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Aurantii Fructus Immaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stanniocalcin 1 (Stc1) is well known for its role in regulating calcium uptake in fish by acting on ionocytes or NaR cells. A hallmark of NaR cells is the expression of Trpv6, a constitutively open calcium channel. Recent studies in zebrafish suggest that genetical deletion of Stc1a and Trpv6 individually both increases IGF signaling and NaR cell proliferation. While trpv6 -/- fish suffered from calcium deficiency and died prematurely, stc1a -/- fish had elevated body calcium levels but also died prematurely. The relationship between Stc1a, Trpv6, and IGF signaling in regulating calcium homeostasis and organismal survival is unclear. Here we report that loss of Stc1a increases Trpv6 expression in NaR cells in an IGF signaling-dependent manner. Treatment with CdCl 2 , a Trpv6 inhibitor, reduced NaR cell number in stc1a fish to the sibling levels. Genetic and biochemical analysis results suggest that Stc1a and Trpv6 regulate NaR cell proliferation via the same IGF pathway. Alizarin red staining detected abnormal calcium deposits in the yolk sac region and kidney stone-like structures in -/- fish to the sibling levels. Genetic and biochemical analysis results suggest that Stc1a and Trpv6 regulate NaR cell proliferation via the same IGF pathway. Alizarin red staining detected abnormal calcium deposits in the yolk sac region and kidney stone-like structures in stc1a -/- fish. Double knockout or pharmacological inhibition of Trpv6 alleviated these phenotypes, suggesting that Stc1a inhibit epithelial Ca 2+ uptake by regulating Trpv6 expression and activity. stc1a -/- or double knockout of Trpv6 alleviated these phenotypes. These results provide evidence that Stc1a regulates calcium homeostasis and organismal survival by suppressing Trpv6 expression and inhibiting IGF signaling in ionocytes.stc1a -/- fish with CdCl 2 or double knockout of Trpv6 alleviated these phenotypes. These results provide evidence that Stc1a regulates calcium homeostasis and organismal survival by suppressing Trpv6 expression and inhibiting IGF signaling in ionocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Li, Li, Wang and Duan.)

The dynamic balance of Ca 2+ in oocytes promotes the recovery of the meiotic arrest phase, consequently promoting oocyte maturation. Hence, the analysis of the maintenance and role of calcium homeostasis in oocytes has important guiding significance for obtaining high-quality eggs and maintaining the development of preimplantation embryos. Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) are calcium channel proteins that regulate the dynamic balance between the endoplasmic reticulum (ER) and mitochondrial Ca 2+ . Nevertheless, the expression and role of IP 3 R in normal pig oocytes have not been reported, and other studies have focused on the role of IP 3 R in damaged cells. The purpose of this study was to investigate the potential role of IP 3 R in regulating calcium homeostasis in oocyte maturation and early embryonic development. Our results showed that IP 3 R1 is stably expressed at different stages of porcine oocyte meiosis, IP 3 R1 gradually converges to the cortex, and cortical clusters are formed in MII stages. The loss of IP 3 R1 activity contributeds to the failure of porcine oocyte maturation and cumulus cell expansion, as well as the obstruction of polar body excretion. Further analysis showed that IP 3 R1 plays an important role in affecting calcium balance by regulating the IP 3 R1-GRP75-VDAC1 channel between mitochondria and the endoplasmic reticulum (ER) during porcine oocyte maturation. Inhibiting IP 3 R1 expression-induced ER dysfunction, contributeding to ER calcium concentration ([Ca 2+ ] ER) release outwards into mitochondria and causing mitochondrial free calcium concentration ([Ca 2+ ] m ) overload and mitochondrial oxidative stress, which was confirmed by the increase in the level of reactive oxygen species (ROS) and apoptosis. Thereby, IP 3 R1 plays an important role in affecting calcium balance by regulating the IP 3 R1-GRP75 -VDAC1 channel between mitochondria and the ER during porcine oocyte maturation, inhibiting IP 3 R1 expression-induced calcium overload and mitochondrial oxidative stress, and increasing ROS levels and apoptosis., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “IP(3)R1 regulates calcium balance in porcine oocyte maturation and early embryonic development”., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Although vascular calcification is a recognised complication for haemodialysis patients, peritoneal dialysis (PD) patients are also at risk. As such we wished to review peritoneal and urinary calcium balance and the effect of calcium containing phosphate binders (CCPBs)., Methods: Twenty-four-hour peritoneal calcium balance and urinary calcium were reviewed in PD patients undergoing their first assessment of peritoneal membrane function., Results: Results from 183 patients, 56.3% male, 30.1% diabetic, mean age 59.4 ± 16.4 years, median 2.0 (2-6) months of PD, 29% treated by automated PD (APD), 26.8% continuous ambulatory (CAPD) and 44.2% APD with a day-time exchange (CCPD) were reviewed. Peritoneal calcium balance was positive in 42.6%, and remained positive in 21.3% after including urinary calcium losses. PD calcium balance was negatively associated with ultrafiltration (odds ratio 0.99 (95% confidence limits 0.98-0.99), p = 0.005. PD calcium balance was lowest with APD (APD - 0.45 (- 0.78 to 0.05) vs CAPD - 0.14 (- 1.18 to 0.59) vs CCPD - 0.03) - 0.48 to 0.5) mmol/day), p < 0.05, with 82.1% of patients with a positive balance prescribed icodextrin, when combining peritoneal and urinary losses. When considering CCPB prescription, then 97.8% of subjects prescribed CCPD had an over-all positive calcium balance., Discussion: Over 40% of PD patients had a positive peritoneal calcium balance. Elemental calcium intake from CCPB had a major effect on calcium balance, as median combined peritoneal and urinary calcium losses were < 0.7 mmol/day (26 mg), so caution is required to prevent excessive CCPB prescribing, increasing the exchangeable calcium pool and thus potentially increasing vascular calcification, particularly for anuric patients., (© 2023. The Author(s).)

