Serum Calcium Concentrations Research Articles

Stunting and wasting in neurological Wilson disease: Role of copper, zinc, and insulin-like growth factor-I.

Copper (Cu) and zinc (Zn) are important trace elements for the growth and development of children. In Wilson disease (WD), impaired Cu metabolism may affect growth. This study was conducted to evaluate the height and weight of children with neurological WD and correlate these with serum Cu, Zn, and insulin-like growth factor-I (IGF-I). This prospective cohort study was conducted in a tertiary care teaching institute. Children with neurologic WD were included. The height, weight, and body-mass index of each child were measured and categorized according to the revised national growth chart. Serum Cu, Zn, calcium, alkaline phosphatase, albumin, thyroid-stimulating hormone, and urinary-Cu were measured. Serum IGF-1 was measured by enzyme-linked immunosorbent assay. The relationship between height and weight with trace elements and IGF was analyzed using parametric or non-parametric tests. There were 52 children (5-18 years) with neurologic WD. Thirty-six (69.2%) children had normal height, 12 (23.1%) were tall, and 4 (7.7%) were stunted. Forty-six (88.5%) children had normal weight and six (11.5%) children were underweight. IGF-1 correlated with height, weight, duration of treatment, and serum Zn level. About 15.4% of children had stunting and/or wasting, which was associated with low levels of serum IGF-I, Zn, and calcium. Stunting and/or wasting occurs in 15.4% of children with neurologic WD and is associated with reduced serum IGF-I, Zn, and calcium concentration. Adjunctive Zn and calcium treatment may help in achieving normal growth.

Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank.

Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.

Establishment of a reference interval for 12-hour fasted serum gastrin concentration in adult dogs.

Adherence to traditional 24-h fasting periods for serum gastrin concentration in dogs can be challenging and may delay the institution of therapies for suspected hypergastrinemia. Peer-reviewed publications regarding serum gastrin reference intervals (RI) are lacking. Hypercalcemia is associated with hypergastrinemia in people; limited data exist in dogs. The objective of the study was to generate a RI for a 12-h fasted serum gastrin concentration in dogs and to investigate whether correlations exist with age, weight, sex, and total calcium concentration. Fifty-five healthy adult dogs (>1 year of age). The screening included: medical history, physical examination, CBC (15 dogs), and serum chemistry (55 dogs). Gastrin was measured via a commercial radioimmunoassay. The RI for 12-h fasted serum gastrin concentration was calculated according to the recommendations of the American Society for Veterinary Clinical Pathology. Additionally, data were evaluated for correlation with selected variables. The RI for serum gastrin following a 12-h fasting period was 15.1-78.9 ng/L with 90% confidence intervals for the lower and upper limits of 14.0-22.9 and 68.3-83.0 ng/L, respectively. A generalized linear model did not detect significant relationships between gastrin and age (P = 0.48), sex (P = 0.30), weight (P = 0.93), or total calcium concentration (P = 0.84). A 12-h fasted serum gastrin concentration RI has been established. Given the limited range of serum calcium concentrations in our healthy study population, additional investigations are needed to determine the effects of hypercalcemia on serum gastrin concentrations in dogs and for any potential clinical consequences thereof.

Cystic Parathyroid Adenomas as a Risk Factor for Severe Hypercalcemia.

(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.

Assessing the Role of Initial Serum Calcium Concentration in Patients with Ethylene Glycol Poisoning.

Assays for ethylene glycol (EG) with a rapid turn-around time are not routinely available. Clinicians must rely on historical features and readily available clinical tests, combined with clinical acumen, to guide the initial management of suspected EG poisoning. Hypocalcemia has been suggested as a clue supporting the diagnosis of EG poisoning in patients presenting with an unexplained high anion gap metabolic acidosis (HAGMA). A previous small study challenged this assumption. This was a retrospective case series of one state's poison control system of confirmed EG-poisoned patients between September 2017 and April 2021. The definition of EG poisoning was based on suspected EG ingestion and a serum EG concentration > 5 mg/dL. Patients who were suspected to have EG toxicity but did not have a confirmed EG concentration or the EG concentration was less than 5 mg/dL were excluded. Routine laboratory studies were recorded for all patients. Comparisons between serum calcium on presentation to presenting blood pH, bicarbonate, anion gap, and creatinine were assessed for correlation. There was no correlation between the presenting calcium and either pH or creatinine. There was a weak positive correlation between the initial serum calcium and anion gap, a weak negative correlation between the initial serum calcium and bicarbonate. On hospital presentation, hypocalcemia was not associated with EG poisoning, even in patients with a HAGMA. A normal serum calcium on presentation does not exclude the diagnosis of EG poisoning.

