Serum Parathyroid Hormone Levels Research Articles

Rare genetic disorders that impair parathyroid hormone synthesis, secretion, or bioactivity provide insights into the diagnostic utility of different parathyroid hormone assays.

Parathyroid hormone (PTH) is the major peptide hormone regulator of blood calcium homeostasis. Abnormal PTH levels can be observed in patients with various congenital and acquired disorders, including chronic kidney disease (CKD). This review will focus on rare human diseases caused by PTH mutations that have provided insights into the regulation of PTH synthesis and secretion as well as the diagnostic utility of different PTH assays. Over the past years, numerous diseases affecting calcium and phosphate homeostasis have been defined at the molecular level that are responsible for reduced or increased serum PTH levels. The underlying genetic mutations impair parathyroid gland development, involve the PTH gene itself, or alter function of the calcium-sensing receptor (CaSR) or its downstream signaling partners that contribute to regulation of PTH synthesis or secretion. Mutations in the pre sequence of the mature PTH peptide can, for instance, impair hormone synthesis or intracellular processing, while amino acid substitutions affecting the secreted PTH(1-84) impair PTH receptor (PTH1R) activation, or cause defective cleavage of the pro-sequence and thus secretion of a pro- PTH with much reduced biological activity. Mutations affecting the secreted hormone can alter detection by different PTH assays, thus requiring detailed knowledge of the utilized diagnostic test. Rare diseases affecting PTH synthesis and secretion have offered helpful insights into parathyroid biology and the diagnostic utility of commonly used PTH assays, which may have implications for the interpretation of PTH measurements in more common disorders such as CKD.

Circadian Regulation of Bone Remodeling

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

The value of ultrasound in combination with 99mTc-MIBI imaging department of ultrasound medicine, for the diagnosis of ectopic parathyroid glands in the thyroid gland in patients with secondary hyperparathyroidism.

To investigate the value of preoperative ultrasound combined with 99mTc-MIBI imaging for the diagnosis of ectopic intrathyroid parathyroid gland (ETPG) in patients with secondary hyperparathyroidism (SHPT). One hundred and eleven patients with SHPT who underwent total parathyroidectomy plus forearm transplantation from January 2015 to January 2022 in the Third Hospital of Hebei Medical University were selected. All patients underwent routine preoperative ultrasonography and 99mTc-MIBI imaging, and with pathological diagnosis as the gold standard, the clinical data of ETPG patients were selected, including clinical manifestations, laboratory tests, preoperative ultrasonography and 99mTc-MIBI imaging for localization and diagnosis, intraoperative exploration and postoperative pathology, and postoperative follow-up. To analyze the ultrasound manifestations of preoperative parathyroid hyperplasia and the results of 99mTc-MIBI imaging in patients with ETPG. Among 111 patients with SHPT, there were 5 patients with ETPG, 1 male and 4 females with a mean age of (45.00 ± 5.05) years, and 6 ectopic parathyroid glands were located in the thyroid gland. The incidence of ETPG was 4.5% (5/111), 4 were detected by ultrasound, 2 were not detected with a diagnostic accuracy of 66.7% (4/6), 3 were positive for 99mTc-MIBI imaging, 3 were negative with a diagnostic accuracy of 50.0% (3/6). Among them, one was not detected by ultrasound, but was positive for 99mTc-MIBI imaging, 2 with negative 99mTc-MIBI imaging, but all were detected by ultrasound, and one with negative 99mTc-MIBI imaging was detected by ultrasound but misdiagnosed as a thyroid nodule. A total of 5 ETPGs were detected by ultrasound combined with 99mTc-MIBI imaging, with a diagnostic accuracy of 83.3% (5/6). Patients' postoperative serum calcium and serum parathyroid hormone (PTH) levels were normalized or significantly decreased from preoperative levels. Ultrasound combined with 99mTc-MIBI imaging can achieve higher accuracy than either examination alone in the preoperative localization and diagnosis of ETPG in SHPT patients.

Effects of dietary supplementation of vitamin A on the tibia quality of goslings.