Background: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients., Methods: This is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n = 324 in 42 patients) and a validation set (n = 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021., Results: Calcium excretion (mmol/24 h) was - 1.2877 + 0.646*[Ca] blood,total * ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was - 1.0 ± 6.7 mmol/24 h, the mean absolute error was 4.8 ± 4.8 mmol/24 h. Calculated calcium excretion was 105.8 ± 19.3 mmol/24 h. Mean daily CVVH calcium balance was - 12.0 ± 20.0 mmol/24 h. Mean cumulative calcium balance ranged from - 3687 to 448 mmol., Conclusion: During citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH., (© 2022. The Author(s).)

Microorganisms living on the surface and inside the human body play an important role in the physiological activities of the human body. The largest microecosystem in the human body is the gut microbiome. Calcium disorders are found in many diseases. For example, patients with chronic renal insufficiency present with secondary hyperparathyroidism, which is caused by a calcium imbalance in the body. In addition, calcium dysregulation may affect lipid metabolism in the liver through the calmodulator pathway, leading to cirrhosis, etc. Currently, a considerable number of probiotics have been proven to enhance the body's absorption of calcium. This paper reviews the effects of intestinal flora and related factors such as short-chain fatty acids, estrogen, immune factors and vitamin D on calcium balance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wu, Zhang, Yang and Hu.)

Background: The potential effects of dietary oxalate (Ox) intake on cardio-renal function have remained unestablished. We evaluated the effect of usual Ox intake and its interaction with dietary calcium (Ca) on incident hypertension (HTN) and chronic kidney disease (CKD)., Methods: Adult men and women, free of HTN and CKD at baseline (2006-2008), were recruited. Dietary intakes were assessed using a validated food frequency questionnaire, and the outcomes were documented up to 2014-2017. Multivariate Cox proportional hazard regression models were used to estimate the development of HTN and CKD in relation to Ox intakes. Repeated-measures generalized estimating equation (GEE) linear regression models were used to assess possible effect of Ox-intake on the estimated glomerular filtration rate (eGFR) and blood pressure levels over eight years., Results: Dietary Ox intakes were positively associated with incident CKD (HR = 2.59, 95% CI = 1.46-4.64) and HTN (HR = 1.79, 95% CI = 1.05-3.04). Compared to high-Ca consumers, subjects who had lower Ca intakes (< 990 vs. 1580 mg/d) had a higher incidence of CKD and HTN (HR = 2.43, 95% CI = 1.06-5.55, and HR = 1.72, 95% CI = 0.76-3.78). Participants with higher intakes of Ox (> 220 vs. < 150 mg/d) had lower eGFR values (75.3, 95% CI = 75.0-76.5 vs. 77.3, 95% CI = 76.6-78.1 mL/min/1.73m 2 , P time×group  = 0.004) and higher SBP levels (112, 95% CI = 111-113 vs. 109, 95% CI = 108-110 mmHg, P time×group  = 0.007) overtime., Conclusion: Higher dietary Ox intake may increase the risk of HTN and CKD. The relation between dietary Ox and risk of HTN and CKD seems to be varied by Ca intake, and subjects with lower Ca intakes may be more burdened by excessive amounts of dietary Ox., (© 2022. The Author(s).)

Background: The effect of the dialysate calcium concentration (D[Ca]) on mineral and bone metabolism in patients on peritoneal dialysis (PD) is overlooked. D[Ca] of 1.75 mmol/L is still prescribed to many patients on PD around the world. Previous studies on the effects of reducing D[Ca] have been carried out before the incorporation of calcimimetics in clinical practice. We hypothesized that a reduction in D[Ca] is safe and without the risk of a rise in serum parathyroid hormone (PTH)., Methods: In this non-randomized clinical trial, the D[Ca] was reduced from 1.75 mmol/L to 1.25 mmol/L for one year in prevalent patients on PD. Demographic, clinical, and CKD-MBD-related biomarkers were evaluated at baseline, 3, 6, and 12 months of follow-up., Results: 20 patients completed 1-year follow-up (56 ± 16 years, 50 % male, 25 % diabetic, 55 % with baseline parathyroid hormone - PTH >300 pg/mL). Over time, there was no significant change in calcium, phosphate, total alkaline phosphatase, 25(OH)-vitamin D or PTH, although adjustments in calcitriol and sevelamer prescription were required. After 1 year, absolute and percentual change in PTH levels were 36 (-58, 139) pg/mL, and 20 % (-28, 45) respectively. The proportion of patients with PTH > 300 pg/mL did not change during the follow-up (p = 0.173)., Conclusion: Knowing the risk of a positive calcium balance in patients on PD, reducing the D[Ca] concentration is a safe and valuable option, although medication adjustments are needed to detain PTH rising., Competing Interests: The author(s) declare no competing interests., (© 2022 The Authors.)

Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42 Ca and 44 Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42 Ca is preferentially incorporated into bone, while heavier 44 Ca is excreted. The ratio ( 44/42 Ca serum ) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42 Ca serum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42 Ca serum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42 Ca serum ratio and parathyroid hormone. The  44/42 Ca serum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42 Ca serum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Serum calcium isotopes (δ 44/42 Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ 44/42 Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ 44/42 Ca Serum with bone histology are unknown. We analyzed Ca and δ 44/42 Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ 44/42 Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ 44/42 Ca Bone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ 44/42 Ca Bone was similar in the femora and ribs. At the time of sacrifice, δ 44/42 Ca Serum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ 44/42 Ca Bone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ 44/42 Ca in growing rats. δ 44/42 Ca Serum inversely correlated with markers of bone mineralization.