Pokaznyky kaltsiievo-fosfornoho obminu ta remodeliuvannia kistok yak chynnyky ryzyku vynyknennia porushen mineralnoi shchilnosty kistkovoi tkanyny u khvorykh na revmatoidnyi artryt

Introduction. Osteoporosis (OP) is one of the most common causes of disability decrease in life expectancy among the elderly. The main risk factors for the occurrence of osteoporosis in patients with rheumatoid arthritis (RA) include family predisposition, female sex, age, the presence of menopause, chronic inflammatory process and its treatment. The current task remains the assessment of risk factors for the occurrence of OP in patients with RA, and there is also the need to assess risk factors for the occurrence of OP in patients with RA based on the results of laboratory parameters of calcium-phosphorus metabolism and markers of bone remodeling, which will improve the diagnosis of bone mineral density (BMD) disorders. The aim of the study. To determine the indices of calcium-phosphorus metabolism and bone remodeling as risk factors for the occurrence of bone mineral density disorders in patients with rheumatoid arthritis. Materials and methods. To the study were randomly enrolled 76 patients with RA (64 women (84.21%) in the premenopausal period and 12 men (15.78%) 38-60 years old (the average age at the time of examination of women – 48.67 ± 2.34 years, men – 45.42 ± 2.78). All patients were receiving methylprednisolone at a dose of 4.0 mg/day and a short course during an exacerbation up to 24.0 mg/day for RA treatment, but received no drugs for the treatment of BMD disorders. All patients underwent an assessment of BMD using ultrasound bone densitometry of the calcaneus, indicators of calcium-phosphorus metabolism and markers of bone remodeling were determined. Based on the obtained results, patients were stratified into three groups as follows: (1) 18 patients – 15 women and 3 men, aged 38-52, with RA without BMD disorders; (2) 34 patients – 31 women and 3 men, aged 38-54, with RA and osteopenia; (3) 24 patients – 18 women and 6 men, aged 41-53, with RA and OP. The control group consisted of 22 practically healthy individuals. Results. Patients with RA without BMD disorders significantly more often observed a decrease in the content of total calcium (p is less than 0.015) and ionized calcium (p is less than 0.000) in the blood serum, as well as a decrease in the individual osteocalcin (OK) index (р is less than 0.000). These patients were also endangered with reduced OC and/or total Ca in blood serum (p is less than 0.005). It was also revealed that in RA patients a decrease in urinary phosphorus indicates higher risk of osteopenia compared to RA patients with normal reference values of the same index (p is less than 0.000). Moreover, in patients with RA increased ionized calcium and decreased phosphorus indeces in urine correlated with significantly higher risk of osteoporosis compared to RA patients with these indeces normal levels (p is less than 0.050). According to the obtained data, an increase in the β-CrossLaps index in patients with RA is a risk factor for the occurrence both osteopenia and OP (p is less than 0.050). It was also founded that the reduced OC and increased ionized calcium levels can be treated as a risk factor for the occurrence of OP in patients with RA (p is less than 0.023). Conclusions. The risk of osteopenia in patients with rheumatoid arthritis without a violation of the mineral density of bone tissue is significantly higher in case of decreased content of blood serum total calcium or ionized calcium levels, or reduced osteocalcin index, or a simultaneous decreased content of total calcium and osteocalcin levels in blood serum. The risk of osteopenia in patients with rheumatoid arthritis is significantly higher if there is detected decreased phosphorus content in urine, or an increasede content of C-terminal telopeptide in blood serum, specific for the degradation of type I collagene. The risk of osteoporosis in patients with rheumatoid arthritis is significantly higher if there is a statistically significant increased level of ionized calcium in blood serum, or decreased content of phosphorus in the urine, or increased serum level of C-terminal telopeptidee, or an increased level of ionized calcium in the blood serum accompanied by a reduced level of osteocalcin. Keywords: calcium-phosphorus metabolism, bone remodeling markers, osteoporosis, osteocalcin, rheumatoid arthritis, bone mineral density.

