Secondary Hyperparathyroidism Group Research Articles

A prospective cross-sectional study on hypocalcemia after total thyroidectomy in patients with Graves' disease: insights on secondary hyperparathyroidism.

To investigate the parathyroid function and calcium (Ca) levels in the secondary hyperparathyroidism (SHPT) state in patients with Graves' disease. We examined 31 consecutive patients with Graves' disease without chronic kidney disease, who were treated with total thyroidectomy. The patients were divided into a normal parathyroid hormone (PTH) group (NPTH group; n = 19) with a PTH level ≤ 65pg/mL, and a secondary hyperparathyroidism group (SHPT group; n = 12), with a PTH level > 65pg/mL. The PTH and Ca-related parameters were examined and the risk factors for postoperative hypocalcemia were analyzed. The preoperative Ca level was significantly lower (2.24 ± 0.06 vs. 2.31 ± 0.07mmol/L, p < 0.05) in the SHPT group than in the NPTH group. The reduction in PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), and Ca levels from the preoperative day to the next morning was significantly greater in the SHPT group than in the NPTH group (p < 0.05). When intraoperative factors were included, the decrease in the PTH level alone was significant. SHPT was a significant factor in determining the extent of PTH reduction. Hyperfunctioning parathyroid glands in the SHPT state were more susceptible to postoperative PTH reduction, which, combined with low preoperative Ca levels, increased the risk of postoperative hypocalcemia in patients with Graves' disease.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism: a retrospective study

There is now growing interest in the use of Ultrasound-guided radiofrequency ablation (RFA) to treat hyperparathyroidism. But the efficacy and limitations of this treatment have not been described in sufficient detail. Assessing and contrasting the effectiveness and safety of RFA in treating primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). This retrospective study included 57 HPT patients (48 for PHPT and 9 for SHPT) who underwent RFA between January 2017 and April 2021. The serum intact parathyroid hormone (iPTH) and calcium, hyperplastic parathyroid volume, volume reduction rate (VRR) before and after RFA, clinical success rate, symptoms, and complications were analyzed and compared. In SHPT group, bone pain (7/9, 77.8%), skin pruritus (4/9, 44.4%), and multiple hyperplastic parathyroid glands (4/9, 44.4%) were more common compared to the PHPT group. After 12 months of follow-up, the serum iPTH, calcium, and the volume of PHPT and SHPT groups had decreased by more than 60%, 10%, and 90%, respectively (P < 0.05). In the VRR, 13 glands of SHPT (72.2%) and 42 glands of PHPT (87.5%) had achieved the clinical success. In addition, the preoperative and postoperative serum iPTH were higher in the SHPT group than in the PHPT group (P < 0.05). In terms of the serum iPTH and calcium, the PHPT group had substantially higher rates of clinical success, with 42 patients (87.5%) and 46 patients (95.8%) meeting the criteria, respectively compared to 3 patients (33.3%) and 6 patients (66.7%) of SHPT group (P < 0.05). After RFA, the clinical symptoms improved in both groups. The overall incidence of complications (hoarseness and postoperative hematoma) of RFA in the two groups was 10.5% (6/57), and hoarseness (3/9, 33.3%) of SHPT group was more common than PHPT group. All the complications were resolved spontaneously within 12 months after symptomatic treatments. In the treatment of PHPT and SHPT, ultrasound-guided RFA is both successful and safe. PHPT patients have better results in restoring normal iPTH by RFA, and have no considerable difference with the SHPT patients in terms of serum calcium, the volume of the ablation area, and the VRR.

Changes in Bone Mineral Density and Related Influencing Factors Assessed by Quantitative Computed Tomography in Maintenance Dialysis Patients.

To investigate the changes in volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT) in chronic kidney disease (CKD) patients on maintenance dialysis. Descriptive study. Place and Duration of the Study: Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China, from March to July 2022. Maintenance dialysis patients were selected for this study, and parameters related to renal function and bone metabolism markers were recorded. Patients undergoing routine physical examination were age-matched with maintenance dialysis patients to serve as the control group. vBMD scans of the lumbar spine (L1-3) were obtained by QCT for all participants. Among the 141 maintenance dialysis patients, there were 67 patients with secondary hyperparathyroidism (SHPT) and 74 patients with non-secondary hyperparathyroidism (non-SHPT) with mean vBMDs of 145.99±55.13 mg/cm3 and 129.10±44.20 mg/cm3, respectively. The 159 individuals in the control group had mean age of 52.77±11.66 years and mean vBMD of 129.62±36.36 mg/cm3. The vBMD of the SHPT group was greater than that of both the non-SHPT group and the control group (all p<0.05). For dialysis patients, vBMD was positively correlated with calcium-phosphorus product and intact parathyroid hormone (iPTH) levels (r = 0.181, 0.214, respectively, p<0.05); vBMD was inversely correlated with age (r = -0.555, p<0.05). After adjusting for the covariates, vBMD remained positively correlated with iPTH (r = 0.184, p<0.05). Increased lumbar vertebral vBMD in maintenance dialysis patients may be associated with high iPTH, providing clinicians with a new understanding of the changes in bone mineral density in maintenance dialysis patients. Bone mineral density, Quantitative computed tomography, Chronic kidney disease, Maintenance dialysis.

