Serum iPTH Research Articles

Etiology and Diagnosis of Permanent Hypoparathyroidism after Total Thyroidectomy.

Postoperative parathyroid failure is the commonest adverse effect of total thyroidectomy, which is a widely used surgical procedure to treat both benign and malignant thyroid disorders. The present review focuses on the scientific gap and lack of data regarding the time period elapsed between the immediate postoperative period, when hypocalcemia is usually detected by the surgeon, and permanent hypoparathyroidism often seen by an endocrinologist months or years later. Parathyroid failure after thyroidectomy results from a combination of trauma, devascularization, inadvertent resection, and/or autotransplantation, all resulting in an early drop of iPTH (intact parathyroid hormone) requiring replacement therapy with calcium and calcitriol. There is very little or no role for other factors such as vitamin D deficiency, calcitonin, or magnesium. Recovery of the parathyroid function is a dynamic process evolving over months and cannot be predicted on the basis of early serum calcium and iPTH measurements; it depends on the number of parathyroid glands remaining in situ (PGRIS)—not autotransplanted nor inadvertently excised—and on early administration of full-dose replacement therapy to avoid hypocalcemia during the first days/weeks after thyroidectomy.

Role of postoperative intact serum PTH as an early predictor of severe post-thyroidectomy hypocalcemia: a prospective study.

Post thyroidectomy hypocalcemia is a major sequel of thyroidectomy and continues to trouble the endocrinologists and the endocrine surgeons as there is no ideal predictive marker of hypocalcemia which has the potential to develop into a life-threatening complication. The role of early serum intact parathormone (iPTH) to predict post thyroidectomy hypocalcemia is becoming useful but the literature is still unclear regarding the optimal time of testing and the optimal cut-off value of serum iPTH. This is a prospective cohort study of 111 patients who underwent total thyroidectomy in a tertiary care endocrine surgery referral unit. Serum iPTH was measured after 20min and 4h of surgery. Receiver-Operator characteristic Curve (ROC) was used to find out of the best cut-off value of S. iPTH 20min and 4h after surgery in predicting hypocalcemia. Hypocalcemia was noted in 60 (54%) out of 111 subjects who underwent total thyroidectomy. The best cut-off values of Serum iPTH to predict hypocalcemia was found to be 4.28pmol/l at 20min post total thyroidectomy with a sensitivity and specificity of 81.7% and 51%, respectively. In addition, patients with malignancy or central lymph nodal dissection were significantly over-represented in the hypocalcemia group with serum iPTH above the threshold level of 4.28pmol/l. Below the cut off level, parenteral calcium supplementation was required in 23% (17/74) subjects while the rate was only 5.4% (2/37) patients when serum iPTH was above the cut-off level. The decline of serum iPTH below a specific level after surgery has predictive value together with other factors strictly related to patient, the thyroid disease itself and surgery. The risk of development of hypocalcemia and consequent need for calcium supplementation should be evaluated by clinical assessment along with serum PTH measurement.

Clinical phenotypes of primary hyperparathyroidism in hospitalized patients who underwent parathyroidectomy.

ObjectiveThe aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy.Materials and methodsMedical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed.ResultsThree hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2% being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/mL, P = 0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r = ¯0.294, P = 0.005), iCa (r = ¯0.268, P = 0.010) and total Ca (r = ¯0.284, P = 0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7 and 63.4%, P = 0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, P < 0.0001; 30.4 vs 26.0 kg/m2, P < 0.0001, respectively).ConclusionsThis experience illustrates that symptomatic phenotype is still the most common form of PHPT.

Disorders in bone-mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study.

Abnormalities of bone mineral parameters are associated with increased mortality in patients on dialysis, but their effects and the optimal range of these biomarkers are less well characterized in non-dialysis chronic kidney disease (CKD). PECERA (Collaborative Study Project in Patients with Advanced CKD) is a 3-year, prospective multicenter, open-cohort study of 966 adult patients with non-dialyzed CKD stages 4-5 enrolled from 12 centers in Spain. Associations between levels of serum calcium (Ca) (corrected for albumin), phosphate (P), and intact parathyroid hormone (iPTH) with all-cause mortality (primary outcome) and cardiovascular mortality (secondary outcome) were examined using time-dependent Cox proportional hazards models and penalized splines analysis adjusted by demographics and comorbidities, treatments and biochemical values collected every 6months for 3years. After a median follow-up of 29months (IQR: 13-36months) there were 181 deaths (19%). The association of calcium with all-cause mortality was J-shaped, with an increased risk for all-cause mortality at levels > 10.5mg/dL. For phosphate and iPTH levels, the association was U-shaped. The serum values associated with the minimum risk of mortality were 3.8mg/dL for phosphate and 70pg/mL for iPTH, being the lowest risk ranges between 2.8 and 5.0mg/dL, and between 38 and 112pg/mL for phosphate and iPTH, respectively. Our study provides evidence on the non-linear association of serum calcium, phosphate and iPTH levels with mortality in stage 4 and 5 CKD patients, and suggests potential survival benefits for controlling bone mineral parameters in this population, as previously reported for dialysis patients.