Effect of probiotic biologics on morpho-biochemical parameters of broiler chicken blood

In the production of broiler poultry products, market operators use intensive technologies that involve the use of various, environmentally friendly nutraceuticals, in particular, probiotic preparations. In the technology of raising broiler chickens, probiotic preparations are necessary as a means for the prevention and treatment of gastrointestinal diseases, stimulating the growth and increasing the productivity of poultry. The purpose of the study is to investigate the effect of probiotic biologics on haematological parameters when it is fed to broiler chickens. The experiment used 20 broiler chickens, which were given a probiotic from 28 to 42 days in the following amounts: 0.5 g/10 dm3 , 2.0 and 4.0 g/10 dm3 of water. It was found that the morpho-biochemical parameters of poultry blood corresponded to the physiological standards for broiler chickens of the established age and confirmed the absence of pathophysiological changes in their body. On days 35 and 42 of rearing, an increase in the number of leukocytes from 4.4 to 17.2% and the haemoglobin content by 3.9 and 6.2%, respectively, was observed in the blood of broiler chickens fed the probiotic at a dose of 4.0 g/10 dm3 compared to the control group. On day 35 of the study, a 1.2-fold increase in total serum protein was observed when drinking a probiotic in poultry, respectively, at doses of 2.0 and 4.0 g/10 dm3 of water, and on day 42 – 1.0 times for its drinking at a dose of 4.0 g/10 dm3 of water. It was found that the content of inorganic calcium and phosphorus in the poultry blood serum corresponded to physiological limits, which indicates a sufficient level of mineral nutrition in the body of broiler chickens. The absence of changes in the activity of alanine aminotransferase and aspartate aminotransferase, the content of total lipids, cholesterol, and creatinine in the blood serum of broiler chickens of the experimental groups indicates the hepato- and nephronethoxicity of the probiotic. Based on the results obtained, the drug under study can be recommended to increase the resistance of the poultry body and regulate metabolism

Association between urinary phthalate metabolites and nephrolithiasis in adults: A cross-sectional analysis with NHANES 2007–2018

Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.

Fam83h mutation causes mandible underdevelopment via CK1α-mediated Wnt/β-catenin signaling in male C57/BL6J mice.

Truncation mutations in FAM83H are the major cause of autosomal dominant hypocalcified amelogenesis imperfecta. Some studies also indicated that FAM83H could be involved in osteogenic differentiation; however, the function of FAM83H in bone formation was rarely explored. This study aimed to explore the effect of Fam83h mutation on skeletal development. We generated Fam83h c.1186C>T (p.Q396*) knockin C57/BL6J mice by CRISPR/Cas9 technology and found that the Fam83hQ396⁎/Q396⁎ male mice presented skeletal development retardation that was inconspicuous at birth but progressively worsened as they grew up. Alcian and Alizarin Red staining of the whole-mount skeleton showed Fam83hQ396⁎/Q396⁎ mice presented obvious skeletal development retardation. Moreover, Micro-computed tomography (Micro-CT) analysis and H&E staining showed that the mandible of Fam83hQ396⁎/Q396⁎ mice exhibited decreased bone trabecula and slight bone rarefaction compared with wild-type mice. Calcium and phosphorus content of serum and bone, and serum ALP activity analysis showed that the serum ALP activity and value of bone calcium were decreased in Fam83hQ396⁎/Q396⁎ mice. The reduced expression of mineralization markers of RUNX2, OSX, OCN, and COL1, the reduced ALP activity and the weakened ARS staining exhibited in osteoblasts isolated from 3-day-old Fam83hQ396⁎/Q396⁎ mice. The increased protein expression of casein kinase 1α (CK1α) in the cytoplasm and the decreased expression of β-CATENIN in the nucleus indicated the inhibiting Wnt/β-catenin signaling in osteoblasts from Fam83hQ396⁎/Q396⁎ mice. Furthermore, agonists of Wnt/β-catenin signaling and Ck1α siRNA partially reversed the mineralization inhibition and the decreased expression of key signaling molecules in osteoblasts of Fam83hQ396⁎/Q396⁎ mice. In conclusion, Fam83h mutation caused the increase of cytoplasmic CK1α (as one of the components of the degradation complex), which in turn promoted degradation of β-CATENIN in the cytoplasm and reduced β-CATENIN translocation into the nucleus, subsequently inhibited Wnt/β-catenin signaling in osteoblast differentiation, and thus resulted in the mandible underdevelopment in Fam83hQ396⁎/Q396⁎ male mice.

