Corrected Serum Calcium Levels Research Articles

Calcium-Alkali Syndrome Associated with Hypoparathyroidism Following Total Thyroidectomy

Background: Patients with permanent postsurgical hypoparathyroidism, a complication of total thyroidectomy, often require high calcium supplementation with vitamin D to maintain serum calcium levels. The epidemiology of calcium-alkali syndrome (CAS) in patients with hypoparathyroidism after total thyroidectomy remains unclear. This study aimed to investigate the incidence of hypercalcemia, renal impairment, metabolic alkalosis, and CAS in patients treated for presumed hypoparathyroidism after total thyroidectomy. Methods: Twenty-seven patients with neck cancers who underwent total thyroidectomy without parathyroid autotransplantation between January 2010 and October 2013 at our hospital were consecutively included. All patients received calcium lactate and alfacalcidol for postsurgical hypocalcemia. We defined hypercalcemia as a corrected serum calcium level (cCa) ≥10.5 mg/dL, metabolic alkalosis as a difference in serum sodium and serum chloride ([sNa-sCl]) ≥39 mEq/L, and renal impairment as a ≥50% increase in serum creatine and/or ≥35% decrease in estimated glomerular filtration rate (eGFR) compared to baseline. Results: cCa peaked (11.1 ± 1.5 mg/dL) at a median of 326 days (interquartile range 78–869) after surgery. At peak cCa, [sNa-sCl] was significantly higher (p < 0.01), and eGFR was significantly lower (p < 0.01) than that at baseline. Fifteen patients (55.6%) had hypercalcemia, 19 (70.3%) had alkalosis, 12 (44.4%) had renal impairment, and 9 (33.3%) had CAS. Patients with CAS (mean age 67.1 ± 10.8 years) were older than those without CAS (56.7 ± 13.6 years, p = 0.06). The mean dose of alfacalcidol in the CAS group (3.1 ± 1.2 μg/day) was significantly larger than that in the non-CAS group (2.1 ± 1.0 μg/day, p = 0.03). Conclusions: This retrospective study reveals the high incidence of CAS in patients with hypoparathyroidism after total thyroidectomy. Furthermore, these findings suggest that the serum calcium level, acid-base balance, and renal function should be closely monitored in patients with postsurgical hypoparathyroidism who receive large doses of active vitamin D.

Evaluation of parathyroid function in adult male patients with transfusion dependent thalassemia

Background: In transfusion dependent thalassemic (TDT) patients regular blood transfusion leads to iron overload. This increased iron is deposited in the tissue of various system and causes organ damage. Endocrine dysfunction is very common due to iron deposition into the endocrine glands including parathyroid dysfunction.&#x0D; Objective: To measure plasma intact parathyroid hormone(iPTH), serum total calcium and inorganic phosphate levels in adult male patients with TDT.&#x0D; Methods:This cross sectional study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University, Dhaka from March 2018 to February 2019. Total 35 TDT male patients aged 18 to 40 year and 35 age matched apparently healthy male subjects were enrolled for this study as control. The TDT patients were selected from the outpatient department of Hematology and Transfusion Medicine. For assessment of parathyroid function serum albumin, plasma iPTH, serum total calcium and inorganic phosphate levels were estimated by colorimetric method using automated analyzer. For statistical analysis, independent sample t test was done.&#x0D; Results: In this study, plasma iPTH and serum corrected calcium levels were significantly (p &lt; 0.001) lower in patients with TDT than those of healthy control. Again, Serum inorganic phosphate and ALP levels were significantly (p &lt; 0.001) higher in patients with TDT than those of healthy control. Moreover, 2.86% of TDT patients had low iPTH.&#x0D; Conclusion: From this study, it can be concluded that reduced parathyroid function was associated with TDT.&#x0D; J Bangladesh Soc Physiol. 2019, December; 14(2): 77-81

Ultrasound-guided ethanol injection for the treatment of parathyroid adenoma: A prospective self-controlled study.

