Serum iPTH Levels Research Articles

Long-Term Efficacy and Safety of Upacicalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: Open-Label 52-Week Study

Plain Language SummaryCalcimimetics are widely used for the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. However, conventional calcimimetics have risks of upper gastrointestinal disturbances and hypocalcemia. Upacicalcet, a novel intravenous calcimimetic, is expected to reduce these risks. To assess the long-term efficacy and safety of upacicalcet, a phase 3 open-label, 52-week study in HD patients with SHPT was conducted in Japan. A total of 157 Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Of those, 138 completed the 52-week upacicalcet treatment. Upacicalcet achieved the target serum iPTH level (60–240 pg/mL) in 94.2% of patients at 52 weeks. Moreover, upacicalcet decreased bone metabolism markers, intact fibroblast growth factor-23 levels, and parathyroid gland volume. Upacicalcet reduced corrected calcium-phosphate product levels even in patients with mild SHPT, i.e., serum iPTH level ≤300 pg/mL. Upacicalcet caused neither symptomatic hypocalcemia nor cCa levels <7.5 mg/dL despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Gastrointestinal symptoms leading to upacicalcet dose reduction were not occurred. In conclusion, upacicalcet stably reduced the serum iPTH levels in HD patients with mild-to-severe SHPT, with few safety concerns. Serum cCa and P levels were well controlled, with a low incidence of hypocalcemia. Upacicalcet is a novel calcimimetic that may provide safe and appropriate long-term treatment of SHPT.

Role of Postoperative Intact Parathyroid Hormone Levels in Predicting Hypocalcaemia after Thyroidectomy.

To determine the sensitivity and specificity of intact parathyroid hormone (iPTH) levels in predicting hypocalcaemia after thyroidectomy. A descriptive cross-sectional study. Place and Duration of the Study: Department of General Surgery, Shifa International Hospital and Shifa Foundation, Islamabad, from May 2021 to 2022. The sample size was calculated to be 205 with consecutive non-probability sampling. Serum iPTH levels and serum calcium levels were measured postoperatively at 6 hours and 24 hours and recorded in a proforma for analysis. After collection, the data were entered and analysed using SPSS version 24.0. Among 205 patients, 157 (76.6%) were females and 48 (23.4%) were males. At 6 hours postoperatively, 121 (59%) patients had normal iPTH levels and 123 (60%) patients had normal serum calcium levels (p = 0.15). At 24-hour, 130 (63.4%) patients had normal iPTH levels and 92 (44.9%) patients had normal serum calcium levels (p = 0.001). Overall, 8 (3.9%) patients developed symptomatic hypocalcaemia (p = <0.001). The sensitivity and specificity of iPTH levels at ≤15 pg/ml were 100% and 70%, respectively, but at 24 pg/ml cut-off level, the specificity increased to 90% with sensitivity of 100%. Low serum iPTH levels at 6 hours after surgery can predict hypocalcaemia in patients undergoing thyroidectomy, even if serum calcium levels appear normal at that time. Parathyroid hormone, Serum calcium, Hypocalcaemia, Total thyroidectomy, Calcium homeostasis.

The Effect of Periodontitis on Fibroblast Growth Factor 23 Levels in Predialysis Chronic Kidney Disease Patients.

Introduction Chronic kidney disease (CKD) is known to cause an increase in fibroblast growth factor 23 (FGF23). Periodontitis, a condition recognized as a risk factor for CKD, is also potentially associated with the increment of FGF23. This study aims to compare FGF23 levels in CKD patients with and without periodontitisand non-CKDpatients with and without periodontitis. Correlation with serum phosphate, calcium, and intact parathyroid hormone (iPTH) was assessed. Additionally, associations between FGF23, calcium, phosphate, iPTH, creatinine, urea, plaque score, and bleeding score with periodontitis in CKD patients were determined. Method A total of 124 participants were categorized into four groups: CKD patients with periodontitis (n=31), CKD patients without periodontitis (n=32), periodontitis patients without CKD (n=32), and healthy population (n=29). The selected CKD patients include those from stages 3 and 4 (predialysis) patients. Serum levels of FGF23, calcium, phosphate, iPTH, creatinine, and urea were analyzed. Oral examinations were conducted to determine the presence and absence of periodontitis and assess plaque and bleeding scores. Result A significantly higher level of FGF23 was found in CKD compared to non-CKD groups; however, no difference was observed with the presence of periodontitis in both CKD and non-CKD. There was no significant correlation found between FGF23 and serum calcium, phosphate, or iPTH concerning periodontal status. Apart from the bleeding score, there was no association between FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score with the presence of periodontitis in CKD patients. Conclusion The presence of periodontitis was not associated with higher FGF23 levels in CKD patients. Changes in FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score could not be attributed to the presence of periodontitis in CKD patients.

