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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.

There is controversy about the choice of dialysate calcium concentration (DCa), with strong arguments both in favor of and against the use of a low or high DCa, as they can both be potentially harmful. Evidence suggests that calcium mass balance is positive with a DCa 3.5 mEq/L, negative or neutral with the use of DCa 2.5 mEq/L, whereas both positive and negative balances have been observed with the use of DCa 3.0 mEq/L. Overall, the use of DCa >2.5 mEq/L is usually associated with an increase in serum calcium level and a decrease in serum PTH level and use of lower vitamin D analogue dose, with the opposite effects usually observed with the use of lower DCa. Most of the available evidence is from small-sized and crossover studies; hence, evidence should be regarded with caution and applied in a patient-specific manner. As there are a lot of significant unanswered questions regarding calcium balance and the optimal DCa in hemodialysis patients, further high-quality research is needed to clarify many still unclear aspects of calcium homeostasis and balance in these patients. In conclusion, with the existing evidence the choice of DCa needs to be individualized and contextualized in the setting of each patient's calcium balance needs and homeostatic response, taking also into account oral calcium intake (dietary and medicinal), any other relevant therapy administered, such as vitamin D analogues, the type of renal mineral bone disorder, and associated cardiovascular comorbidity.

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. Graphical abstract

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, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) 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 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum 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 44/42Caserum ratio and parathyroid hormone. The 44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum 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.

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 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 Graphical abstract

Objective: This study's objective is to explore the effect of venous calcium (Ca) load on Ca metabolism using an isotope tracer in both healthy rats and rats with chronic renal failure (CRF). Materials and Methods: The methods included inducing CRF by feeding rats with food that containing 0.75% adenine. Both the rats in the control and CRF group received an intravenous injection of 100 mg/kg CaCl2 mixed with 0.5 mg/kg 42Ca for over 2 minutes in order to induce hypercalcemia. Blood samples, urine, and feces were collected for Ca kinetics and metabolism testing before and 24 hours after the injection. Results: Peak blood Ca levels were presented at 5 minutes in both groups but returned to baseline levels differently: within 3 hours in the CRF group and 1 hour in the control group. 24-hour hypercalciuria and a higher weight-corrected fecal Ca loss were consistently detected in the CRF rats before and after the injection, along with a decrease in the percent fractional Ca absorption and true fractional calcium absorption compared to the control group. The increased fecal Ca in the CRF rats primarily resulted from changes in decreased absorption rate, which indirectly lead to an increase in endogenous fecal Ca (EFC). Body weightcorrected EFC levels in the CRF group were significantly higher than those in the control group (207.58 ± 107.18 mg/kg/day vs. 62.44 ± 20.49 mg/kg/day). In addition, EFC was 22.6% and 26.02% of the total fecal Ca in the CRF group and the control group. Conclusion: These results may be useful in the evaluation of calcium metabolism and may have important implications for stable isotopes that are widely used in exploring calcification studies in the CRF.

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.

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.

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.

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 (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. vs. 77.3, 95% CI = 76.6–78.1 mL/min/1.73m2, Ptime×group = 0.004) and higher SBP levels (112, 95% CI = 111–113 vs. 109, 95% CI = 108–110 mmHg, Ptime×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.

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. Summary 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.

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.

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 Са2+ 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 Ca2+ balance.

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 (PP>0·05). 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.