Background:Parathyroidectomy, the standard treatment of primary hyperparathyroidism (PHP) due to parathyroid adenoma, is not suitable for all patients. We evaluated the efficacy of ultrasound-guided ethanol ablation of parathyroid adenoma in a group of patients with PHP.Materials and Methods:In a prospective self-controlled trial, 39 patients with parathyroid adenoma, who were not candidates for surgery, were enrolled. Ethanol injections were performed by two experienced interventional radiologists under the guidance of real-time ultrasonography. Adenoma size changes were assessed at about 1 month later. Serum levels of parathyroid hormone, calcium, phosphate, 25-OH Vitamin D, and alkaline phosphatase were evaluated at the baseline, 1, 3, 6, and 12 months after the injections. The treatment effects on outcome variables were assessed by repeated measures analysis.Results:Volume of the adenomas decreased during the study period from 1.87±6.45 cm3 to 0.38± 0.48cm3 (P < 0.001). Corrected serum calcium levels decreased from 10.40 ± 0.96 mg/dl to 8.82 ± 0.58 mg/dl (P < 0.001), and remained stable during one year follow-up. Serum levels of parathyroid hormone decreased gradually from 129.85 ± 63.37 to 72.58 ± 53.86 pg/mL after 3 months and to 44.78 ± 28.04 pg/mL after 1 year (P < 0.001). Overall, 46% of the patients improved after 1 month of ethanol ablation therapy which increased to 84.5% during 1-year follow-up. No major complications were observed.Conclusion:The current study showed the efficacy of ultrasound-guided ethanol injection in PHP and may be considered as a suitable alternative treatment in patients who are not candidates for the surgery. It has also a good safety profile without major complications if performed by experienced hands.

Hypoparathyroidism, Sensorineural deafness and renal disease (Barakat syndrome) caused by a reduced gene dosage in GATA3: a case report and review of literature

BackgroundBarakat syndrome is an autosomal dominant rare genetic disease caused by haploinsufficiency of the GATA binding protein 3 (GATA3) gene. It is also known as HDR syndrome, and is characterized by varying degrees of hypoparathyroidism, sensorineural deafness and renal disease. This is the first report of a heterozygous GATA3 whole gene deletion causing HDR syndrome in a Sri Lankan family.Case presentationA 13-year-old boy with an acute febrile illness, hypocalcaemia and bilateral carpopedal spasm was referred for evaluation. A past medical history of treatment for persistent hypocalcaemic symptoms since the age of 7 months was obtained. Biochemical investigations showed persistent low serum corrected calcium levels with hyperphosphataemia, hypomagnesaemia, low parathyroid hormone levels, hypercalciuria, and low total 25-hydroxy vitamin D levels. His renal functions and renal sonography were normal. Audiometry showed bilateral moderate to severe sensorineural hearing loss. On screening, his mother was also found to have asymptomatic hypocalcaemia, hypomagnesaemia, hyperphosphataemia, hypercalciuria and low total 25-hydroxy vitamin D levels. She had impaired renal functions and chronic parenchymal changes in the renal scan. Audiometry showed bilateral profound sensorineural hearing loss. Genetic analysis using multiplex-ligation dependent probe amplification showed a reduced gene dosage for GATA3 that is consistent with a heterozygous whole gene deletion in both the child and mother.ConclusionsThis report demonstrates the wide intra-familial phenotypic variability observed in HDR syndrome and adds further to the existing scientific literature on the genotype-phenotype correlation of this syndrome. It highlights the need for HDR syndrome to be considered in the differential diagnosis of persistent hypocalcaemia with sensorineural deafness and/or renal involvement, and for appropriate genetic evaluation to be done to confirm the diagnosis.

The Incidence and Associated Factors of Sudden Death in Patients on Hemodialysis: 10-Year Outcome of the Q-Cohort Study.

