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1.
Parathyroid Hormone-Related Changes of Bone Structure.
Kužma, M, Jackuliak, P, Killinger, Z, Payer, J
Physiological research. 2021;(Suppl 1):S3-S11
Abstract
Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D.
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The role of Rapid Intraoperative Parathyroid Hormone (ioPTH) assay in determining outcome of parathyroidectomy in primary hyperparathyroidism: A systematic review and meta-analysis.
Medas, F, Cappellacci, F, Canu, GL, Noordzij, JP, Erdas, E, Calò, PG
International journal of surgery (London, England). 2021;:106042
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Abstract
BACKGROUND Primary hyperparathyroidism (PHPT) is a common endocrine disorder. In the last few decades, the introduction of Rapid Intraoperative Parathyroid Hormone (ioPTH) monitoring has allowed to ensurance of the excision of all hyperfunctioning parathyroid tissues, reducing the risks of persistent and recurrent PHPT. However, the use of ioPTH is still debated among endocrine surgeons. MATERIAL AND METHODS The objective of this systematic review and meta-analysis was to assess if ioPTH monitoring is able to reduce the incidence of persistent or recurrent PHPT. A systematic literature search was performed using PubMed, Scopus, ISI-Web of Science and Cochrane Library Database. Prospective and retrospective studies addressing the efficacy of ioPTH monitoring were included in the systematic review and meta-analysis. The random-effects model was assumed to account for different sources of variation among studies. The overall effect size was computed through the inverse variance method. Heterogeneity across studies, possible outlier studies, and publication bias were evaluated. RESULTS A total of 28 studies with 13,323 patients were included in the quantitative analysis. The incidence of operative failure was 3.2% in the case group and 5.8% in the control group. After excluding three outlier studies, the quantitative analysis revealed that ioPTH reduced significantly the incidence of postoperative persistent or recurrent PHPT. (Risk Difference = -0.02; CI = -0.03, -0.01; p < 0.001). There was no evidence of heterogeneity among the studies (Q = 19.92, p = 0.70; I2 = 0%). The analysis of several continuous moderators revealed that the effectiveness of ioPTH was larger in studies with lower preoperative serum calcium values and higher incidences of multiple gland disease. CONCLUSION ioPTH monitoring is effective in reducing the incidence of persistent and recurrent PHPT. Its routine use should be suggested in the next guidelines regarding management of PHPT.
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Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial.
Boer, W, Fivez, T, Vander Laenen, M, Bruckers, L, Grön, HJ, Schetz, M, Oudemans-van Straaten, H
BMC nephrology. 2021;(1):409
Abstract
BACKGROUND Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. METHODS Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325-0.4 mmol/L vs. 0.2-0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). RESULTS 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs - 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was - 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th-75th percentile 140-384) to 162 (111-265) pg/ml (p = 0.002); oxPTH from 192 (124-353) to 154 pg/ml (87-231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. CONCLUSIONS A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. TRIAL REGISTRATION ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.
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Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients.
Liao, CT, Zheng, CM, Lin, YC, Wu, MY, Lin, YF, Hsu, YH, Hsu, CC, Wu, MS
Scientific reports. 2021;(1):1171
Abstract
Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.
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Mild Idiopathic Infantile Hypercalcemia-Part 1: Biochemical and Genetic Findings.
Lenherr-Taube, N, Young, EJ, Furman, M, Elia, Y, Assor, E, Chitayat, D, Uster, T, Kirwin, S, Robbins, K, Vinette, KMB, et al
The Journal of clinical endocrinology and metabolism. 2021;(10):2915-2937
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Abstract
CONTEXT Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. OBJECTIVE This work aims to characterize the genetic associations and biochemical profile of mild IIH. METHODS This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. RESULTS The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. CONCLUSION The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants.
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The Association between Changes in Low Parathyroid Hormone Levels and Cardiac Function Decline in Maintenance Hemodialysis Patients: A Prospective Observational Study.
Lu, XH, Li, MS, Li, YY, Zheng, YD, Wu, XY, Gao, P
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2021;(6):550-556
Abstract
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.