The optimal range of serum intact parathyroid hormone for a lower risk of mortality in the incident hemodialysis patients

The serum intact parathyroid hormone (iPTH) is associated with the prognosis of hemodialysis (HD) patients, however, its optimal range for reducing mortality remains inconsistent. We designed a prospective cohort study of 346 incident HD patients to assess the association between different serum iPTH level and mortality. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) international guidelines (2003), we divided patients into three groups (iPTH < 150 pg/mL, 150–300 pg/mL and >300 pg/mL). During the median follow-up of 58 months, 157 patients (45.38%) died. Multivariate Cox regression analysis showed that iPTH < 150 pg/mL and >300 pg/mL were associated with all-cause and cardiovascular mortality. Then, we performed a sensitivity analysis of patients divided into 6 serum PTH levels groups according to the folds of the K/DOQI target range. Multivariate Cox regression analysis showed that patients with serum iPTH ≥750 pg/mL, 600–749 pg/mL, 450–599 pg/mL had significantly higher risk of all-cause and cardiovascular mortality compared with those with serum iPTH in the range of 150–299 pg/mL. The association between serum iPTH and mortality shows a U-shaped curve. The optimal serum iPTH level which confers the lowest risk of all-cause and cardiovascular mortality could range from 150 pg/mL to 450 pg/mL in this group of incident HD patients.

Cross-sectional Study of Calcium Phosphate Product and Intact Parathyroid Hormone Levels in Predialysis and Postdialysis Patients with Stage 5 Chronic Kidney Disease.

Chronic kidney disease (CKD) gradually deteriorates the mineral homeostasis, with a disruption of normal serum phosphorus, calcium, and intact parathyroid hormone (iPTH). Hemodialysis is one of the replacement therapies used to treat CKD patients to achieve normal kidney function. The present study aimed to evaluate the impact of dialysis on serum levels of calcium, phosphorus, and iPTH in CKD patients. A cross-sectional observational study was conducted between May 2015 and April 2017 in patients with CKD stage 5. The demographic characteristics including age, sex, body weight, and estimated glomeruli filtration rate were recorded. Serum levels of calcium, phosphorus, and iPTH were measured. A total of 100 patients divided into predialysis (n = 50) and postdialysis group (n = 50) with the mean age 50.34 and 51.88 years were included in this study, respectively. Mean levels of serum calcium and iPTH in the postdialysis patients were significantly lower than predialysis patients (P = 0.0183 and P <0.001). The proportion of patients (74%) with serum phosphorus level >4.5 mg/dL was significantly higher in postdialysis group (0.003). The risk of having high level of iPTH was 3.20 times more among the patients with level of phosphorus between 2.5 and 4.5 mg/dL [odds ratio (OR), 3.20; 95% confidence interval (CI), 1.16-8.80; P = 0.02] and 2.82 times more among patients with level of calcium <8.5 mg/dL (OR, 2.82; 95% CI, 1.13-7.01; P = 0.02). Overall observations suggest a significant reduction in levels of serum calcium and iPTH after dialysis in patients with CKD stage 5.

High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism.

Introduction:Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population.Methods:We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting.Results:The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019).Conclusion:The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.

Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial

Background Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations. Methods This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models. Results Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2–0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, −0.11 to −0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4–9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0–8.0, p = .001). Dietary phosphorus intake was not related to cFGF23. Conclusions Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.