Aim: The incidence of sudden death and its risk factors in patients on hemodialysis remain unclear. This study aimed to clarify the incidence of sudden death and its risk factors in Japanese patients on hemodialysis.Methods: A total of 3505 patients on hemodialysis aged ≥ 18 years were followed for 10 years. Multivariate-adjusted hazard ratio (HR) with 95% confidence interval (95% CI) of each risk factor of sudden death were calculated using a Cox proportional hazards model.Results: During the 10-year follow-up, 1735 patients died, including 227 (13%) sudden deaths. The incidence rate of sudden death was 9.13 per 1000 person-years. In multivariable-adjusted Cox analysis, male sex (HR 1.67; 95% CI 1.20–2.33), age (HR 1.44; 95% CI 1.26–1.65 per 10-year higher), the presence of diabetes (HR 2.45; 95% CI 1.82–3.29), history of cardiovascular disease (HR 1.85; 95% CI 1.38–2.46), cardiothoracic ratio (HR 1.21; 95% CI 1.07–1.39 per 5% higher), serum C-reactive protein (HR 1.11; 95% CI 1.03–1.20 per 1-mg/dL higher), and serum phosphate (HR 1.15; 95% CI 1.03–1.30 per 1-mg/dL higher) were independent predictors of sudden death. A subgroup analysis stratified by sex or age showed that lower serum corrected calcium levels, not using vitamin D receptor activators in women, and a shorter dialysis session length in men or older people (≥ 65 years) increased the risk for sudden death.Conclusions: This study clarified the incidence of sudden death and its specific predictors in Japanese patients on hemodialysis.

Factores de riesgo y evolución del calcio y hormona paratiroidea en el síndrome de hueso hambriento tras paratiroidectomía por hiperparatiroidismo primario

IntroductionHungry bone syndrome (HBS) is a complication occurring after parathyroid surgery that can cause severe and prolonged hypocalcemia. The study objective was to know the risk factors for HBS after surgery for primary hyperparathyroidism and its relationship with serum calcium and parathyroid hormone levels. Material and methodsA case-control, observational, analytical study was conducted in patients who had undergone surgery for primary hyperparathyroidism in the past 10 years (2007-2016). Changes over time in serum calcium and PTH levels and the general characteristics of patients were analyzed. ResultsThe incidence rate of HBS in our series was 12.2%. HBS was found to be significantly associated to thyroid surgery during the surgical procedure itself (adjusted odds ratio [aOR]=17.241), to age older than 68 years (aOR=6.666), and to lesions greater than 1.7cm (aOR=7.165). A statistically significant relationship was seen between presence of HBS and corrected serum calcium levels higher than the mean the day after surgery and one week and 3 months later, and also with PTH levels higher than the mean before, during, and one day after surgery. ConclusionIn our series, independent risk factors for development of HBS included patient age, lesion size, and whether or not the procedure was accompanied by thyroid surgery, which requires closer monitoring of mineral metabolism during the perioperative period.

Clinical Significance of Postoperative Nutritional Status as a Prognostic Factor in Kidney Transplant Recipients

BackgroundDespite advancements in the management of kidney transplantation (KT), kidney transplant recipients (KTRs) have a higher risk of mortality than the age-matched general population. Improvement of long-term graft and patient survival is a significant issue. Therefore we investigated the effects of postoperative nutritional status on graft and patient survival and explored the predictive factors involved in nutritional status. MethodsOur retrospective study included 118 KTRs who underwent KT at our hospital. Clinical and laboratory data were obtained from medical charts. The prognostic nutritional index (PNI) was used to assess nutritional status. Changes in nutritional status after KT were monitored and the effect of nutritional status on graft and patient survival was investigated. The variables involved in nutritional status were also explored. ResultsThe KTRs in this cohort comprised 66 men and 52 women with a median age of 47 years at KT. There were 16, 32, and 22 cases of cadaveric, preemptive, and ABO-incompatible KTs, respectively. Postoperative PNI gradually improved and was stable from 6 months after KT. Although graft survival was regulated by ABO-compatibility, independent predictors for patient survival were history of dialysis, PNI, and serum-corrected calcium levels. Preemptive KT and inflammatory status contributed to PNI. ConclusionsNutritional status of KTRs improved over time after KT and could contribute to patient survival. Optimal nutritional educational programs and interventions can lead to better outcomes in KTRs. Further studies are needed to validate our results and develop appropriate nutritional educational programs, interventions, and exercise programs.

Association between serum calcium levels and prognosis, hematoma volume, and onset of cerebral hemorrhage in patients undergoing hemodialysis

BackgroundHigh serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient’s prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage.MethodsThis cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis.ResultsOf the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43–4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50–10.4; P = 0.005) had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07–2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23–1.59; P < 0.001).ConclusionsAlthough the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient’s calcium level.