For 63 years in the agro-industrial complex ofCherkasy region there was a radical transformationof the structure of sown areas, when the whole period can be divided into a period of increasing intensity of livestock (1956–1995), a transition period (1996–2005) from intensive livestock to intensive grain production. and 2006–2019 — a period of business management of the structure of sown areas and weak development of the livestock industry. Such changes in management lead to the fact that in agriculture the main means of fertility management is by-products of crop production, the yield of which directly depends on the existing structure of sown areas. Circulation of Ca in agriculture of Cherkasy region directly correlates with changes in the structure of sown areas and the type of applied organic fertilizers. With the introduction of manure on an increasing trend are the conditions for increasing the capacity of the balanceof Ca, but with the saturation of the structure of sown areas with fodder crops and removal of by-products for economic purposes, calcium removal increases to 36–47%, and for by-products total removal decreases to 28–35% for reducing the capacity of the balance of Ca. If we do not take into account the content of Ca in the root system in the balance, the balance indicators deteriorate, both during the application of manure and when it is replaced by by-products. It was found that during the period of increasing the yield of manure for growing livestock, the ratio between the newly formed humus and calcium involved remained in the range of 8.1–9.9 to 1 with increasing components of the ratio, and the increase in areas and volumes of liming in this period should be associated with an excess of fresh organic matter from manure and unilateral withdrawal of calcium from livestock and insufficient return to the agrocenosis, which required an increase in liming areas to consolidate the excess of newly formed humus. When replacing manure with by-products, the ratio between the newly formed humus and calcium remained stable against the background of a decrease in the amount of newly formed humus and circulating calcium (up to 12 to 1 in 2016–2019) while reducing the average humus content and soil area with acid reaction, indicating insufficient amount of calcium per unit of humus formed during the critical transformation of the structure of sown areas and increased mineralization of its excess, which should be compensated by theintroduction of lime. Analysis of the dynamics of the economic balance of Ca shows that livestock and poultry is an aggressive factor against agrocenoses in terms of Ca removal. With developed animal husbandry, it is possible to reach a deficit of Ca balance with a population of about 9.56 million heads, and further increase of the population to 12.2 million heads makes the balance negative. With the transformation of livestock in the direction of poultry there is an increase in the deficit of the economic balance in terms of area of agricultural land, which indicates the need for soil liming.

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).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.20 patients completed 1-year follow-up (56 ± 16 years, 50 % male, 25 % diabetic, 55 % with baseline parathyroid hormone - PTH300 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).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.

Tomato fruits of high quality and yield are of interest to greenhouse growers. As potassium (K) and calcium (Ca) have been associated with fruit quality, we studied the effect of the balance between such cations and the electrical conductivity (EC) on fruit yield and quality. Plants were fertigated with K (Kext) and Ca (Caext) balances in the nutrient solution varying from 0.54–1.22 and 0.69–1.44 at ECs of 2.3 ± 0.1 dS m−1 and 2.7 ± 0.1 dS m−1, respectively. Optimum balance for fruit yield was 0.82–0.85, and it was associated with high fruit K internal (Kint) concentration (~ 200 mmol kg−1). Higher EC increased firmness when the balance was ≤ 1.00, with the optimum at 0.85; firmness was correlated with Caint when EC was 2.3 dS m−1; however, at 2.7 dS m−1, increasing Kext increased firmness and intensified the effect of Caext. Increasing a* values were associated with high lycopene and uniform maturation when that balance was 0.82 and 1.00 at low and high EC, respectively. Highest a* values were observed when Kint in the fruit was ~ 200 mmol kg−1, while 91 to 130 mmol kg−1 were associated with lower a* values. Fruits contained higher starch (+ 20%), total (+ 12%), and reducing sugars (+ 29%) at high EC. The optimum K and Ca balance, 0.82–0.85, is independent of their concentration and was associated with high yield and firmness, improved fruit color, and increased lycopene and sugar concentrations.

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)2D3levels 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 D3-1[Formula: see text]-hydroxylase (1-OHase) mRNA expressions and simultaneously repressed renal 25-dihydroxyvitamin D3-24-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)2D3levels 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.

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.

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.

Agnieszka Makowka, Michal Nowicki Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Lodz, PolandCorrespondence: Michal NowickiDepartment of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Central University Hospital, Pomorska Str 251, Lodz, 92-213, PolandTel +48 42 2014400Fax +48 42 2014401Email nefro@wp.plObjective: 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.Keywords: calcium, chronic kidney disease – mineral bone disorder, hyperphosphatemia, phosphate-binders, PTH

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 Conclusion: An accelerated algorithm for regional citrate anticoagulation achieves substantial time saving while maintaining efficacy and safety. The 4 episodes of systemic ionized calcium

A major objective in modern biology is generation of comprehensive atlases of various organs identifying all cell types and their expressed genes. In kidney, extensive data exists for proximal tubule and collecting duct cells, but not for non-abundant intermediate epithelial cell types. Here, we coupled a FACS-enrichment protocol with single-cell RNA-seq analysis to profile the transcriptomes of 9099 cells from the nephron region adjacent to the macula densa. Clusters containingSlc12a3+/Pvalb+andSlc12a3+/Pvalb-cells were identified as DCT1 and DCT2 cells. The DCT1 cells appear to be heterogeneously associated with variable expression ofSlc8a1, Calb1, andCkbamong other mRNAs. No DCT2-specific transcripts were found. The analysis also identified two distinct cell types in theSlc12a1+portion of Henle’s loop as well asNos1+/Avpr1a+macula densa cells. Thus, we identify unexpected cell diversity in the intermediate region of the nephron and create a web-based data resource for these cells.