A good therapeutic response to evocalcet for dropped head due to primary hyperparathyroidism: A case report

AbstractAn 83‐year‐old woman presented with an acute course of dropped head syndrome (DHS) with muscle weakness localized to the neck. Serum calcium and intact parathyroid hormone (iPTH) levels were elevated to 12.2 mg/dL and 173 pg/mL, respectively, and 99mTc‐MIBI scintigraphy showed a hyperfunctioning parathyroid gland. Electromyography revealed myopathic features in the posterior neck extensor muscles. Primary hyperparathyroidism (PHPT)‐associated myopathy was diagnosed as the cause of the DHS. Oral administration of evocalcet ameliorated DHS and normalized the elevated serum calcium levels, whereas iPTH levels remained elevated. Subsequently, parathyroidectomy reduced the iPTH level to normal, and DHS did not flare‐up. Cases of PHPT with DHS as the initial symptom are extremely rare, and to our knowledge, this is the first report of remission of DHS with evocalcet. Therefore, serum iPTH levels may not necessarily correlate with muscle weakness.

Longitudinal study on the change trend of serum alkaline phosphatase and its possible influencing factors in peritoneal dialysis patients

The aim of the study was to analyze the change trend of serum ALP over time and identify factors influencing its levels in peritoneal dialysis patients. Then to investigate the impact of serum ALP changes on calcium and phosphorus metabolism in single peritoneal dialysis center utilizing repeated measurement data. A retrospective cohort study was conducted with a total follow-up duration of 30 months. Serum ALP and other biomarkers, including calcium (Ca), phosphorus (P), 25(OH)D, intact parathyroid hormone (iPTH), albumin(ALB), and hemoglobin(Hb) were measured every 3 months. The generalized estimation equation (GEE) was utilized to analyze the change trend of serum ALP over time, and to assess whether there were differences in changes over time between different genders and different primary disease groups. Additionally, factors influencing serum ALP levels were analyzed, and the impact of serum ALP changes on calcium and phosphorus metabolism was also explored. A total of 34 patients were included in the study. Serum ALP and other indicators were measured repeatedly, with a maximum of 8 times and a minimum of 4 times. The median of serum ALP values at all measurement times for all selected patients was 89 U/L. The GEE analysis revealed that serum ALP gradually increased with time, and patients in diabetes group increased faster than those in non-diabetes group. A positive correlation was observed between serum ALP and dialysis duration, also between serum ALP and hemoglobin. However, variations in serum ALP did not significantly affect serum corrected calcium, phosphorus, or iPTH concentrations. The serum ALP levels of peritoneal dialysis patients increase gradually over time, and the concentrations are influenced by dialysis duration. The changes in serum ALP values do not have a significant impact on serum calcium, phosphorus, and iPTH levels.

#2028 Efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate: a systematic review and meta-analysis