Ethnopharmacological Relevance: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear., Aim of the Study: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats., Materials and Methods: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy., Results: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats., Conclusions: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling., Objective: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis., Methods: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05., Results: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger., Conclusion: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.

Introduction: To assess the safety, efficacy, and calcium flux of an accelerated algorithm for regional citrate anticoagulation in membrane-based plasma exchange., Methods: This was an observational study in patients receiving citrate anticoagulated, membrane-based plasma exchange at the Canberra Hospital between July 2017 and May 2020. Data were collected prospectively using an electronic medical record and compared to data from our previous published algorithm., Results: There were 134 plasma exchange sessions performed during the observational period. Circuit clotting occurred in 4 sessions, and 1 session was affected by symptomatic hypocalcaemia. A systemic ionized calcium <0.96 mmol/L was seen in 19.4% of sessions, which was a similar frequency to that seen in our previous algorithm. A systemic ionized Ca <0.81 mmol/L occurred in 4 sessions (all asymptomatic). This hypocalcaemia occurred towards the end of the sessions, after switching from albumin to fresh frozen plasma replacement fluid. Median treatment time was 135 min, compared to 219 min in our previously published algorithm. Mean net Ca gain/session was 7.7 ± 2.3 mmol., Conclusion: An accelerated algorithm for regional citrate anticoagulation achieves substantial time saving while maintaining efficacy and safety. The 4 episodes of systemic ionized calcium <0.81 mmol/L may have been due to recirculation of infused citrate but, probably more likely, are due to the additional citrate load imposed by use of fresh frozen plasma in these sessions. Future algorithms need to better account for the citrate load present in fresh frozen plasma., (© 2021 S. Karger AG, Basel.)

Objective: Opposite to lanthanum carbonate (LC), sevelamer hydrochloride (SH) may increase intestinal calcium absorption. The study compared the effects of LC and SH on serum and urine phosphate and calcium, and on hormones regulating mineral-bone metabolism., Patients and Methods: A prospective randomized crossover study included 34 patients with eGFR <60 mL/min. A single oral dose of LC (1,000 mg) or SH (2,400 mg) was administered in random order 15 minutes after a standardized meal fortified with 5 g calcium carbonate. Serum calcium, phosphate, and parathormone were measured before and 3, 6, 12, and 24 hours after each medication. Bone alkaline phosphatase (BAP), sclerostin, calcitriol, and FGF-23 were measured at baseline and after 12 and 24 hours. A 24-hour calcium and phosphate excretion was measured after each drug., Results: Serum calcium increased 3 and 6 hours after SH then returned to baseline. After LC calcium was unchanged for up to 3 hours then transiently increased and eventually returned to baseline. The area under curve (AUC) of serum calcium for 12 hours after SH was larger than after LC ( p =0.04). Serum phosphate decreased after each drug with a nadir 3 hours post-SH and 6 hours post-LC. AUC of serum phosphate was similar after both medications. PTH decreased transiently after both drugs. BAP did not change. FGF-23 was constant for the first 12 hours but later decreased after each drug., Conclusion: A 2,400 mg SH and 1,000 mg LC are similarly effective in lowering serum phosphate in CKD, but LC induce in less intestinal calcium absorption after a meal. The trial was registered on February 23, 2018 in the clinicaltrial.gov database - NCT03451019., Competing Interests: The authors declare no conflicts of interest., (© 2021 Makowka and Nowicki.)

Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.

Introduction: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate., Methods: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients' treatment remained unchanged during the study period., Results: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD., Conclusions: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes., (© 2021 S. Karger AG, Basel.)

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established. Recent studies have shown impairments in the calcium homeostasis in striatal neurons in HD. These cells are extremely sensitive to changes in the cytoplasmic concentration of calcium and its excessive increase leads to their death. One of the possible ways to normalize the balance of calcium in striatal neurons is through the sigma 1 receptor (S1R), which act as a calcium sensor that also exhibits modulating chaperone activity upon the cell stress observed during the development of many neurodegenerative diseases. The fact that S1R is a ligand-operated protein makes it a new promising molecular target for the development of drug therapy of HD based on the agonists of this receptor.

Previous research documented that furosemide negatively impacted calcium balance for 3 days but did not determine when calcium balance returned to baseline. This study hypothesized that furosemide's impact on calcium would return to control values before 7 days post-administration. Ten mature geldings were assigned to either control (CON, n = 5) or treatment (FUR, n = 5) for the first of two 8-day total collections in crossover design. Treatment horses received one administration of furosemide (1 mg/kg, IV). A 10% sample of pooled faeces and urine from each day was kept. Calcium concentrations in hay, faeces and urine were determined by an atomic absorption spectrophotometer. Data were analysed using mixed-model-repeated measures ANOVA to determine influence of day and treatment. For urine output, FUR urinated twice as much during the 24 hr after administration than CON (p < .001). Horses in FUR excreted more urinary calcium 24-hr post-administration as compared to CON (9.3 ± 1.0 and 4.2 ± 1.0 g, respectively; p < .001). Calcium balance in FUR was more negative on day 1 than day 3 (p < .05). Faecal calcium concentrations remained the same from day 1 to day 7 in CON (6.3 ± 1.3 and 5.5 ± 1.3 g/kg, respectively; p > .10) but were lower in FUR on day 7 as compared to day 1 (4.8 ± 1.3 and 7.3 ± 1.3 g/kg, respectively; p < .001), indicating a potential mechanism to restore calcium balance. These findings corroborate previous studies on furosemide and calcium balance and provide evidence for a possible mechanism to recover net calcium losses after furosemide administration. Since calcium balance returns to baseline in 3 days and previous results have examined frequent, long-term use, furosemide may not negatively impact bone mineral content even if used over long periods., (© 2020 Blackwell Verlag GmbH.)

