[Clinical value of renal phosphorus threshold in the diagnosis and treatment X-linked hypophosphatemic rickets in children]. / 肾磷阈在儿童X-è¿žé”ä½Žç£·æ€§ä½å»ç— è¯Šæ²»ä¸­çš„ä¸´åºŠä»·å€¼.

OBJECTIVES: To explore the clinical value of the renal phosphorus threshold (ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate, TmP/GFR) in the diagnosis and treatment of children with X-linked hypophosphatemic rickets (XLH). METHODS: A retrospective study was conducted, including 83 children diagnosed with XLH at Children's Hospital of Nanjing Medical University from January 2010 to January 2023. Initial diagnosis and follow-up data were collected to investigate the correlation of TmP/GFR with the severity of rickets, calcium and phosphorus metabolism indicators, and the dosage of phosphate treatment. Children were divided into two groups based on the occurrence of renal calcification: the renal calcification group (n=47) and the non-renal calcification group (n=36). Clinical data between the two groups were compared. Multivariate logistic regression analysis was used to identify factors influencing renal calcification in XLH children. The predictive value of TmP/GFR for renal calcification in XLH children was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the 83 XLH children, the initial TmP/GFR was (0.78±0.21) mmol/L, with significant individual variation (range: 0.28-1.24 mmol/L). TmP/GFR showed no significant correlation with the severity of rickets (P>0.05). Parathyroid hormone was negatively correlated with TmP/GFR (rs=-0.020, P=0.008), while blood phosphorus (rs=0.384, P<0.001), blood calcium (rs=0.251, P<0.001), and 25-hydroxyvitamin D (rs=0.179, P<0.001) were positively correlated with TmP/GFR. No significant correlation was found between TmP/GFR and alkaline phosphatase (rs=-0.002, P=0.960) or phosphate treatment dosage (rs=0.012, P=0.800). Blood calcium and TmP/GFR levels were significantly lower in the renal calcification group than in the non-renal calcification group (P<0.05), while parathyroid hormone and urine calcium levels were significantly higher in the renal calcification group (P<0.05). Multivariate logistic regression analysis indicated that TmP/GFR and urine calcium levels were closely associated with renal calcification in XLH children (P<0.05). ROC curve analysis revealed that the areas under the curve for TmP/GFR, urine calcium, and their combined detection predicting renal calcification in XLH children were 0.696, 0.679, and 0.761, respectively. CONCLUSIONS: TmP/GFR may serve as an important diagnostic indicator for pediatric XLH; however, it does not reflect the severity or activity of rickets and cannot be used to judge the efficacy of traditional treatment. Urine calcium and TmP/GFR are valuable predictors for renal calcification in XLH children.

Thiazide Dose, Urine Calcium, and Symptomatic Kidney Stone Events.

This cohort study examines the association between thiazide dose and urine calcium reduction and correlates urine calcium changes with the occurrence of symptomatic kidney stone events.

A new system of phosphorus and calcium requirements for lactating dairy cows.