Microwave ablation versus radiofrequency ablation for primary hyperparathyroidism: a multicenter retrospective study

Objective To compare the clinical outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of primary hyperparathyroidism (pHPT). Method This retrospective study included 104 pHPT patients treated by MWA or RFA between January 2015 and March 2020 in four centers. The clinical outcomes including effectiveness and complications were compared between the two groups. Ablation cure was defined as the reestablishment of normal values of serum calcium and intact parathyroid hormone (iPTH) at least more than 6 months. Clinical cure was defined as the reestablishment of normal values of serum calcium and iPTH throughout the entire follow-up period. Results A total of 77 patients underwent MWA (mean age, 55.5 ± 16.4 years) and 27 underwent RFA (mean age, 58.9 ± 15.6 years). During the follow-up (median, 18.7 months in the MWA group; 12 months in the RFA group), no difference was observed between ablation cure rates (88.3% vs. 88.9%, p = 1.000), clinical cure rates (87.0% vs. 82.3%, p = .880), recurrent pHPT (5.2% vs. 3.7%, p = .447), persistent pHPT (11.7% vs. 11.1%, p = 1.000) and complication rate (9.1% vs. 3.7%, p = .677). A maximum diameter less than 0.7 cm was an independent prognostic factor of uncured pHPT in ablation (hazard ratio, 0.1; 95% confidence interval: 0.02, 0.54; p = .007). Major complication – voice change encountered in five patients (6.5%) in the MWA group and in one patient (3.7%) in the RFA group. Conclusion Both RFA and MWA are safe and effective techniques for patients with pHPT, with comparable clinical outcomes.

Cinacalcet for Severe Secondary Hyperparathyroidism in Children with End-stage Kidney Disease.

Advanced chronic kidney disease with mineral and bone disorder have a significant obstacles to control serum bone profile [serum intact parathyroid hormone (iPTH), calcium and phosphorus] which subsequently have major effect on optimal bone strength, final adult height, and cardiovascular health. A retrospective, observational study, including a total of 36 children with end-stage kidney disease (ESKD). Fourteen children who were prescribed cinacalcet had been compared with the remaining 22 children who were managed with standard care. We report the efficacy and safety of cinacalcet for treatment of refractory secondary hyperparathyroidism (SHPT) in children with ESKD. After 6 months of cinacalcet treatment, the mean level of iPTH serum level decreased by 56% from 202 pmol/L [95% confidence interval (CI): 150-253] to 88 pmol/L (95% CI: 41-136), compared to the change observed in the control group (P <0.001). None of our patients reported serious adverse effects or developed hypocalcemia. Cinacalcet could be an effective and safe alternative to treat severe SHPT in children with ESKD. Further long-term and large-scale studies are necessary to confirm its safety and efficacy.

The relationship between bone mineral indices and survival in patients on peritoneal dialysis

Introduction: Disorders of minerals metabolism are common metabolic problems in patients undergoing peritoneal dialysis (PD) which causes increase in mortality and morbidity in these patients. Objectives: In this study, the relationship between bone metabolic indices and mortality rate in patients on PD was assessed. Patients and Methods: Data were collected from Iranian peritoneal dialysis registry database, covering the period 2009–2015 and comprised 2000 adult patients. Patients with less than three months follow-up and incomplete data were excluded. Demographic and some laboratory data (including age, gender, body mass index, serum albumin, dialysis vintage and comorbidities) of patients recorded. Additionally, the unadjusted and adjusted, hazard ratios (HRs) of serum phosphorus (P), calcium (Ca) and parathyroid hormone (PTH) levels, to find their association with mortality were calculated, using the Cox proportional-hazards model. Results: In total, 1197 out of 2000 patients had the inclusion criteria and were included in the study. We found that serum iPTH (intact parathyroid hormone) over 600 pg/mL significantly increased the mortality rate by 2.7 times compared to iPTH levels between 200 to 600 pg/ mL (HR: 2.7, P=0.002). Additionally, the serum phosphorus level less than 4 mg/dL was significantly (P=0.0001) related to higher mortality rate (HR: 1.6). There was no significant association of serum calcium and alkaline phosphatase (ALP) levels with mortality (P &gt; 0.05). Conclusion: Although high serum iPTH and low-serum phosphorus levels could determine the mortality risk in PD patients, Ca and ALP levels were not risk factors for mortality.

Mineral and bone disorder biomarkers and inflammation indexes in patients with end stage renal disease.

