Decrease In Parathyroid Hormone Levels Research Articles

#1286 Utility of cinacalcet treatment in kidney transplant recipients with persistent hyperparathyroidism

Abstract Background and Aims Secondary hyperparathyroidism occurs in the majority of patients with chronic kidney disease (CKD). It may persist in up to 50-66% of patients despite the initial decrease in PTH levels after successful kidney transplantation (KT). Maintaining parathyroid hormone (PTH) levels within the normal range during the post-transplant period is crucial because it is related to hypercalcemia, hypophosphatemia, and reduced bone mass in KT recipients. Studies have already demonstrated that persistent hyperparathyroidism is associated with graft loss and all-cause mortality. Vitamin D, vitamin D analogs, and calcimimetics are most commonly used to manage hyperparathyroidism. However, studies about the long-term effect of calcimimetic therapy on the allograft are still limited. In this study, we aim to investigate the long-term allograft results of patients who received cinacalcet treatment for hyperparathyroidism. Method This study was conducted in Gazi University nephrology dialysis and transplantation unit with 312 patients who were transplanted between 1996 and 2019 and continued routine follow-up visits. Persistent hyperparathyroidism is defined as elevated PTH levels after the first year of KT (serum PTH>88 pg/mL). All patients without concurrent hypercalcemia were treated with vitamin D or analogs according to their vitamin D levels. Patients with non-functional allograft and parathyroidectomy after KT were excluded from this study. In addition, patients with rejection episodes, which could be confounding factor for allograft survival, were excluded to evaluate the isolated effect of cinacalcet on the allograft function. We identified 115 patients with persistent hyperparathyroidism, of whom were treated with cinacalcet (n = 21) or not (n = 94). We analyzed the baseline characteristics, comorbidities, and immunosuppressive treatments of the groups. Additionally, annual eGFR changes (Δ eGFR) calculated based on baseline (post-transplantation 6th month) eGFR after KT was also examined to evaluate the effect of cinacalcet on the graft. Results The mean age of the patients was 44.3 ± 12.6 years, and 47 (41%) were women. The median follow-up time of the patients was 87 (49-117) months. Twenty-nine patients (25%) underwent cadaveric transplantation, and 47 (41%) patients received anti-thymoglobulin (ATG) in induction therapy. While all patients were given glucocorticoids as maintenance immunosuppressive therapy, 93 (81%) of the patients received tacrolimus and, 9 (8%) cyclosporin as CNI, 78 (68%) received anti-metabolite therapy. Fifty-eight patients (19%) were used mTORi. A total of 21 patients with persistent hyperparathyroidism (21%) were treated with cinacalcet. Dialysis time is longer in the cinacalcet-treated group than in the patients not treated with cinacalcet (p < 0.001). The preemptive transplantation rate was lower (p = 0.03), and the delayed graft function was higher in the cinacalcet-treated group (p = 0.04). In the first year after KT, serum median PTH levels were 227 (167-341) pg/ml in the cinacalcet group and 110 (86-160) pg/ml in the other group, respectively (<0.001). Also, serum phosphate level is lower in the treatment group (2.7 ± 0.4 mg/dl vs. 3.1 ± 0.7 mg/dl, p = 0.03). At the last visit of patients, we observed similar median PTH levels between groups [141 (100-222) vs. 108 (73-159), p = 0.08]. During the follow-up, CMV episodes and BKV nephropathy diagnosis rates were similar between the groups (Table 1). Δ eGFRs in the first year (p = 0.7), second year (p = 0.2), third year (p = 0.4), and fifth year (p = 0.6) after KT were similar between both groups. Conclusion Our study suggests that cinacalcet treatment could be a safe and effective treatment for patients with persistent hyperparathyroidism. In long-term follow-up, there is no evidence of a reduction of kidney function. However, more trials are still required for other clinical outcomes such as fracture risk and cardiovascular morbidity and mortality.

Significant role of 1,25-dihydroxyvitamin D on serum calcium levels after total thyroidectomy: a prospective cohort study.

Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy. Serum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery. Serum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p<0.0001), with 28% of patients showing increases in 1,25(OH)2D. The only factor predicting a postoperative 1,25(OH)2D decrease was a high preoperative 1,25(OH)2D concentration. Postoperative 1,25(OH)2D concentrations, as well as the magnitude and rate of decrease from preoperative levels, showed strong positive correlations with preoperative 1,25(OH)2D concentrations (p<0.0001 for all three variables) but not with PTH concentrations. These findings suggest that 1,25(OH)2D concentrations after thyroidectomy were more strongly dependent on preoperative concentrations than on the effect of PTH decrease and were relatively preserved, possibly preventing sudden severe postoperative hypocalcemia. A high 1,25(OH)2D level was the most important preoperative factor for hypocalcemia (<2 mmol/L; p<0.05) on the first postoperative day; however, only PTH decrease was statistically significant (p<0.001) when intraoperative factors were added. In the PTH >10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p<0.05). Similarly, in the PTH levels >15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant. 1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

Multiscale effects of the calcimimetic drug, etelcalcetide on bone health of rats with secondary hyperparathyroidism induced by chronic kidney disease

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels and prevented mineralization defect. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, and decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects in a bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes.

Brown Tumor, a Deceptive and Rare Entity: A Case Report

A case of 27 years old male from Jhapa district, who presented to Oral and Maxillofacial department of B&amp;C hospital with firm, non-tender swelling over buccal vestibule for 2 months. Computed tomography (CT) revealed an expansile lytic bony lesion with soft tissue component at the right hemimandible with cortical destruction. Provisional diagnosis of ameloblastoma was made. Incisional biopsy done and specimen was sent to the Pathology department. Haematoxylin and Eosin- stained slides revealed disorderly, fascicular architecture exhibiting clustered distribution of osteoclastic giant cells, surrounded by fibroblastic stromal cells along with reactive new bone formation. The differentials considered were CGCG (Central giant cell granuloma), GCT (Giant Cell tumor), ABC (Aneurysmal Bone Cyst) and Brown tumor. Serum Calcium and Serum PTH (Parathyroid hormone) were advised to ruleout brown tumor in histopathology report and for rest of the differentials excisional biopsy was suggested. Serum calcium and serum PTH were found to be raised. On further probing, the patient has been having right lower back pain and thin urine stream on and off for few months. USG abdomen was done for the same which revealed bilateral nephrolithiasis with left sided PUJ calculus causing gross hydronephrosis along with bilateral medullary nephrocalcinosis. DJ stenting was thus advised by the nephrologist. On identifying the primary cause, hemithyroidectomy with parathyroid removal was done. The decrease in parathyroid hormone level was drastic after the surgery. His urine stream was normal during his post –op stay at the hospital. The patient was advised for regular follow up.

Evaluating the effect of vitamin D supplementation on serum levels of 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, parathyroid hormone and renin–angiotensin–aldosterone system: a systematic review and meta-analysis of clinical trials

BackgroundVitamin D, one of the most essential micronutrients, is crucial in various health outcomes. However, previous studies showed conflicting results and uncertainty about vitamin D supplementation's optimal dosage and duration. In this study, we aimed to evaluate the vitamin D supplements efficiency on serum levels of 25-hydroxy vitamin D (25(OH)D), 1,25-dihdroxy vitamin D (1,25(OH)2D), parathyroid hormone (PTH) and renin–angiotensin–aldosterone system (RAAS) in adults.MethodsA systematic analysis of eligible and relevant randomized-controlled trials (RCT) published before April 2023 assessing the effect of vitamin D supplementations applied. The studies were identified by searching several databases, including Pubmed, Scopus, Web of Science, ProQuest, and Cochrane Register of controlled trials.ResultsFive eligible RCTs with 346 participants in the intervention and 352 participants in the control group were assessed in our project. According to the results, there was a substantial change in 25(OH)D (SMD: 2.2, I2: 92.3, 95% Confidence Interval (CI): 1.38–3.02, P-value: 0.048) and 1,25(OH)2D (SMD:1.23, I2: 86.3, 95% CI: 0.01- 2.44, P-value < 0.010) affected by vitamin D intervention. Regarding Parathyroid hormone (PTH), however, vitamin D intervention showed a remarkable decrease (SMD: -0.75, I2: 82.4, 95% CI: (-1.3)—(-0.18), P-value < 0.010). Moreover, sensitivity analysis showed significant publication bias in terms of 25(OH)D.ConclusionVitamin D supplements significantly increase the serum levels of 25(OH)D and 1,25(OH)2D and decrease PTH levels. While some studies reported decreasing effect of vitamin D supplements on RAAS activity, some reported no changes.

Neck Reoperation for Recurrent or Persistent Renal Hyperparathyroidism.