This study was conducted to evaluate the effect of dietary supplementation of VA on the tibial growth, calcium (Ca) and phosphorus (P) metabolism, VA and vitamin D (VD) deposition, and associated gene expression in goslings. A total of 180 healthy, 1-day-old male goslings were randomly divided into 3 treatment groups (0, 9,000, and 15,000 IU VA/kg), with 6 replicates containing 10 goslings each. They were weighed and sampled on days 14, 28, 42, 56, and 70. No addition of VA reduced VA content in the serum and liver of goslings, and supplementation of 15,000 IU/kg VA increased VA content from day 14 (p<0.05). The trend of VA concentration in the serum and liver was in line with the relative mRNA expression of retinoic acid receptor β in the jejunal mucosa. In both no addition of VA and supplementation of 15,000 IU/kg VA reduced 25-hydroxycholecalciferol (25-OH-VD3) content in the serum and VD content in the liver (p<0.05). From day 28, no addition of VA or supplementation of 15,000 IU/kg VA had a negative effect on tibia length, strength, and Ca, P, and ash content in goslings (p<0.05). Tibia P content was lower in the supplementation of 15,000 IU/kg VA group than in the no addition of VA group (p<0.05). No addition of VA or supplementation of 15,000 IU/kg VA had the most effect on early serum parathyroid hormone (PTH) levels in goslings (p<0.05). The effect of no addition of VA on the bone gla protein (BGP) content of goslings started from day 14 (p<0.05). The relative mRNA expression of BGLAP and bone morphogenetic protein 4 (BMP4) in the liver and jejunal mucosa was decreased by either no addition of VA or supplementation of 15,000 IU/kg VA (p<0.05). Both no addition of VA and supplementation of 15,000 IU/kg VA affected the mineralization process of the bone, and ultimately reduced tibial quality.

Video-Assisted Thoracoscopic Surgery Is a Safe and Feasible Technique for Mediastinal Parathyroid Lesions.

Introduction: Hyperfunctional ectopic parathyroid glands in the mediastinum pose a challenge to diagnosis and require optimal surgical management. Video-assisted thoracoscopic surgery (VATS) has emerged as a promising minimally invasive approach, offering potential benefits in terms of both patient comfort and oncological principles. This study aimed to evaluate the effectiveness and safety of VATS for the treatment of hyperfunctional ectopic parathyroid glands in the mediastinum. Methods: Among the 538 patients with mediastinal tumors who underwent thoracoscopic surgery at Istanbul University (2008-2021), 11 exhibited hyperfunctional ectopic parathyroid glands. The localization of the glands was performed using various diagnostic techniques, including neck ultrasound, sestamibi scan, CT (computerized tomography), and SPECT (Single-photon emission computed tomography). VATS (Video-assisted thoracoscopic surgery) was used to remove ectopic parathyroid glands in all 11 patients, with no need for conversion to open surgery. Results: The pathological results showed that VATS successfully removed the ectopic glands in all 11 patients. Serum parathyroid hormone (PTH) levels were monitored intraoperatively, and frozen sections were used to confirm the presence of parathyroid adenomas in all cases. Postoperative analysis showed that PTH levels dropped by at least 50% within 10-15 minutes after adenoma removal. Conclusion: VATS is a safe and effective method for the treatment of hyperfunctional ectopic parathyroid glands in the mediastinum with a low risk of complications.

Correlation Between Serum 1,25(OH)2D3, Serum Phosphorus, and Parathyroid Hormone and Parathyroid Function After Central Lymph Node Dissection in Patients with Papillary Thyroid Carcinoma.

This work was to demonstrate the relationship between serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), serum phosphorus (SP), and parathyroid hormone (PTH) and parathyroid function after central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). 200 PTC patients after CLND were included, who were rolled into a control group (CG) (n = 89 cases without hypoparathyroidism) and an observation group (OG) (n = 111 cases with complicated hypoparathyroidism). The 1,25(OH)2D3, SP, and PTH levels were detected, and the diagnostic effect of these indicators was assessed. The serum PTH levels of patients in CG after surgery were normal relative to those before surgery, while the serum PTH of patients in OG was relatively lower. 1,25(OH)2D3 concentration of patients in OG was also inferior to CG, while the SP level was superior (P < 0.05). Hypoparathyroidism was positively correlated with serum PTH (r = 0.382) and 1,25(OH)2D3 (r = 0.321) and negatively correlated with SP (r =  - 0.211). The area under the curve (AUC) (0.893), sensitivity (90.83%), and specificity (94.77%) of the joint diagnosis of 1,25(OH)2D3 + SP + PTH were greatly superior to those of the single diagnosis and the pairwise diagnosis with the three indicators (P < 0.05). Hypoparathyroidism in patients with PTC after CLND surgery was positively correlated with 1,25(OH)2D3 and PTH and negatively correlated with SP concentration. In addition, the combination diagnosis of 1,25(OH)2D3, PTH, and SP worked well.

