Albumin-corrected Calcium Levels Research Articles

Biochemical characteristics and clinical manifestation of normocalcemic primary hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level - with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12-2.62 mmol/l), without other causes for secondary hyperparathyroidism. The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures.

Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis.

Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients. In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves. Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD. Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.

Multiple Bone Cysts Caused by Hyperparathyroidism: A Case Report and Review of the Literature.

Brown tumor, a skeletal complication of severe hyperparathyroidism, comprises reparative granulation tissue and proliferating fibrous tissue with hemosiderin deposition. Multiple brown tumors are extremely rare complications of primary hyperparathyroidism. A 41-year-old woman presented with pain in the left knee. Radiography showed multiple cystic lesions in both femurs and the left proximal tibia, and additional radiography showed multiple cystic lesions in the left humerus and ulna. Magnetic resonance imaging (MRI) revealed multiple cystic lesions in the bilateral femurs, left proximal tibia, and ilium. Laboratory tests revealed hypercalcemia (albumin-corrected calcium level, 13.9 mg/dl), hypophosphatemia (phosphate level, 1.6 mg/dl), elevated level of alkaline phosphatase level (614 U/l), and markedly elevated parathyroid hormone (PTH) level (1,070 pg/ml; normal range=10-65 ng/l). 99mTc-hexakis-2-methoxyisobutyl-isonitrile scintigraphy revealed tracer accumulation in the left upper parathyroid gland, which was consistent with parathyroid tumor. Although resection of the parathyroid tumor was planned, the patient developed parathyroid apoplexy before tumor excision. After the parathyroid apoplexy, serum calcium and PTH levels temporarily normalized. Resurgence of the PTH level was observed 2 years after the diagnosis, and the patient underwent left upper parathyroidectomy. One year after the tumor excision, the patient had no symptoms, and MRI showed shrinkage of the cystic bone lesions. This report emphasizes the importance of considering hyperparathy-roidism as a differential diagnosis for patients with multiple bone lesions.

Cinacalcet increases renal calcium excretion in PTHrP-mediated hypercalcemia: a case report

BackgroundIn the acute setting, PTH-independent hypercalcemia is typically treated with anti-resorptive agents such as zoledronic acid or denosumab. When these agents are no longer able to control hypercalcemia, several case reports have shown the utility of cinacalcet. However, it is not known if cinacalcet can be effective in patients naïve to anti-resorptive therapy or how cinacalcet ameliorates the hypercalcemia.Case presentationA 47-year-old male with a history of alcohol-induced cirrhosis was admitted for left cheek bleeding and swelling from an infiltrative squamous cell carcinoma of the oral cavity. On admission, he was found to have an elevated albumin-corrected serum calcium of 13.6 mg/dL, a serum phosphorus of 2.2 mg/dL and an intact PTH of 6 pg/mL (normal 18–90) with a PTHrP of 8.1 pmol/L (normal < 4.3), consistent with PTHrP-dependent hypercalcemia. Aggressive intravenous saline hydration and subcutaneous salmon calcitonin were initiated, but his serum calcium remained elevated. Given tooth extractions scheduled for the next day and possible irradiation to the jaw in the near future, alternatives to antiresorptive therapy were sought. Cinacalcet was initiated at 30 mg twice daily then increased to 60 mg twice daily the following day. The albumin-corrected serum calcium level decreased from 13.2 to 10.9 mg/dL within 48 h. The fractional excretion of calcium increased from 3.7 to 7.0%.ConclusionsThis case demonstrates the utility of cinacalcet for the treatment of PTHrP-mediated hypercalcemia without prior anti-resorptive therapy via increased renal clearance of calcium.

Effect Modification of Kidney Function on the Non-linear Association Between Serum Calcium Levels and Cardiovascular Mortality in Korean Adults.

This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality. This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: <2.5th, 2.5-25.0th, 25.0-50.0th, 50.0-75.0th, 75.0-97.5th, and >97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate. Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (<2.5th: HR, 6.23; 95% confidence interval [CI], 1.16 to 33.56; >97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (<2.5th: HR, 1.37; 95% CI, 0.58 to 3.27; >97.5th: HR, 1.65; 95% CI, 0.70 to 3.93). We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association.

B-mode ultrasound assessment of carotid artery structural features in patients with normocalcaemic hyperparathyroidism.

