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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).)

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.

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.

Glucocorticoid induced osteoporosis has been associated with high doses and it has been partially attributed to decreased absorption and to increased calcium excretion. The present study examined the effect of low but effective doses of methylprednisolone (MP) on calcium balance and on skeleton in rats. Total duration of the experiment 29 days. Thirty-one male Wistar rats (MP group) were injected with 4mg/kg body weight MP s.c. at the 1st, 11th and 20th day of the experiment and 28 rats (C group) were used as matched controls. The 1st, 11th and 20th day of the experiment rats were placed in individual metabolic cages for three days. Food and water consumption were measured at the 2nd and 3rd days after each injection; urine and faeces were collected at the same days for calcium estimation. Calcium intake and excretion after each injection was significantly lower in the MP group as compared to controls. A statistically significant positive correlation between calcium consumption and calcium excretion was found in both groups resulting in a negative final balance. Rats were killed the 29th day. Adrenal weight was statistically significant lower in MP group (p<0.001). Morphometric properties were evaluated for the right femur. No significant difference was found between the two groups. Mineral and calcium content was slightly increased in the MP group. According to these results, it seems that methylprednisolone while effective on HPA axis did not have any effect on calcium absorption and on bone calcium deposition in rats.

Background: The optimal dialysate calcium (Ca) concentration for patients undergoing hemodialysis remains inconclusive, particularly concerning cardiovascular protection., Methods: We conducted a systematic review of 19 randomized controlled trials (RCTs) and a meta-analysis of eight RCTs to determine the optimal dialysate Ca concentration for cardiovascular protection. We compared outcomes in patients receiving maintenance hemodialysis treated with either a low-Ca dialysate (LCD) (1.125 or 1.25 mmol/L) or a high-Ca dialysate (HCD) (1.5 or 1.75 mmol/L). The outcomes were coronary artery calcification score (CACS), all-cause and cardiovascular death, cardiovascular function and structure, and serum biochemical parameters., Results: There was no significant difference between LCD and HCD concerning CACS (standardized mean difference [SMD] = -0.16, 95% confidence interval [CI]: [-0.38, 0.07]), the risk of all-cause death, and cardiovascular death in patients treated with chronic maintenance hemodialysis. Conversely, LCD was associated with a significantly lower intima-media thickness (SMD = -0.49, 95% CI [-0.94, -0.05]) and pulse wave velocity than HCD (SMD = -0.86, 95% CI [-1.21, -0.51]). Furthermore, LCD significantly decreased serum Ca levels (mean difference [MD] = 0.52 mg/dL, 95% CI [0.19, 0.85]) and increased serum parathyroid hormone levels (MD = 44.8 pg/mL, 95% CI [16.2, 73.3]) compared with HCD. Notably, most RCTs examined in our analysis did not include patients receiving calcimimetics., Conclusions: Our meta-analysis showed no significant differences in cardiovascular calcification and death between LCD and HCD and revealed a paucity of RCTs on dialysate Ca concentrations, including those involving patients on calcimimetics, indicating the urgent need for further studies., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Eels are exposed to Ca 2+ changes during migration between seawater and freshwater. The gill is the main organ of active calcium transport and has a large surface area to be particularly sensitive to environmental changes in the aquatic environment. In this research, we focused on the morphological changes of gill tissues when eels are faced with the environmental calcium challenges. Based on the results of hematoxylin and eosin (HE) staining and immunohistochemistry, compared with the control group (normal Ca 2+ environment), the filament and lamella lengths and lamellar frequency (LF) appeared higher in high calcium environment and lower in deficient calcium environment, while the lamella width and filamental lamellar surface area (SA FL ) decreased in high calcium environment and increased in deficient calcium environment. And there was no difference in the number filaments in first right gill arch in the three Ca 2+ water environment. Transmission electron microscopy was employed to examine the ultrastructural changes in gills in different Ca 2+ water environment. The nucleus and endoplasmic reticulum had a tendency to expand in calcium-deficient water, but had a tendency to shrink in high-calcium water comparing with the control group. This study provides the support that branchial surface areas are regulated in different Ca 2+ waters through a list of calcium transporters including CACNB2.