Impact of supplementation with iron–folic acid (IFA) and vitamin D3 compared with IFA alone on haemoglobin levels in elderly people with mild-to-moderate anaemia: protocol for the double-blind, randomised, placebo-controlled Iron and vitamin D trial in Elderly Anemia (IDEA)

IntroductionAnaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high...

Parathyroid fine needle aspiration with PTH washout: Can it lead to parathyroid cell seeding in primary hyperparathyroidism?

Although parathyroid fine-needle aspiration (P-FNA) with parathyroid hormone (PTH) washout is effective in detecting preoperative parathyroid lesions, it also presents risks such as fibrosis, hematoma, and, in rare cases, tumor seeding. This study aimed to investigate whether P-FNA with PTH washout leads to the seeding of parathyroid cells along the path of the needle. A retrospective analysis was conducted on patients undergoing minimally invasive parathyroidectomy guided by preoperative PTH washout. Permanent pathology reports, imaging data, and postoperative serum parathyroid hormone and calcium levels were assessed to determine the effectiveness and safety of the procedure. Complications following P-FNA with PTH washout were also reviewed using data from the patient registration system of Bulent Ecevit University. The procedure accurately localized parathyroid adenomas in 87 patients who underwent ultrasound-guided parathyroidectomy following preoperative P-FNA and PTH washout. Postoperatively, 75 patients showed normal parathyroid hormone and calcium levels. Two patients required secondary surgery for contralateral adenomas. Critically, there was no evidence of P-FNA with PTH washout-induced parathyromatosis or seeding during the follow-up. Effective adenoma localization is crucial for successful minimally invasive surgery of hyperparathyroidism. Our study indicates that combining preoperative P-FNAB with PTH washout and imaging enhances adenoma detection, especially when intraoperative PTH measurements are not available, thus improving surgical outcomes. Notably, we found no evidence of cell implantation after P-FNA, suggesting the safety and efficacy of this method for preventing parathyroid cell seeding.

Reference values of parathyroid hormone in very low birth weight infants.

The primary goal was to estimate reference values of parathyroid hormone (PTH) in very low birth weight infants without severe neonatal morbidity. A secondary objective was to assess the relationship between PTH serum levels and selected laboratory markers of bone metabolism. Ninety two infants with birth weight less than 1500g met the inclusion criteria of the study. Serum levels of PTH, 25-hydroxyvitamin-D [25(OH)D], C3-epi-25(OH)D, total calcium, phosphorus, and alkaline phosphatase, and urinary levels of calcium, phosphorus, and creatinine were examined on day 14 and subsequently every 2weeks until discharge. Of the total 167 serum samples examined for PTH levels in infants without 25(OH)D deficiency the estimated range was 0.9-11.9 pmol/l (8.5-112.3 pg/mL). During the first month, no statistically significant correlation was observed between PTH level and that of 25(OH)D, C3-epimers of 25(OH)D, S-Ca, S-P, or ALP, nor with urinary excretion of calcium and phosphorus. From the second month of life, there was a moderately significant correlation between PTH and 25(OH)D (Rho = -0.40, P =< .001), between PTH and calcium/creatinine ratio (Rho = -0.56, P = < .001), and between PTH and phosphorus/creatinine ratio (Rho = 0.51, P = < .001). The physiological range for PTH levels for preterm neonates without 25(OH)D deficiency was estimated as 0.9-11.9 pmol/l (8.5-112.3 pg/mL). It seems that elevation of serum PTH above this range can be considered as hyperparathyroidism in very low birth weight infants.

A Rare Parathyroid Carcinoma in Young Adult Man: Therapeutic Challenges in Tertiary Hospital with its Limitations

Introduction: Parathyroid carcinoma is a rare malignant neoplasm. The symptoms that arise are related to hyperparathyroid conditions, which are clinically difficult to distinguish between benign and malignant disorders. These conditions make the diagnosis and treatment of parathyroid carcinoma challenging. Case Presentation: : In this case report, a 27-year-old male presented with weak limbs and a history of multiple recurrent fractures. Serum calcium ions and parathyroid hormone levels were increased. A comprehensive history taking, laboratory testing, and radiographic examination were used to confirm the diagnosis of parathyroid cancer. However, a histological study is still necessary to make a certain diagnosis. The patient underwent parathyroidectomy accompanied by intraoperative frozen section examination, then confirmed to have parathyroid carcinoma. Calcium serum evaluations were performed on the patient after surgery. Conclusions: Parathyroid carcinoma is a very rare case. Clinical manifestations and the results of investigations that are not typical and rarely found together in one patient’s condition make the diagnosis of this case very difficult. Although recommendations or standard protocols in the management of parathyroid carcinoma do not yet exist, the results of case reports are expected to increase the knowledge and management of parathyroid carcinoma patients.