Potential indicators for hyperparathyroidism progression: Calcium, phosphorus, alkaline phosphatase, 25 hydroxyvitamin D and hemoglobin

Purpose: To compare the differences in perioperative biochemical indices between patients with primary hyperparathyroidism (PH) and secondary hyperparathyroidism (SH).&#x0D; Methods: One hundred and ten patients with hyperparathyroidism who were treated in The Affiliated Hospital of Chengde Medical University, from June 2016 to April 2021, were enrolled and divided into two groups, viz, PH group (50 patients) and SH group (60 patients). Automatic biochemical analyzer was used to determine the levels of calcium, phosphorus, alkaline phosphatase and 25-hydroxyvitamin D, while hemoglobin was determined by liquid chromatography coupled with tandem mass spectrometry in the perioperative period.&#x0D; Results: Compared to PH group, SH group had higher levels of indicators (p &lt; 0.05). There were significant differences in body mass index (BMI), somatic cell index and blood albumin in patients from 18 to 70 years (p &lt; 0.05). BMI and blood albumin increased significantly with age (p &lt; 0.05). The complication rate was higher in SH than PH group (p &lt; 0.05). The scores of pruritus and bone pain of patients after surgery were lower than those before the operation (p &lt; 0.05). Blood calcium levels increased significantly with age, while ALP and iPTH levels decreased significantly (p &lt; 0.05). SH group showed lower scores of physiological, emotional, social, and cognitive functions than PH group (p &lt; 0.05).&#x0D; Conclusion: Patients with PH and SH have differences in perioperative biochemical indicators. Furthermore, the levels of calcium, phosphorus, alkaline phosphatase, 25 hydroxyvitamin D, and hemoglobin may be used as indicators of disease progression, and this may facilitate the development of suitable therapeutic measures.

Study on the correlation between mineral bone metabolism and CRP in patients with SHPT during perioperative period.

This study mainly observes changes in perioperative mineral bone metabolism-related indicators and inflammatory factors in patients with secondary hyperparathyroidism (SHPT), and analyzed the correlation between mineral bone metabolism-related indicators and inflammatory factors. Clinical data were collected. The study detects mineral bone metabolism-related indicators and inflammatory factor of perioperative patients with SHPT before and 4 days after operation. The production of high-sensitivity c-reactive protein (hs-CRP) in human hepatocytes cells (LO2 cells) stimulated by different concentrations of parathyroid hormone-associated protein was detected by enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction(RT-PCR), and western blot. The levels of mineral bone metabolism-related indicators and hs-CRP in SHPT group were significantly higher than those of control group. After operation, serum calcium, serum phosphorus, iPTH, FGF-23 decreased, and the level of osteoblast active biomarkers increased, while the level of osteoclast active biomarkers decreased. The levels of hs-CRP decreased significantly after operation. With the increase of PTHrP concentration, hs-CRP level in supernatant of LO2 cells decreased first and then increased. RT-PCR and western blot shows the same trend. Parathyroidectomy can significantly improve bone resorption and inflammation in SHPT patients. We speculate that there may be an optimal range of PTH concentrations to minimize inflammation in the body.

Predictive value of characteristics of resected parathyroid glands for persistent secondary hyperparathyroidism during parathyroidectomy

