High Parathyroid Hormone Levels Research Articles

Parâmetros clínicos e bioquímicos de pacientes renais crônicos em hemodiálise com níveis elevados de fosfatase alcalina

Introduction: Chronic kidney disease (CKD) is a global public health problem, which implies poor health and high risk of cardiovascular disease contributing to high mortality rates, whichhas been associated with high levels of alkaline phosphatase (AF) in this public. The aim of this study was to compare clinical and biochemical parameters in relation to alkaline phosphatase levels of chronic renal patients on hemodialysis. Methods: Cross-sectional and analytical study, performed in 93 male and female patients, aged 18 years or older, from a hemodialysis center in the city of Belém, Pará. Data collection included interviews through a semi-structured questionnaire and consultation of medical records. Descriptive statistics consisted of mean, standard deviation, median, interquartile range, relative and absolute frequency. For alkaline phosphatase analysis, the interquartile range of 120 U/L was used. Results: Of the 93 patients, 58 were men with a mean age of 54.5 ± 4.5 years. The sample was divided into two groups: the first, with low alkaline phosphatase - less than 120 U/L (n= 50; 82.24 ± 21.67); and the second, with high alkaline phosphatase - greater than or equal to 120 U/L (n= 43; 288.82 ± 300.05). After analyzing the clinical and biochemical profile of each group, we found a statistical difference in the values of parathyroid hormone and hemoglobin, in which the group with high alkaline phosphatase obtained higher parathyroid hormone levels and lower hemoglobin values. Considerable prevalence of elevated phosphatase was observed in chronic renal patients on hemodialysis. Conclusion: The study identified high parathyroid hormone and lower hemoglobin in patients with high alkaline phosphatase. We emphasize the importance of monitoring and correcting AF levels, when possible.

Serum vitamin D status in sick cats with and without cholestatic liver disease.

Vitamin D deficiency accompanies chronic cholestatic liver disease (CLD) in humans. The vitamin D status of cats with CLD is unknown. The objectives of this study were to describe serum vitamin D concentrations in cats with CLD and to determine if they correlated with indices of liver disease severity. Thirty-six cats with CLD, defined by increases in serum bilirubin and serum alanine aminotransferase, and 23 sick cats with non-hepatobiliary diseases were prospectively enrolled. Serum 25-hydroxyvitamin D (25[OH]D), parathyroid hormone (PTH) and ionized calcium were measured. Signalment, clinical signs, comorbidities, diet history, serum bilirubin, liver enzyme activity, albumin, phosphorus, white blood cell count, prothrombin time and final hepatic cytologic/histopathologic diagnosis, when available, were recorded. Median serum 25(OH)D levels were similar in cats with CLD (89.5 nmol/l; range 21-112 nmol/l) and sick cats (89.0 nmol/l; range 49-115 nmol/l). Overall 12/36 (33%) cats with CLD and 4/23 (17%) sick cats had 25(OH)D levels below the lower limit of the reference interval (<65 nmol/l). Median PTH concentrations in cats with CLD were significantly higher (0.95 pmol/l; range 0-11.3 pmol/l) than in sick cats (0.70 pmol/l; range 0.5-6 pmol/l). In cats with CLD, 6/36 (17%) had high PTH levels in contrast to only 1/23 (4%) sick cats. In cats with CLD, 25(OH)D concentrations did not correlate with serum bilirubin, albumin or serum liver enzymes but were moderately negatively correlated with white blood cell count (r = - 0.402, P = 0.013). Cats with hepatic lipidosis had the highest prevalence of 25(OH)D concentrations that fell below the reference interval. Many cats with CLD have serum 25(OH)D concentrations below the lower limit of the reference interval. Further study is warranted to determine the clinical relevance and whether supplementation would provide benefits.