Abstract Background and Aims Hyperphosphatemia is a common and clinically significant complication in severe chronic kidney disease (CKD), associated with higher cardiovascular adverse events and higher mortality rates. High serum phosphate is also associated with a heightened risk of cardiovascular issues such as hypertension, left ventricular hypertrophy, atherosclerosis, and vascular calcifications. Phosphate binders are commonly used in patients receiving renal replacement therapy (RRT), aiming to reduce and maintain serum phosphorus. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving RRT. Method Data sources included MEDLINE(PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with the search cut-off in October 2023. We examined RCTs that comparing sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving RRT. Data extraction followed the PICOS protocol and bias risk was assessed using the Rob-2 tool. We performed a meta-analysis combining the data from RCTs, using R-studio. The primary endpoint of this study is the change in the serum phosphorus levels from baseline to end of treatment. Secondary outcomes included changes in serum intact parathormone (i-PTH) levels from baseline to end of treatment as well as the adverse events ratio during the study period. Given the prevalence of gastrointestinal side effects for both drugs, which often leads to drug discontinuation or patient non-adherence, a separate analysis focused on gastrointestinal-related adverse events. Results Inclusion criteria were met by 5 RCTs. No statistically significant difference was found in serum phosphorus reduction between the two groups {MD: −0.07 mmol/l,95% CI-random effects: −0.15 to 0.02}. Similarly, serum i-PTH reduction showed no statistically significant difference between the two drugs {MD = −1.53 mg/dl, 95% CI = (−4.45, 1.4), p = 0.26, random effects model}. Adverse events were comparable between the groups (OR: 1.11, 95% CI: 0.65-1.88, random effects model). However, further analysis of gastrointestinal adverse evets indicated a 60% increase with sevelamer carbonate {OR: 1.60, 95% CI 1.31-1.97, common(fixed) effect model}. Funnel plot examination for both continuous and dichotomous outcomes revealed a high chance for small study effect and publication bias. Conclusion This meta-analysis found that sucroferric oxyhydroxide and sevelamer carbonate are equally effective in controlling serum phosphorus and i-PTH levels. Sucroferric oxyhydroxide, however, demonstrated a more favorable profile regarding gastrointestinal adverse events. Our findings suggest sucroferric oxyhydroxide as a valuable alternative for RRT patients who have difficulty tolerating sevelamer carbonate.

Serum 25(OH)D Levels and Mitral Valve Calcification in Patients with Severe Rheumatic Mitral Stenosis

Background: Rheumatic heart disease (RHD) imposes a significant burden on patients and the health system, especially in the developing countries. Recently, the role of vitamin D deficiency in increasing the severity of valve involvement and calcification in patients with RHD has been suggested. However, its role in the severe stenosis of the mitral valve is unknown. The aim of this study was to determine the relationship between serum levels of 25(OH)D and mitral involvement severity scores in patients with severe mitral stenosis (MS). Materials and Methods: In this cross-sectional study conducted in Shahid Madani Heart Center, Tabriz, Iran, 104 patients with severe rheumatic MS were reviewed, in the absence of other underlying diseases. Trans-esophageal Echocardiography was performed for all patients, and mitral valve Wilkins score and mitral valve area were calculated. Blood samples were taken from patients and levels of 25(OH)D, total calcium, phosphorus, and i-PTH were measured. Results: Eighty eight cases were female and 16 were male. Eighty-one patients had mild to moderate mitral calcification and in 23 patients with mitral valve was severely calcified. Furthermore, 54 were vitamin D deficient, while 35 had insufficient vitamin D levels, and only 15 had normal blood levels of vitamin D. In addition high serum iPTH levels were present in 83 patients (80%). The levels of 25(OH)D, calcium, phosphorous, and iPTH with total Wilkins score, calcification score and mitral valve area were not significantly correlated (p&gt;0.05 for all above). Conclusions: Although no correlation was found between the severity of mitral valve involvement, and vitamin D and iPTH levels, vitamin D deficiency and secondary hyperparathyroidism tend to be common among patients with severe rheumatic MS, which may play a role in the progression of the disease.

Bone Mineral Density and Fracture Risk Assessment in Patients of Systemic Sclerosis

Background: Systemic sclerosis (SSc) is a chronic disease presenting in the age group of 20-50yrs and females are more affected than males. Osteoporosis is common in many rheumatological diseases and an association has been well established in Rheumatoid Arthritis and Systemic Lupus Erythematosus. However, there is no such robust data in patients affected with SSc. Our study aimed to measure Bone Mineral Density and assess the risk of fracture in patients of systemic sclerosis using the Fracture Risk Assessment using (FRAX) algorithm. Methodology: The case control study conducted in a tertiary care hospital included 24 patients of age 18-45years with systemic sclerosis and 24 age and sex matched healthy controls. 62.5% cases were antiScl-70 antibody positive, 62.5% had interstitial lung disease and 37.5% had pulmonary arterial hypertension. The BMD of Scl-70 antibody positive patients was 0.64± 0.08 gm/sq.cm at neck of femur, 0.70± 0.08 gm/sq cm at lumbar spine and 0.37± 0.06 gm/sq. cm at forearm. A significant lower T score at neck of femur was noted in cases as compared to controls (-1.91± 10 vs -0.32± 1.06, p=0.001). The mean FRAX score value for major osteoporotic fracture in cases, was 1.46± 0.61% with maximum value of 3% and minimum value of 0.9%. Whereas, for the hip fracture mean FRAX was 0.83± 0.07% with range of 0.7% to 1.9%. A significant difference was noted in risk of major osteoporotic fractures between cases and controls (p=0.017). On multivariate regression models computed to analyse the covariates of BMD for neck of femur, lumbar spine and forearm, it was observed that serum vitamin D levels, presence of pulmonary hypertension and/or ILD were significant covariates of BMD neck of femur. Conclusion: Systemic sclerosis is associated with significantly low bone mineral density compared to controls. The bone mass was negatively correlated with involvement of internal organs and serum iPTH levels. SSc may be considered as an independent risk factor for osteoporosis and patients of SSc should be evaluated for BMD with DEXA scan to prevent osteoporotic fractures.