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.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.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 p0.05.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.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.O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco.Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica.Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p0,05.Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+.Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.

Calcium balance during hemodialysis (HD) is important in determining short-term cardiovascular function, this influences the hemodynamic tolerability of dialysis. In the longer term, calcium flux during HD is an important determinant of overall calcium balance in a patient and may also influence the development and progression of vascular calcification, with its attendant consequences. This article aims to review the assessment and mechanisms of calcium flux during HD, choice of dialysate calcium concentration, influence of HD modality, and potential consequences of therapy choices (cardiovascular and skeletal) resulting from an inappropriate intradialytic calcium balance.

Calcium regulation in sturgeon is of special interest because they are a representative of the ancient fishes possessing mainly cartilaginous skeletons and a supposedly low calcium demand. The present study aimed to characterize the effect of a chronic absence of dietary calcium and the effect of parathyroid hormone-related protein (PTHrPA) (1-34) ( 7 ) on calcium balance in juvenile sturgeon ( Acipenser naccarii). At rest, sturgeon juveniles are in net positive calcium balance, since whole body calcium uptake is significantly higher than efflux and calcium accumulates in the body. To study the importance of dietary calcium, the sturgeon were kept on a calcium-free diet for 8 wk. This manipulation impaired growth as measured by failure to gain weight or increase in length and indicates that dietary calcium is important for growth in sturgeon. An increased whole body calcium uptake partially compensated dietary calcium deficiency and was associated with increased gill chloride cell number in lamellae and filaments in parallel with increased gill Na+K+-ATPase activity. In addition, a single injection of piscine PTHrP(1-34) significantly increased whole body calcium uptake and decreased whole body calcium efflux. Administration of PTHrP significantly increased circulating plasma calcium 4–24 h postinjection. The increase in net calcium transport and increased plasma levels of calcium is consistent with the actions of a hypercalcemic factor. It would appear that the sturgeon rely on calcium for growth and tightly regulate calcium transport. The action in calcium balance is consistent with PTHrP acting as a hypercalcemic factor in sturgeon.

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.

Aim. To evaluate the state of bone tissue in comparison with calcium balance, to clarify the risk for fracture development in women of different age groups. METHODS. 92 females aged 19 to 89 years were examined clinically with densitometry of lumbar spine and femoral neck and measuring the concentration of total calcium in the blood. RESULTS. In females younger than 50 years decreased bone density according to Z-score was revealed in 30% of cases, among patients with its normal values significant trend to bone rarefaction (-2.0 SD Z-score ≤-1.5 SD) was registered with the same rate. In the group of females older than 50 years osteopenia was revealed in 46.3% of cases and osteoporosis - in 42.7%, while more significant decrease in bone mineral density was found in the lumbar spine. Past medical history of fractures increased the rate of osteoporosis by 18%. In females older than 50 years compared to younger patients a significant increase of blood calcium concentration was revealed. Besides, statistically significant increase of its level was noted in cases of fractures in the past and osteoporosis. The revealed changes of bone tissue in females below 50 years of age are indicative of increased risk of osteoporosis development in the future. CONCLUSION. High prevalence of osteoporosis and osteopenia is revealed in the examined patients older than 50 years, and bone mineral density parameters were significantly inversely correlated with calcemia; hence, blood calcium level can be one of the criteria of bone tissue state and in combination with other risk factors for osteoporosis should be taken into account during periodic health examination of females older than 50 years.

Editor's Note: This paper is one of the first suggesting that idiapathic osteoporosis may be n disorder of calcium metabolism for which increased intakes calcium mas be preventative.

The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p0.05, vs. OVX) and urinary deoxypyridinoline (p0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p0.01, vs. OVX), suppressing urinary Ca excretion (p0.05, vs. OVX) as well as increasing bone calcium content (p0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis.

Objective: The purpose of this study was to examine the effects of vitamin K2 administration on calcium balance and bone mass in young rats fed a normal or low calcium di

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 2000mg of elemental calcium per day are in marked positive balance. Methodological limitations such as unproven steady state warrant caution and confirmatory studies.