A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet

Background: Chronic kidney disease (CKD) with known valve calcification (VC) places individuals at high risk of cardiovascular disease. The study of VC in CKD is challenging due to the lack of a suitable research model. Here, we established a rat model of multivalve calcification induced by subtotal nephrectomy and a high-phosphate (HP) diet and analyzed the valve characteristics. Methods: We established a CKD model in Sprague-Dawley rats by performing 5/6 nephrectomy (5/6Nx) followed by feeding with chow containing different phosphate concentrations for 8, 12, or 16 weeks. The rats were divided into 4 groups: sham+normal phosphate (NP, 0.9% P), sham+high phosphate (HP, 2.0% P), 5/6Nx+NP, and 5/6Nx+HP. Serum creatinine (Scr), blood urea nitrogen (BUN), parathyroid hormone (PTH), calcium, phosphorus, and 24-h urine protein levels were investigated. Pathological examinations included histological characterization, safranin staining, Alcian blue staining, and von Kossa staining at different time points. Using nanoanalytical electron microscopy, we examined valves from rats in the 5/6Nx+HP and sham+HP groups and detected spherical particles using energy-dispersive spectroscopy (EDS) to observe microscopic changes in the valves. In addition, the calcified tissues were analyzed for phase and crystallization properties using an X-ray powder diffractometer. Results: The rats in the 5/6Nx+HP and 5/6Nx+NP groups presented with increased levels of Scr, BUN, and 24-h urine protein compared with those of the rats in the sham+HP and sham+NP groups. High levels of PTH were observed, and hematoxylin and eosin staining and immunohistochemistry for proliferating cell nuclear antigen showed parathyroid hyperplasia in rats in the 5/6Nx+HP group but not in the 5/6Nx+NP group. In rats in the 5/6Nx+HP group, extracellular matrix glycosylation was observed in the aortic valve in the 12th week and the mitral valve in the 16th week. In the 16th week, chondrocytes appeared in the aortic valve, as confirmed by immunofluorescence and Western blotting. Calcified particles mainly composed of phosphorus and calcium were observed in both the aortic and mitral valves by transmission electron microscopy and scanning electron microscopy (SEM). The main mineral component of the calcified aortic valve particles was hydroxyapatite [Ca₅(PO₄)₃(OH)], as shown by X-ray diffraction. However, there were no obvious differences in heart function between rats in the 5/6Nx+HP and sham+HP groups. Conclusions: Our findings demonstrate that multivalve calcification is involved in CKD following 16-week HP and that hydroxyapatite [Ca₅(PO₄)₃(OH)] is the main component of the calcified aortic valve particles of rats in the 5/6Nx+HP group.

Parathyromatosis in a patient with parathyroid carcinoma and hypercalcemic crisis: Findings on MIBI scan and 4D CT

Parathyroid carcinoma is a rare tumor associated with significantly high levels of parathyroid hormone (PTH) and primary hyperparathyroidism (HPT) and is difficult to distinguish from parathyroid adenoma, which is a much more common cause of HPT. Parathyromatosis is a rare condition in which several nodules of hyperfunctioning parathyroid tissue form in the neck and mediastinum, and it presents as recurrent hyperparathyroidism. We describe the case of a 44-year-old woman with recurrent hyperparathyroidism who presented with hypercalcemic crisis and biochemical investigations showed a severely raised serum intact parathyroid hormone (iPTH) level of 2513 pg/ml and serum calcium level of 17 mg/dl. A four-dimensional computed tomography (4D CT) of the neck was done, which showed few arterially enhancing nodular lesions in the right paratracheal and retrotracheal location at the level of thoracic inlet showing washout in delayed images suggestive of recurrent/residual parathyroid lesions. A technetium-99 m methoxyisobutylisonitrile (Tc-99 m MIBI) scan was done, and the planar neck anterior early images showed an area of increased radiotracer uptake in the right lower neck region with persistent uptake in the delayed images. Single photon emission computed tomography/ computed tomography (SPECT/CT) images showed a soft-tissue lesion in the right paratracheal region at the level of C7 vertebra showing increased radiotracer uptake suggestive of a recurrent/residual parathyroid lesion. Exploration and excision of the recurrent parathyroid mass was planned, and the right paratracheal mass with nodes above the aortic arch along with the subcutaneous and intramuscular lesions were excised. Postoperative serum calcium was 7.8 mg/dl, and serum iPTH was 135 pg/ml. Histopathological examination of the excised tissue showed the features of parathyroid carcinoma. Thus, Tc-99 m MIBI scan and 4D CT were critical in evaluating this case of parathyroid carcinoma with recurrent hyperparathyroidism and planning its management.