Extent of Achieving KDOQI Targets For hemodialysis Adequacy in Libyan dialysis patients: A Multicentre Cross-Sectional Study

Dialysis is a therapy to maintain the lives of end stage renal disease patients (ESRD), and the adequacy of hemodialysis is essential as it can improve patient’s survival, quality of life and biochemical profiles. This study aimed to evaluate the extent of achieving Kidney Disease Outcomes Quality Initiative (KDOQI) targets for dialysis adequacy, haemoglobin level, mineral bone disorders and nutritional status among hemodialysis patients. patients and method: This study was carried out on 286 regular haemodialysis adult patients from eleven hemodialysis centers in Libya. Patients subjected to BMI calculations. Blood samples collected for complete blood count, serum albumin, blood urea pre and post dialysis session, serum creatinine, total serum calcium, serum phosphate, serum alkaline phosphatase, C reactive protein, and serum iPTH levels. Targets measures based on the KDOQI Clinical Practice Guidelines. Result: Mean Kt/V was 1.31±0.40.only 174 (60.84%) patients had adequate dialysis dose (Kt/V&gt;1.2). Mean iPTH was 490.08±694.7. According to the KDOQI, guideline 19.2% of the patients was within the target range for parathormone level. 26.92 % of studied patients had a haemoglobin level of 11gm/dl or more. Mean serum albumin is 3.81±0.64, hypoalbuminemia (albumin &lt;3.5g/dl) was in 27.98% of studied patients. Conclusion: According to KDOQI guidelines 39.16% of the studied patients did not achieve the target dose for adequate clearance, 73.08% did not achieve the target haemoglobin level; and, only 19.2% of the studied patients were within the target range for parathyroid hormone level. According to BMI as nutritional markers, 14.0% of studied patients were underweight and 27.98% were with serum albumin below (3.5 g/dl).

Sex-dependent differences in patients treated with regular hemodialysis

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Introduction.&amp;lt;/strong&amp;gt; The aims of the study were to find out sex differences among patients starting regular hemodialysis (HD) in 2014 and to check whether these differences change over a five-year period.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Methods.&amp;lt;/strong&amp;gt; The retrospective five-year study included 35 patients (24 men; 11 women) starting HD in HD centers in Leskovac and Pirot in 2014. Demographic data, clinical data, laboratory findings, and medication used for examined patients were taken from medical records.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Results.&amp;lt;/strong&amp;gt; A comparison of patients of different sexes at the beginning of the study showed that women were significantly older (70.55 &amp;amp;plusmn; 13.27 vs. 58.88 &amp;amp;plusmn; 15.27 years), but diabetes and hypertension were more frequent causes of chronic kidney disease in men. Women had significantly lower body mass index and serum creatinine level than men in the first year of the study. During all five years, the HD adequacy index spKt/V was higher in women than in men, but the difference reached statistical significance only in the third year (1.4 &amp;amp;plusmn; 0.2 vs. 1.2 &amp;amp;plusmn; 0.2). Serum iPTH level was higher in women than in men in almost the entire study period. There was no significant sex difference in blood pressure, type of vascular access, number of HD hours per week, in the percentage of patients who used erythropoiesis-stimulating agents or phosphate binders. During the study period 10 (42.7%) men and five (45.5%) women died and the most frequent causes of death were cerebrovascular and cardiovascular diseases.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Conclusion. &amp;lt;/strong&amp;gt;The study revealed several differences between men and women on regular HD, but no treatment inequality was found.&amp;amp;nbsp;&amp;lt;/p&amp;gt;

Radiofrequency ablation for patients with recurrent or persistent secondary hyperparathyroidism after parathyroidectomy: initial experience.