Serum Calcium and Phosphorus Concentration in Egyptian Patients with Non-Alcoholic Fatty liver disease

Background and aim Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. NAFLD is a multisystem disease that affecting the liver and extrahepatic organs. This study aimed to assess serum calcium, phosphorus levels in patients with NAFLD, and to investigate the association between NAFLD and serum calcium and phosphorus levels. Patients and methods A case–control study was conducted on 200 patients; 100 diagnosed with NAFLD cross-matched with 100 individuals without NAFLD regarding to age, sex, and BMI. Serum calcium and phosphorus levels were assessed in both studied groups. Results Patients with NAFLD had low levels of serum calcium compared to individuals without NAFLD with highly significant P value less than 0.001. Conclusion NAFLD was associated with decreased level of serum calcium.

D-Pinitol Ameliorated Osteoporosis via Elevating D-chiro-Inositol Level in Ovariectomized Mice.

A natural sugar alcohol, D-pinitol, has been reported to be a potential compound for osteoporosis treatment via inhibiting osteoclastgenesis. However, research on the effects of pinitol on osteoporosis in vivo is still limited. The present study investigated the protective effects of pinitol on ovariectomized mice and attempted to elucidate this mechanism in vivo. Four-week-old female ovariectomized ICR mice were employed as a postmenopausal osteoporosis model and treated with pinitol or estradiol (E2) for 7 wk. Thereafter, serum calcium content, phosphorus content, tartrate-resistant acid phosphatase (TRAcP) and bone-specific alkaline phosphatase activity (BALP) were measured. Bilateral femurs were isolated, and bone marrow protein was collected through centrifuge. Dry femurs were weighed, while femur length, cellular bones, and bone mineral content were measured. D-chiro-Inositol (DCI) and myo-inositol (MI) content in serum and bone marrow was measured by GC-MS. At the end of experiment, the serum BALP and TRAcP activities of the OVX mice were suppressed significantly by treatment with either pinitol or E2. Femur weight, cellular bone rate, Ca and P content were improved by pinitol or E2. The DCI content of the serum of OVX decreased significantly, although it recovered to some extent after pinitol treatment. Pinitol significantly increased the ratio of DCI to MI in serum or bone marrow protein in the observed OVX mice. Besides, pinitol had no significant effects on osteoblast viability and differentiation. The present results showed that continuous pinitol intake exerts potent anti-osteoporosis activity via elevating DCI content in serum and bone marrow in OVX mice.

US-guided percutaneous radiofrequency ablation of secondary hyperparathyroidism as a bridge to renal transplantation

Purpose Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD) prior to renal transplantation (RTP), and the successful management of SPHP currently is challenging. In this study, we aimed to investigate the effectiveness of radiofrequency ablation (RFA) for SHPT as a bridge to RTP and to evaluate post-transplantation outcomes. Methods Patients with SHPT receiving RFA treatment were retrospectively reviewed, and those underwent RTP after ablation were enrolled. Serum parathyroid hormone (PTH), calcium, and phosphate levels were collected before ablation and at follow-up periods. The primary endpoints are PTH values at time of transplantation and at the final follow-up. The secondary endpoints were RFA-related complications, serum calcium and phosphate concentrations, and allograft function. Results Eleven patients with 43 enlarged parathyroid glands were treated with 16 RFA sessions and enrolled in the study. Complete ablation was achieved in all glands with transient hoarseness and hypocalcemia occurring in two and five of the treatments, respectively. At time of transplantation, serum PTH levels (246.7 ± 182.6 pg/mL) were significantly lower than that before RFA (1666.55 ± 874.48 pg/mL, p < 0.001) and were all within guideline-oriented range. The median follow-up period was 57.2 months. At last visit, all patients were alive, with normal PTH values and functioning grafts. Conclusions Ultrasound-guided RFA is effective for destroying hyperplastic parathyroid tissues in SHPT patients, whose PTH values fall within the guideline-oriented range both pre-and post-transplantation. Percutaneous RFA acts as an effective bridge to RTP and might provide a new management paradigm designed to improve post-transplant outcomes.