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Effect of parathyroid hormone levels on the functional capacity and pulmonary function of patients on dialysis

Abstract Introduction: Chronic kidney disease is characterized as the gradual loss of kidney function, with patients on dialysis experiencing a decline in functional capacity and pulmonary function. One of the non-traditional risk factors is parathyroid hormone (PTH), which influences metabolism and the status of the disease. Objective: Assess the effect of parathyroid hormone levels on functional capacity and pulmonary function in patients on dialysis. Method: Cross-sectional study with hemodynamically stable dialysis patients of both sexes, aged 18 to 59 years, who did not gain more than 2.5kg between dialysis sessions. Two groups were created according to PTH blood levels: PTH (A), with values outside the normal range, and PTH (C), who exhibited normal levels of the hormone. Pulmonary function (PF) was assessed by spirometry and functional capacity (FC) via the six-minute walk test (6MWT). Results: The PTH A group displayed a negative association between PTH levels and PF, based on the values obtained for the spirometric variables forced expiratory volume in 1 second (FEV1) (r = -0.54) and forced vital capacity (FVC) (r= -0.69). The average distance walked by the PTH (C) group was 343.85 ± 98.14 meters. Conclusion: The results suggest that high PTH levels have a negative effect on the PF of patients on dialysis.

Post-menopausal osteoporosis: do body composition, nutritional habits, and physical activity affect bone mineral density?

Aim: to evaluate the effect of body composition, nutritional habits (NH), and physical activity (PA) levels on bone mineral density (BMD) in osteoporotic postmenopausal women (OPW). Subjects and method: the demographic characteristics, anthropometric measurements, PA status, information on NH, some biochemical findings, and BMD measurements of 100 OPWs were evaluated. Results: in this study, 48 % of the women were classified as obese. The obese women were found to have lower vitamin D levels and higher parathyroid hormone levels than those of the over-weight women. A positive correlation was found between body mass index and L1L4, L2L4, and femur BMD (r = 0.268, p < 0.001; r = 0.241, p < 0.01; r = 0.369, p < 0.001, respectively). There was a significant decrease in L1L4 and femur BMD with increasing age (r = -0.224, p < 0.05; r = -0.366, p < 0.001, respectively). Femur BMD showed a positive correlation with duration (hours/week) and frequency of PA (days/week). According to the logistic regression analysis, body weight, daily tea consumption, and PA were positively associated with femur BMD, while advanced age, the age of menarche, salt and coffee consumption, and postmenopausal fracture status were negatively associated. Conclusion: we observed that body weight, some nutritional factors, and active lifestyle have seemed to effect BMD in OPWs. An adequate, balanced nutrition maintaining the ideal weight, and regular physical activity may improve bone health in OPWs.