Reoperation for recurrent or persistent secondary hyperparathyroidism (SHPT) after parathyroidectomy is challenging due to surgical scars and postoperative adhesions. Therefore, there is an increasing need to develop a new minimally invasive therapy. To analyze the efficacy of ultrasound (US)-guided radiofrequency ablation (RFA) in patients with recurrent or persistent SHPT after parathyroidectomy. From March 2013 to January 2022, 20 enlarged parathyroid glands in 10 patients with recurrent or persistent SHPT were treated with US-guided RFA. The levels of serum intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP), as well as clinical symptoms, were compared before and after RFA. The ablation procedure-related complications were also evaluated. The target range for iPTH levels was approximately 2-9 times the upper limit of normal (130-585 pg/mL). The mean follow-up time was 49.6 ± 34.5 months (range from 6 to101 months). The levels of serum iPTH, Ca, and P decreased significantly one day post-ablation. Six months after RFA, 70% of patients reached the targets for iPTH, and 50% of patients reached targets at the end of follow-up. Two patients underwent repeat ablation at 9 months and 6 years after RFA, respectively, due to persistently elevated iPTH levels, and both had serum iPTH concentrations in the recommended range at the recent follow-up visit. The patients' clinical symptoms significantly improved after ablation. Major complications after RFA included hoarseness (2/10) and permanent hypoparathyroidism (1/10). Severe hypocalcemia occurred in four patients (4/10) after ablation. US-guided percutaneous RFA for recurrent or persistent SHPT is safe, efficacious, and repeatable, and can significantly improve hyperparathyroidism-related symptoms.

Ultrasound-guided microwave ablation for tertiary hyperparathyroidism in patients with renal transplantation

Objective To explore the safety and efficacy of ultrasound-guided microwave ablation (MWA) for tertiary hyperparathyroidism (THPT) in patients with renal transplantation (RT). Methods In total, fifteen patients with THPT after renal transplantation who underwent MWA were enrolled in the study. The pre- and post-MWA intact parathyroid hormone (iPTH), serum calcium, phosphorus, creatinine, urea nitrogen and estimated glomerular filtration rate (eGFR) values were compared. Results A total of 38 parathyroid hyperplastic nodules in 15 RT patients were treated with ultrasound-guided MWA. The mean (median, range) size of the hyperplastic parathyroid nodules was 11.5 mm (11 mm, 5–25 mm), and the average (median, range) ablation time was 163.5s (121 s, 44–406 s). The average levels of serum iPTH and calcium at 1 d, 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly lower than those pre-MWA (all p < 0.05). Compared with the pre-MWA value (0.76 mmol/L), the serum phosphorus levels at 1 d post-MWA (0.63 mmol/L) were significantly decreased, and those at 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly increased, but all were within the normal range. There was no significant difference in serum creatinine and eGFR pre-MWA and post-MWA. No major MWA-related complications occurred. Conclusion Ultrasound-guided MWA shows potential as a viable treatment for THPT in RT patients. However, further studies are required to confirm its safety and effectiveness in larger cohorts of longer duration.

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study.

Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT). A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52weeks; the starting dose was 50μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60-240pg/mL (target achievement rate) at week 18. A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of <7.5mg/dL recovered to ≥7.5mg/dL immediately after the interruption. In haemodialysis patients with SHPT, upacicalcet doses of 25-300μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.