One of the most important features of innate immunity is the presence of a special group of pattern recognition receptors (PRRs) called toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), resulting in a quick and effective immune response to them. Glomerulonephritis (GN) is one of the most important categories of renal disorders characterized by destructive responses of the immune system to the glomerulus. To date, the association of TLRs as important innate immune system members with GN has been one of the topics that attracted the attention of researchers in this field. However, the exact role of these receptors in the immunopathogenesis of GN has not yet been fully discussed. Therefore, this study aims to overview the role of TLRs in GN and the possibility of using them as a potential therapeutic target., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Hypercalciuria is one of the most important urinary risk factors in kidney stone formers. This study aimed to delineate the interaction of some demographic, serum, and urinary risk factors influencing 24-h urinary (24-U) calcium excretion., Methods: This study was secondary data analysis, using data from 593 kidney stone patients referred to the Labbafinejad kidney stone prevention clinic from March 2015 to May 2019. The study considered serum, urinary and demographic factors that interact to influence 24-U calcium using path analysis. In addition to the direct impact of predictors on the 24-U calcium, this analysis considered the effects of the predictors on the 24-U calcium transmitted by a mediating variable named indirect effects., Results: The results showed that age indirectly affected on 24-U calcium through 25-hydroxy vitamin D (25(OH)D), serum and 24-U creatinine. As well, weight had an indirect effect through 24-urine metabolites (creatinine, citrate, urea, and sodium). Among serum variables, PTH and creatinine significantly directly affected on 24-U calcium. In comparison, 25(OH)D and phosphorus appeared to influence 24-U calcium indirectly through serum parathormone. Regarding 24-U metabolites, sodium, urea, and citrate had a significant direct effect on 24-U calcium. Moreover, 24-U creatinine has a significant direct and indirect effect on 24-U calcium through citrate and urea as mediator variables., Conclusion: Serum 25(OH)D and phosphorus, along with age and weight, indirectly affected urinary calcium through a third variable. Other variables (PTH, serum creatinine, and 24-U sodium, urea, and citrate) showed a direct effect on 24-U calcium excretion., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients., Method: A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables., Results: This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed., Conclusions: In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients., (© 2021. Italian Society of Nephrology.)