The Association Between Hyperparathyroidism and Ischemic Stroke Subtypes

Background: Up to date, a substantial amount of research has remarked on the potential role of parathormone (PTH) in the development of subclinical and clinical vascular diseases. However, the association between the hyperparathyroidism and cerebrovascular disease has rather been underestimated in the literature. Herein, we aimed to investigate the association between serum PTH levels and ischemic stroke. Methods: Serum PTH levels were measured in all patients with ischemic stroke who were hospitalized in the Yozgat City Hospital between January 1, 2017 and January 1, 2019. Clinical and demographic findings were retrospectively evaluated via computer-based patient record system of Yozgat City Hospital (AKGUN). Results: Overall, 158 patients with ischemic stroke with a median age of 71.5 ± 11.5 were enrolled in this study. Parathyroid hormone was found to be high in 31 of the patients (19.6%). The stroke subtype of extracranial atherosclerosis was found to be more common in the group of patients with a high level of PTH (12%/3%; P = 0.008). Remarkably, logistic regression analyses also confirmed that high PTH level was a significant variable in the determination of the stroke subtype of extracranial atherosclerosis (P = 0.024). Conclusions: We have found a high rate of hyperparathyroidism in our group of patients with ischemic stroke. Remarkably, the elevation of PTH was found to be significantly associated with the ischemic stroke subtype of extracranial atherosclerosis. Clarification of these results in the future large-scale studies may provide crucial perspectives regarding our understanding of the pathophysiology of some subtypes of ischemic stroke and potentially lead to a large public health implication in this area. J Neurol Res. 2020;10(1):7-12 doi: https://doi.org/10.14740/jnr564

Impact of altered dietary calcium-phosphorus ratio caused by high-phosphorus diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal arteries.

This study aimed to establish a rat chronic kidney disease (CKD) model by studying the effects of a high-phosphorus diet in rats that had undergone partial ligation of the renal arteries (RL). Separate groups of 10-week-old male Slc:Sprague-Dawley rats underwent RL and were fed diets with varying phosphorous levels for a period of 48 days. A marked suppression of body weight gain necessitating humane euthanization occurred on day 28 in rats that had undergone RL and were given high-phosphorus feed. By contrast, the group of intact animals on a high-phosphorus feed exhibited a slightly decreased body weight gain from day 21 and survived until scheduled euthanization. In rats with RL, hematological, blood biochemical, and histopathological analyses demonstrated the presence of CKD-like conditions, particularly in the group that were fed a high-phosphorus diet. Hyperphosphatemia and hypocalcemia were induced by a high-phosphorus diet in both the RL and intact groups, both of which had high levels of FGF23 and parathyroid hormone in the blood. Rats with RL on a high-phosphorus diet showed decreased hematopoiesis by the hematopoietic cell area being narrower in the medullary cavity, proliferation of mesenchymal cells and osteoblasts/osteoclasts, and expansion of the osteoid area, a furthermore generalized vascular lesions, such as calcification, were observed. These findings demonstrate that the partial ligation of the renal arteries combined with a calcium–phosphorus imbalance induced by a high-phosphorus diet serves as an animal model for CKD-like conditions accompanied by bone lesions, helping to elucidate this clinical condition and its underlying molecular mechanisms.

CLINICAL MANIFESTATIONS OF PARATHYROID CANCER IN 29 YEARS OLD MAN

Parathyroid cancer is an extremely rare cause of primary hyperparathyroidism, accounting less than 1% of cases. The neoplasm is detected in people 40-50 years old. Ratio of men and women is 1: 1, in contrast to hyperparathyroidism caused by adenoma of epithelial bodies, when there are 3-4 times more women than men among the patients. Due to the rarity of this disease, surgeons and morphologists may have difficulties in verification of the tumor. Distinctive features of the course of the disease include the extremely rapid progression of bone changes, the development of hypercalcemic crises with a high level of blood calcium and serum parathyroid hormone. Radical surgery involves the removal of malignant parathyroid tumor in a single block with the ipsilateral thyroid gland, as well as paratracheal lymph nodes. The aim of investigation is to show a rare observation of bone manifestations of parathyroid cancer. Material and methods. Parathyroid cancer was diagnosed in 2 (0.7%) of 283 patients with primary hyperparathyroidism, operated in the Center of Endocrine Surgery. Male 29 years old was operated on in January 2016. Disease duration was about 2 years. The clinical picture was characterized by multiple bone fractures, generalized cystic osteodistorofy, renal failure, severe electrolyte disorders, cachexia. The diagnosis was confirmed by high values of total calcium and blood parathyroid hormone. The patient underwent removal of the parathyroid tumor, during the histological and immunohistochemical study of which parathyroid cancer was verified. The patient was able to sit on his own after 3 months, get up with support after 6 months and walk with the help 10 months later after the operation. In May 2017 an increase of parathyroid hormone to 1900 pg / ml was detected with a normal value of blood calcium, which indicates recurrence of parathyroid cancer. Findings. The high grade of the disease is due to both the aggressive course of parathyroid cancer and the late diagnosis.