BackgroundParathyroidectomy (PTX), an effective treatment for refractory secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, still has a high persistent rate. This study aimed to analyze the predictive value of characteristics of resected parathyroid glands for postoperative persistent SHPT.MethodsThe clinical data of patients with persistent SHPT and successful PTX controls who had or underwent total parathyroidectomy with forearm autotransplantation (TPTX + AT) was retrospectively collected. The characteristics including the number, minimum weight, maximum weight and total weight of resected parathyroid glands from each patient were recorded. Characteristics and cutoff value of resected parathyroid glands for the prediction of persistent SHPT were analyzed.ResultsA total of 227 patients (62 persistent SHPT patients and 165 successful PTX controls) were enrolled in the study. Forty-one (66%) persistent SHPT cases related to supernumerary parathyroid and the remaining 21 (34%) cases related to residual undetected parathyroid. In addition, ectopic parathyroid was found in 8 patients (13%) before PTX. The average number of resected glands in the persistent SHPT group and successful PTX group was 3.53 ± 0.72 and 3.93 ± 0.25 respectively (p < 0.001). There was significance in the number of patients with different resected parathyroid glands between two groups (p < 0.001). When the resected gland number was 4, minimum weight of the parathyroid was noted to be heavier in the persistent SHPT group than that in the successful PTX group (0.52 ± 0.31 g vs. 0.38 ± 0.19 g, p < 0.001). For persistent SHPT prediction, cutoff value of minimum weight was 0.535 g, with sensitivity of 46% and specificity of 82% (AUC = 0.611; p = 0.029).ConclusionsMajor reason for the persistent SHPT is the existence of supernumerary parathyroid glands or resection of less than 4 glands. When 4 glands were resected, a minimum total parathyroid gland weight heavier than 0.535 g implied the potential presence of a missed supernumerary parathyroid gland, which also contributed to the persistent SHPT.

Low Parathyroid Hormone Versus Secondary Hyperparathyroidism and Survival in Patients Undergoing Hemodialysis: A Propensity-Matched Analysis.

IntroductionLow serum parathyroid hormone (PTH) and secondary hyperparathyroidism (SHPT) are very common in patients undergoing hemodialysis. However, it remains unclear which of these has a lower mortality.ObjectiveIn this study, we compared outcomes between hemodialysis patients with low PTH and those with SHPT.MethodsThis was a multi-center, retrospective, matched cohort study. Median intact PTH (iPTH) was used as the cutoff for allocating participants to low PTH (iPTH<100 pg/mL) and SHPT groups (iPTH ≥600 pg/mL). Sex, diabetes, age, and dialysis vintage were matched between the groups. The primary outcome was all-cause death at 72 months.ResultsThe study cohort comprised 2282 patients (1166 in each study group). Prior to matching, the primary outcome occurred in 429/1166 patients (36.79%) in the low PTH group and in 284/1116 (25.45%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.423). The hazard ratio for low PTH versus SHPT was 1.08 (95% confidence interval, 0.90–1.30). Propensity matching created 619 pairs of patients. Baseline characteristics, including age, sex, diabetes, and dialysis vintage were comparable between the groups. The primary outcome occurred in 195/619 patients (31.50%) in the low PTH group and in 193/619 (31.18%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.43). The adjusted hazard ratio for low PTH versus SHPT was 1.10 (95% confidence interval, 0.87–1.39).ConclusionsHemodialysis patients with low PTH have similar all-cause death rates to the rates for those with SHPT.

MO521: Paricalcitol Direct Increases Hemoglobin Levels. A Repurposing Possibility for Treating Renal Anemia

Abstract BACKGROUND AND AIMS The anti-inflammatory properties of the paricalcitol have been related to benefits in renal anemia; however, in chronic kidney disease (CKD) patients, the presence of secondary hyperparathyroidism (SHPT) represents a bias for determining the real effect of paricalcitol in hemoglobin levels. Whether the paricalcitol directly increases hemoglobin regardless of SHPT should be considered an opportunity for treating renal anemia, where the current treatments have safety concerns. To determine the effect of the oral paricalcitol on hemoglobin levels administered in different types of patients. Group A: n = 10, CKD patients not on dialysis under erythropoietin stimulating agents (ESA), Group B: n = 37, CKD patients not receiving ESA. A sub-group of patients without SHPT (Group C, n = 20) and glomerulonephritis patients without CKD (Group D, n = 18). Seven patients had hyperparathyroidism without CKD (plasma creatinine &amp;lt;1,2 mg/dL) and five CKD patients without SHPT (iPTH: 24–100 pg/mL). We also evaluated the effect of the paricalcitol according to Hb at baseline (≤10, ≤11 and ≤ 12 g/dL). METHOD A total of 52 consecutive patients were included and followed up by 6 months. Exclusion criteria were bleeding or recent blood transfusion history. No changes in ESA doses and iron supplements were required for inclusion. The mean paricalcitol dose was 6 mcg/week (min: 2–max: 7). RESULTS Age: 71(14) years, female 21(40%). As a whole, hemoglobin [mean: 95% confidence interval (CI)] increased 0.8 g/dL (0.4–1.2), partial η2: 0.24, P &amp;lt; .001. In group A: Hb increased 0.9 (0.2–1.6) g/dL, partial η2: 0.15, P = .015; in group B: 1.0 (0.4–1.5) g/dL, partial η2: 0.32, P &amp;lt; .001; in group C: 0.7 (0.2–1.2) g/dL, partial η2: 0.31, P = .008 and in group D: 0.4 (−0.02–0.9) g/dL, partial η2: 0.18, P = .06. In the seven patients only with hyperparathyroidism, Hb increased 1.3 (0.4–2.1) g/dL, partial η2: 0.67, P = .012 and in the five patients only with CKD the hemoglobin change 0.5 (−0.3–1.3) g/dL, partial η2: 0.40, P = .174. Interestingly, according to the baseline hemoglobin levels: ≤10, ≤11 and ≤ 12 g/dL, it significantly increased to 2.6, 2.3 and 1.2 g/dL, respectively. CONCLUSION The paricalcitol significantly increased the hemoglobin levels independently of ESA therapy, the renal function and the degree of hyperparathyroidism. A greater effect was observed in patients with lower baseline hemoglobin levels. Our results suggest that paricalcitol is a potential repurposing drug for treating renal anemia.