Normocalcaemic hyperparathyroidism is a condition first defined in 2008, characterized by normal serum calcium and high parathormone levels. Although normocalcaemic hyperparathyroidism is considered to have a milder clinical picture compared to asymptomatic primary hyperparathyroidism, recent studies have shown that it may be associated with osteoporosis, insulin resistance, metabolic syndrome, and cardiovascular risk factors. Considering that normocalcaemic hyperparathyroidism may pose a cardiovascular risk in the setting of carotid atherosclerosis, we sought to examine the structural features of the carotid artery in patients with normocalcaemic hyperparathyroidism compared to a control group. After excluding patients with hypertension, diabetes, and dyslipidaemia (other factors contributing to atherosclerosis), 37 (32 females, 5 males) patients with normocalcaemic hyperparathyroidism with a mean age of 51.2 ± 8 (min: 32, max: 66) years and 40 controls (31 females, 9 males) with a mean age of 49.3 ± 7.5 (min: 34, max: 64) years with normal serum albumin-corrected calcium and parathyroid hormone levels were included in the study. Structural features of the carotid artery including intima-media thickness (mean and maximum), lumen diameter, and the presence of plaque were assessed using B-mode ultrasound. On ANCOVA analysis corrected for atherosclerotic factors (body mass index, waist circumference, fasting plasma glucose, serum cholesterol, lipid, and blood pressure), greater mean intima-media thickness was found in patients with normocalcaemic hyperparathyroidism than in controls (0.65 mm vs. 0.59 mm, respectively) (p = 0.023). Maximum carotid intima-media thickness was also greater in patients with normocalcaemic hyperparathyroidism compared to controls (0.80 mm vs. 0.75 mm, respectively) (p = 0.044). The study groups did not show a significant difference in lumen diameter and the presence of carotid plaque. In addition, a negative correlation was found between parathormone (PTH) level and lumen diameter. The findings of this study show that as with asymptomatic primary hyperparathyroidism, normocalcaemic hyperparathyroidism may be associated with increased cardiovascular risk by predisposing to atherosclerosis.

Lithium induced hypercalcemia: an expert opinion and management algorithm

BackgroundLithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking.MethodsBased on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment.ResultsIn the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed.ConclusionsStandardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.

Association between Hypocalcemia and Outcome in COVID-19 Patients: A Retrospective Study.

Background  Calcium has been shown to play a vital role in the pathophysiology of severe acute respiratory syndrome-coronavirus-2 and middle east respiratory syndrome coronavirus diseases, but less is known about hypocalcemia in coronavirus disease 2019 (COVID-19) patients and its association with the disease severity and the final outcome. Therefore, this study was conducted with an aim to assess clinical features in COVID-19 patients having hypocalcemia and to observe its impact on COVID-19 disease severity and the final outcome. Methods  In this retrospective study, consecutive COVID-19 patients of all age groups were enrolled. Demographical, clinical, and laboratory details were collected and analyzed. On the basis of albumin-corrected calcium levels, patients were classified into normocalcemic ( n  = 51) and hypocalcemic ( n  = 110) groups. Death was the primary outcome. Results  The mean age of patients in the hypocalcemic group was significantly lower ( p  < 0.05). A significantly higher number of hypocalcemic patients had severe COVID-19 infection (92.73%; p  < 0.01), had comorbidities (82.73%, p  < 0.05), and required ventilator support (39.09%; p  < 0.01) compared with normocalcemic patients. The mortality rate was significantly higher in the hypocalcemic patients (33.63%; p  < 0.05). Hemoglobin ( p  < 0.01), hematocrit ( p  < 0.01), and red cell count ( p  < 0.01) were significantly lower with higher levels of absolute neutrophil count (ANC; p  < 0.05) and neutrophil-to-lymphocyte ratio (NLR; p  < 0.01) in the hypocalcemic patients. Albumin-corrected calcium levels had a significant positive correlation with hemoglobin levels, hematocrit, red cell count, total protein, albumin, and albumin-to-globulin ratio and a significant negative correlation with ANC and NLR. Conclusion  The disease severity, ventilator requirement, and mortality were considerably higher in hypocalcemic COVID-19 patients.