Metabolic Disturbance in Women with Polycystic Ovary Syndrome and its Impact on Bone Turnover

Background: Insulin resistance and abdominal obesity are main characteristics of polycystic ovary syndrome, women with this syndrome at high risk for prolong term metabolic disorders. Obesity, insulin resistance, and hyperinsulinemia affect the hormones that control calcium homeostasis. Lower levels of serum vitamin D and higher levels of serum parathyroid hormone were found in women with polycystic ovary syndrome. However, high levels of parathyroid hormone can reduce bone mineral density and increase bone turnover. Objectives: The present study aimed to measure the parameters of bone metabolism including parathyroid hormone, calcium, and phosphorous in serum of women with polycystic ovary syndrome and compare their levels with healthy controls. Also, investigate the possible impact of metabolic alterations in polycystic ovary syndrome on bone turnover. Material and Method: This case-control study included 82 women from 20 to 37 years of age. All women were selected from Infertility Center in Baghdad Teaching Hospital during the period from 1 June 2019 to 30 August 2019. Women were divided into two groups: group (1) involved 42 women with polycystic ovary syndrome and group (2) involved 40 healthy women (act as controls). Each Serum specimen was analyzed for the measuring of parathyroid hormone, calcium, phosphorous, fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance (HOMA-IR). Results: Significantly higher serum levels of parathyroid hormone, calcium,fasting insulin, and fasting glucose with lower levels of serum phosphorous in women with polycystic ovary syndrome as compared with healthy women. In addition, significant positive correlation was found between serum parathyroid hormone and waist circumference (r=0.609, p=0.00001) as well as between serum parathyroid hormone and HOMA-IR (r= 0.781, p=0.00001). Conclusion: The metabolic disturbance found in polycystic ovary syndrome tend to support the relation between this syndrome and defective bone metabolism. High prevalence of obesity and high levels of insulin, HOMA-IR, and parathyroid hormone were found in women with this syndrome which in turn affect bone turn over. Thus, women with polycystic ovary syndrome are at risk for the development of metabolic bone disease.

Markers of mineral metabolism and vascular access complications: The Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study.

Vascular access dysfunction is a major cause of morbidity in patients with end-stage renal disease (ESRD) on chronic hemodialysis. The effects of abnormalities in mineral metabolism on vascular access are unclear. In this study, we evaluated the association of mineral metabolites, including 25-hydroxy vitamin D (25(OH)D) and fibroblast growth factor-23 (FGF-23), with vascular access complications. We included participants from the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study who were using an arteriovenous fistula (AVF; n = 103) or arteriovenous graft (AVG; n = 116). Serum levels of 25(OH)D, FGF-23, parathyroid hormone (PTH), calcium, phosphorus, C-reactive protein (CRP) and interleukin-6 (IL-6) were assessed from stored samples. Participants were followed for up to 1 year or until a vascular access intervention or replacement. A total of 24 participants using an AVF and 43 participants using an AVG experienced access intervention. Those with 25(OH)D level in the lowest tertile (<11 ng/mL) had an increased risk of AVF intervention compared to those with higher 25(OH)D levels (adjusted relative hazard [aHR] = 3.28; 95% confidence interval [CI]: 1.31, 8.20). The highest tertile of FGF-23 (>3750 RU/mL) was associated with greater risk of AVF intervention (aHR = 2.56; 95% CI: 1.06, 6.18). Higher PTH was associated with higher risk of AVF intervention (aHR = 1.64 per SD of log(PTH); 95% CI: 1.02, 2.62). These associations were not observed in participants using an AVG. None of the other analytes were significantly associated with AVF or AVG intervention. Low levels of 25(OH)D and high levels of FGF-23 and PTH are associated with increased risk of AVF intervention. Abnormalities in mineral metabolism are risk factors for vascular access dysfunction and potential therapeutic targets to improve outcomes.