Patients with renal hyperparathyroidism undergoing parathyroidectomy may experience relapse. Reoperation for persistent or recurrent disease, particularly in the neck region, is challenging and has a high complication rate because of difficult exploration. We aimed to evaluate the effectiveness of neck reoperation in renal hyperparathyroidism. Patients with recurrent or persistent renal hyperparathyroidism who underwent neck reoperation between January 2015 and August 2022 were investigated, focusing on operative findings, perioperative biochemical changes, and significance of intraoperative parathyroid hormone (PTH) measurements. During reoperation, 35 parathyroid glands were identified and removed from the 26 enrolled patients, with one, two, and three glands retrieved from 19 (73.2%), five (19.2%), and two (7.6%) patients, respectively. Most removed glands (68.6%) were located in the lower neck, followed by the mediastinum, carotid sheath, and upper neck. Successful resection, defined as a postoperative PTH level of <300pg/mL, was achieved in 21 patients (80.8%). The remaining four (15.4%) and one (3.9%) patients were classified as having persistent and recurrent disease, respectively. The extent of PTH reduction was correlated with specimen weight, specimen volume, and preoperative alkaline phosphatase (ALP) level. The mean intraoperative PTH ratio (10 min after excision/pre-excision) was 0.23, and all patients with persistent or recurrent disease had a PTH ratio >0.3. Severe hypocalcemia (<7.5mg/dL) occurred in 19 (73.0%) patients after reoperation. Neck reoperation is an effective therapeutic option in patients with recurrent or persistent renal hyperparathyroidism. A decrease in PTH level by >70% during reoperation (PTH ratio <0.3) predicts successful resection.

Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease.

The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

Vitamin D Deficiency and its Relation to Lipid Profile

Background Vitamin D deficiency is considered as a major public health problem all over the world. Vitamin D acts as a hormone with multi-functions. The main source of vitamin D is solar UV radiation, which converts 7-dehydrocholesterol to pro-vitamin D which is modified to vitamin D given normal skin temperature. Vitamin D deficiency is a common disorder presents in all ages and in both genders. Vitamin D plays an important role in modulating the immune response to infections and reduction inflammatory response. Vitamin D deficiency has a genetic predisposition. There is a correlation between low 25-hydroxyvitamin D levels and dyslipidemia, so correction of vitamin D deficiency is important for treating disturbance in lipid profile. Repletion of 25-hydroxy vitamin D levels raised serum calcium level and decrease parathyroid hormone levels.

Study of vitamin D3 level in Egyptian hemodialysis patients and the effect of replacement therapy

Background The ability of extrarenal tissues to convert 25-hydroxyvitamin D into 1,25-hydroxyvitamin D and its dependence on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both calcitriol and vitamin D. The primary aim of the study was to detect serum vitamin D3 levels in a cohort of Egyptian hemodialysis patients and to check the effect of 12-week therapy of cholecalciferol on serum calcium, phosphate, and parathyroid hormone (PTH) in vitamin D-naïve hemodialysis patients with vitamin D deficiency. Patients and methods A total of 40 patients (25 males and 15 females) with chronic kidney disease on regular hemodialysis, attending the Nephrology Unit of internal Medicine Department, Mansoura University Hospital, during the period from January to June 2017, were included. According to laboratory investigations and clinical examination, deficient patients were treated with Devarol-S (cholecalciferol) for 3 months and then revaluated. Deficient patients received intramuscular injection of 50 000 IU monthly for 3 consecutive months. Results The patient group included 40 persons, comprising 27 (73%) male patients and 13 (27%) female patients. Their mean age was 47.16 ± 14.92 years. The mean dialysis duration was 4.68 ± 2.42 years. At 3 months after vitamin D replacement, significant increase in serum calcium (8.33–8.89 mg/dl), phosphorous (4.99–5.85 mg/dl), and vitamin D3 (4.01–28.43 ng/ml) levels were observed compared with pretreatment levels. There was also significant decrease in PTH level (419.30–377.20 pg/ml). After 3 months of follow-up, there were no significant changes in the levels of hemoglobin, Kt/v, albumin, and alkaline phosphatase in the study group. Conclusions In most patients, treatment with cholecalciferol in a 50 000 IU/month dose permits safe correction of vitamin D deficiency and control of PTH level, yet serum phosphorus should be monitored.