The Relation between Vitamin D Status and Anemia in Patients with End Stage Renal Disease on Regular Hemodialysis

Abstract Background Anemia is a common complication in end stage renal disease patients on regular hemodialysis (HD). several factors are linked to the pathogenesis of anemia in this population. There has been a lot of interest in the non-classical effects of vitamin D, including its association with erythropoiesis and anemia pathogenesis. Objectives To establish whether there is an association between anemia and the status of 25 OH (Hydroxy) vitamin D level in dialysis patients Methods This study is a cross sectional study that enrolled 90 patients on regular hemodialysis. Laboratory tests included Serum calcium, phosphorus, 25(OH) vitamin D and intact parathyroid hormone (iPTH) levels, Hemoglobin level, ferritin level, serum iron, total iron binding capacity and calculation of transferrin saturation. 25(OH) vitamin D level was measured by ELISA (Calbiotech. USA, REF: VD2208. Vitamin D status was classified into deficient (&amp;lt; 20 ng/ml), insufficient (20-30 ng/ml) and sufficient (&amp;gt;30 ng/ml). Results The level of Vitamin D measured in the patients ranged between 3.5 to 66 ng/ml with median 16.35 (8 – 34). 24 patients had vitamin D deficiency (vitamin D levels &amp;lt; 20 ng/dl), Patients with insufficient levels (vitamin D levels 20-30 ng/dl) were 32 patients, while patients with sufficient (&amp;gt; 30 ng/dl) levels were 34 patients. there were no statistically significant relations between vitamin D levels and the gender of the patients (p = 0.536), their age (p = 0.973), duration of HD (p = 0.600), Diabetes mellitus (p = 0.064) and hypertension (p = 0.249). There were statistically significant positive correlations between Vitamin D levels and the level of hemoglobin of the patients (P = 0.000), serum calcium levels (P = 0.000) and serum PO4 levels (P = 0.023). However, significant negative correlation between Vitamin D levels and serum iPTH levels (p = 0.000), serum iron (p = 0.019) and Transferrin saturation (%) (p = 0.012). Using Spearman correlation coefficient, there were highly significant positive correlations between vitamin D3 levels in all patients and both hemoglobin levels (p = 0.000) and serum calcium levels (p = 0.000). Meanwhile, there were highly significant negative correlations between vitamin D3 levels in all patients and serum iPTH levels (p = 0.000) and T.SAT of the patients (p = 0.003). Conclusion There was a significant association between the status of vitamin D and the level of hemoglobin in dialysis population who were studied, other associations with hemoglobin levels included PTH level and calcium.

Incidence and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy.

The incidence and risk factors for hypoparathyroidism after total thyroidectomy is well-known. However, the characteristics of hypoparathyroidism and hypocalcemia after hemithyroidectomy have not been investigated well. In this study, we aimed to evaluate the incidence, characteristics, and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy. We retrospectively analyzed the medical data of 321 patients who underwent hemithyroidectomy, with or without central neck dissection, from January 2012 to April 2019. We analyzed the serum intact parathyroid hormone (iPTH), calcium, and ionized calcium (iCa) levels serially (preoperatively and postoperatively on the operation day; days 1 and 3; and months 1, 3, 6, and 12) and evaluated risk factors for postoperative hypoparathyroidism and hypocalcemia. The mean iPTH and calcium levels decreased significantly after hemithyroidectomy on the operation day and postoperative days 1 and 3, and returned to the preoperative level at the postoperative 1-month follow-up. The mean iCa level decreased significantly on the operation day and postoperative day 1. Transient hypoparathyroidism and transient hypocalcemia occurred in 16 (5%) and 250 (78%) participants, and they recovered to normal levels postoperatively by 1month. Eight (2.5%) patients had mild symptoms of hypocalcemia necessitating oral calcium supplementation. No permanent hypoparathyroidism or hypocalcemia was observed. Preoperatively low serum iPTH and calcium levels were associated with transient hypoparathyroidism and hypocalcemia after hemithyroidectomy. Approximately 5% and 2.5% of participants showed transient hypoparathyroidism and mild symptomatic hypocalcemia after hemithyroidectomy. The risk factors for transient hypoparathyroidism and hypocalcemia include preoperative low serum iPTH and calcium levels.