Seed priming has long been explored as an effective value-added potential technique that results in improved germination, reduced seedling emergence time, shortened crop duration, increased stress tolerance and eventually increased higher grain production. However, the wider applicability of water or chemical-based conventional methods of seed priming is often restricted considering its deleterious effects on post-treatment storability or agricultural pollution due to the persistence of chemicals in plant systems or in the environment. In this context, the utilization of physical methods of seed priming for enhancing plant productivity has created a new horizon in the domain of seed technology. Being eco-friendly and cost-effective approaches, priming with extra-terrestrial or physical agents such as ionizing radiation such as X-rays and gamma rays and non-ionizing radiation such as ultrasonic wave, magnetic field, microwaves, and infrared light offers many advantages along with ensuring enhanced production over conventional methods. Ultraviolet radiations, bridging between ionizing and non-ionizing radiation, are important electromagnetic waves that would also be an effective priming agent. Non-ionizing radiation has certain biological advantages over ionizing radiation since it does not generate charged ions while passing through a subject, but has enough energy to cause biological effects. Extensive research works to study the effects of various non-ionizing physical priming methods are required before their wider exploitation in agriculture. With this background, this review aims to highlight the current understanding of non-ionizing physical methods of seed priming and its applicability to combat present-day challenges to achieve agro-ecological resilience., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the imaging features of patients with long-term continuous ambulatory peritoneal dialysis (CAPD) on nonenhanced abdominal CT and to identify adverse factors for long-term CAPD., Methods: A total of 109 patients with less than 5 years of CAPD for peritoneal ultrafiltration failure who switched to hemodialysis (withdrawal group) and 23 patients with more than 10 years of CAPD (long-term group) were retrospectively enrolled. Nonenhanced CT manifestations in both groups were compared, including thickening and calcification of the parietal peritoneum, calcification of the mesangial margin and free margin of the small intestine wall, and calcification of the mesentery and abdominal aorta. A risk stratification model was proposed based on CT manifestations with statistically significant differences., Results: The presence of the following CT findings was significantly different between two groups: extensive thickening of the parietal peritoneum (78.9% vs. 21.7%, P < 0.01); severe calcification of the parietal peritoneum (60.6% vs. 8.7%, P < 0.01); calcification of the mesentery (32.1% vs. 4.3%, P < 0.05); and calcification of the free margin of the small intestine wall (49.5% vs. 13.0%, P < 0.05). However, there was no significant difference in calcification of the mesangial margin of the small intestine wall (40.3% vs. 30.4%) or in abdominal aortic calcification (56.9% vs. 61.1%) (P > 0.05). The area under the receiver operating characteristic curve (AUC) was 0.906 (sensitivity 87.6% and specificity 82.6%)., Conclusion: Extensive thickening of the parietal peritoneum, severe calcification of the parietal peritoneum, and calcification of the mesentery and the free margin of the small intestine wall are adverse factors for long-term CAPD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endoplasmic reticulum (ER) stress is involved in inflammation-induced neurotoxicity. Mitofusin 2 (Mfn2), a member of the GTPase family of proteins, resides in the ER membrane and is known to regulate ER stress. However, the potential role and underlying mechanism of Mfn2 in inflammation-induced neuronal dysfunction is unknown. In our study, we explored the potential of Mfn2 to attenuate inflammation-mediated neuronal dysfunction by inhibiting ER stress. Our data show that Mfn2 overexpression significantly ameliorated tumor necrosis factor alpha (TNF[alpha])-induced ER stress, as indicated by the downregulation of the ER stress proteins PERK, GRP78 and CHOP. Mfn2 overexpression also prevented the TNF[alpha]-mediated activation of caspase-3, caspase-12 and cleaved poly (ADP-ribose) polymerase (PARP). Cellular antioxidant dysfunction and reactive oxygen species overproduction were also improved by Mfn2 in the setting of TNF[alpha] in mouse neuroblastoma N2a cells in vitro. Similarly, disordered calcium homeostasis, indicated by disturbed levels of calcium-related proteins and calcium overloading, was corrected by Mfn2, as evidenced by the increased expression of store-operated calcium entry (SERCA), decreased levels of inositol trisphosphate receptor (IP3R), and normalized calcium content in TNF[alpha]-treated N2a cells. Mfn2 overexpression was found to elevate Yes-associated protein (Yap) expression; knockdown of Yap abolished the regulatory effects of Mfn2 on ER stress, oxidative stress, calcium balance, neural death and inflammatory injury. These results lead us to conclude that re-activation of the Mfn2-Yap signaling pathway alleviates TNF[alpha]-induced ER stress and dysfunction of mouse neuroblastoma N2a cells. Our findings provide a better understanding of the regulatory role of Mfn2-Yap-ER stress in neuroinflammation and indicate that the Mfn2-Yap axis may be a focus of research in terms of having therapeutic value for the treatment of neurodegenerative diseases. Keywords: Yap, Mfn2, ER stress, Neuroinflammation, Dysfunction of mouse neuroblastoma N2a cells, Author(s): Shu Hou[sup.1], Lili Wang[sup.1] and Guoping Zhang[sup.1] Introduction Huntington's disease (HD), a neurodegenerative disorder primarily caused by instable and abnormally long expansion of the polyglutamine (polyQ) tract, is characterized [...]