Effect of vitamin D on myocardial remodeling and inflammatory status in children with congenital heart disease.

Vitamin D insufficiency is a common public health problem that is often unrecognized in children with congenital heart disease, and is not generally evaluated at congenital heart disease (CHD) follow-up. Recent studies have suggested that inadequate vitamin D status may have an adverse effect on cardiovascular health. This study investigates the relationship between vitamin D levels and hemodynamic parameters in children with CHD. Included in the study 40 patients (25 females, 15 males) with CHD, who were evaluated for Ross heart failure score, vitamin D, parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase (ALP), whole blood count (WBC) and echocardiographic measurements, and all measurements were repeated in the third month of the therapy. The mean vitamin D level was 16.4 ± 6.6 ug/L before and 27.5 ± 9.9 μg/L in the third month of therapy, while the mean PTH level was 53.3 ± 34.9 pg/mL before and 43.8 ± 21.4 pg/mL in the third month of therapy. The mean WBC was 8084 ± 2324/µL before and 7378±1893/µL in the third month of the therapy, and the mean platelet (PLT) count was 280,897 ± 80,119/µL before and 307,179 ± 60,202/µL in the third month of the therapy. The mean ejection fraction (EF) was 64% ± 7.2% before and 66.7% ± 6.2% in the third month of therapy, while the right ventricle (RV) myocardial performance index (MPI) was 32.1% ± 6.7% before and 28.9% ± 6.5% in the third month of the therapy. IL10 level was increased in four patients in the third month of therapy. A statistically significant decrease in PTH level and WBC, and an increase in PLT number and IL-10 level were detected by the therapy. Furthermore, echocardiographic findings revealed a statistically significant increase in EF and a decrease in RVMPI attributable to the therapy. The decreased levels of PTH, which is a proinflammatory marker, the increases in IL-10, which is an antiinflammatory cytokine, and the decreases in the number of WBC resulting from vitamin D treatment demonstrate the antiinflammatory effects of vitamin D. An improvement in EF means improvement in left ventricular contractility, while a decrease in RV MPI has been shown to improve the systolic and diastolic function of the right ventricle. These results suggest that vitamin D therapy has a positive effect on the heart, and so vitamin D levels should be evaluated during the routine follow-up of congenital heart disease.

Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels.

Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.

The acute effects of milk intake on calcium homeostasis and cardiovascular outcome: A randomized crossover trial in postmenopausal women.

ObjectiveThe importance of calcium intake from dairy in regard to cardiovascular health has been investigated in several studies with discrepant results. Hence, we aim to investigate the immediate effects of milk intake on cardiovascular function.DesignA randomized crossover study with at least 10 days for washout between the two interventions, 500 ml of water with 200 µg of cholecalciferol or 500 ml of semi‐skimmed milk containing approximately 600 mg of calcium with 200 µg of cholecalciferol.PatientsTwenty community‐based postmenopausal women aged 60–80 years.MeasurementsParathyroid hormone and ionized calcium were measured at baseline and after 2 and 4 h on each study day. Pulse wave analysis and velocity were measured at baseline and after 4 h on each study day.ResultsCompared to water, milk intake increased ionized calcium levels by 0.02 mmol/L (p = .029) and decreased parathyroid hormone levels by 1.78 pmol/L (p < .001). The two interventions caused no changes as measured 4 h after the intervention in the following indices of cardiovascular health; pulse wave velocity, brachial diastolic or systolic blood pressure, central diastolic or systolic blood pressure, mean arterial pressure, pulse pressure, augmentation pressure, augmentation index, heart rate or pulse transit time.ConclusionsDespite significant changes in calcium homeostasis with increased levels of ionized calcium following milk intake, no acute effects seem to occur on measures of cardiovascular health.

Biochemical and X-ray micro-computed tomographic analyses of critical size bone defects grafted with autogenous bone and mercerized bacterial cellulose membranes salified with alendronate