The value of clinical-ultrasonographic feature model to predict the severity of secondary hyperparathyroidism

Objectives To analyze conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in patients with secondary hyperparathyroidism (SHPT) and to evaluate the clinical-ultrasonographic feature based model for predicting the severity of SHPT. Methods From February 2016 to March 2021, a total of 59 patients (age 51.3 ± 11.7 years, seCr 797.8 ± 431.7 μmol/L, iPTH 1535.1 ± 1063.9 ng/L) with SHPT (including 181 parathyroid glands (PTGs)) without the history of intact parathyroid hormone (iPTH)-reducing drugs using were enrolled. The patients were divided into the mild SHPT group (mSHPT, iPTH <800 ng/L) and the severe SHPT group (sSHPT, iPTH ≥ 800 ng/L) according to the serum iPTH level. The clinical test data of patients were collected and CUS and CEUS examinations were performed for every patient. Multivariable logistic regression model according to clinical-ultrasonographic features was adopted to establish a nomogram. We performed K-fold cross-validation on this nomogram model and nomogram performance was determined by its discrimination, calibration, and clinical usefulness. Results There were 19 patients in the mSHPT group and 40 patients in the sSHPT group. Multivariable logistic regression indicated serum calcium, serum phosphorus and total volume of PTGs were independent predictors related with serum iPTH level. Even though CEUS score of wash-in and wash-out were showed related to severity of SHPT in univariate logistic regression analysis, they were not predictors of SHPT severity (p = 0.539, 0.474 respectively). The nomogram developed by clinical and ultrasonographic features showed good calibration and discrimination. The accuracy and the area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 0.888, 92.5%, 63.2% and 83.1%, respectively. When applied to internal validation, the score revealed good discrimination with stratified fivefold cross-validation in the cohort (mean AUC = 0.833). Conclusions The clinical-ultrasonographic features model has good performance for predicting the severity of SHPT.

P0890EFFICACY AND SAFETY OF CINACALCET IN CHINESE MAINTENANCE HEMODIALYSIS PATIENTS WITH DIFFERENT STAGES OF SECONDARY HYPERPARATHYROIDISM: INTERIM ANALYSIS RESULTS OF ACTIVE STUDY