Repeated epistaxis caused by primary hyperparathyroidism with multiple brown tumors: One case report

To report the clinical, imaging and pathological feature of a case of primary hyperparathyroidism(PHPT) with multiple brown tumors whose complain was repeated epistaxis, and to conduct a retrospective analysis with relevant literatures. A postmenopausal middle-aged woman, with a history of joint pain, fracture, and kidney stone which were neglected due to the lack of specificity of symptoms for years, went to hospital due to repeated epistaxis. Laboratory results showed high blood calcium, hypophosphatemia, alkaline phosphatase(ALP), and parathyroid hormone(PTH) levels, as well as increased urinary calcium. Imaging examination showed systemically multiple brown tumors and extensive osteoporosis. Meanwhile an abnormal mass was found behind the right thyroid. Taking all findings into account, the diagnosis was made with PHPT, and the histopathology further confirmed that the lesion was a parathyroid adenoma. This case seems to be a rare case of multiple brown tumor caused by parathyroid adenoma, which compressed and destructed nasal blood vessels, thus induced a repeated nasal discharge. After resection of parathyroid adenoma, the patient experienced a transient hypocalcemia and PTH level elevation. After 5-month follow up, part of the brown tumors spontaneously regressed, bone density increased, and her clinical symptoms were mostly relieved. Key words: Primary hyperparathyroidism; Parathyroid adenoma; Brown tumor; Epistaxis

Giant parathyroid adenoma: a case report and review of the literature

BackgroundGiant parathyroid adenoma is a rare type of parathyroid adenoma defined as weighing > 3.5 g. They present as primary hyperparathyroidism but with more elevated laboratory findings and more severe clinical presentations due to the larger tissue mass. This is the first reported case of giant parathyroid adenoma from the Middle East.Case presentationA 52-year-old Indian woman presented with a palpable right-sided neck mass and generalized fatigue. Investigations revealed hypercalcemia with elevated parathyroid hormone and an asymptomatic kidney stone. Ultrasound showed a complex nodule with solid and cystic components, and Sestamibi nuclear scan confirmed a giant parathyroid adenoma. Focused surgical neck exploration was done and a giant parathyroid adenoma weighing 7.7 gm was excised.ConclusionsGiant parathyroid adenoma is a rare cause of primary hyperparathyroidism and usually presents symptomatically with high calcium and parathyroid hormone levels. Giant parathyroid adenoma is diagnosed by imaging and laboratory studies. Management is typically surgical, aiming at complete resection. Patients usually recover with no long-term complications or recurrence.

Hepatitis B virus vaccine immune response and mortality in dialysis patients: a meta-analysis.

We performed a systematic review and meta-analysis to examine factors associated with HBV immune response in dialysis patients, and the association between the immune response to the HBV vaccine and mortality. Electronic databases were searched for studies of dialysis patients that compared the characteristics of HBV vaccine responders and non-responders. Mortality was also analyzed according to the vaccine immune response (defined by hepatitis B surface antibody titer > 10mIU/mL). Random-effects model meta-analyses were performed to compute a weighted mean difference (WMD), a pooled odds ratio (OR), and a pooled risk ratio (RR) between groups. We identified 61 studies with a total of 6628 dialysis patients who completed the course of HBV vaccination, 4582 responders (69%) and 2046 non-responders (31%). By meta-analysis, relative to non-responders, HBV vaccine responders had a higher dialysis adequacy as measured by Kt/V (WMD 0.08, P < 0.001), a higher serum albumin (WMD 0.12 gm/dL, P < 0.001), a higher normalized protein catabolic rate (WMD 0.12 gm/kg/day, P = 0.001), a higher hemoglobin (WMD 0.15 gm/L, P = 0.03), and a higher parathyroid hormone level (WMD 44pg/mL, P = 0.004). HBV vaccine responders were younger (WMD - 4.68years, P < 0.001), had been on dialysis for longer (WMD 2.60months, P < 0.001), were less likely to have diabetes mellitus (pooled OR 0.65, P < 0.001), and were less likely to carry the human leukocyte antigen (HLA) DR3 (pooled OR 0.38, P = 0.01). Compared to non-responders, HBV vaccine responders had lower risk for all-cause mortality (pooled RR 0.64, P < 0.001), and lower risk for cardiovascular-related mortality (pooled RR 0.74, P = 0.02). In dialysis patients, the lack of immune response to the HBV vaccine is associated with older age, diabetes mellitus, HLA-DR3 status, shorter time on dialysis, lower nutritional status, lower hemoglobin, lower PTH level, and lower dialysis adequacy. Tackling some of these modifiable factors might improve the HBV vaccine immune response.