During pregnancy, female physiology adapts to meet the additional mineral demands of the developing fetus. Meanwhile, the fetus actively transports minerals across the placenta and maintains high circulating levels to mineralize the rapidly developing skeleton. Most of this mineral is accreted during the last trimester, including 30 g of calcium, 20 g of phosphate and 0.8 g of magnesium. Given the dependence of calcium homeostasis on vitamin D and calcitriol in the adult and child, it may be expected that vitamin D sufficiency would be even more critical during pregnancy and fetal development. However, the pregnant mother and fetus appear to meet their mineral needs independent of vitamin D. Adaptations in maternal mineral and bone metabolism during pregnancy appear to be invoked independent of maternal vitamin D, while fetal mineral metabolism and skeletal development appear to be protected from vitamin D deficiency and genetic disorders of vitamin D physiology. This review discusses key data from both animal models and human studies to address our current knowledge on the role of vitamin D and calcitriol during pregnancy and fetal development.

We studied the effect of different doses of ammonium chloride (ACl) and ammonium carbonate (ACr) on immunological parameters of the peripheral blood in rats during high-intensity exercise. Changes in the absolute and relative numbers of granulocytes, lymphocytes, natural killers, naive and mature effector cells one day after the end of the forced swimming cycle were found by using a hematological analyzer and a flow cytometer. Immunological indicators were analyzed relative to swimming duration on the last day of ultimate load. The revealed changes indicate the onset of the effector phase of the development of the inflammatory processes in the positive control group (physiological saline) and in rats receiving a higher dose of ACr (20 mg/kg), while administration of ACl prevented the development of inflammatory processes and shifts in the physiological balance of lymphocyte subpopulations. Immunological profiling indicates that ACl in a dose of 20 mg/kg most effectively improved physical performance in our forced swimming model.

Sepsis-associated encephalopathy is a serious consequence of sepsis, triggered by the host response against an infectious agent, that can lead to brain damage and cognitive impairment. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after sepsis as neuroinflammation, oxidative stress, and mitochondrial dysfunction. Stanniocalcin-1 (STC-1), an endogen neuroprotective protein, acts as an anti-inflammatory and suppresses superoxide generation through induction of uncoupling proteins (UCPs) in the mitochondria. Here, we demonstrated a protective role of STC-1 on inflammatory responses in vitro, in activated microglia stimulated with LPS, and on neuroinflammation, oxidative stress, and mitochondrial function in the hippocampus of rats subjected to an animal model of sepsis by cecal ligation and puncture (CLP), as well the consequences on long-term memory. Recombinant human STC-1 (rhSTC1) suppressed the pro-inflammatory cytokine production in LPS-stimulated microglia without changing the UCP-2 expression. Besides, rhSTC1 injected into the cisterna magna decreased acute hippocampal inflammation and oxidative stress and increased the activity of complex I and II activity of mitochondrial respiratory chain and creatine kinase at 24 h after sepsis. rhSTC1 was effective in preventing long-term cognitive impairment after CLP. In conclusion, rhSTC1 confers significant neuroprotection by inhibiting the inflammatory response in microglia and protecting against sepsis-associated encephalopathy in rats.

This is the first prospective study to investigate the association between kidney stones, bone mineral density, serum testosterone, colon cancer and O. formigenes colonization. 40 kidney stone patients and 85 controls were enrolled. O. formigenes colonization was established. BMD was examined from T- and Z-scores using dual energy absorptiometry. O. formigenes was found in 28 of 40 cases and 80 of 85 controls. BMD was significantly reduced in patients (p < 0.05). The evaluation revealed a significant association between lowered O. formigenes colonization and low testosterone. Urinary calcium and oxalates levels were greater in patient. Serum testosterone and urinary citrate concentrations was reduced in patients with a significant difference. Also an association between O. formigenes and colon cancer was noted. Absence of O. formigenes might stand for a pathogenic factor in calcium oxalate stone, low bone mineral density, low testosterone levels and also colon cancer, when antibiotics are prescribed generously.

The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with single-chamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised., Author(s): Claus Peter Schmitt [sup.1] , Sevcan A. Bakkaloglu [sup.2] , Günter Klaus [sup.3] , Cornelis Schröder [sup.4] , Michel Fischbach [sup.5] Author Affiliations: (1) Division of Pediatric Nephrology, Center [...]