Abstract Background and Aims Chronic kidney disease (CKD) is a major public health issue worldwide including in China. One of the most common complication in advanced Chronic kidney disease (CKD) is secondary hyperparathyroidism (SHPT). Reports show higher risk of bone fracture, cardiovascular events and all-cause mortality is associated with uncontrolled SHPT in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce iPTH levels without Ca increase in patients with SHPT previously. However there has been no large-cohort study and stratified analysis of cinacalcet based on the level of iPTH in China. Moreover, the optimal therapeutic doses of cinacalcet with mild-to-severe SHPT is remaining unknown. ACTIVE study is an IV, open-label, multicenter clinical trial aimed to: (1) evaluate the efficacy and safety of cinacalcet in maintenance hemodialysis patients with mild-to-severe SHPT; (2) explore optimal combinations therapy with cinacalcet and other agents for treating patients with CKD-mineral and bone disorder. (3) investigate the benefit of long-term, continuous medication with cinacalcet in the real-world setting. Method The study design was reported on 2019 ASN. Key inclusion criteria were a baseline iPTH ≥300 pg/mL with life expectancy of ≥2 years, and ≥12 weeks of maintenance dialysis (three dialysis sessions per week) prior to enrollment. The enrollments were grouped based on their iPTH level as having mild (300-600 pg/mL), moderate (600-900 pg/mL) or severe (≥900 pg/mL). Patients initiated treatment with cinacalcet orally at a starting dose of 25 mg once daily (qd). The primary efficacy endpoint is the proportion of patients achieving iPTH targets (iPTH between 150-300pg/mL) at 20 and 32 weeks after the initiation of cinacalcet treatment. Adverse events and serious adverse events were recorded. An interim analysis was scheduled as 375 patients completed 32 weeks visit. Results 911 patients were recruited and of 750 eligible patients, 275 were identified as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT. The study flowchart of 375 patients including mild(127), moderate(106) and severe(142) SHPT for interim analysis was shown in Fig 1. The baseline results including demographic and biomarkers level were reported on 2019 ASN. After 4 weeks’ cinacalcet treatment, serum PTH decreased in all three group, while extremely remarkable in the severe SHPT group. Interim analysis results revealed that the proportion of patients achieving iPTH target (150-300 pg/mL) at 20 wk visit among mild, moderate and severe groups were 38.61% (39/101), 30.11% (28/93) and 10.91% (12/110) respectively. The proportion of patients achieving iPTH target at 32 wk visit in 3 groups increased to 44.68% (42/94), 27.27% (24/88) and 14.56% (15/103) respectively (Table.1). The trends of the proportion of patients achieving iPTH target increased in all 3 different groups (Fig.2). The safety analysis showed the most common treatment-related AE in top 3 including hypocalcemia, hyperlipidemia, and loss of appetite. In vital signs, electrocardiogram (ECG) and laboratory examination of descriptive analysis, found no obvious safety tips. This study is sponsored by Kyowa Hakko Kirin (China) Pharmaceutical Co., Ltd. The analysis is still ongoing and results will be released at EDTA meeting this year. Conclusion Oral cinacalcet HCl was effective and safe in reducing iPTH in patients receiving HD with mild-to-severe SHPT.

Comparison of microwave ablation treatments in patients with renal secondary and primary hyperparathyroidism

Purpose Microwave ablation (MWA) is feasible for severe renal secondary hyperparathyroidism (SHPT) and primary hyperparathyroidism (PHPT) patients ineligible for parathyroidectomy (PTX). Here we compared the clinical manifestations and characteristics of parathyroid glands in these two groups, and summarized the techniques, safety and efficacy of MWA. Methods Baseline clinical characteristics, ablation-related techniques, adverse events/complications, and efficacy were recorded. Results In SHPT group, malnutrition, cardiovascular/pulmonary complications, and abnormal bone metabolism were severe. SHPT patients had more hyperplastic parathyroid glands. The volume of each gland was smaller, and the time of ablation for a single parathyroid was shorter in the SHPT group, although there were no significant differences compared with patients in the PHPT group. Three patients in both groups had recurrent laryngeal nerve injuries and all recovered, except for one SHPT patient. By the end of follow-up, serum iPTH levels had decreased from 2400.26 ± 844.26 pg/mL to 429.39 ± 407.93 pg/mL (p < .01) in SHPT and from 297.73 ± 295.32 pg/mL to 72.22 ± 36.51 pg/mL in PHPT group (p < .01). Hypocalcemia was more common (p < .001) and serum iPTH levels were prone to rebound in SHPT patients after MWA. Conclusion MWA can be reserved for those who had high surgical risks because of less invasiveness. Injuries of recurrent laryngeal nerves should be noticed. The health status, perioperative, and intraoperative procedures were more complicated and all parathyroids found by ultrasound should be ablated completely in SHPT patients.

Hemodialysis patients with low serum parathyroid hormone levels have a poorer prognosis than those with secondary hyperparathyroidism.