Accurately predicting phosphorous (P) and calcium (Ca) dietary requirements is critical for optimizing dairy cattle performance, and minimizing mineral excretions and ecosystems eutrophication. This study provides a new factorial system to determine net and dietary P and Ca requirements for maintenance and lactation, derived from a meta-regression of mineral trials involving lactating dairy cows. A comprehensive global database was constructed from 57 peer-reviewed articles of mineral balance trials, with a wide range of dietary and animal performance data. We estimated the net requirements for maintenance from the intercept of a nonlinear equation between mineral intake and the sum of total fecal and urinary excretions, which is an estimate of endogenous mineral loss. Mineral secreted in milk was used to obtain net requirements for lactation. The mineral metabolizable coefficient was quantified through observed (treatment means) mineral intake and total fecal and urinary excretions, discounting the estimated endogenous excretions from our proposed models. The nonlinear models of total fecal and urinary mineral excretion were evaluated (observed versus predicted values) using a 5-fold cross validation approach. The models to estimate the sum of endogenous fecal and urinary excretions of P (0.135±0.043 g P/kg BW0.75) and Ca (0.360±0.144 g Ca/kg BW0.75) exhibited suitable precision and accuracy; r = 0.89 and 0.79, concordance correlation coefficient = 0.85 and 0.77, and root mean square prediction error = 24.1 and 20.5% observed means, respectively. Dietary variables (forage level, fiber, starch, crude protein, and ether extract) did not affect the metabolizable coefficient (MC) of P and Ca; therefore, an overall dietary MC of P (0.69±0.01) and Ca (0.65±0.02) were proposed. Our new system estimates lower net and dietary P requirements for lactating dairy cows compared to the NASEM-2021 and NRC-2001 models, but slightly higher Ca requirements than NASEM-2021.This proposed system holds potential to reduce the use of phosphorus in diets for dairy cows, and thus to enhance economic efficiency and environmental sustainability of the dairy industry.

Caffeine and Ovariectomy Debilitate Bone Health in Rats on Calcium-deficient Diet.

This study investigated the effects of ovariectomy and caffeine intake on bone health in rats on calcium-deficient diet. Forty adults female Wistar rats were divided into 4 groups in a 2x2 factorial design: Ovary (OVX/SHAM) and Caffeine (placebo/caffeine). The animals were housed in individual cages for 8 weeks, receiving 18-20g of AIN-93M diet per day, containing 50% of the daily recommended intake of calcium. The rats underwent ovariectomy (OVX) or laparotomy (SHAM) surgery. Caffeine groups received 6mg of caffeine/kg/day. After euthanasia, the tibia and femur were dissected to determine the calcium content and bone fracture strength, respectively. Blood sample was collected to determine serum Ostase. 24-hour urine was analyzed for excreted calcium and NTx. Reduced bone fracture strength and calcium content were observed in OVX and Caffeine groups. When observed separately, OVX group showed increased urinary NTx and lower bone weight, blood ostase, and urinary calcium. Caffeine groups showed elevated urinary calcium. There was a positive correlation between bone fracture strength and calcium content. NTx correlated negatively with bone calcium, fracture strength and thickness. In conclusion, both OVX and caffeine intake debilitate bone health in rats on calcium-deficient diet.

Calcium isotope composition in serum and urine for the assessment of bone mineral balance (BMB) - The Osteolabs post-market follow-up study.

To further explore the clinical applicability of the calcium (Ca) isotope marker (CIM), we determined the 44Ca/42Ca isotope ratio in blood serum and urine. This ratio is expressed in the conventional δ-notation (as defined in the text below) specifically as CIM-serum for serum and as CIM-urine for urine. Our study tested the hypothesis that CIM values can differentiate between positive and negative bone mineral balance (BMB) across a diverse clinical population considering variables such as age, gender, and diet. The threshold values (CIM-serum: -0.85 ± 0.06 ‰ and CIM-urine: 0.23 ± 0.06 ‰) established in the OsteoGeo study (NCT02967978, Eisenhauer et al., 2019) were evaluated in 2320 participants as part of a surveillance study referred to as Osteolabs study. The earlier study revealed women with osteoporosis had an average CIM-serum value of -0.91 ± 0.21 ‰ (N = 24) and a CIM-urine value of 0.18 ± 0.33 ‰ (N = 71) that are significantly below the threshold values (p = 0.02 for urine, one-sided Wilcoxon rank test, p < 0.001 for serum, one-sided Student's t-test). Diseases affecting BMB such as osteoporosis, acute and chronic kidney disease (CKD), hyperthyroidism, breast cancer, prostate cancer, and myeloma were associated with significantly lower average CIM values, falling below the equilibrium thresholds and indicating negative BMB. In contrast, patients receiving osteoprotective treatments such as denosumab, Romosozumab, bisphosphonates, or hormone replacement therapy for certain diseases, had CIM values above the equilibrium thresholds indicating a positive BMB. Additionally, Ca supplements taken by some of the patients ((N = 22 (serum), N = 49 (urine), median dose: 500 mg) showed a Ca isotope composition approximately 1 ‰ higher than that from a normal diet. Consequently, their CIM values need to be adjusted to account for the amount and duration of supplementation to be comparable to those with a normal diet. Participants taking vitamin D (237 women; 58 men) showed no significant difference from the average values of the study group. Counterintuitively, the possible impact of malnutrition on individual BMB was most pronounced in vegans, who exhibited the highest average CIM-urine values compared to patients on a normal diet (p < 0.001, N = 17). The results of this study were consistent with the registered OsteoGeo study (NCT02967978) and other earlier published Ca isotope-based studies on BMB. We confirm that the CIM threshold values determined in the OsteoGeo study are generally valid for this much larger and diverse surveillance study group covering a diverse population encompassing various medical conditions and therapies.