Plasma phosphate levels are important in the evolution of hyperparathyroidism and ectopic calcification in chronic kidney disease (CKD). Although dietary management may be adequate to control plasma phosphate in its early stages, most patients develop hyperphosphataemia by CKD stages 3-4 and require the addition of a phosphate binder. Calcium-containing phosphate binders are the most used and cheapest binders but have fallen out of favour because of the potential for positive calcium balance and calcium toxicity. This problem may be attenuated by newer phosphate binders such as sevelamer hydrochloride and lanthanum carbonate. In this review, the role of phosphate as a uraemic toxin and the advantages and disadvantages of the currently available phosphate binders are discussed. Keywords Children * Phosphate * Calcium * Phosphate binders * Calcium carbonate * Calcium acetate * Sevelamer * Lanthanum, Introduction Phosphate has probably the best described spectrum of toxicity of all molecules that circulate in excess in chronic kidney disease (CKD). Decreased renal phosphate excretion plays a major role [...]

Byline: Laura Valencia (1), Estela Melendez (3), Maria C. Namorado (1), Dolores Martin (1), Michel Bidet (2), Philippe Poujeol (2), Jose L. Reyes (1,4) Keywords: cAMP; Phorbol myristate acetate; Parathyroid hormone; Staurosporin; Cycloheximide; Nifedipine; Newborn Abstract: In mammals, neonatal positive calcium balance is required for adequate growth. Parathyroid hormone (PTH) plays a central role in this process mainly through its action on the distal nephron. We studied the effect of PTH on cytosolic calcium in distal segments from neonatal rat kidney. PTH elicited a concentration-dependent increase in cytosolic calcium in neonatal distal nephron (EC.sub.50=0.5 nM) but not in proximal tubules. At similar PTH concentrations the response was higher in the neonatal than in the adult tubules. The response was associated with protein kinase C (PKC), since phorbol myristate acetate (100 nM) increased [Ca.sup.2+]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca.sup.2+]i. The response was diminished in low external calcium (0.1 mM) and absent at zero calcium, indicating dependency on external calcium. Resting calcium decreased from 80+-10.8 to 28.6+-2.6 nM at zero [Ca.sup.2+]e. PTH and nifedipine increased cytosolic calcium in an additive fashion. We show for the first time that PTH increased cytosolic calcium in the distal nephron of neonatal kidney, in a concentration-dependent pattern and in association with PKC activation. Higher sensitivity of the neonatal tubule might facilitate absorption of this cation during the neonatal period, when growth requires a positive balance of calcium. Author Affiliation: (1) Department of Physiology, Biophysics, and Neurosciences, Research Center for Advanced Studies, D.F.07000, Mexico (2) UMR CNRS 6548, Universite de Nice, Cedex 2, Nice, France (3) Department of Pharmacy, National School of Biological Sciences, National Polytechnic Institute, Mexico (4) Department of Physiology and Biophysics, Centro de Investigacion y de Estudios Avanzados, P.O. Box 14--740, D. F. 07000, Mexico Article History: Registration Date: 14/05/2004 Received Date: 01/05/2003 Accepted Date: 28/04/2004 Online Date: 05/08/2004

Byline: S. A. Brown (1,2), D. A. Ontjes (1), G. E. Lester (4), R. K. Lark (4), M. B. Hensler (3), A. D. Blackwood (4), M. J. Caminiti (3), D. C. Backlund (3), R. M. Aris (3) Keywords: Bone turnover markers; Calcium; Calcitriol; Cystic fibrosis; Osteoporosis; Vitamin D Abstract: Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of 45.sup.Ca was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(O[H).sub.2]D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 Aug p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of 45.sup.Ca after calcitriol (p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls (p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups (p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0+-16.0 vs 63.9+-12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(O[H).sub.2]D concentrations (69.9+-4.2 vs 90.7+-9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of 45.sup.Ca and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover. Author Affiliation: (1) Division of Endocrinology, Department of Medicine, The University of North Carolina at Chapel Hill, North Carolina, USA (2) Division of Endocrinology, UNC, CB 7172, Bioinformatics Building 1163A, 130 Mason Farm Road, Chapel Hill, NC 27599-7172, USA (3) Division of Pulmonary Medicine, Department of Medicine, The University of North Carolina at Chapel Hill, North Carolina, USA (4) Departments of Orthopedics, The University of North Carolina at Chapel Hill, North Carolina, USA Article History: Received Date: 12/04/2002 Accepted Date: 16/08/2002 Online Date: 28/05/2003