Treatment of hyperphosphatemia: the dangers of high PTH levels.

The control of secondary hyperparathyroidism (SHPT) in pediatric chronic kidney disease is of utmost importance. Even though parathyroid hormone (PTH) is an important biomarker of mineral and bone disorders associated to CKD (CKD-MBD), calcium, phosphate, alkaline phosphatase, and vitamin D are also crucial and should be assessed together. In pediatric dialysis, high PTH levels have been associated with impaired longitudinal growth, bone disease, cardiovascular comorbidities, left ventricular hypertrophy, anemia, and even mortality (when PTH levels were above 500 pg/mL, i.e., 8.3-fold the upper normal limit (UNL)). As such, high PTH levels are for sure deleterious, but too low PTH levels have also been shown to impair growth and to promote vascular calcifications because of the underlying adynamic bone. This manuscript is part of a pros and cons debate for keeping PTH levels within the normal range in pediatric CKD, focusing on the pros. High bone turnover lesions can occur at lower PTH levels than "current" guidelines would suggest; thus, PTH alone is not a good predictor of the underlying osteodystrophy. PTH results can vary locally depending on the assay. Existing guidelines for PTH targets are conflicting and based on a very little evidence. However, the 120-180 pg/mL (2- to 3-fold the UNL) range is common to most of the guidelines; it seems to be a reasonable target in children undergoing dialysis, even though it does not correspond to "normal" PTH levels. As always, the philosophy of PTH levels in pediatric dialysis may be balanced, i.e., "not too low, not too high, and keep phosphate under control."

Independent association of vitamin D and insulin resistance in obstructive sleep apnea

BackgroundVitamin D insufficiency and/or high levels of parathyroid hormone (PTH) seem to be associated with abnormal glucose metabolism, which is frequent in obstructive sleep apnea (OSA). The purpose of this study was to investigate vitamin D and PTH concentrations in OSA, and to explore potential links between vitamin D, PTH and insulin resistance (IR). MethodsA total of 112 subjects with suspected OSA were recruited consecutively, and evaluated by polysomnography (PSG) to determine the number of apnea and hypopnea episodes per hour of sleep (apnea/hypopnea index: AHI). OSA was diagnosed for AHI≥5. Average (APO2) and minimum pulse oxygen saturation (MPO2) were assessed during PSG as indices of nocturnal hypoxemia. After overnight fasting, a standard 75g oral glucose tolerance test was performed. Serum 25-hydroxyvitamin D, PTH, fasting glucose and fasting insulin were also measured. Homeostasis model assessment (HOMA) was used to evaluate IR: HOMA-IR=fasting plasma insulin×fasting plasma glucose/22.5, with “insulin resistance” defined as HOMA-IR>2.7. ResultsPatients were classified into 4 groups according to AHI: control group (AHI<5, n=8), mild OSA (5≤AHI<15, n=18), moderate OSA (15≤AHI<30, n=33), and severe OSA (AHI≥30, n=53). They were also classified, according to HOMA-IR, as insulin-resistant (HOMA-IR>2.7, n=59) or non-insulin-resistant (HOMA-IR≤2.7, n=45). There were no significant differences in vitamin D or PTH levels between AHI groups. HOMA-IR was significantly higher in severe OSA than in controls (P=0.019). Vitamin D concentration correlated negatively with AHI (r=−0.242, P=0.01) and with HOMA-IR (r=−0.338, P<0.001). PTH concentration correlated negatively with vitamin D concentration (P<0.001), but not with AHI or HOMA-IR. HOMA-IR correlated positively with AHI (r=0.368, P<0.001) and negatively with MPO2 (r=−0.414, P<0.001). Finally, stepwise linear multivariate regression showed that vitamin D concentration (β=−0.209, P=0.014) and MPO2 (β=−0.221, P=0.011) were independently associated with HOMA-IR. ConclusionSubjects with severe OSA may have a low vitamin D level associated with increased risk of IR. Vitamin D was independently associated with IR in OSA. Vitamin D insufficiency may play a role in the pathogenesis of IR in OSA.

