUND: This study examined the effects of animal protein- and plant protein-rich diets on postprandial phosphorus metabolism in healthy male subjects. METHODS: The study was conducted by randomised parallel-group comparison of healthy men aged 21-24 years. In Study 1, participants were divided into two groups and consumed either a 70% animal protein diet (AD, n = 6) or a 70% plant protein diet (PD, n = 6). In Study 2, participants were divided into three groups and consumed either AD (n = 10), PD (n = 10) or AD + DF, a 70% animal protein diet loaded with the same amount of fibre as PD (n = 9). The phosphorus contents of the diets used in this study were nearly equivalent (AD, 710.1 mg; PD, 709.7 mg; AD + DF, 708.9 mg). Blood and urine samples were collected before, and 2 and 4 h after the meal to measure phosphorus and calcium levels. RESULTS: In Study 1, PD consumption resulted in lower blood and urinary phosphorus concentrations 2 h postprandially compared with AD (p < 0.05). In Study 2, blood phosphorus levels in AD + DF after the diet remained lower, but not significantly so compared with AD, and urinary phosphorus levels were significantly lower 2 h postprandially (p < 0.05). CONCLUSIONS: A plant protein-rich diet reduced rapid postprandial increases in blood and urinary phosphorus concentrations compared with the animal protein-rich diets, suggesting that dietary fibre may play a partial role in the postprandial decreases in blood and urinary phosphorus concentrations.


Subject(s)
Postprandial Period , Humans , Male , Young Adult , Dietary Fiber/administration & dosage , Animal Proteins, Dietary , Phosphates/blood , Phosphates/urine , Calcium/blood , Calcium/urine , Phosphorus/blood , Phosphorus/urine , Plant Proteins, Dietary/administration & dosage , Adult , Diet/methods , Plant Proteins/administration & dosage
8.
Urolithiasis ; 52(1): 40, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38427040

ABSTRACT

This retrospective study aims to examine the correlation between calcium oxalate (CaOx) stones and common clinical tests, as well as urine ionic composition. Additionally, we aim to develop and implement a personalized model to assess the accuracy and feasibility of using charts to predict calcium oxalate stones in patients with urinary tract stones. A retrospective analysis was conducted on data from 960 patients who underwent surgery for urinary stones at the First Affiliated Hospital of Soochow University from January 1, 2010, to December 31, 2022. Among these patients, 447 were selected for further analysis based on screening criteria. Multivariate logistic regression analysis was then performed to identify the best predictive features for calcium oxalate stones from the clinical data of the selected patients. A prediction model was developed using these features and presented in the form of a nomogram graph. The performance of the prediction model was assessed using the C-index, calibration curve, and decision curve, which evaluated its discriminative power, calibration, and clinical utility, respectively. The nomogram diagram prediction model developed in this study is effective in predicting calcium oxalate stones which is helpful in screening and early identification of high-risk patients with calcium oxalate urinary tract stones, and may be a guide for urologists in making clinical treatment decisions.


Subject(s)
Body Fluids , Urinary Calculi , Humans , Calcium Oxalate/chemistry , Retrospective Studies , Nomograms , Urinary Calculi/diagnosis , Calcium/urine
9.
J Trace Elem Med Biol ; 84: 127419, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38461620

ABSTRACT

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, ß-CrossLaps (ß-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between ß-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca2+, ß-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and ß- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while ß-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.


Subject(s)
Biomarkers , Bone and Bones , Fluorides , Osteocalcin , Parathyroid Hormone , Humans , Child , Biomarkers/blood , Male , Fluorides/blood , Fluorides/urine , Female , Adult , Bone and Bones/metabolism , Osteocalcin/blood , Parathyroid Hormone/blood , Cross-Sectional Studies , Adolescent , Alkaline Phosphatase/blood , Calcium/blood , Calcium/urine , Middle Aged , Calcitonin/blood
10.
Aktuelle Urol ; 55(1): 54-59, 2024 Feb.
Article in German | MEDLINE | ID: mdl-38330954

ABSTRACT

Hypercalcaemia is a life-threatening electrolyte imbalance, which not only occurs in the context of an endocrinological disease but is also frequently associated with a tumour. Its severity is determined by the level of deviation from normal, acuity of occurrence, and severity of the symptoms. These are unspecific, can affect any organ system and ultimately result in a life-threatening hypercalcaemic crisis characterised by cardiac arrhythmia, metabolic acidosis, exsiccosis, fever, psychotic states and, ultimately, coma. Endocrinological disorders, drugs such as vitamin D3, vitamin A, checkpoint inhibitors, but also malignancies can be causative for the development of hypercalcaemia. Up to 30% of tumour patients are affected by hypercalcaemia. It is associated with a poor prognosis and a high tumour burden. Malignant hypercalcaemia is mainly caused by PTHrP (parathormone-related peptide), which is secreted by the tumour cells. In oncological patients, serum calcium (ionised calcium and non-ionised calcium) should be evaluated regularly. As the level of serum calcium depends on the albumin concentration, the latter should also be evaluated. Treatment consists of increasing the intravasal volume, increasing calcium excretion and inhibiting calcium reabsorption.