One Anastomosis Gastric Bypass Surgery: Consequences Over Ascorbic Acid, Cobalamin, Calciferol, and Calcium

Background: Nutrient deficiency after malabsorptive bariatric procedure is a common phenomenon. The study aims to determine the prevalence of nutritional insufficiencies (specific with Ascorbic acid, Cobalamin, calciferol and calcium) in obese population opting for One Ananstomosis Gastric Bypass surgery (OAGB), and also to understand the association of these nutrients with change in Body Mass Index (BMI) after the surgery.&#x0D; Methods: One hundred fifty subjects comprising males and females aged 20-60 years were randomly selected at a bariatric center in India. Subjects belonged to both grade III and grade II obesity. Plasma aa, serum vitB12, serum VitD3 and serum calcium concentrations were prospectively assessed at 0m, 3m, and 6m of surgery through high-performance liquid chromatography.&#x0D; Result: The values of nutrients beyond the standard levels are considered as deficiency. Both follow up values showed a significant increase in cobalamin, Calciferol, and ascorbic acid levels compared to baseline data.&#x0D; Conclusion: Nutrition depletion and deficiency are often seen in post bariatric cases. The contributing factors included high BMI, food intolerance, and non-adherence to supplements and correct dietary regimens. With the correction of weight and comorbidities, the levels also showed a stable and positive level.&#x0D; Bangladesh Journal of Medical Science Vol. 22 No. 03 July’23 Page : 695-708

#5123 EFFICACY AND SAFETY OF PATIROMER IN THE TREATMENT OF CHRONIC HYPERKALEMIA IN ASTURIAS: THE K-ASTUR STUDY

Abstract Background and Aims Hyperkalemia is a frequent problem in patients with chronic kidney disease (CKD), especially in those on hemodialysis (HD) and confers increased morbidity and mortality. It is common to carry out urgent HD sessions or increase the number of weekly sessions due to toxic hyperkalemia. Hyperkalemia also prevents the administration or adequate titration of drugs such as renin-angiotensin-aldosterone system (RAAS) inhibitors despite the evidence of their cardiovascular benefits and on the progression of CKD. New drugs have recently entered the market that can help treat chronic hyperkalemia. The aim of the present study was to analyse the efficacy and safety of Patiromer in patients with CKD Method Multicenter, prospective, clinical practice study in patients with CKD stages 3-5. Patiromer was administered with the indication of chronic hyperkalemia. Epidemiological and clinical data were analyzed; the evolution of serum potassium and elements involved in bone and mineral metabolism were taken into account. Results Finally, 52 patients (71±12 years old, 75% male, 63% diabetic, 54% with heart failure, and 42% receiving RAAS inhibitors) were included in the study. Regarding CKD, 17% were in stage 3b, 31% in stage 4, 38% in stage 5 (not on dialysis) and 13% were on HD. Of the 52 patients included, 46 reached 6 months of follow-up, 2 died, 2 underwent a kidney transplant and 2 were transferred to another center. The initial dose of Patiromer was in all cases 8.4 g administered orally in a single dose. Only one patient required doubling the dose because the therapeutic objectives were not achieved. Taking Patiromer was associated with a decrease in the levels of serum potassium of 27% (5.9 vs 4.6 mEq/L; P&amp;lt;0.001), a decrease that was more pronounced in the first month of treatment. There were no changes in the concentration of serum calcium and magnesium. We did find a decrease of 18% in serum phosphorus (5.1 vs 4.2 mg/dl; P 0.022), with no changes in dieto r phosphate binders. Patiromer was well tolerated and only 2 patients reported mild constipation; none discontinued the medication due to adverse effects. Conclusion Patiromer is effective and safe in reducing serum potassium concentrations. Due to its calcium content, it is possible that it favors the reduction in phosphoremia due to a decrease in the intestinal absorption of phosphorus. The use of this drug can help us control potassium levels in patients with CKD, properly titrate the use of ISRAAs, and even reduce the number of HD sessions or dialysis emergencies in some patients.