Prognostic Value of Corrected Levels of Serum Calcium and Serum Lactate Dehydrogenase for Newly Diagnosed Multiple Myeloma Patients

To investigate the prognostic value of the serum calcium level corrected by serum albumin (cCA) and corrected serum lactate dehydrogenase (LDH) level for the risk stratification for newly diagnosed multiple myeloma (MM) patients. The clinical data and survival of 186 newly diagnosed MM patients admitted to our hospital from June 1, 2015 to November 1, 2017 were collected. The patients's survival time was obtained by telephone and follow-up visits to patients and their families. The value of the prognostic system consisting of cCA levels and LDH levels in the survival time of MM patients was retrospectively analyzed. Moreover, the post-corrected hypercalcemia and high LDH as 2 factors were used for risk stratification, then according to these 2 factors, the MM patients were divided into 3 groups: group 1 (no risk factor), group 2 (1 risk factor) and group 3 (2 risk factors), and the effect of risk factors on the prognosis of MM patients was analyzed. The median follow-up time was 16 months. The cumulative OS rate of the post-corrected hypercalcemia group was lower than that of the non-hypercalcemia group. The 1-year cumulative OS rate in the 2 groups was 79.0%±6.7% and 88.6%±3.0%, the 3-year cumulative OS rate was 53.0%±10.5% and 74.6%±6.6% (P=0.016), respectively. The cumulative OS rate of the high LDH group [LDH ＞upper limit of normal (ULN), ULN=250 U/L] was lower than that in the normal LDH group. The 1-year cumulative OS rate in the 2 groups was 71.6%±8.6% and 90.0%±2.8%, the 2-year cumulative OS rate was 44.9%±12.1% and 83.1%±4.0%, respectively, and the median OS time was 19 months (95%CI: 15.32-23.34) and not reached (P=0.001). The risk stratification analysis showed that the median OS time of the 3 group was not reached (n=103, 57%), not reached (n=70, 39%) and 17 months (n=7, 4%, 95%CI: 5.19-28.41, P＜0.001). Patients with two risk factors had a prognosis worse than patients with 0-1 risk factor. The prognostic combination of corrected serum calcium and LDH levels may provide a basis for risk stratification and prognosis in MM patients in clinical practice.

Long-Term Efficacy and Safety of Evocalcet in Japanese Patients with Secondary Hyperparathyroidism Receiving Hemodialysis

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD), and as the disease progresses SHPT is associated with systemic consequences, termed CKD-mineral and bone disorder. Currently, cinacalcet is indicated for the treatment of SHPT; however, cinacalcet is associated with upper gastrointestinal adverse events. Evocalcet has been developed to address these issues, but the long-term safety and efficacy of evocalcet need to be evaluated. To more accurately reflect clinical practice, this phase 3, multicenter, open-label study was specifically designed without a cinacalcet washout period, and focused on those patients who switched from cinacalcet to evocalcet. A total of 137 SHPT patients undergoing hemodialysis were enrolled, of whom 113 switched from cinacalcet to evocalcet. The most frequent type of adverse drug reaction was decreased adjusted calcium. The incidence of gastrointestinal-related adverse events did not increase in a dose-dependent manner as the dose of evocalcet was increased. The percentage of patients achieving the target intact parathyroid hormone concentration increased from 40.9% to 72.3% with 52-week treatment. The corrected serum calcium and phosphorus levels remained largely unchanged throughout the study. The long-term safety and efficacy of evocalcet was confirmed using a clinically relevant intra-subject dose-adjustment strategy in SHPT patients undergoing hemodialysis.

Lower Serum Calcium as a Potentially Associated Factor for Conversion of Mild Cognitive Impairment to Early Alzheimer's Disease in the Japanese Alzheimer's Disease Neuroimaging Initiative.