Evaluating initial screening practices for calcium dysregulation after acute traumatic spinal cord injury: a retrospective review.

OBJECTIVES: The purpose of this study was to determine the frequency of which calcium homeostasis markers are obtained in the acute setting after an initial traumatic spinal cord injury (TSCI). DESIGN: Retrospective chart review of a limited data set linking ICD 10 codes designating TSCI to corresponding calcium homeostasis markers for patients with an initial chart encounter for TSCI. SETTING: A level 1 trauma center in Virginia, United States METHODS: The statistical software SPSS was used to calculate summary statistics including frequency, mean, and standard deviation for calcium homeostasis markers (basic metabolic panel, magnesium, spot urine calcium, testosterone panel, liver function tests, Vitamin D level, C-telopeptide, parathyroid hormone, celiac panel, DXA imaging report) as well as the mean and standard deviation for time to first check of the marker. RESULTS: Most markers were not obtained besides calcium. Only 10 of 80 (12.5%) of subjects had a Vitamin D level (mean 28, SD 23) checked during acute admission (mean days to check 1.5, SD 1.6), with most other markers checked much less frequently. CONCLUSIONS: Most calcium homeostasis markers were not checked on acute admission after TSCI. Future studies on implementing a standardized calcium homeostasis marker protocol for monitoring and potential medical intervention should be explored.

Urinary concentrations of mineral elements and their predictors in pregnant women in Jinan, China.

BACKGROUND: The essential mineral elements play important roles in proper growth, development and maintenance of physiological homeostasis of an organism. Women are at greater risk of mineral deficiency during pregnancy. However, the predictors of mineral element levels in pregnant women remain unclear. This study was conducted to determine the urinary levels of calcium (Ca), iron (Fe), copper (Cu), manganese (Mn) and selenium (Se) in women during early pregnancy and to explore the predictors of urinary exposure to each mineral element and high co-exposure to mineral element mixture. METHODS: 298 pregnant women in first trimester were recruited when they attended antenatal care in a hospital in Jinan, Shandong Province, China. We collected their spot urine samples and questionnaire data on their sociodemographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment. The concentrations of Ca, Fe, Cu, Mn and Se in all urine samples were measured. LASSO regression, multiple linear regression and binary logistic regression were used to analyze the predictors affecting mineral element levels. RESULTS: The geometric means of creatinine-corrected Ca, Fe, Cu, Mn and Se concentrations were 99.37 mg/g, 1.75 µg/g, 8.97 µg/g, 0.16 µg/g and 16.83 µg/g creatinine, respectively. Factors that influenced the concentrations of individual mineral element were as follows: (1) Se and Ca concentrations increased with maternal age; (2) women taking tap water as family drinking water had higher Ca levels and those taking polyunsaturated fatty acids intermittently had higher Cu levels; (3) Fe was adversely related to consumption frequency of barbecued foods; (4) Pregnant women with more frequent consumption of shellfish/shrimp/crab and living near green spaces or parks had higher Mn exposure, and those with higher frequency of meat consumption had lower Mn exposure. In addition, maternal age and the frequency of egg consumption were associated with odds of exposure to a mixture of high Ca, Fe, Cu and Se. CONCLUSIONS: The pregnant women in this study had comparable concentrations of urinary Cu and Se but lower concentrations of Ca, Fe and Mn compared with those in other areas. Predictors of urinary mineral elements included maternal age (Se and Ca), type of domestic drinking water (Ca), consumption frequency of barbecued food (Fe), polyunsaturated fatty acid use (Cu), the presence of urban green spaces or parks near the home and frequency of meat and shellfish/shrimp/crab intake (Mn). Moreover, maternal age and egg consumption frequency were significant predictors of high-level co-exposure to urinary Ca, Fe, Cu and Se.