ObjectivesThis study aimed to evaluate the repair of critical-sized bone defects grafted with autogenous bone and mercerized bacterial cellulose membranes (BCm) salified with alendronate (ALN). MethodsForty-eight male Wistar rats underwent surgery to create a 5 mm-diameter bone defect in the calvarium. The removed bone was particularized, regrafted into the defect, and covered by a BCm according to the group: control group (CG), simply mercerized BCm; group 1 (G1), negatively charged BCm (BCm-CM-) salified with ALN; and group 2 (G2), positively charged BCm (BCm-DEAE+) salified with ALN. Serum samples were collected preoperatively and before euthanasia to analyze osteoprotegerin (OPG), parathyroid hormone (PTH), sclerostin (SOST), and fibroblast growth factor 23 (FGF23) levels. The animals were euthanized after 15 or 60 d. Calvaria were analyzed using quantitative microtomography (μCT). ResultsThere was an increased level of PTH in the CG compared to the G2 group, at day 60 (p = 0.019). When analyzing the same group over time, G1 presented an increased FGF23 level on days 15 and 60 (p < 0.05). CG presented an increase in PTH (p = 0.037) at day 60. The μCT analysis detected increased trabecular separation on day 15 in G2 compared to G1 (p = 0.040). ConclusionsSalification of ionized BCm with ALN had no direct effect on bone repair; however, BCm-CM- increased the levels of FGF23 over time. BCm-DEAE+ decreased PTH levels compared to mercerized BCm. BCm-CM-salified with ALN-induced superior bone quality, with respect to trabecular separation, compared to BCm-DEAE+.

The Association between Changes in Low Parathyroid Hormone Levels and Cardiac Function Decline in Maintenance Hemodialysis Patients: A Prospective Observational Study

Objectives: The aim of this study was to investigate a possible association between changes in low parathyroid hormone (PTH) levels and cardiac function decline in maintenance hemodialysis (MHD) patients. Methods: A total of 150 MHD patients were included and followed for 24 months. The enrolled patients were divided into 3 groups based on their PTH status at baseline and 24 months. Factors potentially involved in changes in the PTH level and cardiac function were compared using multivariate logistic regression analysis. Results: At 24 months, the presence of low PTH levels increased by 26.7%. The main independent factors for low PTH levels were a low BMI, hemoglobin, and serum albumin and high serum calcium (p < 0.05). A persistently low PTH level at 24 months was associated with a decrease in the left ventricular ejection fraction (LVEF) and increase in valvular calcification (p < 0.05). Additionally, a decrease in PTH levels from normal or high to low values was associated with a decrease in LVEF and cardiac output (CO) and an increase in valvular calcification (p < 0.05). Furthermore, compared with those of the persistently low PTH level group, LVEF values were lower at 24 months in the group with a decrease from high/normal to low PTH level (p < 0.05). Conclusion: Persistently low PTH levels and changes in the PTH level from high/normal to low were associated with cardiac function decline in MHD patients. Moreover, a PTH level change from high/normal to low showed a stronger correlation with cardiac function decline.

MO1020EFFICACY OF CALCITRIOL COMPARING TO ALFACALCIDOL FOR THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN CHILDREN ON PERITONEAL DIALYSIS

Abstract Background and Aims Active vitamin D analogues are used routinely for the treatment of secondary hyperparathyroidism in children with end-stage renal disease (ESRD) on peritoneal dialysis (PD). Calcitriol is preferred active form of vitamin D, while data on efficacy of alfacalcidol in children on PD are limited. The aim of this study was to compare the efficacy of these two active vitamin D analogues for the treatment of secondary hyperparathyroidism in children on PD. Method This retrospective cohort study included data from 26 pediatric patients under 18 years of age with ESRD on PD who were treated at the National Research Center for Maternal and Child Health, Astana, Kazakhstan. Patients were allocated by initial treatment into two groups: oral alfacalcidol (n=21) and oral calcitriol (n=5). The first step of the study was to compare the efficacy of treatment between this two groups 3 and 6 months after. The second step was to compare the efficacy of calcitriol in subgroup of patients from alfacalcidol group who were switched to calcitriol later (n=12). The following characteristics were analyzed: parathyroid hormone (PTH), total plasma calcium, ionized plasma calcium, plasma phosphorus, initial dose of active vitamin D and corrected dose of vitamin D after 3 months. Independent t-test and repeated measures Anova were used for comparison between alfacalcidol and calcitriol groups. To compare data in subgroup between baseline and 3 months after conversion from alfacalcidol to calcitriol we used paired Student t-test. Results The mean age and baseline characteristics were no different between alfacalcidol and calcitriol groups (Table 1). The initial dose of alfacalcidol was 2.42±1.03 µg/week (0.157±0.097 µg/kg/week) and 2.09±0.74 µg/week (0.105±0.039 µg/kg/week) for calcitriol were not significantly different (P=0.5 and P=0.25 respectively). After 3 months of treatment there was statistically significant decrease of PTH level in calcitriol group 180±168 pmol/L comparing to alfacalcidol group 869±670 pmol/L (P=0.006). After 6 months, there was statistically significant decrease of PTH level in calcitriol group 261±259 pmol/L in contrast with alfacalcidol group 1080±716 pmol/L (P=0.047) and rise in total calcium in calcitriol group 2.46±0.17 mmol/L compared with alfacalcidol group 2.09±0.25mmol/L (P=0.035). The mean dose of calcitriol was also significantly lower as opposed to alfacalcidol dose: 0.04±0.039 µg/kg/week and 0.17±0.076 µg/kg/week respectively (P=0.002). The median age of children who were switched from alfacalcidol to calcitriol were significantly younger comparing with those who continued alfacalcidol (5±4.6 and 10±4.3 years of age respectively (P=0.022)). 3 months after conversion there was significant increase in ionized calcium level and decrease in PTH level comparing with baseline (Table 2). The dose of alfacalcidol before and dose of calcitriol after switch were differed (0.18±0.1 µg/kg/week and 0.13±0.05 µg/kg/week respectively, P=0.025) Conclusion Calcitriol showed superior efficacy for the treatment of secondary hyperparathyroidism in children on PD with the dose 4.25 times lower that of alfacalcidol. Alfacalcidol had limited efficacy for the treatment of secondary hyperparathyroidism in younger children when prescribed in recommended doses.