Serum Biochemical Evaluation of Patients with Chronic Renal Failure on Hemodialysis

Introduction: Chronic renal failure (CRF) is associated with aberrations in the metabolism of minerals, such as calcium, phosphates, sodium, and potassium and other biochemical parameters. Various studies have identified parathyroid hormone (PTH) as the main regulator of minerals and biochemical parameters homeostasis. This study was conducted to evaluate the biochemical profile in CRF patients on hemodialysis in Aden. Methods: This study is a descriptive, cross sectional study, conducted in Aden Hemodialysis Center for the period Jan.1st to June 30th, 2022. Included 82 patients with CRF on HD. The data collected included demographic with clinical data, and blood samples taken for complete blood count and serum creatinine; urea; sodium; potassium; total calcium, ionized calcium; phosphate; alkaline phosphatase, and parathyroid hormone. Results: More male were found than female patients with CRF (67.1% vs. 32.9% respectively), with a mean age of 48.8 ± 12.6 years. The mean body mass index was (23.3 ± 4.7 kg/m2) and the mean duration of CRF was (4.8 ± 2.9 years). For renal function, the mean serum creatinine, urea, and estimated creatinine clearance were (9.9 mg/dl, 128.6 mg/dl, and 7.1 mL/min per 1.73 m2 respectively). For minerals, the mean serum sodium, potassium, chloride, phosphorus, calcium and ionized calcium were (134.4 mmol/L, 5.04 mmol/L, 104.1 mmol/L, 4.37 mg/dl, 9.4 mg/dl, and 1.12 mmol/L, respectively). The mean Calcium x Phosphorus product was in the recommended range (40.7mg2/dl2). The mean alkaline phosphatase was (286.2 U/L), and the mean parathyroid hormone was (322.7 pg/ml). Secondary hyperparathyroidism (PTH level of ≥130 pg/ml) was detected in (58.5%) of them. Parathormone concentration showed significant positive correlation to alkaline phosphatase (r: 0.640, p:0.001) in patients with CRF on hemodialysis. Conclusion: This study concluded that in patients with CRF on HD, there is an increase level of alkaline phosphatase which is considered as an adjunct marker of high-turnover bone disease associated with disturbed level of calcium and phosphorus that increase serum PTH level.

PREVALENCE AND PATHOPHYSIOLOGY OF POST-THYROIDECTOMY HYPOCALCAEMIA

Post-thyroidectomy hypocalcemia is a recognised and potentially significant complication arising from the surgical removal of the thyroid gland. The study's main objective is to find the prevalence and pathophysiology of post-thyroidectomy hypocalcemia. This prospective observational study was conducted in Civil Hospital Quetta from June 2021 to July 2022. A total of 162 patients undergoing thyroidectomy for various indications, including thyroid cancer, hyperthyroidism, and goiter, were enrolled in the study. Before surgery, baseline data were gathered, including demographic information, medical history, and preoperative serum calcium and parathyroid hormone (PTH) levels, from the 162 enrolled patients scheduled for thyroidectomy. Data were collected from 162 patients from both genders. The mean age of patients was 48.5 ± 8.2 years, with 70% female. The diagnoses included 40% with thyroid cancer, 30% with hyperthyroidism, and 30% with a large goiter. Preoperative serum calcium levels were 9.0 ± 0.5 mg/dL, parathyroid hormone (PTH) levels were 45 ± 9.80 pg/mL, and vitamin D levels were 25.5 ± 6.3 ng/mL. A history of hypocalcemia was noted in 5% of the participants. The mean serum calcium level was 9.0 mg/dL, with a standard deviation of 0.5. However, at 48 hours post-op, there was a decrease in the mean serum calcium level to 7.8 mg/dL, with a standard deviation of 0.7. It is concluded that the interaction between reduced serum calcium and parathyroid hormone levels highlights the immediate impact of surgery on calcium homeostasis.

Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis.

Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.

International variations in serum PTH and calcium levels and their mortality associations in peritoneal dialysis patients: Results from PDOPPS.