Higher serum albumin-corrected calcium levels are associated with revascularization and poor outcome after mechanical thrombectomy

BackgroundSerum calcium abnormalities have been determined to be associated with the risk and outcome of stroke. The aim of the present study was to examine the associations of serum calcium with vascular recanalization, symptomatic intracranial haemorrhage and functional outcome in stroke patients after mechanical thrombectomy.MethodsA total of 192 patients treated with mechanical thrombectomy for anterior circulation large vessel occlusion were consecutively included from August 2017 to June 2021. Serum calcium levels were measured on admission, and albumin-corrected calcium levels were calculated for subsequent analysis. Successful arterial revascularization was defined as a modified Thrombolysis in Cerebral Infarction scale score ≥ 2b. Symptomatic intracranial haemorrhage was assessed according to the European Cooperative Acute Stroke Study (ECASS) III criteria. Poor functional outcome was defined as a modified Rankin Scale score > 2 at 3 months.ResultsPatients with poor outcomes had higher albumin-corrected calcium levels than patients with good outcomes before (2.20 (2.10, 2.30) mmol/L vs. 2.13 (2.04, 2.24) mmol/L, P = 0.002), and after adjusting for other factors (AOR 95% CI, 1.812 (1.253, 2.621), P = 0.002). Patients with unsuccessful recanalization had higher albumin-corrected calcium levels than those with recanalization (2.26 (2.09, 2.46) mmol/L vs. 2.17 (2.07, 2.27) mmol/L, P = 0.029), and after adjusting for other factors (AOR 95% CI, 2.068 (1.214, 3.524)), P = 0.008). No association was found between albumin-corrected calcium and symptomatic intracranial haemorrhage.ConclusionsHigher serum albumin-corrected calcium levels are independently associated with revascularization and poor outcome in stroke patients after mechanical thrombectomy.

The circadian rhythm of calcium and bone homeostasis in Maasai.

ObjectivesEthnic groups differ in prevalence of calcium‐related diseases. Differences in the physiology and the endogenous circadian rhythm (CR) of calcium and bone homeostasis may play a role. Thus, we aimed to investigate details of CR pattern in calcium and bone homeostasis in East African Maasai.MethodsTen clinically healthy adult Maasai men and women from Tanzania were examined. Blood samples were collected every 2nd hour for 24 h. Serum levels of total calcium, albumin, parathyroid hormone (PTH), 25(OH)D, creatinine, C‐terminal telopeptide (CTX), bone‐specific alkaline phosphatase (BSAP), procollagen type 1 N‐terminal propeptide (P1NP), and osteocalcin were measured. Circadian patterns were derived from graphic curves of medians, and rhythmicity was assessed with Fourier analysis.ResultsPTH‐levels varied over the 24 h exhibiting a bimodal pattern. Nadir level corresponded to 65% of total 24‐h mean. CTX and P1NP showed 24‐h variations with a morning nadir and nocturnal peak with nadir levels corresponding to 23% and 79% of the 24‐h mean, respectively. Albumin‐corrected calcium level was held in a narrow range and alterations were corresponding to alterations in PTH. There was no distinct pattern in 24‐h variations of 25(OH)D, creatinine, osteocalcin, or BSAP.ConclusionsAll participants showed pronounced 24‐h variations in PTH and bone turnover markers CTX and P1NP. These findings support that Maasai participants included in this study have typical patterns of CR in calcium and bone homeostasis consistent with findings from other ethnic populations.

Optimal targets of chronic kidney disease-mineral and bone disorder markers for Chinese patients with maintenance peritoneal dialysis: a single-center retrospective cohort study

Background The chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation. Methods This is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model. Results Of these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH <100 pg/mL (HR = 1.97, 95% CI 1.32 to 2.94, p < 0.001) and ≥300 pg/mL (HR = 2.24, 95% CI 1.32 to 3.81, p = 0.003) were associated with increased all-cause mortality than that of PTH 100–200 pg/mL. Patients with albumin-corrected serum calcium level < 2.13 mmol/L also had higher risk of death than patients with level of 2.13 to 2.38 mmol/L (HR = 2.06, 95% CI 1.06 to 4.01, p = 0.02). Serum phosphorus ≥1.45 mmol/L were associated with increased all-cause mortality. However, lacking of data on 25-hydroxy vitamin D, alkaline phosphatase, and activated vitamin-D are limitations of our analysis. Conclusions As one of the largest PD cohort study focusing on CKD-MBD, we demonstrated that the level of CKD-MBD markers in the first PD year are independent predictors of all-cause mortality. PTH 100–300 pg/mL might be the best target for Chinese PD patients.