Subject(s)
Hypercalcemia , Neoplasms , Humans , Hypercalcemia/diagnosis , Hypercalcemia/etiology , Hypercalcemia/therapy , Calcium/urine , Patients' Rooms , Neoplasms/complications , Neoplasms/therapy , Neoplasms/metabolism , Critical Care
11.
Microbiol Res ; 282: 127663, 2024 May.
Article in English | MEDLINE | ID: mdl-38422861

ABSTRACT

Formation of calcium oxalate (CaOx) crystal, the most common composition in kidney stones, occurs following supersaturation of calcium and oxalate ions in the urine. In addition to endogenous source, another main source of calcium and oxalate ions is dietary intake. In the intestinal lumen, calcium can bind with oxalate to form precipitates to be eliminated with feces. High intake of oxalate-rich foods, inappropriate amount of daily calcium intake, defective intestinal transporters for oxalate secretion and absorption, and gastrointestinal (GI) malabsorption (i.e., from gastric bypass surgery) can enhance intestinal oxalate absorption, thereby increasing urinary oxalate level and risk of kidney stone disease (KSD). The GI microbiome rich with oxalate-degrading bacteria can reduce intestinal oxalate absorption and urinary oxalate level. In addition to the oxalate-degrading ability, the GI microbiome also affects expression of oxalate transporters and net intestinal oxalate transport, cholesterol level, and short-chain fatty acids (SCFAs) production, leading to lower KSD risk. Recent evidence also shows beneficial effects of urinary microbiome in KSD prevention. This review summarizes the current knowledge on the aforementioned aspects. Potential benefits of the GI and urinary microbiomes as probiotics for KSD prevention are emphasized. Finally, challenges and future perspectives of probiotic treatment in KSD are discussed.


Subject(s)
Kidney Calculi , Microbiota , Humans , Oxalates/metabolism , Calcium/urine , Kidney Calculi/prevention & control , Kidney Calculi/urine , Calcium Oxalate/metabolism , Ions
12.
Int Urol Nephrol ; 56(5): 1595-1603, 2024 May.
Article in English | MEDLINE | ID: mdl-38194188

ABSTRACT

PURPOSE: The present study aimed to investigate the effects of α-Klotho and oxidative stress markers on urinary stone disease (USD) and demonstrate their use as biochemical markers in USD. METHODS: Among the 90 individuals included, 30 individuals were healthy controls (Group 1), 30 individuals presented with USD for the first time (Group 2), and 30 individuals demonstrated recurrent USD (Group 3). Serum levels of α-Klotho, vitamin D, malondialdehyde (MDA), total oxidant status, and total antioxidant status were determined using spectrophotometry analysis. Serum calcium and parathormone levels and 24-h urine calcium levels were measured via biochemical analysis. RESULTS: No significant intergroup difference was noted in terms of age and sex. The groups had significant differences regarding α-Klotho, oxidative stress index (OSI), MDA, and 24-h urine calcium levels. α-Klotho was a determinant of 24-h urine calcium level and OSI. An increase of 1 pg/mL in α-Klotho level appeared to result in a decrease of 8.55 mg in 24-h urine calcium level and a decrease of 0.04 Arbitrary Unit in OSI. In patients experiencing USD for the first time, α-Klotho values were < 21.83 pg/mL and showed 66% sensitivity and 64% specificity. In individuals with recurrent stone formation, α-Klotho values below 19.41 pg/mL had 60% sensitivity and 77% specificity. CONCLUSIONS: The biochemical markers investigated herein, i.e., α-Klotho, OSI, and MDA, were involved in the pathogenesis of stone formation and can be used in day-to-day clinical practices of urology clinics to identify patients at risk for both first time and recurrent USD.