Byline: A. G. Need (1), A. Kemp (3), N. Giles (3), H. A. Morris (2), M. Horowitz (3), B. E. C. Nordin (1) Keywords: Key words:Calcium absorption -- Parathyroid hormone -- Postmenopausal women -- Serum calcitriol -- Smoking -- Vitamin D Abstract: Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27) p= 0.004], as were serum calcitriol (p&lt 0.001) and parathyroid hormone (PTH) (p&lt 0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r= 0.38) and non-smokers (r= 0.28) hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH--calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH--calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation. Author Affiliation: (1) The Division of Clinical Biochemistry, AU (2) Hanson Institute, Institute of Medical and Veterinary Science, Frome Road, Adelaide, AU (3) Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia, AU Article note: Received: 21 May 2001 / Accepted: 4 September 2001

Byline: U. Lange (1), O. Jung (2), J. Teichmann (3), G. Neeck (1) Keywords: Key words:Ankylosing spondylitis -- Disease activity -- Osteopenia -- Osteoporosis -- Vitamin D metabolism Abstract: Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication of ankylosing spondylitis (AS) and various factors may contribute to the development of osteoporosis in AS. It is known that inflammatory activity in rheumatic disease (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. 1,25-Dihydroxyvitamin D.sub.3 (1,25(O[H).sub.2]D.sub.3) seems to be another possible candidate for mediatory function in regulating both the inflammatory process and bone turnover. The aim of this study was to evaluate the relation between disease activity, bone turnover and calciotropic hormones. In 70 patients with established AS and an age- and sex-matched control group, the relation between disease activity (erythrocyte sedimentation rate, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index), and serum levels of vitamin D metabolites, parathyroid hormone (PTH), bone alkaline phosphatase (bAP) and urinary pyridinium crosslinks were determined. Serum levels of 1,25(O[H).sub.2]D.sub.3 (p&lt 0.01) and PTH (p&lt 0.01) were negatively correlated with disease activity, the excretion of urinary pyridinium crosslinks showed a positive correlation with disease activity (p&lt 0.01), and 1,25(O[H).sub.2]D.sub.3 and PTH were positively correlated with bAP (p&lt 0.01). These results indicate that high disease activity in AS is associated with an alteration in vitamin D metabolism and increased bone resorption. Furthermore, the decreased levels of 1,25(O[H).sub.2]D.sub.3 may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest further research is necessary to determine whether low levels of 1,25(O[H).sub.2]D.sub.3 as an endogenous immune modulator suppressing activated T cells and cell proliferation may accelerate the inflammation process in AS. Author Affiliation: (1) Kerckhoff Clinic and Foundation, Department of Rheumatology, University of Giessen, Bad Nauheim, DE (2) IV. Medical Clinic -- Nephrology, University of Frankfurt , DE (3) III. Medical Clinic, University of Giessen, Germany, DE Article note: Received: 29 January 2001 / Accepted: 3 August 2001

Background Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. Methods PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. Results We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). Conclusion As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. Graphical Abstract, Author(s): Justine Bacchetta [sup.1] [sup.2] [sup.3] , Claus Peter Schmitt [sup.4] , Sevcan A. Bakkaloglu [sup.5] , Shelley Cleghorn [sup.6] , Maren Leifheit-Nestler [sup.7] , Agnieszka Prytula [sup.8] , Bruno [...]