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Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response.
di Filippo, L, Allora, A, Locatelli, M, Rovere Querini, P, Frara, S, Banfi, G, Giustina, A
Endocrine. 2021;(2):219-225
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Abstract
BACKGROUND Hypocalcemia has been identified as a major distinctive feature of COVID-19, predicting poor clinical outcomes. Among the mechanisms underlying this biochemical finding, high prevalence of vitamin D (VD) deficiency in COVID-19 patients reported so far in several studies was advocated. However, robust data in favor of this hypothesis are still lacking. Therefore, aim of our study was to investigate the role of hypovitaminosis D and parathyroid hormone (PTH) levels in the development of hypocalcemia in COVID-19 patients. METHODS Patients admitted to IRCCS Ospedale San Raffaele for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing calcium and VD metabolism. Serum levels of total calcium (tCa), ionized calcium (Ca2+), 25-OH-VD, and PTH were evaluated at admission. We defined VD deficiency as VD below 20 ng/mL, hypocalcemia as tCa below 2.2 mmol/L or as Ca2+ below 1.18 mmol/L, and hyperparathyroidism as PTH above 65 pg/mL. RESULTS A total of 78 patients were included in the study. Median tCa and Ca2+ levels were 2.15 and 1.15 mmol/L, respectively. Total and ionized hypocalcemia were observed in 53 (67.9%) and 55 (70.5%) patients, respectively. VD deficiency was found in 67.9% of patients, but secondary hyperparathyroidism was detected in 20.5% of them, only. tCa levels were significantly lower in patients with VD deficiency and regression analyses showed a positive correlation between VD and tCa. CONCLUSIONS In conclusion, we confirmed a high prevalence of hypocalcemia in COVID-19 patients and we showed for the first time that it occurred largely in the context of marked hypovitaminosis D not adequately compensated by secondary hyperparathyroidism.
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Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences.
Panizo, S, Martínez-Arias, L, Alonso-Montes, C, Cannata, P, Martín-Carro, B, Fernández-Martín, JL, Naves-Díaz, M, Carrillo-López, N, Cannata-Andía, JB
International journal of molecular sciences. 2021;(1)
Abstract
Fibrosis is a process characterized by an excessive accumulation of the extracellular matrix as a response to different types of tissue injuries, which leads to organ dysfunction. The process can be initiated by multiple and different stimuli and pathogenic factors which trigger the cascade of reparation converging in molecular signals responsible of initiating and driving fibrosis. Though fibrosis can play a defensive role, in several circumstances at a certain stage, it can progressively become an uncontrolled irreversible and self-maintained process, named pathological fibrosis. Several systems, molecules and responses involved in the pathogenesis of the pathological fibrosis of chronic kidney disease (CKD) will be discussed in this review, putting special attention on inflammation, renin-angiotensin system (RAS), parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, microRNAs (miRs), and the vitamin D hormonal system. All of them are key factors of the core and regulatory pathways which drive fibrosis, having a great negative kidney and cardiac impact in CKD.
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Parathyroid Hormone: A Uremic Toxin.
Duque, EJ, Elias, RM, Moysés, RMA
Toxins. 2020;(3)
Abstract
Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]2D3). PTH promotes calcium release from the bone and enhances tubular calcium resorption through direct action on these sites. Hallmarks of secondary hyperparathyroidism associated with chronic kidney disease (CKD) include increase in serum fibroblast growth factor 23 (FGF-23), reduction in renal 1,25[OH]2D3 production with a decline in its serum levels, decrease in intestinal calcium absorption, and, at later stages, hyperphosphatemia and high levels of PTH. In this paper, we aim to critically discuss severe CKD-related hyperparathyroidism, in which PTH, through calcium-dependent and -independent mechanisms, leads to harmful effects and manifestations of the uremic syndrome, such as bone loss, skin and soft tissue calcification, cardiomyopathy, immunodeficiency, impairment of erythropoiesis, increase of energy expenditure, and muscle weakness.
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Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients.
Doi, Y, Hamano, T, Ichimaru, N, Tomida, K, Obi, Y, Fujii, N, Yamaguchi, S, Oka, T, Sakaguchi, Y, Matsui, I, et al
Scientific reports. 2020;(1):13766
Abstract
Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19-2.14, 1.60 per mg/dL; 1.14-2.23 and 0.82 per 10 pg/mL; 0.68-0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.