This study examined how developing fish larvae regulate their Ca2+ balance for acclimation to low ambient Ca2+. Calcium balance in newly hatched larvae was examined individually. Developing larvae not only increased Ca2+ influx but also decreased Ca2+ efflux when they were acclimated to low-Ca2+ environments. After acclimation for 8 days, the influx and efflux of the low-Ca2+ (0.02 mM) group were about 106% and 43%, respectively, compared to those of the high-Ca2+ (1.0 mM) group. Sensitivity and response to low-Ca2+ environments are age-dependent. Upon acute exposure to low Ca2+. newly hatched (H0) larvae increased both Ca2+ influx (from 24% to 67% of high-Ca2+) and net uptake (from 5% to 69%) within 64 h, while 3-day-posthatching (H3) larvae managed to reach the levels of the control within 38 h. Declining Ca2+ efflux in H3 larvae occurred 14 h after exposure, much faster than those in H0 larvae (38 h). It is suggested that modulation of Ca2+-balance mechanisms in developing larvae is dependent upon the levels of Ca2+ in the larval body.

The impact of feeding myristic acid (C14:0; 50 g/kg DM) to sheep was investigated in a 6 × 6 Latin square arrangement. C14:0 was supplemented to two control diets (forage:concentrate ratios of 1:1.5 and 1:0.5) which were adjusted to different dietary Ca contents (4.2 or 9.0 g/kg DM). In combination with the concentrate-based diet, C14:0 reduced methane energy loss by more than 50% but reduced Ca availability of the animals while the additional Ca supply improved Ca and energy retention. Supplementing C14:0 to the forage-based diet did not affect Ca availability and resulted in highest feed energy utilization.

We examined the effect of vitamin D supplementation on bone growth in young rats fed a normal or low calcium diet.Fifty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into five groups with 10 rats in each group: baseline control, 0.5% (normal) or 0.1% (low) calcium diet, and 0.5 or 0.1% calcium diet + vitamin D (25 microg/100 g, food intake). Duration of the experiment was 10 weeks.Vitamin D supplementation stimulated intestinal calcium absorption and increased urinary calcium excretion in rats fed a low or normal calcium diet. Vitamin D supplementation prevented the reduction in periosteal bone gain but enhanced enlargement of the marrow cavity and reduced the maturation-related cancellous bone gain in rats fed a low calcium diet, and increased the maturation-related cancellous and cortical bone gains in rats fed a normal calcium diet.This study shows the differential effects of vitamin D supplementation on born growth in young rats fed a normal or low calcium diet.

The effect of dietary lentils on calcium balance was evaluated in nine healthy male subjects. The Control and Experimental (+ 130 g dry lentils) diets were each fed for three weeks in a cross-over design. Study diets were matched to subjects' usual calcium and energy intakes, and balanced for protein and phytate. Complete fecal collections were made for all weeks and 24-hour urine collections were made in Week 3 of each period. Calcium balance was maintained during both the Control (0.4 ± 0.8 mmol/day, mean ± SEM) and Experimental periods (− 0.6 ± 0.9 mmol/day); fecal calcium remained unchanged (28.5 ± 1.7 mmol/day, 29.7 ± 1.5 mmol/day, respectively). Urinary excretion, however, varied from Control to Experimental periods for the following: calcium decreased from 5.43 ± 0.44 to 4.53 ± 0.41 mmol/day (P

Prior to the advent of calcitriol therapy, haemodialysis (HD) patients were often in negative calcium (Ca) balance between dialyses because of severely impaired Ca absorption [1] that led to the recommendation of dialysate inlet Ca concentration (CdiCa++) 3.0–3.5 mEq/L, higher than plasma concentration [2]. Over the past 25 years since the advent of calcitriol, virtually all haemodialysis patients absorbed a substantial portion of dietary and phosphate binder calcium ingested between dialyses and yet CdiCa++ 3.0 mEq/L has continued to be widely used. The total Ca absorbed between dialyses (CaAbsT) must be removed by the dialyser (JdCaT) to achieve net zero Ca mass balance over the dialysis cycle and prevent chronic Ca overload that likely contributes to the high rate of vascular calcification in haemodialysis patients [3–5]. From this perspective, it follows that the CdiCa++ prescribed should result in neutral Ca mass balance and thus total Ca removed during dialysis (JdCa++), the sum of diffusive (JDiffCa++) and convective Ca++ (JConvCa++) removal, should equal CaAbs in accordance with