Newly Diagnosed Hypoparathyroidism as the Initial Presentation of DiGeorge Syndrome in a 26-Year-Old Man

A 26-year-old African American man was seen for hypocalcemia identified during preoperative assessment for an elective left hemithyroidectomy for a symptomatic multinodular goiter. His albumin-corrected calcium level was 6.1 mg/dL (normal level: 8.7-10.4 mg/dL). He reported some leg cramping and dyspnea. His past history was notable for developmental delay, short stature, delayed eruption of teeth requiring dental surgery in elementary school, scoliosis requiring corrective surgery, and orchidopexy as an infant.

Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios in patients with primary hyperparathyroidism and their relationship with cardiac arrhythmic events.

Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by hypercalcemia caused by excessive parathyroid hormone (PTH) secretion from the parathyroid gland. PHPT was previously shown to increase cardiac arrhythmias. Besides, new indices, such as the Tpeak-Tend (Tp-e) interval, Tp-e interval/QT interval (Tp-e/QT) ratio, and Tp-e interval/corrected QT interval (Tp-e/QTc) ratio may be associated with ventricular arrhythmias and sudden cardiac death. Therefore, we aimed to investigate the relationship between PHPT and the changes to Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. We carried out the study with 41 patients with PHPT and 40 control subjects. We calculated the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio of the participants from the V5 derivations on their ECG papers. While we defined Tp-e interval as the distance between the peak and the end of the T wave, Tp-e/QT and Tp-e/QTc ratios were calculated by dividing Tp-e by QT and Tp-e by QTc, respectively. Total calcium, albumin-corrected calcium, phosphorus, and PTH levels were significantly higher in patients with PHPT. We also found positive correlations between albumin-corrected calcium and PTH levels and Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio (p < 0.001). : Our results suggest that Tp-e may enhance the current knowledge on arrhythmic risk in PHPT patients better than basal ECG. In addition, both high PTH and high calcium levels appear to have the potential to cause arrhythmogenic effects.

Hypoparathyroidism and pseudohypoparathyroidism in pregnancy: an Italian retrospective observational study

BackgroundHypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacological management, and potential adverse events during pregnancy and post-partum in pregnant women with HypoPT or pseudo-HypoPT. This was a retrospective, observational, multicenter, study involving nine Italian referral centers for endocrine diseases affiliated with the Italian Society of Endocrinology and involved in “Hypoparathyroidism Working Group”.ResultsThis study identified a cohort of 28 women (followed between 2005 and 2018) with HypoPT (n = 25, 84% postsurgical, 16% idiopathic/autoimmune) and pseudo-HypoPT (n = 3). In HypoPT women, the mean calcium carbonate dose tended to increase gradually from the first to third trimester (+ 12.6%) in pregnancy. This average increase in the third trimester was significantly greater compared to the pre-pregnancy period (p value = 0.03). However, analyzing the individual cases, in 44% the mean calcium dosage remained unchanged throughout gestation. Mean calcitriol doses tended to increase during pregnancy, with a statistically significant increase between the third trimester and the pre-pregnancy period (p value = 0.02). Nevertheless, analyzing the individual cases, in the third trimester most women with HypoPT (64%) maintained the same dosage of calcitriol compared to the first trimester. Both mean calcium carbonate and calcitriol doses tended to decrease from the third trimester to the post-partum six months. Most identified women (~ 70%) did not display maternal complications and (~ 90%) maintained mean serum albumin-corrected total calcium levels within the low-to-mid normal reference range (8.5 ± 0.8 mg/dl) during pregnancy. The main complications related to pregnancy period included: preterm birth (n = 3 HypoPT women), and history of miscarriages (n = 6 HypoPT women and n = 2 pseudo-HypoPT women).ConclusionThis study shows that mean serum albumin-corrected total calcium levels were carefully monitored during pregnancy and post-pregnancy, with limited evaluation of other biochemical parameters, such as serum phosphate, 24 h urinary calcium, 25-OH vitamin D, and creatinine clearance. To avoid complications in mothers affected by (HypoPT) or (pseudo-HypoPT) and offspring, intense biochemical, clinical and pharmacological monitoring during pregnancy and breastfeeding is highly recommended.

The Role of Serum Calcium Levels in Pediatric Dyslipidemia: Are There Any?