Mineral bone disorder (MBD) in chronic kidney disease (CKD) is associated with high symptom burden, fractures, vascular calcification, cardiovascular disease and increased morbidity and mortality. CKD-MBD studies have been limited in peritoneal dialysis (PD) patients. Here, we describe calcium and parathyroid hormone (PTH) control, related treatments and mortality associations in PD patients. We used data from eight countries (Australia and New Zealand (A/NZ), Canada, Japan, Thailand, South Korea, United Kingdom, United States (US)) participating in the prospective cohort Peritoneal Dialysis Outcomes and Practice Patterns Study (2014-2022) among patients receiving PD for >3 months. We analysed the association of baseline PTH and albumin-adjusted calcium (calciumAlb) with all-cause mortality using Cox regression, adjusted for potential confounders, including serum phosphorus and alkaline phosphatase. Mean age ranged from 54.6 years in South Korea to 63.5 years in Japan. PTH and serum calciumAlb were measured at baseline in 12,642 and 14,244 patients, respectively. Median PTH ranged from 161 (Japan) to 363 pg/mL (US); mean calciumAlb ranged from 9.1 (South Korea, US) to 9.8 mg/dL (A/NZ). The PTH/mortality relationship was U-shaped, with the lowest risk at PTH 300-599 pg/mL. Mortality was nearly 20% higher at serum calciumAlb 9.6+ mg/dL versus 8.4-<9.6 mg/dL. MBD therapy prescriptions varied substantially across countries. A large proportion of PD patients in this multi-national study have calcium and/or PTH levels in ranges associated with substantially higher mortality. These observations point to the need to substantially improve MBD management in PD to optimise patient outcomes. Chronic kidney disease-mineral bone disorder (MBD) is a systemic condition, common in dialysis patients, that results in abnormalities in parathyroid hormone (PTH), calcium, phosphorus and vitamin D metabolism. A large proportion of peritoneal dialysis (PD) patients in this current multi-national study had calcium and/or PTH levels in ranges associated with substantially higher risks of death. Our observational study design limits our ability to determine whether these abnormal calcium and PTH levels cause more death due to possible confounding that was not accounted for in our analysis. However, our findings, along with other recent work showing 48-75% higher risk of death for the one-third of PD patients having high phosphorus levels (>5.5 mg/dL), should raise strong concerns for a greater focus on improving MBD management in PD patients.

Expect the unexpected: Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism.

Hyperparathyroidism (HPT) is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone (PTH), causing disturbances in calcium homeostasis. Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia. Brown tumors are rare, benign, tumor-like bone lesions, occurring in 1.5% to 4.5% of patients with HPT, as a complication of an uncontrolled disease pathway, and are nowadays rarely seen in clinical practice. The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass. Furthermore, it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion. The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium, phosphorus, and PTH. Although when present, brown tumor is quite pathognomonic for HPT, the histologic finding often suggests a giant cell tumor, while clinical presentation might suggest other more frequent pathologies such as metastatic tumors. Treatment of brown tumors frequently focuses on managing the underlying HPT, which can often lead to regression and resolution of the lesion, without the need for surgical intervention. However, in refractory cases or when dealing with large symptomatic lesions, surgical treatment may be necessary.

Long-term treatment of evocalcet in hemodialysis patients with secondary hyperparathyroidism: a five-year prospective cohort study in 147 Japanese patients

BackgroundCinacalcet hydrochloride (cinacalcet), an oral calcimimetics for secondary hyperparathyroidism (SHPT), has been widely used worldwide. In contrast, evocalcet, an improved derivative of cinacalcet, was approved only in Japan in 2018 and has not received approval overseas. Consequently, the available information on the long-term use of evocalcet relies solely on data from a 1-year dosing phase III clinical trial.MethodsThe cohort of 147 chronic hemodialysis patients on cinacalcet to manage SHPT was simultaneously switched to the lowest dose of evocalcet (1 mg/day) and prospectively followed for 5 years in real-world clinical settings.ResultsThe median evocalcet dose was 1 mg/day at 0.5 years, and it remained stable at 2 mg/day from 1 to 5 years after the prescription initiation. Additionally, serum parathyroid hormone, corrected calcium, phosphorus, and total alkaline phosphatase levels showed no significant changes compared with their levels at the time of the switch and remained stable over the 5-year period. Furthermore, no adverse events related to vital signs, serum biochemistries, or upper gastrointestinal symptoms were observed in patients during treatment with evocalcet.ConclusionsThese results suggest that only a small number of patients require higher evocalcet doses, and that SHPT can be effectively managed with low-dose evocalcet for 5 years. Additionally, the drug’s long-term safety has been confirmed.Trial registration: name of the registry: Prescription change from cinacalcet hydrochloride to evocalcet in hemodialysis patients. Trial registration number R000041815. Trial registration UMIN000036702. Registered 10 May 2019—retrospectively registered. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000041815.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7–12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, β-CrossLaps (β-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7–9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose–response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between β-CTX and UF levels in adults. In addition, significant correlations were observed between UF–age and serum Ca2+, β-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and β- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while β-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

The impact of low and high dialysate calcium concentrations on cardiovascular disease and death in patients undergoing maintenance hemodialysis: a systematic review and meta-analysis.