Hypovitaminosis D has been reported to be common in chronic kidney disease (CKD) as well as in proteinuric disorders. We reviewed available evidence to assess clinically relevant effects of low vitamin D status and native vitamin D (NVD) therapy, in pediatric renal diseases. Online medical databases were searched for articles related to vitamin D status, associations of hypovitaminosis D and effects of NVD therapy in kidney disease. Hypovitaminosis D was associated with worse skeletal, cardiovascular, inflammatory, and renal survival outcomes in CKD. Low serum 25 hydroxy-vitamin D (25[OH]D) levels correlated positively with glomerular filtration rate and negatively with serum parathyroid (PTH) levels. However, to date, evidence of benefit of NVD supplementation is restricted mainly to improvements in serum PTH, and biochemical 25[OH]D targets form the basis of clinical practice recommendations for NVD therapy. In nephrotic syndrome (NS) relapse, studies indicate loss of 25[OH]D along with vitamin D binding protein in urine, and serum total 25[OH]D levels are low. Preliminary evidence indicates that free 25[OH]D may be a better guide to the biologically active fraction. NVD therapy in NS does not show consistent results in improving skeletal outcomes and hypercalciuria has been reported when total 25[OH]D levels were considered as indication for therapy. NVD formulations should be regularised, and therapy monitored adequately to avoid adverse effects., Author(s): Sushmita Banerjee [sup.1] , Jayati Sengupta [sup.1] , Surupa Basu [sup.2] Author Affiliations: (1) grid.414710.7, 0000 0004 1801 0469, Department of Pediatric Nephrology, Institute of Child Health, , Kolkata, [...]

Background Idiopathic infantile hypercalcemia (IIH) etiologies include pathogenic variants in CYP24A1, leading to increased 1,25(OH).sub.2 D, hypercalciuria and suppressed parathyroid hormone (PTH), and in SLC34A1 and SLC34A3, leading to the same metabolic profile via increased phosphaturia. IIH has not been previously described in CKD due to kidney hypodysplasia (KHD). Methods Retrospective study of children with bilateral KHD and simultaneously tested PTH and 1,25(OH).sub.2D, followed in a tertiary care center between 2015 and 2021. Results Of 295 screened patients, 139 had KHD, of them 16 (11.5%) had IIH (study group), 26 with normal PTH and any 1,25(OH).sub.2D were controls. There were no differences between groups' gender, obstructive uropathy rate and baseline eGFR. Study patients were younger [median (IQR) age: 5.2 (3.2-11.3) vs. 61 (13.9-158.3) months, p < 0.001], had higher 1,25(OH).sub.2D (259.1 ± 91.7 vs. 156.5 ± 46.4 pmol/l, p < 0.001), total calcium (11.1 ± 0.4 vs. 10.7 ± 0.3 mg/dl, p < 0.001), and lower phosphate standard deviation score (P-SDS) [median (IQR): - 1.4 (- 1.9, - 0.4) vs. - 0.3 (- 0.8, - 0.1), p = 0.03]. During 12 months of follow-up, PTH increased among the study group (8.8 ± 2.8 to 22.7 ± 12.4 pg/ml, p < 0.001), calcium decreased (11 ± 0.5 to 10.3 ± 0.6 mg/dl, p = 0.004), 1,25(OH).sub.2D decreased (259.5 ± 91.7 to 188.2 ± 42.6 pmol/l, p = 0.1), P-SDS increased [median (IQR): - 1.4 (- 1.9, - 0.4) vs. - 0.3 (- 0.9, 0.4), p = 0.04], while eGFR increased. Five of 9 study group patients with available urine calcium had hypercalciuria. Five patients had nephrocalcinosis/lithiasis. Genetic analysis for pathogenic variants in CYP24A1, SLC34A1 and SLC34A3 had not been performed. Conclusions Transient IIH was observed in infants with KHD, in association with hypophosphatemia, resembling SLC34A1 and SLC34A3 pathogenic variants' metabolic profile. Graphical abstract, Author(s): Evgenia Gurevich [sup.1] [sup.2] , Yael Borovitz [sup.1] , Shelli Levi [sup.1] , Sharon Perlman [sup.3] [sup.4] , Daniel Landau [sup.1] [sup.4] Author Affiliations: (1) grid.414231.1, 0000 0004 0575 [...]