The acute effects of milk intake on calcium homeostasis and cardiovascular outcome: A randomized, crossover trial in postmenopausal women

OBJECTIVE The importance of calcium intake from dairy in regard to cardiovascular health has been investigated in several studies with discrepant results. Hence, we aim to investigate the immediate effects of milk intake on cardiovascular function. DESIGN A randomized crossover study with at least 10 days for washout between the two interventions, 500 ml of water with 200 µg of cholecalciferol or 500 ml of semi-skimmed milk containing approximately 600 mg of calcium with 200 µg of cholecalciferol. PATIENTS Twenty community-based postmenopausal women aged 60-80 years. MEASUREMENTS Parathyroid hormone and ionized calcium were measured at baseline and after 2 and 4 h on each study day. Pulse wave analysis and velocity were measured at baseline and after 4 h on each study day. RESULTS Compared to water, milk intake increased ionized calcium levels by 0.02 mmol/L (p = .029) and decreased parathyroid hormone levels by 1.78 pmol/L (p < .001). The two interventions caused no changes as measured 4 h after the intervention in the following indices of cardiovascular health; pulse wave velocity, brachial diastolic or systolic blood pressure, central diastolic or systolic blood pressure, mean arterial pressure, pulse pressure, augmentation pressure, augmentation index, heart rate or pulse transit time. CONCLUSIONS Despite significant changes in calcium homeostasis with increased levels of ionized calcium following milk intake, no acute effects seem to occur on measures of cardiovascular health.

Morbidity and mortality of parathyroid surgery - a retrospective analysis.

The incidence of parathyroid - glandula parathyreoideae (PTG) diseases has been increasing worldwide. Unlike benign tumours, the incidence of malignant PTG tumours is rather arare diagnosis. The morbidity of parathyroid surgery is associated with surgical removal of one or more pathologically altered parathyroid glands, particularly parathyroid adenoma associated with primary hyperparathyroidism (HPPT), but also hyperplasia associated with secondary or tertiary HPPT, and last but not least, HPPT due to parathyroid cancer. Aretrospective statistical analysis was performed in the set of patients undergoing surgery for aparathyroid disorder at the Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine, Charles University and Military University Hospital in Prague in 2013-2019 (7-year period). In this period, 127 procedures were performed. The incidences of morbidity, mortality, complications and lethality were analysed. Parathyroid surgery was performed in 20 male and 107 female patients. The mean age was 54.7 years, and the morbidity expressing recurrent laryngeal nerve (RLN) palsy was 0.7% of the nerves exposed during the procedure. The incidence of permanent normal postoperative calcaemia was 98.43%, demonstrated by adecrease in serum parathyroid hormone (PTH) levels. In 12 cases, this state was achieved only after asurgical revision (primary procedure for primary HPPT in 2 cases; 10 patients came for surgical revision with secondary or tertiary HPPT from other centres). Decreased PTH levels were demonstrated intraoperatively in 12.6% patients using the so-called PTH assay (arapid serum PTH assay). Surgery for secondary or tertiary hyperparathyroidism was done in 33 patients (26% procedures). PTG surgery lethality (mortality) was divided into perioperative mortality within 24 hours from the procedure and early mortality within 120 hours. Lethality related to PTG surgery was 0.0% including patients undergoing the surgery while being in adialysis programme and those with kidney transplant. Surgery is always associated with complications, with morbidity and mortality. Experience of endocrinology surgeons of all specialties is reflected in avery low incidence of RLN injuries and in sufficient oncological, or respectively, surgical radicality. This, in connection with other medical fields of endocrinology, nephrology, transplantology, nuclear medicine and oncology, allows asafe and effective treatment of all PTG disorders with agood prognosis for the patients. In those with secondary or tertiary HPPT, it not only improves their quality of life, which was not explored in our study, but in many cases it is an essential step for listing the patient for the transplant surgery. The current level of experience in the field of parathyroid carcinoma does not enable us to formulate any conclusions in terms of prognosis which should be considered as very serious in all cases.