Oleanolic acid (OA) and ursolic acid (UA) are the major chemical constituents in Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herb that is previously shown to improve bone properties and enhance calcium balance in aged female rats. The present study was designed to study if OA and UA act as the active ingredients in FLL to exert the positive effects on bone and mineral metabolism in aged rats. Aged (13-month-old) Sprague-Dawley female rats were randomly assigned to four groups with oral administration of drug or vehicle treatment for 12 weeks: medium calcium diet (MCD, 0.6% calcium), high calcium diet (HCD, 1.2% calcium), MCD + FLL (700 mg/kg/day), MCD + OA (23.6 mg/kg/day) + UA (8.6 mg/kg/day). A group of mature (3-month-old) female rats fed with MCD was included as positive control. The results demonstrated that FLL and OA+UA increased bone mineral density and improved microarchitectural properties of aged female rats. The osteoprotective effects of FLL and OA+UA might be, at least in part, associated with their actions on enhancing calcium balance and suppressing age-induced secondary hyperparathyroidism in aged female rats. FLL and OA+UA also significantly induced renal CYP27B1 protein expression and OA+UA treatment decreased CYP24A1 mRNA and protein expressions in aged female rats. In addition, FLL and OA+UA significantly increased the promoter activity, mRNA and protein expressions of renal CYP27B1 in vitro in human proximal tubule HKC-8 cells. The present findings suggest that OA+UA can be regarded as the active ingredients of FLL and might be a potential drug candidate for prevention and treatment of osteoporosis.

Aim: To assess the efficacy, safety and calcium balance of a membrane based regional citrate anticoagulation plasma exchange protocol., Methods: This was an observational, prospective, single centre study of membrane separation plasma exchange using regional citrate anticoagulation. It was performed using a fixed dose pre-filter citrate infusion that was based on the plasma flow rate. Patients received a post filter calcium infusion that was modified during treatment based on systemic ionized calcium monitoring. Post filter ionized calcium was not assessed. Safety and efficacy were assessed by extraction of clinical events and laboratory data contemporaneously recorded in electronic health records., Results: Thirty-six sessions in five patients were performed. No patients developed symptomatic hypocalcaemia, and no patient had a recorded ionized calcium below 0.81 mmol/L. Filter clotting occurred in two sessions. The mean net calcium gained was 9.6 ± 1.8 mmol per session., Conclusion: Regional citrate anticoagulated membrane separation plasma exchange can be performed safely and effectively without the need for post filter ionized calcium monitoring. The algorithm employed resulted in a net calcium gain., (© 2017 Asian Pacific Society of Nephrology.)

We studied the role of calcium-regulating structures of slow- (m. soleus, SOL) and fast-twitch (m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са 2+ elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca 2+ balance.

Purpose of Review: The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area., Recent Findings: Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Although the implications of long-term high Ca intakes have been well documented in growing dogs, the health consequences of Ca excess in adult dogs remain to be established. To evaluate the impact of feeding a diet containing 7·1 g/4184 kJ (1000 kcal) Ca for 40 weeks on Ca balance and health parameters in adult dogs, eighteen neutered adult Labrador Retrievers, (nine males and nine females) aged 2·5-7·4 years were randomised to one of two customised diets for 40 weeks. The diets were manufactured according to similar nutritional specifications, with the exception of Ca and P levels. The diets provided 1·7 and 7·1 g/4184 kJ (1000 kcal) (200(SD26) and 881(SD145) mg/kg body weight0·75 per d, respectively) Ca, respectively, with a Ca:P ratio of 1·6. Clinical examinations, ultrasound scans, radiographs, health parameters, metabolic effects and mineral balance were recorded at baseline and at 8-week intervals throughout the study. Dogs in both groups were healthy throughout the trial without evidence of urinary, renal or orthopaedic disease. In addition, there were no clinically relevant changes in any of the measures made in either group (all P>0·05). The high-Ca diet resulted in a 3·3-fold increase in faecal Ca excretion (P0·05). Ca intakes of up to 7·1 g/4184 kJ (1000 kcal) are well tolerated over a period of 40 weeks, with no adverse effects that could be attributed to the diet or to a high mineral intake.

Context: Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D., Objective: To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D., Design: Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks., Setting and Participants: Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic., Outcome Measures: Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio., Results: Baseline total (22.2 ± 3.3 vs 23.3 ± 7.2 ng/mL; P = .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P = .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P = .001) and free (+3.6 vs +6.2 pg/mL; P = .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium., Conclusions: D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity.