Chronic kidney disease (CKD) is an independent risk factor for bone and mineral metabolism disorder. Bone and mineral metabolism disorder develop gradually with the progression of renal failure. Various abnormalities include elevated fibroblast growth factor-23, decreased levels of 1,25-Dihydroxy Vitamin D (1,25-(OH)2D), and secondary hyperparathyroidism. This study aimed to evaluate the biomarkers and inflammation indexes of CKD-mineral and bone disorder (MBD), and to examine the associations of serum alkaline phosphatase (ALP) levels with serum C-reactive protein (CRP) levels and leukocyte count, in patients with end-stage renal disease (ESRD). ESRD patients who were yet to initiate dialysis were enrolled as the study subjects. All CKD patients who were discharged from our hospital between January 1, 2013, and December 31, 2017, were screened. Based on quartiles of serum ALP, all subjects were categorized into four subgroups. The clinical characteristics of patients in the four subgroups were investigated. The prevalence of hypocalcemia, hyperphosphatemia, elevated intact parathyroid hormone (iPTH), and elevated CRP level was calculated in the four subgroups. The association between serum ALP and inflammation indexes was examined using regression analysis. Based on the inclusion criteria and exclusion criteria, 256 cases with ESRD were included in our study. The overall prevalence of hypocalcemia and hyperphosphatemia was 57.81% and 89.84%, respectively. Of the patients with ESRD, 174 (68.75%) had an elevated iPTH level >2 times of the upper limit of normal value), and 40 (15.63%) had an elevated iPTH level >9 times of the upper limit of normal value Discrepancies between serum ALP and iPTH levels were found in 29 patients. In the adjusted model, log-transformed CRP, log-transformed iPTH, and leukocyte count were significantly associated with log-transformed ALP. Hypocalcemia, hyperphosphatemia, and increased levels of iPTH and CRP were found to be extremely common in ESRD patients. Discrepancies between serum ALP and iPTH were also observed. Our results also indicate that serum ALP level is associated with the levels of iPTH and CRP, as well as leukocyte count.

Malnutrition as a risk factor for cardiac valve calcification in patients under maintenance dialysis: a cross-sectional study

Cardiac valve calcification (CVC) is a significant risk factor for cardiovascular morbidity and mortality in patients with chronic kidney disease on maintenance hemodialysis. The aim of this study was to investigate the association of several risk factors and particularly of malnutrition on CVC. In this cross-sectional cohort study, we included stable adult patients on maintenance hemodialysis. Calcification of cardiac valves was evaluated using two-dimensional echocardiography. Nutritional assessment and body composition measurements were performed using the MQSGA clinical tool and bioelectrical impedance analysis, respectively. Biochemical parameters such as serum calcium, phosphorus, iPTH, 1.25 hydroxy-vitamin-D, triglycerides, total cholesterol, HDL-C, LDL-C, total proteins, albumin, creatinine and CRP were assessed as potentially risk factors. The receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic ability of the aforementioned variables on severe degree CVC. Binary logistic regression analysis was also performed to identify independent variables of severe CVC. Overall, 42 patients were included in the study with half of them exhibiting mitral calcification, 38% aortic valve calcification, and 16.7% calcification in both valves. ROC analysis indicated that aging (p = 0.011), increased CRP (p = 0.038) and decreased value of serum albumin to total proteins ratio (p = 0.012) were positive prognostic factors for moderate to severe degree cardiac valve calcification. Low phase angle was also associated with CVC, although with moderate specificity. Aging, inflammation, low serum albumin to total proteins ratio and low phase angle values as indicators of malnutrition are predictors of severe CVC in end-stage renal disease patients on hemodialysis.

Relationship between parathyroid hormone and renin–angiotensin–aldosterone system in hemodialysis patients with secondary hyperparathyroidism

Hyperparathyroidism (HPT) is associated with mortality and cardiovascular disease (CVD) in dialysis patients. However, its mechanism is still unclear. It is suspected that parathyroid hormone (PTH) is associated with the renin-angiotensin-aldosterone system (RAAS) as a possible mechanism. Thus, we examined their hormonal interaction in hemodialysis patients with secondary HPT. Seventeen hemodialysis patients with HPT were included. All patients underwent total parathyroidectomy (PTx). Serum intact PTH (iPTH), calcium and phosphate levels, plasma renin activity (PRA), and plasma aldosterone levels (ALD) were measured pre- and post-PTx. Pre-serum iPTH tended to be correlated with pre-PRA and were significantly correlated with pre-ALD (pre-PRA: r = 0.44, p = 0.07, pre-ALD: r = 0.49, p < 0.05). With the reduction in serum iPTH after PTx, PRA and ALD significantly decreased after PTx. Additionally, the change in serum iPTH tended to be correlated with the changes in PRA and ALD (PRA; r = 0.46, p = 0.05, ALD; r = 0.45, p = 0.06). Our results suggest that PTH could be interrelated with RAAS in hemodialysis patients with secondary HPT.