Native vs. active vitamin D in children with chronic kidney disease: a cross-over study.

The rationale for the prescription of vitamin D analogues in patients with chronic kidney disease (CKD) is still a matter of debate. We aimed to compare native vs. active forms of vitamin D on pre-dialysis children with CKD and evaluate effects on calcium (Ca), phosphorus (P), and parathyroid hormone (PTH). Thirty children with pre-dialysis CKD were enrolled in a prospective cross-over study. Patients were randomly classified into two groups. Group A received native cholecalciferol while group B received alfacalcidol for 3months. After 1month (washout period), patients were switched to receive the opposite form for another 3months. Serum Ca, P, alkaline phosphatase (ALP), PTH, and 25(OH)D3 were measured at study start (BL-1), end of first period (FU-1), before second period (BL-2), and after second period (FU-2). There was significant increase in levels of 25(OH)D3 after administration of either native or active vitamin D in the first period in both groups (p < 0.001 and < 0.001, respectively) and also in the second period for both groups (p = 0.02 and < 0.001, respectively). There was no significant difference between both groups regarding changes in serum Ca (1st period; p = 0.770 and 2nd period; p = 0.412), serum P (1st period; p = 0.835, 2nd period; p = 0.052), and serum PTH (1st period; p = 0.250, 2nd period; p = 0.539). Alfacalcidol and native vitamin D3 were equally effective in decreasing PTH levels and increasing serum 25(OH)D3 in pre-dialysis CKD patients. There was no significant difference between the two forms regarding changes in serum Ca or P. Graphical abstract.

Metabolic Disorders with Kidney Transplant.

Metabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient's ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%-30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.

Primary and Secondary Hyperparathyroidism in Patients with Primary Aldosteronism - Findings From the German Conn's Registry.

Recent studies support a bidirectional interaction between aldosterone and parathyroid hormone (PTH), possibly increasing the individual cardiovascular risk. Primary aldosteronism (PA) and primary hyperparathyroidism can occur simultaneously. Our aim was to investigate the prevalence of hyperparathyroidism in PA. We performed a case finding of primary hyperparathyroidism in a retrospective series of 503 patients with PA (cohort 1). We analysed primary and secondary hyperparathyroidism in 141 prospective PA patients who underwent PTH, serum calcium and phosphate measurements at time of diagnosis of PA (cohort 2). The prevalence for primary hyperparathyroidism was 1.2% in cohort 1, and 2.1% in cohort 2. Secondary hyperparathyroidism was found in 54.6% of the patients. Patients with secondary hyperparathyroidism had significantly higher aldosterone and lower potassium levels and took more antihypertensive medications compared to those with normal PTH levels. In multivariate analysis, aldosterone and 25-hydroxyvitamin D levels were significantly correlated with serum PTH levels. There was a nonsignificant trend to a higher cardiovascular morbidity in patients with secondary hyperparathyroidism. Patients with aldosterone producing adenoma had significantly higher PTH levels compared to patients with bilateral adrenal hyperplasia. After treatment, there was a significant decrease of PTH levels in both groups. Patients with PA frequently have primary or secondary hyperparathyroidism, which is alleviated by correction of PA by surgical or medical means. Patients affected by secondary hyperparathyroidism seem to have a more severe phenotype of PA and have a trend towards more cardiovascular co-morbidities.