Background: Regional citrate hemodialysis anticoagulation is used when heparin is contraindicated, but most protocols require large infusions of calcium and frequent intradialytic plasma ionized calcium measurements., Objectives: The objective of this study was to determine the safety, efficacy, and effect on calcium balance of regional citrate anticoagulation using sparse plasma ionized calcium sampling., Design: The design of this study was observational., Setting: The setting of this study was the hospital hemodialysis center., Patients: The subjects of this study were the hospital hemodialysis patients., Measurements: Dialysate calcium concentration by atomic absorption spectroscopy and total dialysate weight were used as measurements., Methods: Regional citrate anticoagulation was introduced using zero calcium dialysate, pre-dialyzer citrate infusion, and post-dialyzer calcium infusion. Infusions were adjusted based on pre- and post-dialyzer calcium measurements obtained at least twice during a 4-h dialysis. The protocol was simplified after the first 357 sessions to dispense with post-dialyzer calcium measurements. Heparin-anticoagulated sessions were performed using acetate-acidified 1.25 mmol/L calcium or citrate-acidified 1.5 mmol/L calcium dialysate. Calcium balance assessment was by complete dialysate recovery. Safety and efficacy were assessed prospectively using a point-of-care database to record ionized calcium and clinical events. Groups were compared using t test, ANOVA, Wilcoxon rank sum, or Kruskal-Wallis as appropriate., Results: Seventy-five patients received regional citrate-anticoagulated dialysis over 1051 dialysis sessions. Of these, 357 dialysis sessions were performed using the original citrate anticoagulation protocol and 694 using the simplified protocol. Dialysis was effective and safe. Only 3 dialyzers clotted; 1 patient suffered symptomatic hypercalcemia and none suffered symptomatic hypocalcemia. Calcium balance was assessed in 15 regional citrate-anticoagulated dialysis sessions and 30 heparin-anticoagulated sessions. The median calcium loss was 0.8 mmol/h dialyzed in both groups (p = 0.43), and end of treatment ionized calcium was the same in both groups (1.07 ± 0.04 mmol/L)., Limitations: Our findings for calcium balance, efficacy, and safety are valid only for the protocol studied, which excluded patient with severe liver dysfunction., Conclusions: Regional citrate dialysis can be performed safely and effectively using a sparse plasma calcium sampling protocol. The calcium balance induced by this protocol is not different to that seen in standard heparin-anticoagulated dialysis, but in the absence of prospective studies, it is unknown whether this is optimal for patient care.

Our previous studies found that different extracts or fractions of Fructus ligustri lucidi (FLL) played different roles in altering the regulation of bone and mineral metabolism in different animal models. The present study was designed to compare the actions of FLL ethanol (EE) and water extracts (WE) on bone and mineral metabolism in a 6-month-old mature ovariectomized (OVX) rat model. Our results showed that FLL extracts did not significantly improve systematic Ca balance in mature OVX rats. However, EE, but not WE treatment, significantly increased serum 1,25(OH) 2 D 3 levels in mature OVX rats. An in vitro study using human proximal tubule (HKC-8) cells showed that EE, but not WE, significantly enhanced renal 25-dihydroxyvitamin D 3 -1[Formula: see text]-hydroxylase (1-OHase) mRNA expressions and simultaneously repressed renal 25-dihydroxyvitamin D 3 -24-hydroxylase (24-OHase) mRNA expressions. Further investigation indicated that EE could significantly induce the protein expression of 1-OHase, but did not alter 24-OHase expression in HKC-8 cells. Our results demonstrated that EE increased circulating 1,25(OH) 2 D 3 levels in OVX rats, possibly via upregulation of renal 1-OHase expressions in renal proximal tubule cells. Our study indicates that FLL is a natural oral agent that could directly regulate renal vitamin D metabolism in vivo and in vitro.

Background: Online hemodiafiltration (oHDF) is increasingly used in children; we treated 28 children since 2009, adapting this technique to pediatric patients., Methods: In this service evaluation audit, we assessed plasma electrolytes to evaluate the evolution of total (tCa) and ionized (iCa) during a session, as well as dialysate calcium (dCa) concentrations., Results: Using a 1.25 mmol Ca/L-dialysate, both tCa and iCa decreased during the session, with iCa falling below 1.1 mmol/L in 4/5 patients. In contrast, using a 1.5 mmol Ca/L-dialysate, iCa remained normal in all patients. Major discrepancies were observed between the expected and the measured dCa: 1.25 vs. 1.01 (0.83-1.04), and 1.5 vs. 1.47 (0.85-1.75) mmol/L, respectively (results presented as median [range]). These differences were explained by the modality of reconstituting dialysate: increasing bicarbonates and/or decreasing sodium requested in the dialysate decreases calcium extraction from the acid preparation. Proof of concept was given when requesting in an "ex-vivo" setting modifications in the requested sodium and bicarbonate in dialysate directly on the Fresenius machine., Conclusion: Nephrologists should be aware that "high bicarbonate and/or low sodium" requirements in oHDF decrease calcium in the dialysate., (Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Stanniocalcin-1 (STC-1) was first identified to involve in Ca(2+) homeostasis in teleosts, and was thought to act as a hypocalcemic hormone in vertebrate. Recent studies suggested that STC-1 exhibits broad effects on ion balance, not confines to Ca(2+), but the mechanism of this regulation process remains largely unknown. Here, we used zebrafish embryos as an alternative in vivo model to investigate how STC-1 regulates transepithelial ion transport function in ion-transporting epithelium. Expression of stc-1 mRNA in zebrafish embryos was increased in high-Ca(2+) environments but decreased by acidic and ion-deficient treatments while overexpression of stc-1 impaired the hypotonic acclimation by decreasing whole body Ca(2+), Na(+), and Cl(-) contents and H(+) secretion ability. Injection of STC-1 mRNA also down-regulated mRNA expressions of epithelial Ca(2+) channel, H(+)-ATPase, and Na(+)-Cl(-) cotransporter, suggesting the roles of STC-1 in regulation of ions other than Ca(2+). Knockdown of STC-1 caused an increase in ionocyte progenitors (foxi3a as the marker) and mature ionocytes (ion transporters as the markers), but did not affect epithelium stem cells (p63 as the marker) in the embryonic skin. Overexpression of STC-1 had the corresponding opposite effect on ionocyte progenitors, mature ionocytes in the embryonic skin. Taken together, STC-1 negatively regulates the number of ionocytes to reduce ionocyte functions. This process is important for body fluid ionic homeostasis, which is achieved by the regulation of ion transport functions in ionocytes. The present findings provide new insights into the broader functions of STC-1, a hypocalcemic hormone.