Pharmacological profile of upacicalcet, a novel positive allosteric modulator of calcium-sensing receptor, in vitro and in vivo

Upacicalcet (formerly SK-1403/AJT240) is a novel non-peptide calcimimetic agent that acts as a calcium-sensing receptor (CaSR) agonist for the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). We compared upacicalcet with other calcimimetics (etelcalcetide or cinacalcet) and examined its in vitro and in vivo characteristics in terms of its human CaSR agonistic activity, its efficacy in normal and CKD rats after a single administration, and its effect on gastric emptying in rats. Upacicalcet activated human CaSR depending on the extracellular calcium (Ca2+) concentration without exhibiting an agonistic action when the extracellular Ca2+ level was below the physiological level. On the other hand, etelcalcetide had an agonistic activity even in the absence of physiological levels of extracellular Ca2+. The intravenous administration of upacicalcet to normal and double-nephrectomized rats dose-dependently (0.03–3mg/kg and 0.3–30mg/kg, respectively) decreased the serum intact parathyroid hormone (iPTH) and serum Ca2+ levels; however, the effect of upacicalcet on the reduction in serum Ca2+ disappeared at extracellular Ca2+ levels below the physiologically range, even when administered at a dose higher (100-fold) than the effective dose. Furthermore, upacicalcet did not affect gastric emptying in normal rats when administered up to a dose of 10mg/kg (300-fold higher than the dose affecting serum iPTH levels), while the administration of cinacalcet significantly slowed gastric emptying by approximately 50%. These findings suggest that upacicalcet has potential as an alternative calcimimetic agent with good pharmacological properties and a lower risk of hypocalcemia and gastrointestinal complications.

Association of vitamin D metabolites with arteriovenous fistula function in hemodialysis patients: A single center study.

Arteriovenous fistula (AVF) is a primary dialysis vascular access commonly used for maintaining hemodialysis (MHD) patients. Vitamin D (VD) is a fat-soluble steroid hormone that is closely related to vascular endothelial function. This study aimed to investigate the association between VD metabolites and AVF failure in patients undergoing HD. This study included 443 HD patients using AVF between January 2010 and January 2020. The AVF operations in these patients were newly created by the same physician. We analyzed the AVF patency rates using the chi-square test. Univariate and multivariate logistic regression analyses were performed to explore risk factors for AVF failure. Survival analysis was performed to explore AVF survival at different serum 25-hydroxyvitamin D (25(OH)D) concentrations. Logistic regression analyses showed that male sex; age; BMI; serum albumin, triglyceride, phosphorus, 25(OH)D, iPTH and hemoglobin levels, history of hypertension, CHD, diabetes, stroke, and antiplatelet drug use; and smoking habits were not risk factors for AVF failure. The failure incidence rates of AVF in subjects in the VD deficiency and non VD deficiency group were not statistically significant (25.0% vs. 30.8%, p=0.344). The AVF failure incidence rates at 1, 3, and 5 years in the patients with 25(OH)D levels more than 20 ng/mL were 26%, 29%, and 37%, respectively, and the one-year AVF failure incidence rates were 27% in the patients with 25(OH)D levels less than 20 ng/mL. In addition, the Kaplan-Meier analysis suggested that the no significant differences were noted when calculating the cumulative survival rates of AVF between the two groups within 50 months of AVF using. Our findings suggest that 25(OH)D deficiency is not associated with AVF failure incidence rates, and that 25(OH)D deficiency has no significant impact on long-term cumulative AVF survival rate.

Relationship between serum iPTH and peritonitis episodes in patients undergoing continuous ambulatory peritoneal dialysis.

Peritonitis is considered as one of the most serious complications that cause hospitalization in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). There is limited evidence on the impact of the parathyroid hormone (PTH) on the first peritoneal dialysis (PD)-associated peritonitis episode. We aimed to investigate the influence of serum intact parathyroid hormone (iPTH) on peritonitis in patients undergoing PD. This was a retrospective cohort study. Patients undergoing initial CAPD from a single center in China were enrolled. The baseline characteristics and clinical information were recorded. The primary outcome of interest was the occurrence of the first PD-associated peritonitis episode. Five Cox proportional hazard models were constructed in each group set. In group set 1, all participants were divided into three subgroups by tertiles of the serum concentration of iPTH; in group set 2, all participants were divided into three subgroups based on the serum concentration of iPTH with 150pg/ml interval (<150, 150-300, and >300pg/ml). Hazard ratios and 95% confidence intervals (CIs) were calculated for each model. The multivariate linear regression analysis elimination procedure assessed the association between the clinical characteristics at baseline and the iPTH levels. Restricted cubic spline models were constructed, and stratified analyses were also conducted. A total of 582 patients undergoing initial PD (40% women; mean age, 45.1±11.5years) from a single center in China were recruited. The median follow-up duration was 25.3months. Multivariate Cox regression analysis showed that, in the fully adjusted model, a higher serum iPTH level (tertile 3, iPTH>300pg/ml) was significantly associated with a higher risk of PD-associated peritonitis at 3years [tertile 3: hazard ratio (HR)=1.53, 95%CI=1.03-2.55, p=0.03; iPTH>300pg/ml: HR=1.57, 95%CI=1.08-2.27, p=0.02]. The hazard ratio for every 100pg/ml increase in serum iPTH level was 1.12 (95%CI=1.05-1.20, p<0.01) in the total cohort when treating iPTH as a continuous variable. An elevated iPTH level was significantly associated with an increased risk of peritonitis in patients undergoing CAPD.