Background Maternal lifestyle factors, such as diet and nutritional status are likely to affect the composition of breast milk (BM). This study aimed to investigate the association between adherence to a Dietary Approaches to Stop Hypertension (DASH) dietary pattern (DP) and BM nutrient content. Method A total of 700 milk samples were obtained from 350 lactating women. The dietary intakes of the women in the study were estimated using a validated food frequency questionnaire, which included 65 food items. The total antioxidant activity (TAC) of BM samples was evaluated using the Ferric reducing antioxidant power (FRAP), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARS), and Ellman's assay. Also using commercially available kits, the total protein, calcium, and triglyceride contents in milk were determined. Results Individuals in the 3rd tertile of adherence to the DASH diet (highest adherence) consumed more dietary fiber, fruits, vegetables, nuts, legumes, and seeds, low-fat dairy, whole grain, less red and processed meat, sweetened beverages, and sodium than those in the first tertile (lowest adherence). Subjects in the 3rd tertile of DASH DP had higher values of milk DPPH and calcium compared to those in the first tertile (P < 0.05). Milk MDA and triglyceride were significantly lower in the 3rd tertile of DASH diet versus the first tertile (P < 0.05). Conclusion Our study showed that high adherence to the DASH DP was associated with higher BM DPPH and calcium levels and lower amounts of BM MDA and triglyceride. The adherence to the healthy DPs such as the DASH can improve the quality of BM in lactating women., Author(s): Samira Karbasi [sup.1] , Afsane Bahrami [sup.2] [sup.3] , Mohammad Yahya Hanafi-Bojd [sup.4] [sup.5] , Zahra Khorasanchi [sup.6] , Asghar Zarban [sup.7] [sup.8] , Gordon A. Ferns [sup.9] Author [...]

Background Vitamin D (VitD) supplementation is recommended by the American Academy of Pediatrics (AAP) for preterm infants to improve bone density. Complications of VitD supplementation include hypercalciuria and nephrocalcinosis (NC). NC has been reported in 7-64% infants < 32 weeks gestational age (GA) or < 1500 g birth weight (BW). The relationships between VitD supplementation, serum 25-hydroxy VitD levels, bone density, hypercalciuria and development of NC in preterm infants are not well established. Methods Prospective, observational cohort study of 56 infants with GA [less than or equal to] 32 weeks or BW [less than or equal to] 1800 g. Demographics, dietary intakes, serum 25-hydroxy VitD levels and weekly urinalyses were collected until 40 weeks corrected GA or discharge. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy X-ray absorptiometry (DEXA) scan. NC was identified by kidney ultrasound. Results 56 infants received on average 447 IU/day of VitD with average serum 25-hydoxy VitD level 39.6 ng/mL. DEXA scan showed average BMD 0.13 g/cm.sup.2 and BMC 35.8 g. 23/56 (41%) infants were diagnosed with NC. Infants with NC had lower GA (p < 0.01) and BW (p < 0.01) and increased presence of calcium oxalate crystals (78% vs. 36%) (p = 0.002). There were no differences in VitD intake, urine calcium/creatinine ratios or BMD and BMC in infants with versus without NC. Conclusions VitD supplementation per AAP guidelines resulted in acceptable serum 25-hydroxyVitD levels, but no improvement in BMD or BMC compared to previously reported values. However, infants receiving recommended amounts born at earlier GA and lower BW are at increased risk of NC. VitD supplementation and serum levels should be closely monitored in this high-risk population. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Sabrina Malone Jenkins [sup.1] , Gary Chan [sup.1] , Kimberlee Weaver-Lewis [sup.2] , Tyler Bardsley [sup.3] , Jace Felix [sup.4] , Matthew Grinsell [sup.5] Author Affiliations: (1) grid.223827.e, 0000 [...]