MINERAL METABOLISM ADAPTATION IN LIVING KIDNEY DONORS: PROSPECTIVE OBSERVATIONAL STUDY

Purpose: The aim of this study is to investigate whether uninephrectomy for kidney donation cause change of bone and mineral metabolism and also investigate factors associated with it in prospective kidney donors after uninephrectomy. Methods: Serum and urine creatinine, calcium, phosphorus, and serum intact parathyroid hormone (iPTH), 25(OH) vitamin D and FGF-23 values were obtained pre-donation and postoperatively in 68 donors. Renal fraction excretion rate of phosphate (FEpi) was calculated with 24-hour urine collection. Pre- and post-donation GFR was measured by DTPA scan in all donors. Results: After donor nephrectomy (median 7 months, 4-18months), MDRD eGFR declined (91.4 to 62.2 ml/min/1.73m2) and remnant kidney’s GFR measured by DTPA scan increased (55.1 to 71.3 ml/min), significantly. (both p<0.001) Post-donation serum iPTH increment was marked (43.0 Vs 60.1 pg/ml, p<0.001), whereas 25(OH) vitamin D level change was not significant (25.7 to 25.0 ng/ml, p=0.573). After donation, serum Ca was changed from 9.15 to 9.16 (p=0.856), serum phosphate changed from 3.6 to 3.4 (p=0.005). Renal fraction excretion rate of phosphate (FEpi) was increased after donation. (14.6 to 20.3, p<0.01) In comparison to pre-donation, FGF23 levels are no significantly changed (1094pg/ml vs 1169pg/ml, p=0.766). Conclusions: From after kidney donation, living kidney donor develop secondary hyperparathyroidism related to a decreased serum phaosphate, increased renal fraction excretion of phosphate. FGF23 levels do not rise in living kidney donors. Mineral metabolism adaptation to decreased eGFR in donors might differ from those in CKD patients maybe due to remnant intact nephrons.

Relationship between vitamin D receptor gene polymorphism FokI and fetuin A as marker of vascular calcification in Egyptian hemodialysis patients

Background: Vascular calcification is a common complication in end-stage renal disease patients and the leading cause of morbidity and mortality. Aim of the work: The current work aimed to evaluate the possible relationship between vitamin D receptor gene polymorphism FokI with fetuin-A and intact parathormone hormone in Egyptian hemodialysis patients. Patient and Methods: This study is a cross-sectional study including 50 hemodialysis patients attending the hemodialysis unit in Al-Zahra University Hospital and 30 apparently healthy persons as a control group. For all studied subjects, a detailed history was taken, physical examination, carotid intima-media thickness by carotid duplex, echocardiography, Laboratory investigations included serum levels of calcium, phosphorus, iPTH, fetuin, and genotype frequency by PCR Results: There was a highly significant increase in carotid intimal media thickness in the patient group Vs. control group & a highly significant decrease in serum Fetuin-A in the patient's group Vs. control group. There was a significant difference in the genotype distribution of FokI polymorphism among patients and control. There were significant negative relationships between FF genotype and iPTH and a highly significant negative correlation between serum fetuin-A and iPTH in the patient group. Conclusion: Vitamin D receptor gene FokI polymorphism FF genotyping is more frequent in hemodialysis patients who have higher iPTH and lower fetuin-A levels, which could identify the high-risk group susceptible to vascular calcification in hemodialysis patients. Further studies are needed.

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52\xa0weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan

BackgroundEtelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan.MethodsThis PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician’s discretion.ResultsOf 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60–240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled.ConclusionThis was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.