Effect of serum calcium level to the incidence of mild cognitive impairment (MCI) conversion to early Alzheimer's disease (AD) remains uncertain. To investigate association between baseline serum calcium and the MCI conversion in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study cohort. In this sub-analysis of J-ADNI study, we reviewed data from MCI participants at baseline regarding their conversion to early AD during the 3 years of observation period and assessed the associated factors including serum calcium level. In addition, we compared our results from the J-ADNI study with the corresponding results from the North American (NA)-ADNI. Of 234 eligible MCI participants from the J-ADNI cohort, 121 (51.7%) converted to AD during the first 36 months of observation. Using univariate analysis, being female, having shorter years of education, and lower serum calcium level were correlated with increased risk of MCI-to-AD conversion exclusively in J-ADNI cohort. The lower corrected serum calcium level remained as one of conversion-associated factors in the J-ADNI cohort even after adjustment for multiple confounding variables, although this was not observed in the NA-ADNI cohort. Our findings suggest that lower serum calcium may be associated with an increased risk of MCI conversion to AD in Japanese cohorts. The reason for this correlation remains unclear and further external validation using other Asian cohorts is needed. It would be interesting for future AD studies to obtain serum calcium levels and other related factors, such as vitamin D levels, culture-specific dietary or medication information.

Correlation between hypocalcemia and acute exacerbation of chronic obstructive pulmonary disease in the elderly

ABSTRACTIntroduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important disease of hospitalized elderly patients, who often have electrolyte imbalances. This study was performed to analyze total serum calcium levels in elderly patients with AECOPD and identify the correlation between hypocalcemia and AECOPD.Methods: 153 elderly patients with AECOPD served as the observation group, and 115 healthy elderly people undergoing physical examinations served as the control group. Differences in the corrected serum calcium, albumin (ALB), and neutrophil/lymphocyte ratio (NLR) were analyzed between the observation and control groups before and after treatment. The incidence of hypocalcemia was compared among patients at different ages and with different pulmonary function classifications before treatment. The relationship between hypocalcemia and respiratory infection was analyzed. Differences in the pretreatment NLR, ALB, logarithm of the serum C-reactive protein level (LogCRP), and hospital stay were compared between patients with and without hypocalcemia.Results: The corrected serum calcium level (P < 0.001), NLR (P = 0.001) and albumin level (P < 0.001) were significantly different among the pretreatment group, post-treatment group, and control group. The serum calcium level, LogCRP, and NLR were significantly lower after than before treatment (P < 0.05). Significant differences in the incidence of hypocalcemia were found among patients of different ages (P = 0.002). The respiratory infection rate (P < 0.001), hospital stay (P < 0.001), NLR (P = 0.007), and LogCRP (P < 0.001) was higher in patients with than without hypocalcemia. However, the albumin level was lower in patients with than without hypocalcemia (P < 0.001).Conclusions: In elderly patients with AECOPD, hypocalcemia may be related to the disease progression, respiratory infection rate, and hospital stay of patients with AECOPD.

Hypercalcemia and acute kidney injury induced by eldecalcitol in patients with osteoporosis: a case series of 32 patients at a single facility

Background: Eldecalcitol (ELD) is an active vitamin D3 analog that is widely used in Japan for the treatment of osteoporosis. The most common adverse drug reaction of ELD is hypercalcemia. However, few reports have focused on acute kidney injury (AKI) associated with ELD-induced hypercalcemia.Materials and methods: We retrospectively reviewed the medical records at our hospital for cases of hypercalcemia-induced AKI between April 2013 and February 2018. Among them, we focused on patients who developed AKI secondary to ELD-induced hypercalcemia.Results: Among 69 patients who developed hypercalcemia-induced AKI, 32 patients (46.4%) developed AKI associated with ELD-induced hypercalcemia. Their mean age was 82 ± 5 years, 97% of them were female, mean corrected serum calcium level was 12.2 ± 1.5 mg/dL, serum creatinine level was 2.5 ± 2.2 mg/dL, and estimated glomerular filtration rate was 23.9 ± 14.4 ml/min/1.73 m2 on admission. ELD administration was discontinued in all patients and some of them were treated with hydration with or without calcitonin, which was followed by a normalization of serum calcium level. Corrected serum calcium level on admission was significantly higher (p < .05) in patients treated with magnesium oxide. Although there were no significant differences, serum calcium and creatine levels on admission tended to be higher in patients who were treated with other drugs that affect renal hemodynamics and renal calcium metabolism than those not taking these drugs.Conclusions: Prescribers of ELD should regularly monitor serum calcium levels and kidney function to prevent hypercalcemia and AKI associated with ELD and pay more attention to concomitant drugs especially magnesium oxide.

Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan.

PurposeCinacalcet is a positive allosteric modulator of calcium-sensing receptors in the parathyroid gland and an effective treatment for secondary hyperparathyroidism. However, this agent has considerable side effects and dosage limitations, which impair effective treatment. Therefore, we investigated the pharmacokinetics, pharmacodynamics, and safety of the novel calcimimetic, evocalcet.Patients and methodsThis was a multicenter, open-label study of single oral doses of 1, 4, and 12 mg evocalcet using an intrapatient dose escalation protocol in 29 Japanese secondary hyperparathyroidism patients receiving hemodialysis. Pharmacokinetics was assessed by plasma evocalcet concentrations. Pharmacodynamic evaluations consisted of measuring intact parathyroid hormone, serum corrected calcium, and fibroblast growth factor 23 concentrations. Safety and tolerability were evaluated by the analysis of adverse events (AEs).ResultsAfter a single 1-, 4-, or 12-mg dose, plasma evocalcet levels increased dose proportionally in a linear manner. Pharmacodynamic analyses showed that evocalcet effectively reduced intact parathyroid hormone and serum corrected calcium levels in a dose-dependent manner. AEs occurred in 31.0%, 28.6%, and 38.5% of patients receiving a single dose of 1, 4, or 12 mg, respectively. Most AEs were mild in severity.ConclusionEvocalcet is effective in the short term, has linear pharmacokinetics, and is well tolerated as observed by the low incidence of AEs.

Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients

BackgroundThis study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis.MethodsIn this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events.ResultsPlasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE ‘blood calcium decreased’ occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased).ConclusionMultiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.

Multiple endocrine neoplasia type 1: clinical correlates of MEN1 gene methylation

Multiple endocrine neoplasia type 1 (MEN 1) has marked severity variation between individuals with the same mutation. To investigate any relationship between promoter methylation and clinical features, blood and tissue samples were collected from 16 members of the Tasman 1 MEN 1 kindred carrying a common splice site mutation and 7 patients with sporadic MEN 1. Methylation at 39 CpGs in the MEN1 promoter were assessed in formalin fixed, paraffin embedded parathyroid tissue. Clinical disease severity markers included age at first parathyroid operation, parathyroid hormone level and corrected serum calcium levels. Six patients with sporadic hyperparathyroidism were used for comparison. Minimal methylation was observed in all patients across CpG sites 1-23. In contrast, hypermethylation was observed at CpG sites 24-31 in MEN 1 patients, a pattern not observed in patients with non-MEN 1 parathyroid disease. Mean methylation at sites 24-31 was significantly correlated with age at first parathyroid operation (r= 0.652, p= 0.041). A permutation test, utilising the mean correlation coefficient (r= -0.401) revealed a possible association between relative PHPT severity and methylation score for each significant CpG site (p < 0.103). This novel study reveals evidence supporting a possible association between altered MEN1 promoter methylation and clinical severity of disease.

Effects of Lowering Dialysate Calcium Concentration on Bone Metabolic Markers in Hemodialysis Patients With Suppressed Serum Parathyroid Hormone: A Preliminary Study.

Although the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend a dialysate calcium concentration between 2.5 and 3.0 mEq/L, its optimal concentration remains unclear. A total of 53 hemodialysis patients with intact parathyroid hormone (PTH) levels <150 pg/mL were enrolled in this prospective observational study. A dialysate calcium concentration was converted from 3.0 to 2.75 mEq/L and bone metabolic markers including bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase-5b (TRACP-5b) were examined. After 3 months, serum corrected calcium levels decreased (P < 0.001), while serum intact PTH, BAP and TRACP-5b levels increased (P < 0.05, P < 0.05 and P < 0.001, respectively). Multiple regression analyses showed that the amount of change in BAP was significantly associated with dialysis vintage (P < 0.01). In conclusion, the lowering of dialysate calcium concentration stimulated parathyroid gland and bone remodeling in hemodialysis patients with suppressed PTH, particularly with longer dialysis vintage.

Association of pregnancy hypocalcemia and neonatal growth indices.