Background:Low serum parathyroid hormone (PTH) level and secondary hyperparathyroidism (SHPT) are very common in hemodialysis patients. However, the outcomes of patients with low PTH level or SHPT have not been carefully compared. Therefore, in the present study, we compared the outcomes of hemodialysis patients with low PTH level or SHPT.Methods:This was a multi-center, prospective, cohort study of 647 patients. The patients were recruited between 1 September 2016 and 1 January 2017 and followed until 31 December 2018. The participants were allocated to a low PTH group [serum intact PTH (iPTH) concentration < 60 pg/ml] and an SHPT group (iPTH ⩾ 600 pg/ml) according to their mean iPTH concentration across the entire observation period, and the outcomes were compared between these groups. The primary outcome was a composite outcome, which comprised all-cause mortality, non-fatal acute myocardial infarction, non-fatal acute stroke, and acute heart failure.Results:A total of 197 hemodialysis patients were allocated to the two groups: 87 with low PTH level and 110 with SHPT; 450 patients with time-averaged iPTH concentrations of 60–600 pg/ml were excluded. Kaplan–Meier analysis of the composite endpoint revealed a significant difference between participants with low PTH level and those with SHPT (p = 0.002). Cox multiple regression showed that participants with low PTH level had a higher incidence of the composite endpoint than those with SHPT (relative risk: 1.337, 95% confidence interval: 1.059–1.688).Conclusion:Hemodialysis patients with low PTH level had a higher incidence of mortality and non-fatal cardiovascular events than those with SHPT, irrespective of whether the participants were age-matched.

Effects of FGF-23-mediated ERK/MAPK signaling pathway on parathyroid hormone secretion of parathyroid cells in rats with secondary hyperparathyroidism.

This study is supposed to investigate the effect of FGF-23 on parathyroid hormone (PTH) secretion through ERK/MAPK signaling pathway in secondary hyperparathyroidism (SHPT) rat model. Thirty rats were equally served as the normal and SHPT groups. After transfection, parathyroid cells was assigned into blank, NC, pcDNA3.1-FGF-23, siRNA-FGF-23, U0126, and siRNA-FGF-23 + U0126 groups. The serum levels of Calcium (Ca), Phosphorus (P), alkaline phosphatase (ALP), and PTH were detected. HE and immunohistochemical (IHC) staining were used for the histopathological changes and the FGF-23, EKR1/2, and pEKR1/2 expressions. qRT-PCR and Western blotting were performed to determine the mRNA and protein expression of FGF-23, PTH, MAPK, EKR1/2, and Klotho. The proliferation, apoptosis, and cell cycle were all measured for parathyroid cells by CCK-8 assay, TUNEL staining and Flow cytometry. Compared with the normal group, the SHPT group showed increased serum levels PTH, P, ALP, and FGF-23 and mRNA and protein expressions of FGF-23 and PTH, whereas declined Ca and p-ERK1/2 expression, mRNA and protein expression of Klotho, cell apoptosis rate was reduced. Furthermore, compared to the blank and NC groups, the pcDNA3.1-FGF-23 and U0126 groups had a decreased mRNA expression of Klotho, protein expression of EKR1/2 and Klotho, and cell apoptosis rate was down-regulated, whereas the RNA and protein expressions of FGF-23 and PTH were up-regulated, and cell proliferation was elevated. The opposite results were observed in the siRNA-FGF-23 group. Our study demonstrated that FGF-23 could inhibit signaling transduction of ERK/MAPK pathway and accelerate the secretion of PTH in rats with SHPT.

Neutrophil gelatinase-associated lipocalin reflects the severity of anemia without iron deficiency and secondary hyperparathyroidism in hemodialysis patients.

OBJECTIVE:Secondary hyperparathyroidism (SHPT) and anemia are the primary and most common complications in patients receiving hemodialysis (HD). Neutrophil gelatinase-associated lipocalin (NGAL) is a new marker to assess iron deficiency and manage iron therapy for HD patients. The aim of this study was to determine any association between serum NGAL level and anemia without iron deficiency in patients with SHPT on chronic HD.METHODS:Total of 61 SHPT patients on chronic HD were enrolled in the study and divided into 3 groups: mild SHPT group (n=17), moderate SHPT group (n=21), and severe SHPT group (n=23). Hemogram, biochemical assays, and level of ferritin, high sensitivity C-reactive protein (hs-CRP), and NGAL were evaluated in all groups.RESULTS:Serum NGAL level was significantly higher and hemoglobin (Hb) level was significantly lower in severe SHPT patients compared with both mild and moderate SHPT patients. Furthermore, in severe SHPT group, serum NGAL level was significantly positively correlated with serum parathyroid hormone (r=0.79; p=0.00) and hs-CRP (r=0.52; p=0.01) level and negatively correlated with serum Hb (r=-0.56; p=0.00) level.CONCLUSION:SHPT was important factor affecting anemia in HD patients. Even when iron deficiency anemia is excluded in patients with SHPT, there was significant negative correlation between serum NGAL and Hb.

Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene polymorphisms and protein levels

Background: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which is characterized by elevated serum PTH levels, is a common complication of CKD. We investigated the possible associations between CKD with SHPT (CKD SHPT) and single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the Pin1 protein in the CKD SHPT patients with those of the controls.Methods: The study group included 251 CKD SHPT patients and 61 controls. One putative functional SNP (single nucleotide polymorphism) in the Pin1 promoter (rs2233679C > T: c.−667C > T) is the main object. Genotyping was performed on purified DNA using polymerase chain reaction-restriction (PCR) and restriction fragment length polymorphisms (RFLP). The levels of Pin1 were measured in serum using an enzyme-linked immunosorbent assay.Results: Genotyping showed that CT + TT in the Pin1 promoter was significantly more common in the CKD SHPT group than in the control group (p<.05). The correlation analysis demonstrated that a significant difference in the C to T transition in the Pin1 promoter contributed to CKD SHPT (χ2=12.47, p<.05; Odds ratios (OR) = 1.26, 95% confidence (CI) intervals =1.06–1.49). The multivariate logistic regression analysis reported that the OR and 95%CI were 12.693 and 2.029–75.819 (p<.05), respectively, in the Pin1 gene promoter −667T variant genotypes (CT + TT) after adjusting for other factors, and those values in Pin1 were 0.310 and 0.122–0.792 (p<.05).Conclusion: The −667T genetic variants in the Pin1 promoter contribute to an increased risk of CKD SHPT and may be biomarkers of susceptibility to CKD SHPT.

Risk factors associated with secondary hyperparathyroidism in patients with chronic kidney disease.

Secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD), and its development and progression are affected by various factors. The aim of the present study was to identify the risk factors for SHPT in patients with CKD. A retrospective study was performed in 498 patients (305 males and 193 females) with CKD, observed in the The First Hospital of Jilin University between January 2008 and December 2012. The demographic, clinical and laboratory data were collected. Patients were divided into the SHPT group (n=424) with elevated serum parathyroid hormone (PTH) expression levels and the control group (n=74) with normal serum PTH expression levels. Univariate and multivariate regression analyses were employed to explore the risk factors for SHPT. Serum PTH expression levels in women with CKD were significantly higher than in men (P=0.047). Serum PTH expression levels were positively correlated with the expression levels of serum creatinine (P<0.01), phosphorus (P<0.01), C-reactive protein (P<0.05), triglyceride (P<0.05), cholesterol (P<0.05) and low-density lipoprotein cholesterol (P<0.05), but were negatively correlated with the expression levels of hemoglobin (P<0.05), calcium (P<0.01) and CO2 combining power (P<0.01) in patients with CKD. Multivariate analysis showed that the serum expression levels of creatinine [µmol/l; odds radio (OR), 1.003; 95% confidence interval (CI), 1.002-1.004; P=0.001] and phosphorus (mmol/l; OR, 2.19; 95% CI, 1.254-3.826; P=0.006) in patients with CKD significantly influenced serum PTH expression levels. The SHPT risk factors include female gender, low calcium, high phosphorus, acidosis, anemia, hypertension, hyperlipidemia and micro-inflammation, with blood phosphorus and creatinine being independent risk factors.

Effect of secondary hyperparathyroidism serum on endothelial cells and intervention with Klotho.

The aim of the present study was to investigate the effect of the serum of patients with secondary hyperparathyroidism (SHPT) on endothelial cells and to examine the protective effect and the possible mechanism of Klotho. A total of three types of mixed serum from 15 patients with SHPT scheduled for parathyroidectomy, 10 chronic kidney disease (CKD) patients at stage 5 without SHPT and 15 healthy volunteers were collected. Initially, human umbilical vein endothelial cells (HUVECs) were incubated in vitro with the three types of serum and levels of proliferation were compared by assessing viable cell numbers with cell counting kit-8 (CCK-8). Subsequently, HUVECs were divided into three groups: Control group (healthy serum medium), SHPT group (SHPT serum) and Klotho treatment group (SHPT serum and Klotho). The proliferative and apoptotic levels of endothelial cells were evaluated by CCK-8 and flow cytometry, respectively. The levels of extracellular signal-regulated kinase (ERK1/2) and phosphorylated forms of ERK1/2 (p-ERK1/2) were detected using western blotting (with or without ERK1/2 inhibitor PD98059). The synthesis of nitric oxide (NO) was measured using the nitrate reduction method. The proliferation of HUVECs was inhibited by the serum from SHPT patients and CKD-5 patients without SHPT and the inhibitory effects of the SHPT serum were the most marked (P<0.05). Inhibition of HUVEC proliferation by SHPT serum occurred in a concentration-dependent manner within a specific range (5-20%; P<0.05) and also in a time-dependent manner within 6-24 h. Proliferation was partly restored and apoptosis was inhibited when 50-100 ng/ml Klotho was added into 10% SHPT serum (P<0.05). At the same time, the expression of p-ERK1/2 was upregulated, which may be inhibited by PD98059. The synthesis of NO was decreased in the SHPT group (P<0.05) and increased following treatment with Klotho (P<0.05). The results of the present study indicated that the proliferation of HUVECs was inhibited by the serum from SHPT patients. Klotho may partly antagonize this effect due to its inhibition of HUVEC apoptosis and upregulation of p-ERK1/2.