Background: No previous study explored the association between serum calcium levels and dyslipidemia in children. This study aimed to explore this relationship in children, based on a multicenter cross-sectional study population in China.Methods: Cross-sectional data was derived from the Pediatric Reference Intervals in China (PRINCE) study conducted between 2017 and 2018 involving 5,252 males and 5,427 females with a mean age of 10.0 ± 4.6 years. Multivariable logistic regression models were applied to calculate odds ratios (ORs), with 95% confidence intervals (CIs), for dyslipidemia of each serum calcium level and albumin-corrected calcium levels, which were sorted into quartiles. The restricted cubic spline model was fitted for the dose-response analysis. An L-shaped dose-response relation between calcium levels and the probability of dyslipidemia was found after the adjustment for multiple potential confounding factors, p for non-linear < 0.001.Results: Using the middle category of calcium level as the reference, multivariable-adjusted ORs and 95% CIs of the lowest and the highest quartile categories were 0.96 (0.82–1.12) and 1.29 (1.12–1.48), respectively, for total serum calcium levels and 1.06 (0.91–1.23) and 1.39 (1.21–1.60) for albumin-corrected calcium levels.Conclusions: Individuals with higher levels of serum calcium were associated with increased risk of dyslipidemia in a sample of a healthy Chinese pediatric population. The association between serum calcium levels and dyslipidemia needs to be examined prospectively in future studies.

Study of Red Blood Cell Indices and Biochemical Parameters of Mineral Bone Disorders in Hemodialysis Patients

Background: Chronic kidney disease (CKD) is a worldwide public health problem and a major cause of suffering and having a reduced quality of life for those affected. Objective: We aimed to study the changes in red blood cell indices and mineral bone metabolism in hemodialysis patients and to explore the correlation between these studied parameters. Patients and Methods: This is a case control study included 55 adult patients with end stage renal disease on maintenance hemodialysis as well as 55 healthy individuals as a control group. All participants were subjected to laboratory investigations included complete blood count and serum levels of creatinine, urea, total calcium, albumin, phosphate and intact parathyroid hormone (iPTH). Results: Our study showed thathemoglobin (Hb), hematocrit and red blood cell count were significantly reduced in the hemodialysis patients (P<0.001 for all). Regarding mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, no significant differences were found between the hemodialysis patients and the control group (P= 0.362, 0.116, 0.22, respectively). In the hemodialysis group, the albumin-corrected serum calcium level was significantly lower while the serum phosphate and iPTH levels were significantly higher compared to the control group (P<0.001 for all). Hb was inversely correlated with serum iPTH (r=-0.359, P=0.007) and serum phosphate (r=-0.570, P<0.001) in the hemodialysis group and was inversely correlated with serum phosphate (r=-0.495, P<0.001) in the control group. Conclusion: Hemodialysis patients are at high risk of anemia, hypocalcemia, hyperphosphatemia and hyperparathyroidism. In hemodialysis patients, an association was found between anemia and each of hyperphosphatemia and hyperparathyroidism.

Increased serum calcium levels are associated with carotid atherosclerotic plaque in normocalcaemic individuals with type 2 diabetes.

Background:Patients with type 2 diabetes mellitus (T2DM) have an elevated risk of atherosclerotic cardiovascular disease. Although previous data have suggested that serum calcium levels could be involved in T2DM and cardiovascular disease, whether this applies in T2DM patients with atherosclerosis remains unclear. This study therefore aimed to investigate the relationship between serum calcium levels within the physiological ranges and carotid atherosclerotic plaque in T2DM patients.Methods:A total of 594 normocalcaemic in-patients with T2DM were recruited, of whom 231 had carotid atherosclerotic plaque. Serum calcium levels were measured and carotid ultrasonography was performed.Results:Patients with plaque had significantly higher serum albumin-corrected calcium than those without plaque [9.02 (8.78–9.34) mg/dL versus 8.86 (8.66–9.06) mg/dL, p < 0.001]. As serum albumin-corrected calcium levels increased across tertiles, the percentage of plaque increased (27.6%, 35.5%, and 55.7%; p < 0.001). Logistic regression showed that serum albumin-corrected calcium levels were independently and positively correlated with the presence of plaque, but not parathyroid hormone levels. Compared with patients in the lowest serum calcium tertiles, the odds ratio for plaque in patients in the upper quartile was 2.47 (95% confidence interval 1.51–4.03, p < 0.001) after adjustment for potential confounders.Conclusion:Serum albumin-corrected calcium levels are elevated in patients with T2DM and carotid atherosclerotic plaques.