Like hemodialysis patients, peritoneal dialysis (PD) patients are facing an excessively increased burden of vascular and valvular calcification. According to some surveys, more than 80% of prevalent PD patients are complicated with vascular calcification, and more than one third have heart valve calcification. Dysregulated phosphate metabolism is well recognized to play an important role in inducing vascular calcification, but increasing evidence is suggesting that dysregulated calcium metabolism also promotes vascular calcification and might in fact be more potent than phosphate in inducing that calcification. Growing evidence from randomized controlled trials shows more progression of vascular calcification and higher mortality among chronic kidney disease (CKD) patients receiving calcium-based phosphate binders than among those receiving non-calcium-containing phosphate binders. Those results raise important safety concern about the use of high-dose calcium-based phosphate binders in the CKD population, including both non-dialysis and dialysis patients (especially anuric dialysis patients), who have markedly reduced urinary calcium excretion. To prevent calcium overload, this review recommends restricting the dose of calcium-based phosphate binders in CKD patients, especially those who are elderly, who have increased cardiovascular risk, who already have baseline vascular or valvular calcification, or who have low intact parathyroid hormone and adynamic bone disease., (Copyright © 2014 International Society for Peritoneal Dialysis.)

Background: Chinese dietary reference intakes for calcium are largely based on foreign studies. We undertook meta-regression to estimate calcium requirements for Chinese adults derived from calcium balance data in Chinese adults., Methods: We searched PubMed, Cochrane CENTRAL, and SinoMed from inception to March 5, 2014, by using a structured search strategy. The bibliographies of any relevant papers and journals were also screened for potentially eligible studies. We extracted a standardized data set from studies in Chinese adults that reported calcium balance data. The relationship between calcium intake and output was examined by an individual participant data (IPD) and aggregate data (AD) meta-regression., Results: We identified 11 metabolic studies in Chinese adults within 18-60 years of age. One hundred and forty-one IPD (n = 35) expressed as mg/d, 127 IPD (n = 32) expressed as mg×kg body wt(-1)×d(-1), and 44 AD (n = 132) expressed as mg/d were collected. The models predicted a neutral calcium balance (defined as calcium output (Y) equal to calcium intake (C)) at intakes of 460 mg/d (Y = 0.60C+183.98) and 8.27 mg×kg body wt(-1)×d(-1) (Y = 0.60C+3.33) for IPD, or 409 mg/d (Y = 0.66C+139.00) for AD. Calcium requirements at upper intakes were higher than that at lower intakes in all these models., Conclusion: Calcium requirement for Chinese adults 18-60 years of age approximately ranges between 400 mg/d and 500 mg/d when consuming traditional plant-based Chinese diets.

Background: Identification of the underlying causes of secondary hyperparathyroidism (SHPT) in individual patients on hemodialysis (HD) is hampered by the lack of clinically reliable information on calcium balance. The aim of this study was to assess calcium balance during HD sessions with a method that is applicable in day-to-day practice., Methods: Plasma ionized calcium (pCa2+) and parathyroid hormone (PTH) were measured at the beginning and end of HD to evaluate calcium fluxes in 23 patients on a dialysate calcium (DCa) concentration of 1.25 mmol/L., Results: HD with a DCa of 1.25 mmol/L caused a decrease in pCa2+ from 1.15 ± 0.01 mmol/L to 1.09 ± 0.01 mmol/L (p<0.0001) and increased plasma PTH from 26.7 ± 1.8 pmol/L to 37.0 ± 2.9 pmol/L (p<0.0001). The changes in pCa2+ were inversely related to the predialysis pCa2+ levels (R2 = 0.86, p<0.001). Patients with a predialysis pCa2+ >1.06 mmol/L had a calcium efflux, whereas those with a predialysis pCa2+ <1.06 mmol/L had a calcium influx during HD., Conclusion: The results suggest that measurement of pCa2+ and PTH at the beginning and the end of HD provides useful information about calcium fluxes in individual patients. Further validation of this approach 
is warranted.

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects' dietary acid was completely neutralized (-11.3 mmol/d on 60 mmol/d; -29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (-46 ± 15.9 mg/d) and 90 mmol/d (-59 ± 31.6 mg/d) compared with placebo (p < 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus -80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance (p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (-34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; -71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group (p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed., (Copyright © 2013 American Society for Bone and Mineral Research.)

Backgrounds. Calcium (Ca) and bone metabolism in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients show a remarkable difference depending on dialysis modalities. The levels of serum Ca and phosphate (P) in HD patients fluctuate contributing to the intermittent and rapid removal of plasma solute unlike in CAPD. Characteristics of plasma solute transport in automated peritoneal dialysis (APD) patients are resembled with that in HD. The purpose of the present study was to examine the difference of transperitoneal Ca removal between APD and CAPD anuric patients. Subjects and Methods. Twenty-three APD anuric patients were enrolled in this study. Biochemical parameters responsible for transperitoneal Ca removal in 24-hour and 4-hour peritoneal effluents were analyzed on CAPD and APD. Results. Transperitoneal Ca removal on APD was smaller compared with that on CAPD. The Ca removal was related to the ultrafiltration during short-time dwell. Decrease of the Ca removal during NPD induced by short-time dialysate dwell caused negative or small Ca removal in APD patients. The levels of intact PTH were increased at the end of PET. Conclusion. It appears that short-time dwell and frequent dialysate exchanging might suppress the transperitoneal Ca removal in anuric APD patients.