#2918 SERUM 25(OH)-VITAMIN D AND 1,25(OH)2 VITAMIN D IN HEMODIALYSIS PATIENTS: FACTORS AFFECTING THEIR CONCENTRATIONS AND THEIR EFFECT ON SURVIVAL

Abstract Background and Aims In haemodialysis patients, serum levels of vitamin D metabolites, 25-hydroxy-vitamin D (25D), a nutritional status of vitamin D, and 1,25-dihydroxy-vitamin D (1,25D), an active form of vitamin D, are previously reported to be low. In recent years of new CKD-MBD guidelines utilizing calcimimetics, vitamin D receptor agonists (VDRA) and new phosphate binders, relationship between serum 25D, 1,25D concentrations and clinical parameters in haemodialysis patients are not well known. We measured both serum 25D and 1,25D concentrations in chronic haemodialysis patients, and examined their association with several clinical factors and also with survival, in both cross-sectional and longitudinal analyses. Method A total of 108 stable haemodialysis patients (72 ± 10 year-old, 64 males, haemodialysis duration 6.9 ± 7.5 years, 45 with type 2 diabetes) were examined. Serum 25D was measured by a ECRIA method, and 1,25D by a RIA2 antibody method, and serum PTH by a IRMA assay. In a cross-sectional analysis, association of these vitamin D metabolites with clinical parameters was examined. In a longitudinal study, patients were followed for 3 years and survival of the patients was examined in relation with these vitamin D metabolites. Results Serum 25D concentrations were 12.0 ± 4.0 ng/ml, being hypovitaminosis D (&amp;lt;30 ng/ml) in all patients. Serum 1,25D concentrations were 14.7 ± 8.7 pg/ml, being lower than normal ranges (60-120 pg/ml) in 93% of the patients. There was no significant differences in 25D or 1,25D between those with diabetes and without. Although there was no significant correlation between 25D and haemodialysis duration, there was a significant negative correlation between 1,25D and haemodialysis duration (r = -0.187, p = 0.042). Neither of 1,25D or 25D was significantly correlated with serum calcium or phosphate concentrations. There was a significant, positive correlation between 25D and serum albumin (r = 0.172, p = 0.0454), although there was no significant correlation between 1,25D and serum albumin. Although there was no significant correlation between 25D and serum PTH, there was a significant, negative correlation between 1,25D and serum PTH (r = -0.379, p&amp;lt;0.001). Similarly, although there was no significant correlation between 25D and serum alkaline phosphatase, there was a significant, negative correlation between 1,25D and serum alkaline phosphatase (r = -0.309, p = 0.001). There were no significant differences in serum two vitamin D metabolites between patients with (n = 65) and without VDRA treatment, nor between those with (n = 12) and without calcimimetics. In a multiple regression analysis after adjustment of age, gender, haemodialysis duration, and VDRA treatment, serum 25D concentrations were significantly, independently associated with serum albumin (β = -0.244, p = 0.0149) (R2 = 0.125, p = 0.007). In a multiple regression analysis after the same adjustment, serum 1,25D concentrations were significantly, independently associated with serum intact PTH (β = -0.310, p = 0.003) (R2 = 0.200, p = 0.002). In the follow-up of three year, 16 patients died. Kaplan Meier analysis revealed that there tended to be better survival in patients with higher 25D concentration (n = 52) than those with lower concentration (p = 0.1936), although no significant association was seen between 1,25D and survival. Conclusion These results indicate that hypovitaminosis D (low 25D&amp;lt;30 ng/ml) is seen in all haemodialysis patients, and in most of these patients, serum 1,25D concentrations are low. Lower serum 25D concentrations are significantly associated with lower serum albumin, i.e., poorer nutritional status. Higher serum 1,25D, even in low ranges, is significantly associated with lower intact PHT and alkaline phosphatase, i.e. lower bone metabolism status. The results suggest that, in the era of new CKD-MBD treatments with calcimimetics and new VDRA, serum 25D may represent a nutritional status, and that serum 1,25D concentrations with regard to bone metabolism may be re-considered for the assessment of CKD-MBD, particularly in regards to prevention of secondary hyperparathyroidism.

#3775 PHOSPHATE BINDERS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE UNDERGOING DIALYSIS: A NETWORK META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS

Abstract Background and Aims Phosphate binders (PBs) are essential for proper serum phosphorus control in patients with chronic kidney disease (CKD) requiring dialysis along with adequate dialysis and phosphorus restriction. To evaluate the clinical efficacy and safety of each PBs, we conducted a systematic review (SR) using a network meta-analysis (NMA) of randomised controlled trials (RCTs). Method We searched published RCTs in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials (CENTRAL), and Clinical trial.gov databases using the search terms and text words relevant to this SR. We included RCTs involving adults (18 years and older) with at least 8 weeks of follow-up. Interventions and controls were the following: sevelamer-, bixalomer-, tenapanor-, iron- (ferric citrate, sucroferric oxyhydroxide), calcium-, magnesium-, lanthanum-, aluminium-, nicotinic acid-, and standard treatment or placebo). The outcomes were all-cause mortality, gastrointestinal adverse events (AEs), coronary artery calcium score (CACS), and serum calcium, phosphorus, and bicarbonate concentrations. Summary estimates were expressed as relative risk (RR) for binary outcomes and mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, respectively, with 95% confidence intervals (CI). The protocol of this study is registered in PROSPERO: CRD42022328388. Results All-cause mortality was identified and analysed in 29 trials involving 12,622 participants. Compared with calcium-containing PBs, sevelamer reduced the risk of all-cause mortality (RR 0.65, 95%CI 0.45 to 0.96). The risk of gastrointestinal AEs was higher for nicotinic acid (RR 3.79, 95%CI 1.29 to 11.12), sucroferric oxyhydroxide (RR 1.96, 95%CI 1.47 to 2.63), sevelamer (RR 1.47, 95%CI 1.14 to 1.88), and lanthanum (RR 1.36, 95%CI 1.14 to 1.64) than calcium-containing PBs. Lanthanum had an inhibitory effect on CACS progression compared to calcium-containing PBs (SMD -0.63, 95% CI -1.05 to -0.22). Serum calcium was lower than calcium-containing PBs in the following order: magnesium (MD -0.67, 95% CI -1.12 to -0.22), placebo (MD -0.64, 95% CI -1.22 to -0.67), nicotinic acid (MD -0.56, 95% CI -1.11 to -0.005), sevelamer (MD -0.35, 95% CI -0.47 to -0.23), and lanthanum (MD -0.24, 95% CI -0.38 to -0.095). No significant difference was observed in serum phosphorus decrease between any PBs and calcium-containing PBs. Serum bicarbonate concentration increased with ferric citrate (MD 1.16, 95% CI 0.36 to 1.96) and sucroferric oxyhydroxide (MD 1.06, 95% CI 0.29 to 1.82) but decreased with sevelamer (MD -1.24, 95% CI -1.71 to -0.77). Conclusion Our findings from SR based on NMA suggest that lanthanum may attenuate CACS and sevelamer may reduce the risk of all-cause mortality compared to calcium-containing PBs in patients with CKD requiring dialysis.

Incidence and risk factors of fasting hyperglycaemia following first-attack acute pancreatitis before discharge: a retrospective study

BackgroundPancreatic endocrine insufficiency is more likely to occur after acute pancreatitis (AP), but the risk factors affecting pancreatic endocrine function remain controversial. Therefore, exploring the incidence and risk factors of fasting hyperglycaemia following first-attack AP is important.MethodsData were collected from 311 individuals with first-attack AP without previous diabetes mellitus (DM) or impaired fasting glucose (IFG) history treated in the Renmin Hospital of Wuhan University. Relevant statistical tests were performed. A two-sided p-value < 0.05 was considered statistically significant.ResultsThe incidence of fasting hyperglycaemia in individuals with first-attack AP was 45.3%. Univariate analysis showed that age (χ2 = 6.27, P = 0.012), aetiology (χ2 = 11.184, P = 0.004), serum total cholesterol (TC) (χ2 = 14.622, P < 0.001), and serum triglyceride (TG) (χ2 = 15.006, P < 0.001) were significantly different between the hyperglycaemia and non-hyperglycaemia groups (P < 0.05). The serum calcium concentration (Z=-2.480, P = 0.013) was significantly different between the two groups (P < 0.05). Multiple logistic regression analysis showed that age- ≥60 years (P < 0.001, OR = 2.631, 95%Cl = 1.529–4.527) and TG ≥ 5.65 mmol/L (P < 0.001, OR = 3.964, 95%Cl = 1.990–7.895) were independent risk factors for fasting hyperglycaemia in individuals with first-attack AP (P < 0.05).ConclusionsOld age, serum triglycerides, serum total cholesterol, hypocalcaemia, and aetiology are associated with fasting hyperglycaemia following first-attack AP. Age ≥ 60 years and TG ≥ 5.65 mmol/L are independent risk factors for fasting hyperglycaemia following first-attack AP.

Prognostic value of day-of-event serum calcium and magnesium for predicting 1-year prognosis after intracerebral hemorrhage.