Subject(s)
Urinary Calculi , Urolithiasis , Humans , Klotho Proteins , Calcium/urine , Vitamin D , Urolithiasis/metabolism , Oxidative Stress , Vitamins , Biomarkers/metabolism , Recurrence
13.
Biol Trace Elem Res ; 202(5): 2228-2240, 2024 May.
Article in English | MEDLINE | ID: mdl-37721680

ABSTRACT

The present study aims to investigate the ability of CaNa2EDTA (ethylenediaminetetraacetic acid) macroparticles and nanoparticles to treat cadmium-induced toxicity in female rats and to compare their efficacies. Forty rats were divided into 4 equal groups: control, cadmium, cadmium + CaNa2EDTA macroparticles and Cd + CaNa2EDTA nanoparticles. Cadmium was added to the drinking water in a concentration of 30 ppm for 10 weeks. CaNa2EDTA macroparticles and nanoparticles (50 mg/kg) were intraperitoneally injected during the last 4 weeks of the exposure period. Every two weeks, blood and urine samples were collected for determination of urea, creatinine, metallothionein and cadmium concentrations. At the end of the experiment, the skeleton of rats was examined by X-ray and tissue samples from the kidney and femur bone were collected and subjected to histopathological examination. Exposure to cadmium increased the concentrations of urea and creatinine in the serum and the concentrations of metallothionein and cadmium in serum and urine of rats. A decrease in bone mineralization by X-ray examination in addition to various histopathological alterations in the kidney and femur bone of Cd-intoxicated rats were also observed. Treatment with both CaNa2EDTA macroparticles and nanoparticles ameliorated the toxic effects induced by cadmium on the kidney and bone. However, CaNa2EDTA nanoparticles showed a superior efficacy compared to the macroparticles and therefore can be used as an effective chelating antidote for treatment of cadmium toxicity.


Subject(s)
Cadmium Poisoning , Cadmium , Rats , Female , Animals , Cadmium/toxicity , Edetic Acid/pharmacology , Calcium/urine , Creatinine , Kidney , Cadmium Poisoning/drug therapy , Urea/pharmacology , Metallothionein
14.
Pediatr Nephrol ; 39(3): 761-770, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37755464

ABSTRACT

BACKGROUND: Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed (BF) or formula (F), is incompletely known. METHODS: A total of 511 spot urine samples from 136 children, aged 6 days to < 5 years, was collected. Urine was collected no fasting in infants < 18 months and first morning fasting in children aged 2.5-4 years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio. RESULTS: Urinary values were grouped according to the child's age: 6-17 days (G1), 1-5 months (G2), 6-12 months (G3), 13-18 months (G4), and 2.5-4 years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83 mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66 mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37 mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80 mg/mg (< 3 months) and 1.63 mg/mg (3-5 months), much higher than F infants (0.93 and 0.90 mg/mg, respectively). P/Cr and P/Ca were lower in BF infants. CONCLUSIONS: Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5 years were updated. BF infants < 6 months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6 months, according to the type of lactation, are proposed.


Subject(s)
Calcium , Magnesium , Child , Infant , Female , Humans , Child, Preschool , Infant, Newborn , Calcium/urine , Phosphates/urine , Uric Acid/urine , Calcium, Dietary , Creatinine/urine , Reference Values
15.
Saudi J Kidney Dis Transpl ; 34(1): 96-99, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-38092721

ABSTRACT

Citrate in the urine inhibits nephrolithiasis, and oral citrate solutions are used to prevent stones forming. The present study aimed to estimate the normograms of the urinary levels of citrate, creatinine, and their ratio in spot urine samples collected from 237 healthy children, aged from 1 month to 14 years. The findings showed the mean, standard deviation, median, and 5th and 95th percentiles of the values and compared them among age groups and between the sexes by using analysis of variance and independent t-tests. Our findings indicate that the ratio of spot urinary citrate to creatinine was higher for children younger than 18 months of age, possibly related to the consumption of dairy protein as their main meal. The 5th percentiles (lower cut off) for spot urinary citrate-to-creatinine ratio, were 915 mg/g for children aged under 18 months, 109 mg/g and 126 mg/g for older boys and girls.


Subject(s)
Citric Acid , Nephrolithiasis , Child , Male , Female , Humans , Creatinine/urine , Calcium/urine
16.
Chin Med Sci J ; 38(3): 250-256, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37643873

ABSTRACT

Kidney stone is a highly recurrent disease in the urinary tract system. Most kidney stones are calcium stones, usually consisting of either calcium oxalate or calcium phosphate. Supersaturation of soluble calcium, oxalate, phosphate, and citrate in the urine is the basis for calcium stone formation. Genetics, diet, low physical activity, and individual habits contribute to the formation of kidney stones. In this review, the associations of the risk of kidney stones with oxalate consumption and some individual habits, such as smoking, alcohol drinking, and opium consumption, are summarized.