Upacicalcet, a positive allosteric modulator of the calcium-sensing receptor, prevents vascular calcification and bone disorder in a rat adenine-induced secondary hyperparathyroidism model.

Secondary hyperparathyroidism (SHPT) is a major comorbidity of chronic kidney disease (CKD). Chronic elevation of PTH levels is associated with cortical bone deterioration and increase in the risk of fractures in CKD patients. Here, we evaluated the effect of repeated administration of upacicalcet, a novel positive allosteric modulator of the calcium-sensing receptor, in a rat model of adenine-induced renal failure, by determining serum levels of intact PTH (iPTH), calcium, phosphorus, creatinine, and urea nitrogen. Furthermore, parathyroid hyperplasia (parathyroid gland weight and Ki-67-positive cell density), ectopic calcification (calcium content in the thoracic aorta, kidney and heart and positive von Kossa staining in the thoracic aorta), and bone morphometry parameters (cortical porosity and fibrosis volume) were evaluated. Rats treated with either 0.2mg/kg or 1mg/kg upacicalcet exhibited significantly lower serum iPTH levels than CKD-control rats, as early as 7days after the first dose. Repeated administration of upacicalcet reduced serum iPTH levels and inhibited parathyroid hyperplasia in rats with adenine-induced severe renal failure. Moreover, it suppressed ectopic calcification and cortical pore formation. In contrast, serum calcium and phosphorus levels were not significantly affected, suggesting a low risk of hypocalcemia, which often occurs with SHPT treatment. In conclusion, repeated administration of upacicalcet decreased serum iPTH levels and suppressed parathyroid hyperplasia in the adenine-induced CKD rat model of SHPT. Furthermore, ectopic calcification and cortical pore formation were suppressed without significant changes in blood mineral parameters. Upacicalcet safely inhibited the progression of SHPT in an adenine-induced CKD rat model.

Evolving Role of [18F]Flurocholine PET/CT in Assessing Primary Hyperparathyroidism: Can It Be Considered the First-Line Functional Imaging Approach?

The accurate detection of hyperfunctioning parathyroid tissue (HFPT) is pivotal in the preoperative assessment of primary hyperparathyroidism (PHPT). PET/CT using [18F]fluorocholine ([18F]FCH) showed superior diagnostic performance compared to conventional functional imaging modalities. We aimed to evaluate the diagnostic performance of [18F]FCH PET/CT as a first-line functional imaging approach in patients with clinically diagnosed PHPT. The imaging and clinical data of 321 PHPT patients, including 271 overt PHPT and 50 mild PHPT, who underwent [18F]FCH PET/CT as first-line imaging were analysed in this retrospective study. Histopathology was the reference standard. In case of no available histopathology evaluation (conservative management), imaging and clinical follow-ups were considered reference standards. In the overt group (n = 271), [18F]FCH PET/CT showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 0.99, 0.91, 1.00, 0.80, and 0.99, respectively. Regarding the correlation of the index lesions and initial laboratory data, all [18F]FCH PET/CT parameters (SUVs, SULs, and mSAD) were significantly correlated with the serum iPTH level. Additionally, SUVmax, SULpeak, and mSAD were significantly associated with the serum calcium level. In the mild group (n = 50), [18F]FCH PET/CT showed a sensitivity, specificity, PPV, NPV, and accuracy of 0.93, 0.75, 0.95, 0.67, and 0.90. In conclusion, [18F]FCH PET/CT revealed high diagnostic performance in the detection of HFPTs and the potential to be considered as a first-line imaging modality in the assessment of PHPT, including both overt and mild types. However, its cost-benefit concerning the clinical impact of early PHPT detection should be investigated in future studies.