Injection of luteinizing hormone or human chorionic gonadotropin increases calcium excretion and serum PTH in males.

Animal and human studies have suggested that sex steroids have calciotropic actions, and it has been proposed that follicle-stimulating hormone (FSH) may exert direct effects on bone. Here, we demonstrate the expression of the receptor for Luteinizing hormone (LH) and human choriogonadotropin (hCG), LHCGR, in human kidney tissue, suggesting a potential influence on calcium homeostasis. To investigate the role of LHCGR agonist on calcium homeostasis in vivo, we conducted studies in male mice and human subjects. Male mice were treated with luteinizing hormone (LH), and human extrapolation was achieved by injecting 5000 IU hCG once to healthy men or men with hypergonadotropic or hypogonadotropic hypogonadism. In mice, LH treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone (PTH). Similarly, hCG treatment in healthy men led to a significant increase in urinary calcium excretion, serum PTH levels, and 1,25 (OH)2D3, while calcitonin, and albumin levels were reduced, possibly to avoid development of persistent hypocalcemia. Still, the rapid initial decline in ionized calcium coincided with a significant prolongation of the cardiac QTc-interval that normalized over time. The observed effects may be attributed to LH/hCG-receptor (LHCGR) activation, considering the presence of LHCGR expression in human kidney tissue, and the increase in sex steroids occurred several hours after the changes in calcium homeostasis. Our translational study shed light on the intricate relationship between gonadotropins, sex hormones and calcium, suggesting that LHCGR may be influencing calcium homeostasis directly or indirectly.

Impact of Plant and Animal Protein-Based Meals on Serum Fibroblast Growth Factor-23 Levels in Healthy Young Men: A Randomized Crossover Trial.

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.

Identification of novel genetic susceptibility loci for calcium-containing kidney stone disease by genome-wide association study and polygenic risk score in a Taiwanese population.

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.

Renal calcium and magnesium handling during pregnancy: modeling and analysis.

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.

Phosphocalcic metabolism and its potential association with biomarkers of kidney disease in dogs with spontaneous hyperadrenocorticism.

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.

Establishment of an artificial urine model in vitro and rat or pig model in vivo to evaluate urinary crystal adherence.

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.

24-Hour Urinary Chemistries and Kidney Stone Risk.

RATIONALE & OBJECTIVE: Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II. EXPOSURE: Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium. OUTCOME: Incident symptomatic kidney stones. ANALYTICAL APPROACH: Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially nonlinear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor, and dominance analysis was performed to establish the relative importance of each urinary factor. RESULTS: Each urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. By contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified 3 categories of factors' relative importance: higher (calcium, volume, and citrate), intermediate (oxalate, potassium, and magnesium), and lower (uric acid, phosphorus, and sodium). LIMITATIONS: Predominantly White participants, lack of information on stone composition. CONCLUSIONS: Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation. PLAIN-LANGUAGE SUMMARY: Kidney stones are common and likely to recur. Certain urinary factors play a role in the development of stones, but their independent roles, relative importance, and shapes of association with stone formation are not well-characterized. We analyzed 24-hour urine collections from individuals with and without kidney stones. Stones were less likely in those with higher urine volume, citrate, potassium, magnesium, and uric acid and were more likely in those with higher calcium, oxalate, phosphorus, and sodium. The acidity of the urine was not related to stones. The urinary parameters showed different degrees of relative importance, with calcium, volume, and citrate being greatest. All parameters exhibited a linear or close-to-linear shape of association with stone formation.