Clinical value of intact parathyroid hormone levels on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism

Objective: To examine the value serum calcium and intact parathyroid hormone (iPTH) levels measured on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism. Methods: Totally 546 patients with thyroid cancer and benign thyroid lesions who underwent total thyroidectomy at Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University from February 2008 to December 2018 were analyzed retrospectively. There were 158 males and 388 females aging (50.9±13.2) years (range: 19.0 to 79.2 years). Serum calcium and iPTH levels were collected before surgery, on the first day and 6 months after surgery. Logistic regression was used to analyze the correlation between each data and the occurrence of permanent hypoparathyroidism after surgery.The area under the receiver operating characteristic curve was used to evaluate the predictive power of iPTH for postoperative occurrence of permanent hypoparathyroidism. Results: Among the 546 cases of total thyroidectomy, 22 cases of permanent hypoparathyroidism occurred, with an incidence of 4.0% (22/546). Multivariate analysis showed that iPTH levels on the first day after total thyroidectomy (OR=2.932, 95%CI: 1.129 to 7.616, P=0.027) and serum calcium levels (OR=2.584, 95%CI: 1.017 to 6.567, P=0.046) were independent prognosis factors for postoperative permanent hypoparathyroidism. When the threshold value of iPTH at 24 hours after total thyroidectomy was 5.51 ng/L, the AUC was 0.956 (95%CI: 0.936 to 0.972, P=0.000), sensitivity was 100%, specificity was 85.1%, positive predictive value was 22%, negative predictive value was 100%. When the threshold value of serum calcium at 24 hours after total thyroidectomy was 1.93 mmol/L, the AUC was 0.733 (95%CI: 0.694 to 0.770, P=0.000), sensitivity was 63.6%, specificity was 78.1%, positive predictive value of 10.8% and negative predictive value of 98.1%. Conclusions: Serum iPTH and calcium levels on the first day after total thyroidectomy were related to the occurrence of permanent hypoparathyroidism postoperatively. The predictive value of iPTH level is higher than that of serum calcium level.

The predictive value of serum alkaline phosphatase combined with parathyroid hormone in all-cause and cardiovascular mortality in maintenance hemodialysis patients

To analyze the predictive value of serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) on all-cause and cardiovascular mortality in maintaining hemodialysis (MHD) patients. A total of 224 MHD patients were prospectively investigated and followed up for 2 years. Serum iPTH levels were not associated with all-cause death and cardiovascular death (HR=1.001, 95%CI 1.000-1.004, P=0.048) . The level of serum ALP was associated with cardiovascular death (HR=1.002, 95%CI 1.000-1.004, P=0.033) . ALP≥106 IU/L was an independent risk factor for cardiovascular death in MHD patients (P<0.05) . The joint variable was correlated with mortality in MHD patients (HR=1.002, 95%CI 1.000~1.004, P=0.033) , that equal or over 37.28 was an independent risk factor for mortality (P<0.05).

Calcium repletion to rats with calcipenic rickets fails to recover bone quality: A calcipenic “memory”

Calcipenic rickets is prevalent in underprivileged children in developing countries. Calcipenic rickets resulting from dietary calcium (Ca) deficiency decreases bone mass and deteriorates bone microstructure in humans. The effect of dietary Ca replenishment (CaR) on rachitic bones in animal models depends on the amount, critical period and duration of replenishment, however, the extent of recovery in various bone parameters including bone quality remains unclear. We investigated the effect of CaR in rat skeleton after inducing calcipenic rickets. Female SD rats (postnatal 28days/P28) were rendered calcipenic by feeding calcium deficient (CaD) diet (0.1% Ca) till P70 while control SD rats were fed Ca sufficient diet (0.8% Ca). At P70, calcipenic rats were switched to 0.8% Ca diet till P150 for one group and P210 for another group (endpoint). The CaD groups received 0.1% Ca diet throughout the study (P210). In the CaD groups, serum Ca and phosphate, and bone mineral density (BMD) were significantly decreased whereas serum alkaline phosphatase (ALP), iPTH and CTX-1 were increased compared to age-matched controls. Moreover, at the endpoint, the CaD group had reduced bone mass, surface referent bone formation parameters, tissue mineralization and strength accompanied by the increased osteoid thickness and microarchitectural decay (measured by trabecular geometric parameters) with poor crystal packing. The CaR group showed complete recovery in serum Ca, iPTH, ALP and CTX-1, and BMD, however, the bone quality parameters including bone strength, microarchitectural decay, tissue mineralization, and crystallinity were incompletely restored. Decreased surface referent bone formation and increased unmineralized bones (osteoid) indicative of osteomalacia were also observed in the CaR group at P210 compared with control despite prolonged replenishment. We conclude that a prolonged Ca repletion following the induction of calcipenic rickets in rats although shows the recovery of biochemical measures of bone metabolism and bone mass, however, the bone quality remains compromised. This suggests that a "memory" of calcipenia occurring at the early growth stage persists in the skeleton of adult rats despite a prolonged Ca replenishment.