Subject(s)
Calcium , Kidney Calculi , Humans , Calcium/urine , Oxalates , Kidney Calculi/etiology , Kidney Calculi/urine , Calcium Oxalate/urine , Habits
17.
Curr Opin Nephrol Hypertens ; 32(5): 490-495, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37530089

ABSTRACT

PURPOSE OF REVIEW: Kidney stone disease is caused by supersaturation of urine with certain metabolites and minerals. The urine composition of stone formers has been measured to prevent stone recurrence, specifically calcium, uric acid, oxalate, ammonia, citrate. However, these minerals and metabolites have proven to be unreliable in predicting stone recurrence. Metabolomics using high throughput technologies in well defined patient cohorts can identify metabolites that may provide insight into the pathogenesis of stones as well as offer possibilities in therapeutics. RECENT FINDINGS: Techniques including 1H-NMR, and liquid chromatography paired with tandem mass spectroscopy have identified multiple possible metabolites involved in stone formation. Compared to formers of calcium oxalate stones, healthy controls had higher levels of hippuric acid as well as metabolites involved in caffeine metabolism. Both the gut and urine microbiome may contribute to the altered metabolome of stone formers. SUMMARY: Although metabolomics has offered several potential metabolites that may be protective against or promote stone formation, the mechanisms behind these metabolomic profiles and their clinical significance requires further investigation.


Subject(s)
Calcium Oxalate , Kidney Calculi , Humans , Calcium Oxalate/urine , Kidney Calculi/metabolism , Calcium/urine , Oxalates , Metabolomics
18.
Urolithiasis ; 51(1): 95, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37458823

ABSTRACT

The correlation among gut microbiota, biochemical features, and dietary patterns in recurrent stone formers has been inadequately investigated in the Chinese population. Forty-two patients with calcium oxalate stones (CaOxS group), including 34 recurrent stone formers (RS group), and 40 nonstone healthy subjects (NS group) from Changshu Hospital Affiliated with Soochow University, were prospectively recruited. Food frequency questionnaires were completed by participants, fasting vein blood was extracted, 24-h urine was collected for biochemical detection, and fecal samples were gathered for 16S ribosomal RNA (rRNA) gene sequencing. BMI; serum levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), magnesium, and creatinine; and urine levels of magnesium in stone formers were significantly different from those of controls, and RS patients showed significantly low serum phosphate and high urine phosphate levels. Celery, bamboo shoots, and pickled food were the favored foods of local stone formers. Patients with recurrent stones had altered microbiota composition, with Escherichia, Fusobacterium, and Epulopiscium being the predominant pathogenic genera. The gut microbiota in RS patients had stronger functions in fatty acid and amino acid degradation but weaker functions in their biosynthesis. The pathogenic genera were positively correlated with BMI; serum levels of TGs and creatinine; urine levels of calcium, phosphate, and uric acid (UA); and celery, bamboo shoots, and pickled food intake. The abundance of Escherichia and Fusobacterium and the levels of serum magnesium and creatinine were the most relevant factors associated with stone recurrence and could be validated as biomarkers of recurrence. Our research provides a novel prevention strategy for the recurrence of renal calcium oxalate stones in the Han Chinese population of southern China.


Subject(s)
Gastrointestinal Microbiome , Kidney Calculi , Humans , Kidney Calculi/chemistry , Calcium Oxalate/metabolism , Creatinine , Magnesium , East Asian People , Phosphates , Calcium/urine
19.
Ecotoxicol Environ Saf ; 263: 115289, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37499391

ABSTRACT

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.


Subject(s)
Blood Glucose , Fasting , Metals , Selenium , Aged , Female , Humans , Bayes Theorem , Blood Glucose/analysis , Cobalt/urine , East Asian People , Fasting/blood , Fasting/urine , Independent Living , Selenium/urine , Vanadium/urine , Mass Spectrometry , Calcium/urine , Magnesium/urine , Molybdenum/urine , Metals/urine , Complex Mixtures/urine
20.
Am J Clin Nutr ; 118(2): 382-390, 2023 08.
Article in English | MEDLINE | ID: mdl-37269909

ABSTRACT

BACKGROUND: Preclinical studies suggest that blueberry consumption is associated with improved bone health. OBJECTIVES: We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment. METHODS: OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance. RESULTS: In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions. CONCLUSIONS: Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797.


Subject(s)
Blueberry Plants , Bone Resorption , Osteoporosis, Postmenopausal , Female , Humans , Rats , Animals , Calcium/urine , Powders , Postmenopause , Cross-Over Studies , Bone Resorption/prevention & control , Biomarkers , Osteoporosis, Postmenopausal/prevention & control
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