The optimal dialysate calcium (Ca) concentration for patients undergoing hemodialysis remains inconclusive, particularly concerning cardiovascular protection. We conducted a systematic review of 19 randomized controlled trials (RCTs) and a meta-analysis of eight RCTs to determine the optimal dialysate Ca concentration for cardiovascular protection. We compared outcomes in patients receiving maintenance hemodialysis treated with either a low-Ca dialysate (LCD) (1.125 or 1.25mmol/L) or a high-Ca dialysate (HCD) (1.5 or 1.75mmol/L). The outcomes were coronary artery calcification score (CACS), all-cause and cardiovascular death, cardiovascular function and structure, and serum biochemical parameters. There was no significant difference between LCD and HCD concerning CACS (standardized mean difference [SMD] = -0.16, 95% confidence interval [CI]: [-0.38, 0.07]), the risk of all-cause death, and cardiovascular death in patients treated with chronic maintenance hemodialysis. Conversely, LCD was associated with a significantly lower intima-media thickness (SMD = -0.49, 95% CI [-0.94, -0.05]) and pulse wave velocity than HCD (SMD = -0.86, 95% CI [-1.21, -0.51]). Furthermore, LCD significantly decreased serum Ca levels (mean difference [MD] = 0.52mg/dL, 95% CI [0.19, 0.85]) and increased serum parathyroid hormone levels (MD = 44.8pg/mL, 95% CI [16.2, 73.3]) compared with HCD. Notably, most RCTs examined in our analysis did not include patients receiving calcimimetics. Our meta-analysis showed no significant differences in cardiovascular calcification and death between LCD and HCD and revealed a paucity of RCTs on dialysate Ca concentrations, including those involving patients on calcimimetics, indicating the urgent need for further studies.

Role of Rosmarinus officinalis Aqueous Extract in Relieving the Complications Associated with Ethylene Glycol-induced Urolithiasis in Male Rats

Background:: Rosmarinus officinalis is considered one of the famous plants from ancient times for its therapeutic ability in many diseases, such as headache, spasms, brain disorders, and some pathological conditions associated with toxicity cases in the liver and kidneys. Aim:: The current research has aimed, for the first time, to evaluate anti-urolithiatic effect of Rosmarinus officinalis aqueous extract (RMAE) on calcium oxalate stones formation in male rats and its possible therapeutic mechanisms of action. Evaluation of the polyphenols and flavonoid content in the extract was also performed. Methods:: A calcium oxalate nephrolithiasis case was established in rats by adding ethylene glycol (1%) to the rats' daily drinking water for a duration of one month. Treatment was achieved by oral co-administration of RMAE to rats administrated ethylene glycol. Results:: Phytochemical results showed that LC/MS-MS analysis led to the identification of 37 compounds in the phytoconstituent profile of RMAE. The biochemical results revealed significant improvement in serum kidney functions (urea, creatinine, and uric acid) in addition to restoring the calcium x phosphorous product and parathyroid hormone (PTH) levels in the plant-treated group compared to the non-treated one. The data have been supported by the significant decrease in lactate dehydrogenase enzyme (LDH) expression in the liver tissues, reflecting the decrease in oxalate synthesis in the liver compared to the non-treated group. Kidneys' histological examinations showed the absence of oxalate crystals in the treated group and the immunohistochemical findings of osteopontin (OPN) protein revealed the impact of RMAE on OPN expression in kidney tissues. Improvements in the femur bone fractures and the parathyroid gland in the treated group were also noticed during microscopic examinations. Conclusion:: The anti-lithiatic effect of the extract was attributed to its influence on serum phosphate, serum PTH, and OPN levels in kidney tissues and decreasing synthesis of LDH in liver tissues in addition to the prevention of secondary disease incidences, such as secondary hyperparathyroidism and cardiovascular diseases. On the other hand, the plant's considerable content of phenolics and flavonoids has been found to play a role in controlling kidney stone progression episodes.

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group (P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission (P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.