To investigate whether serum calcium and magnesium on the day of symptom onset contribute to prognosis at 1year after intracerebral hemorrhage (ICH). We prospectively enrolled patients admitted < 24h after symptom onset of primary ICH to West China Hospital between January 2012 and October 2014. Blood samples were collected at admission to determine the concentration of serum calcium and magnesium. We analyzed associations of the serum concentration of calcium and magnesium with unfavorable outcome (defined as modified Rankin scale, mRS ≥ 3) at 1year. We included 874 patients (mean age 59.1 ± 13.5years, 67.6% males), of whom 470 patients had mRS ≥ 3 and 284 patients died at 1year. Compared to patients with the highest tertile level of calcium concentration (≥ 2.29mmol/L), patients in the lowest tertile (≤ 2.15mmol/L) had higher odds of unfavorable outcome (odds ratio, OR 1.61, 95% confidence interval [CI] 1.04-2.50, P = 0.034). The Kaplan-Meier survival curve revealed a significant difference of cumulative survival rate across calcium tertiles (log-rank P value = 0.038). There was no significant association between serum concentration of magnesium and functional outcome at 1year. A reduced serum concentration of calcium on the day-of-event was associated with unfavorable outcome at 1year after ICH. Future studies are needed to illustrate the pathophysiological mechanism of calcium and whether calcium could be a treatment target for improving outcomes after ICH.

Nomogram analysis of the influencing factors of rapid renal decline in patients with biopsy-proven diabetic nephropathy in type 2 diabetes.

HbA1c variability may be related to risk of poor prognoses in chronic kidney disease patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether HbA1c variability is associated with rapid renal function decline and the related risk factors in type 2 diabetic nephropathy (DN). An observational analysis was performed on 387 DN patients who were diagnosed by kidney biopsy from January 2006 through January 2016 at the Department of Nephrology, Jinling Hospital Affiliated to Nanjing University. The rapid decliners were defined as an estimated glomerular filtration rate (eGFR) decline slope ≥5 mL/min/1.73m2/year. HbA1c variability and 24 baseline clinicopathologic parameters was evaluated using the least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression. The nomogram method was applied to score the factors, and a scoring model was constructed. HbA1c variability positively correlated with the rate of renal function decline (r=0.277; p<0.001). Higher baseline eGFR, lower serum calcium concentration, glomerular lesions, arteriosclerosis, and interstitial fibrosis and tubular atrophy (IFTA) were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.811 (95% confidence interval (CI) 0.680-0.785). The proposed nomogram and score provide a useful risk estimate of fast renal function decline in patients with type 2 diabetic nephropathy.

Feline precision medicine using whole-exome sequencing identifies a novel frameshift mutation for vitamin D-dependent rickets type 2.

A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. The afflicted kitten had marked hypocalcemia, mild hypophosphatemia and substantial elevations in alkaline phosphatase activity, as well as pathognomonic radiographic findings consistent with rickets. Skeletal changes and hypocalcemia prompted testing of concentrations of parathyroid hormone (PTH) and vitamin D metabolites. Endocrine testing demonstrated significant increases in serum concentrations of PTH and 1,25-dihydroxycholecalciferol (calcitriol), supporting a diagnosis of vitamin D-dependent rickets type 2. Provision of analgesia, supraphysiologic doses of calcitriol and calcium carbonate supplementation achieved normalization of the serum calcium concentration and restoration of normal growth, although some skeletal abnormalities persisted. Once skeletally mature, ongoing calcitriol supplementation was not required. Whole-exome sequencing (WES) was conducted to identify the underlying DNA variant. A cytosine deletion at cat chromosome position B4:76777621 in VDR (ENSFCAT00000029466:c.106delC) was identified and predicted to cause a stop codon in exon 2 (p.Arg36Glufs*18), disrupting >90% of the receptor. The variant was unique and homozygous in this patient and absent in the sibling and approximately 400 other cats for which whole-genome and whole-exome data were available. A unique, heritable form of rickets was diagnosed in a domestic longhair cat. WES identified a novel frameshift mutation affecting the gene coding for the vitamin D3 receptor, determining the likely causal genetic variant. Precision medicine techniques, including whole-exome and whole-genome sequencing, can be a standard of care in cats to identify disease etiologies, and to target therapeutics and personalize treatment.