Albumin-Corrected Calcium and the Prevalence and Categories of Hypercalcemia in Hospitalized Patients With 1-Year Follow-Up of Undiagnosed Cases

ObjectiveTo assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients. MethodsPatients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL. ResultsA group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels <2.8 g/dL. At the 1-year follow–up, 63% of the unidentified cases had normal calcium levels, and 26.8% had mild persistent hypercalcemia. Of those with persisting hypercalcemia at 1 year, 16.8% were diagnosed with hyperparathyroidism. ConclusionUsing albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.

Effect of switching from cinacalcet to etelcalcetide on secondary hyperparathyroidism in patients undergoing hemodialysis: an ESCORT trial

BackgroundEtelcalcetide is the first intravenously administered calcimimetic agent used to manage secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. We evaluated the safety and efficacy of replacing cinacalcet with etelcalcetide in HD patients.MethodsOne hundred and thirty-three patients HD on cinacalcet were screened, and 93 patients with serum-intact parathyroid hormone (iPTH) level of ≥ 60 pg/mL and serum albumin-corrected calcium (cCa) level of ≥ 8.4 mg/dL were enrolled. The patients were divided into three groups based on the dose of cinacalcet (i.e., 25, 50, and ≥ 75 mg) and switched to etelcalcetide. Etelcalcetide was administered three times per week for 24 weeks. The primary and secondary endpoints were etelcalcetide conversion dose and etelcalcetide effectiveness for iPTH levels (target range: 60–240 pg/mL), respectively.ResultsOf the 68 patients whose iPTH level was within the management target at screening, 60 patients maintained the target level at the end of the study. Among patients whose iPTH level exceeded 240 pg/mL at screening, it decreased from 401 ± 246 pg/mL to 220 ± 209 pg/mL (p < 0.001) at the end of the study. Among 22 patients with the iPTH level of ≥ 240 pg/mL, 17 achieved the target level. The mean dose of cinacalcet was 41.4 ± 22.2 mg/day and that of etelcalcetide at the end of the study was 6.4 ± 3.7 mg/session in all patients. In 45 patients whose iPTH level was within the management target throughout the study and active vitamin D agent and calcium-based phosphate binder doses were constant, the mean dose of cinacalcet was 45.0 ± 22.4 mg/day and that of etelcalcetide at the end of the study was 6.1 ± 3.1 mg/session. The spKt/V might affect the ratio of etelcalcetide per session to oral cinacalcet per day (45 patients, p = 0.087; 90 patients, p < 0.05) in the generalized linear model. Etelcalcetide-induced severe adverse events were not observed.ConclusionsThis study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet.Trial registrationUMIN, UMIN000027637; Registered on June 5, 2017.

A Simple-to-Use Score for Identifying Individuals at High Risk of Denosumab-Associated Hypocalcemia in Postmenopausal Osteoporosis: A Real-World Cohort Study.

Since denosumab-associated hypocalcemia occurs infrequently, data on its incidence and risk factors are limited. We aimed to evaluate risk factors and develop a useful score for identifying individuals at risk of denosumab-associated hypocalcemia. In this retrospective cohort, 790 consecutive female patients who received 60mg denosumab at least once between 2016 and 2017 were analyzed. Based on biochemical records from a large-scale single-center, mild and moderate hypocalcemia were defined as albumin-corrected calcium (cCa) levels < 8.5 and < 8.0mg/dL (< 2.12 and < 2.0mmol/L), respectively. Mild and moderate hypocalcemia were observed in 8.2% and 1.0% patients, respectively. Patients who developed mild hypocalcemia had lower baseline cCa (8.9 vs. 9.3mg/dL and 2.22 vs. 2.32mmo/L) and estimated glomerular filtration rate (75.0 vs. 83.2mL/min/1.73m2) and more frequent loop diuretic use (10.8% vs. 4.4%; all p < 0.05). In multivariate analysis, low baseline cCa (OR 1.29; 95% CI 1.20-1.40) and chronic kidney disease (CKD) stages 3b-5 were associated with elevated mild hypocalcemia risk (OR 2.92; 95% CI 1.38-6.20). Loop diuretics use was associated with mild hypocalcemia (OR 2.61; 95% CI 1.11-6.18) by univariate analysis, independent of baseline cCa and CKD stage. A scoring approach identified two risk groups: (1) patients without CKD (eGFR ≥ 45) and cCa < 8.5mg/dL (2.12mmol/L) and (2) patients with CKD (eGFR < 45) and cCa < 9.5mg/dL (2.37mmol/L).