Reference values of parathyroid hormone in very low birth weight infants.

PURPOSE: The primary goal was to estimate reference values of parathyroid hormone (PTH) in very low birth weight infants without severe neonatal morbidity. A secondary objective was to assess the relationship between PTH serum levels and selected laboratory markers of bone metabolism. METHODS: Ninety two infants with birth weight less than 1500 g met the inclusion criteria of the study. Serum levels of PTH, 25-hydroxyvitamin-D [25(OH)D], C3-epi-25(OH)D, total calcium, phosphorus, and alkaline phosphatase, and urinary levels of calcium, phosphorus, and creatinine were examined on day 14 and subsequently every 2 weeks until discharge. RESULTS: Of the total 167 serum samples examined for PTH levels in infants without 25(OH)D deficiency the estimated range was 0.9-11.9 pmol/l (8.5-112.3 pg/mL). During the first month, no statistically significant correlation was observed between PTH level and that of 25(OH)D, C3-epimers of 25(OH)D, S-Ca, S-P, or ALP, nor with urinary excretion of calcium and phosphorus. From the second month of life, there was a moderately significant correlation between PTH and 25(OH)D (Rho = -0.40, P =< .001), between PTH and calcium/creatinine ratio (Rho = -0.56, P = < .001), and between PTH and phosphorus/creatinine ratio (Rho = 0.51, P = < .001). CONCLUSIONS: The physiological range for PTH levels for preterm neonates without 25(OH)D deficiency was estimated as 0.9-11.9 pmol/l (8.5-112.3 pg/mL). It seems that elevation of serum PTH above this range can be considered as hyperparathyroidism in very low birth weight infants.

Association of urinary calcium excretion with chronic kidney disease in patients with type 2 diabetes.

PURPOSE: Herein, we investigated the correlation between urinary calcium excretion (UCaE) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: From August 2018 to January 2023, a total of 2031 T2DM patients providing 24-h urine samples were included in the final analyses. Patients were separated into four cohorts, based on the UCaE quartiles. We then analyzed renal functional indicators like estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE) among the four groups. Lastly, we utilized multivariable logistic regression models to investigate the correlation between UCaE and CKD. RESULTS: After adjusting for confounding factors, we observed a decreasing trend in CKD prevalence (36.3%, 13.0%, 7.5%, and 6.6%, respectively, P < 0.001) across the UCaE quartiles. Albuminuria (55.5% vs. 40.0%, 36.5%, 37.4%) and macroalbuminuria prevalence (20.0% vs. 9.3%, 5.2%, 5.7%) in the lowest quartile were markedly elevated, compared to the remaining three quartiles (P < 0.001). Meanwhile, the eGFR level (P < 0.001) showed a clearly increasing trend across the UCaE quartiles, and patients with moderate-to-severe decreases in eGFR levels (with cutoff limits at 30-59, 15-30, and < 15 mL/min/1.73m2) were mostly found in the lowest quartile (P < 0.001). Logistic regression analysis revealed that patients in the lowest quartile experienced an enhanced prevalence of CKD, relative to those in the highest quartile (odds ratio: 5.90, 95% confidence interval: 3.60-9.67, P < 0.001). CONCLUSION: Decreased UCaE was independently associated with the CKD prevalence in T2DM patients.

Male Lrp5A214V mice maintain high bone mass during dietary calcium restriction by altering the vitamin D endocrine system.

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.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children.

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.

Effect of a plant protein-rich diet on postprandial phosphate metabolism in healthy adult men: a randomised controlled trial.

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.