Introduction: Hypocalcemia is a common condition in pregnancy. Approximately 20-30 g maternal calcium is actively transferred to the fetus during pregnancy for fetal skeletal mineralization. The aim of this study was to determine the association of pregnancy hypocalcemia with neonatal growth indices. Methods: This cohort study was conducted on 112 pregnant women with the gestational age of 22-26 weeks in 2016. Calcium, albumin, 25(OH)D, and urinary calcium/creatinine ratio were measured for all participants. Hypocalcemia was defined as corrected serum calcium level of 0.05). Furthermore, neonatal growth indices were not significantly different in the maternal calcium quartiles. The two groups showed no significant difference in terms of the adjusted mean of neonatal growth indices (P>0.05). Conclusion: According to the findings of the present study, hypocalcemia was a prevalent condition in pregnancy; however, this condition exerted no adverse effects on neonatal growth indices.

Risk of cardiovascular mortality predicted by the serum calcium level and calcification score at the initiation of dialysis

BackgroundThe relationship between serum corrected calcium (CCa) level and vessel calcification at dialysis initiation and survival has seldom been evaluated. Therefore, we evaluated the efficacy of CCa levels and the calcification score at the initiation of dialysis for predicting all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD).MethodsThe study group included 407 patients with ESRD, who started hemodialysis between January 2009 and December 2016 at the Red Cross Ishinomaki Hospital. The primary outcomes were the 1- and 3-year all-cause and CV mortality rate, with the association between CCa level and CVD-specific mortality evaluated using the Kaplan–Meier method and Cox proportional hazard regression analysis.ResultsPatients with a high initial CCa level were at higher risk for CVD-related, but not all-cause, mortality than patients with a low initial CCa level [hazard ratio (HR) 2.81; 95% confidence interval 1.05–7.55]. The HR for CVD-related mortality was also higher for patients with an Agatston vessel calcification score > 2000 (HR 13.9; 95% CI 1.63–118.2). Overall, the 3-year CVD-free rate was 88.2% (range 76.4–94.3%). Higher CCa level was associated with a higher Agatston score and cardiac valve calcification.ConclusionHigh serum CCa levels and an Agatston score > 2000 are independent risk factors of CVD mortality due to advanced vessel calcification.

Current Perspectives on Sudden Cardiac Death in Hemodialysis Patients.

Recent lines of evidence suggest that, as in other countries, sudden cardiac death (SCD) is more common in the Japanese dialysis clinical setting than we previously thought. Three specific important findings may underlie the increased incidence of SCD in dialysis patients. Even after successful coronary revascularization, hemodialysis (HD) patients continue to have a higher incidence of SCD than the general population. Second, about 70% or more of end-stage kidney disease patients have concentric and eccentric left ventricular hypertrophy, which predisposes many dialysis patients to interstitial fibrosis, decreased coronary perfusion reserve, and decreased ischemia tolerance. Third, mildly impaired left ventricular dysfunction, with an ejection fraction <50%, is associated with a greater risk of SCD in dialysis patients. We have believed and accepted a common sense theory that paroxysmal ventricular tachycardia and fibrillation are the central cause of SCD in HD patients, because such cardiac functional morphological abnormalities were observed, and there are many chances for ventricular arrhythmia triggers, such as volume expansion and electrolyte shift, to develop. However, the type of fatal arrhythmia responsible for SCD differs between before and after HD. Sudden cardiac arrest (SCA) from ventricular fibrillation (VF) was more often seen in the post-HD setting, while SCA from non-VF, which may be bradyarrhythmia, was more often seen in the pre-HD setting. This may imply that the causes of SCA are bradyarrhythmia due to hyperkalemia in the pre-HD setting on the day after a long interval, and fatal ventricular arrhythmia due to a prolonged QT interval in the post-HD setting, because some recent evidence suggests that shifts of electrolytes, such as potassium and calcium, during HD cause rapid prolongation of the QT interval after HD, which may lead to the onset of ventricular arrhythmia and SCD. In fact, a higher calcium gradient, defined as the difference between the pre-HD corrected total serum calcium level and the dialysate calcium level, was associated with a higher risk of SCD in HD patients. Key Messages: Further study is needed to determine which combination of calcium, potassium, and bicarbonate concentrations in dialysate is optimal to avoid SCD in high-risk HD patients.