Introduction: Total dialysate calcium concentration has an important influence on calcium metabolism in bicarbonate high-flux dialysis. The aim of the study is to investigate the influence of different dialysate calcium concentrations on serum concentration of ionised calcium and on the balance of total dialysate calcium., Materials and Methods: A total of 20 stable aneuric patients on chronic bicarbonate high-flux haemodialysis with a frequency of 4 hours, 3 times per week with two different concentrations of total dialysate calcium (tdCa) were included in the study. Dialysis in the first session was performed with total dialysate calcium of 1.25 mmol/L, and at the next session with dialysate calcium of 1.5 mmol/L. The serum concentrations of total and ionized calcium were determined before and after each dialysis session. The balance of total dialysate calcium was measured on the dialysate side., Results: Serum concentration of total calcium before and after haemodialysis did not show any significant difference in HD with a total dialysate calcium of 1.25 mmol/L (2.40 ± 0.19 mmol/L before HD and 2.46 ± 0.15 mmol/L after HD). Serum ionized calcium in HD with tdCa 1.25 significantly decreased after HD (1.16 ± 0.09 mmol/L before HD to 1.08 ± 0.04 mmol/after HD, p < 0.05). The total serum calcium significantly increased after HD in comparison to HD with tdCa of 1.5 mmol/L (2.40 ± 0.15 mmol/L to 2.65 ± 0.16 mmol/L, p < 0.05). The concentration of serum ionized calcium did not increase significantly in HD with tdCa 1.50 mmol/L (1.16 ± 0.08 mmol/L to 1.20 ± 0.05 mmol/L). Average values of total dialysate calcium balance (gradient of diffusion between dialysate and patient) were negative in tdCa 1.25 (1.38 ± 0.08 mmol/L versus 1.48 ± 0.43 mmol/L), but in HD with tdCa 1.5 were slightly positive (1.56 ± 0.07 mmol/L versus 1.52 ± 0.07)., Conclusion: The use of total dialysate calcium of 1.5 mmol/L is beneficial because balance values of total dialysate calcium are slightly positive, but serum concentration of ionized calcium stays in the normal range.

Background: Calcium and phosphorus metabolic disturbance are common in dialysis patients and associated with increased morbidity and mortality. Therefore, maintaining the balance of calcium and phosphate metabolism and suitable intact parathyroid hormone (iPTH) level has become the focus of attention. We investigated the effects of different peritoneal dialysate calcium concentrations on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal dialysis (CAPD) patients., Methods: Forty stable CAPD patients with normal serum calcium were followed for six months of treatment with 1.25 mmol/L calcium dialysate (DCa1.25, PD4, 22 patients) or a combination of 1.75 mmol/L calcium dialysate (DCa1.75, PD2) and PD4 (18 patients) twice a day respectively. Total serum calcium (after albumin correction), serum phosphorus, iPTH, alkaline phosphatase (ALP) and blood pressure were recorded before and 1, 3 and 6 months after treatment commenced., Results: No significant difference was found in baseline serum calcium, phosphorus between the two patient groups, but the levels of iPTH were significantly different. No significant changes were found in the dosage of calcium carbonate and active vitamin D during 6 months. In the PD4 group, serum calcium level at the 1st, 3rd, 6th months were significantly lower than the baseline (P < 0.05). There was no significant difference in serum phosphorus after 6 months treatment. iPTH was significantly higher (P < 0.001) at the 1st, 3rd, and 6th months compared with the baseline. No differences were seen in ALP and blood pressure. In the PD4+PD2 group, no significant changes in serum calcium, phosphorus, iPTH, ALP and BP during the 6-month follow-up period., Conclusions: Treatment with 1.25 mmol/L calcium dialysate for six months can decrease serum calcium, increase iPTH, without change in serum phosphorus, ALP, and BP. The combining of PD4 and PD2 can stabilize the serum calcium and avoid fluctuations in iPTH levels.

Fructus Ligustri Lucidi (FLL) is a commonly prescribed herb in many kidney-tonifying Traditional Chinese Medicinal formulae for the treatment of osteoporosis. The present study aimed to identify the active fractions in FLL and to characterise its effects on Ca balance, calciotropic hormone levels as well as bone properties in mature female rats fed diets containing different levels of Ca. In the present study, 4-month-old Sprague-Dawley female rats were treated with either FLL ethanol extract (EE), ethyl acetate-soluble fraction of EE (EAF), water-soluble fraction of EE (WF) or their vehicle for 12 weeks on a medium-Ca diet (MCD, 0·6 % Ca, 0·65 % P). Then, the Sprague-Dawley female rats treated with WF or its vehicle for 12 weeks were fed diets containing different levels of dietary Ca (low-Ca diet (LCD), 0·1 % Ca, 0·65 % P; MCD; high-Ca diet (HCD), 1·2 % Ca, 0·65 % P). The results demonstrated that WF from EE but not EAF exerted a prominent effect on Ca balance by inhibiting urinary and faecal Ca excretion. WF significantly increased Ca balance in rats fed MCD or HCD with an associated increase in serum parathyroid hormone (PTH) levels. WF did not alter bone mineral density or bone mineral content of the tibia in all the rats fed with different levels of dietary Ca. In conclusion, WF was responsible for the positive actions of FLL on Ca absorption and balance. The regulation of Ca balance by WF might involve its action in stimulating PTH production in the mature female rats.