Causes of secondary hyperparathyroidism in a healthy population: the Tromsø study

Secondary hyperparathyroidism (SHPT) develops as a compensatory mechanism when the body is in calcium deficit. SHPT may be harmful and has been associated with elevated blood pressure. The cause of SHPT could be low calcium intake, reduced intestinal calcium absorption, or increased excretion. However, the relative importance of these factors for the development of SHPT is not known. During the 5th Tromsø study, serum PTH and calcium were measured in 7954 subjects. Then 96 subjects with SHPT (defined as serum PTH above 6.4 pmol/l together with serum calcium below 2.40 mmol/l) and 106 control subjects were examined at follow-up with a food frequency questionnaire, calcium absorption test, measurement of 24-h urinary calcium excretion, and serum vitamin D status. The statistical analyses showed several interactions necessitating subgroup analysis. It was found that the calcium intake was significantly lower in the SHPT group, but only in nonsmoking males; the calcium absorption was nonsignificantly higher in the SHPT group; the serum 25-hydroxyvitamin D levels were significantly lower in the SHPT group but only in nonsmokers; and the 24-h urinary calcium excretion was significantly lower in the SHPT group but only in those not on blood pressure medication. The most frequent cause of SHPT appeared to be low calcium intake (18%) and a low serum 25-hydroxyvitamin D level (18%). However, in most subjects with SHPT all tests were within the normal range, and the cause is therefore probably a combination of several factors.

Neuropsychological function in relation to serum parathyroid hormone and serum 25–hydroxyvitamin D levels

There are receptors for parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D in the brain, and there are clinical and experimental data indicating that PTH and vitamin D may affect cerebral function. In the present study 21 subjects who both in the 5th Tromsø study and at a follow-up examination fulfilled criteria for secondary hyperparathyroidism (SHPT) without renal failure (serum calcium < 2.40 mmol/L, serum PTH > 6.4 pmol/L, and normal serum creatinine) and 63 control subjects were compared with tests for cognitive and emotional function. Those in the SHPT group had significantly impaired performance in 3 of 14 cognitive tests (Digit span forward, Stroop test part 1 and 2, and Word association test (FAS)) as compared with the controls, and also had a significantly higher depression score at the Beck Depression Inventory (BDI) (items 1-13). In a multiple linear regression model, a high serum PTH level was significantly associated with low performance at the Digit span forward, Stroop test part 1 and 2, and Digit Symbol tests. A low level of serum 25-hydroxyvitamin D was significantly associated with a high depression score. In conclusion, a deranged calcium metabolism appears to be associated with impaired function in several tests of neuropsychological function.

Coeliac disease in subjects with secondary hyperparathyroidism

ObjectiveCoeliac disease (CD) may present in its classical form with diarrhoea and weight loss, but also with atypical symptoms that are both related and unrelated to malabsorption. Osteomalacia or osteopenia following malabsorption of calcium and vitamin D is known to occur in patients with CD, and in such cases secondary hyperparathyroidism (SHP) caused by low serum calcium levels is frequently found. However, the prevalence of CD in subjects with SHP has not been reported.Material and methodsIn the Tromsø study 2001, serum parathyroid hormone (PTH) and calcium were measured in 7954 subjects of whom 6061 were eligible for follow-up. From this group, 97 subjects with SHP (serum PTH≥6.5 pmol/l and serum calcium <2.40 mmol/l) and 104 matched control subjects were re-examined with serological tests for CD (anti-tissue transglutaminase, anti-gluten IgA and IgG).ResultsCD was diagnosed in 4 subjects, all from the original SHP group. At the re-examination, only 29 of the 97 subjects with SHP still had elevated serum PTH levels. Among these were 3 of the subjects with CD. When grouping the serological test results as negative, borderline or positive, there was a significant difference between the SHP group and the controls for anti-tissue transglutaminase and anti-gluten IgA (p<0.05).ConclusionsSubjects with SHP, at least when SHP is persistent, should be tested for CD.