Calcium supplements for prevention and treatment of mineral and bone disorders in chronic kidney disease (CKD) have been alternately praised and damned. Clinical evidence in favor of either attitude has been lacking. The calcium balance study by Spiegel and Brady in patients with late stage 3 and stage 4 CKD suggests that CKD subjects ingesting 2000 mg of elemental calcium per day are in marked positive balance. Methodological limitations such as unproven steady state warrant caution and confirmatory studies.

Calcium balance in chronic kidney disease is poorly understood as calcium deficiency is a stimulus for secondary hyperparathyroidism and consequent bone loss while calcium excess promotes extraosseous calcifications. To help resolve this, we evaluated calcium balance in normal individuals and in patients with chronic kidney disease (CKD) on daily diets containing 800 and 2000 mg elemental calcium. Both normal individuals and patients with late stage 3 and stage 4 CKD were in slightly negative to neutral calcium balance on the 800-mg calcium diet. Normal individuals were in modest positive calcium balance on the 2000-mg diet, while patients with CKD on the same diet were in marked positive calcium balance at least over the 9 days of study; and significantly greater than the normal individuals. Increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone levels but did not alter the serum calcium concentration. Thus, our findings have important implications for both preventing calcium deficiency and loading in individuals with late stage 3 and stage 4 CKD.

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.

Background: In bicarbonate-based hemodialysis, dialysate total calcium (tCa) concentration may have effects on mineral metabolism., Study Design: Randomized crossover trial of 3 dialysate tCa concentrations (2.5, 2.75, and 3.0 mEq/L)., Setting & Participants: 22 stable anuric uremic patients underwent three 4-hour bicarbonate hemodialysis sessions with the 3 different dialysate tCa concentrations using a single-pass batch dialysis system., Outcomes: Hourly measurements of plasma water ionized calcium (iCa) and plasma parathyroid hormone (PTH) concentrations. tCa mass balances were measured from the dialysate side., Results: Hourly plasma water iCa concentrations were higher with a dialysate tCa concentration of 3.0 compared with 2.75 and 2.5 mEq/L (P < 0.05), as were iCa concentrations at the end of dialysis sessions (2.66 ± 0.1, 2.56 ± 0.12, and 2.4 ± 0.08 mEq/L, respectively; P < 0.001). Mean tCa mass balance values (diffusion gradient from the dialysate to the patient) were positive with all dialysate tCa concentrations and increased progressively with dialysate tCa concentration (75 ± 122, 182 ± 125, and 293 ± 228 mg, respectively; P < 0.001). Plasma PTH levels increased during dialysis using dialysate tCa concentration of 2.5 mEq/L (mean increase, 225 ± 312 pg/mL) and decreased with dialysate tCa concentrations of 2.75 and 3.0 mEq/L (mean decreases, 68 ± 325 and 99 ± 432 pg/mL, respectively)., Limitations: Small sample size and lack of measurement of total-body calcium mass balances., Conclusions: A dialysate tCa concentration of 2.75 mEq/L might be preferable to 2.5 or 3.0 mEq/L because it is associated with mildly positive tCa mass balance values, plasma water iCa levels in the reference range, and stable PTH levels during dialysis., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

Calcium balance is an overall assessment of the net calcium taken in minus the net calcium taken out. It can only be assessed when patients are in steady state and requires complicated isotope methods that can simultaneously assess intestinal absorption and endogenous secretion, urinary and stool excretion, bone calcium uptake and removal, and dialysate calcium removal. By virtue of the need for steady state, formal balance studies cannot be accurately carried out in patients on dialysis. However, many of the components of calcium balance have been assessed. Importantly, because 99% of calcium is in bone, studies must accurately assess both the rapidly exchangeable calcium from the bone surface and the net bone calcium balance that results from the difference in bone formation minus resorption. While it is tempting to adjust the dialysate calcium concentration to correct the net positive calcium balance that is likely present in patients who receive calcium-based phosphate binders, the reality is that the highly variable, yet important, role of bone cannot be easily assessed at the bedside. Thus, it is best to prevent the calcium overload in the first place by avoiding high-dose calcium-based phosphate binders and optimizing bone remodeling.

Auditory transduction occurs by opening of Ca(2+)-permeable mechanotransducer (MT) channels in hair cell stereociliary bundles. Ca(2+) clearance from bundles was followed in rat outer hair cells (OHCs) using fast imaging of fluorescent indicators. Bundle deflection caused a rapid rise in Ca(2+) that decayed after the stimulus, with a time constant of about 50 ms. The time constant was increased by blocking Ca(2+) uptake into the subcuticular plate mitochondria or by inhibiting the hair bundle plasma membrane Ca(2+) ATPase (PMCA) pump. Such manipulations raised intracellular Ca(2+) and desensitized the MT channels. Measurement of the electrogenic PMCA pump current, which saturated at 18 pA with increasing Ca(2+) loads, indicated a maximum Ca(2+) extrusion rate of 3.7 fmol x s(-1). The amplitude of the Ca(2+) transient decreased in proportion to the Ca(2+) concentration bathing the bundle and in artificial endolymph (160 mM K(+), 20 microM Ca(2+)), Ca(2+) carried 0.2% of the MT current. Nevertheless, MT currents in endolymph displayed fast adaptation with a submillisecond time constant. In endolymph, roughly 40% of the MT current was activated at rest when using 1 mM intracellular BAPTA compared with 12% with 1 mM EGTA, which enabled estimation of the in vivo Ca(2+) load as 3 pA at rest. The results were reproduced by a model of hair bundle Ca(2+) diffusion, showing that the measured PMCA pump density could handle Ca(2+) loads incurred from resting and maximal MT currents in endolymph. The model also indicated the endogenous mobile buffer was equivalent to 1 mM BAPTA.