Dystrophic mineralization in uremic dogs: an update

ABSTRACT: Pathological mineralization is the abnormal deposition of minerals in body tissues, previously injured or not. In these lesions, in addition to calcium, other minerals can be found at lower concentrations. Classically, mineralization is divided into two types: dystrophic and metastatic. However, currently, there is no consensus among researchers on the type of mineralization that occurs in uremic dogs. The objective of this study was to elucidate the type of pathological mineralization that occurs in dogs with uremic syndrome through the correlation of biochemical examinations with gross and histopathological changes, given the existence of controversial information on this theme in the specialized literature. The Shapiro-Wilk, D’Agostino and Pearson tests were used to evaluate data normality distribution, and analysis of variance (ANOVA) was applied to compare the data between more than two groups. Additionally, the Dunnett’s multiple comparison test was used in the comparison between the Control Group (CG) and the Experimental Groups (G1, G2, and G3). Serum levels of urea, creatinine, total and ionized calcium, phosphorus, calcium-phosphorus product (CPP), parathyroid hormone (PTH), and albumin of 40 azotemic dogs with chronic kidney disease (CKD) were evaluated. Dogs were categorized by degree of azotemia (mild, moderate, and severe). Ionized hypocalcemia was observed in 97.5% (39/40) of the dogs, and no animals presented ionized hypercalcemia. Hyperphosphatemia was frequent (62.5%), especially in dogs with severe azotemia. PTH concentration increased with progression of azotemia, and high PTH levels were verified in 100% of the dogs with severe azotemia. CPP &gt;60mg2/dl2 was observed in 75% (30/40) of the dogs. Of the 29 dogs that died during the study period, 16 were necropsied. Soft tissue mineralization was observed in 93.7% (15/16) of these dogs at gross and histopathological evaluation (HE and Von Kossa), regardless of the degree of azotemia, in nine organs/tissues: kidneys (75%), lungs (50%), stomach (31.2%), heart (25%), larynx (25%), intercostal muscles (25%), aorta (6.2%), intestines (6.2%), and tongue (6.2%). In one animal, the serosa of all segments of the small intestine showed whitish, rough, irregular, multifocal plaques of varying sizes, confirmed by histopathology as dystrophic mineralization of the longitudinal outer muscular layer, which presented necrosis of coagulation and of the intestinal serosa. This intestinal lesion has not been described in dogs with uremic syndrome to date. In conclusion, the laboratory and histopathologic data previously described, especially regarding tissue and vascular mineralization, which occur in association with previous degenerative/necrotic lesions in the absence of hypercalcemia in dogs with CKD, assist with clarifying inconsistencies found in the existing literature. Therefore, conceptually, mineralization that occurs in uremic dogs should be considered dystrophic.

Dysregulation of calcium metabolism in type 1 myotonic dystrophy.

Patients with type 1 myotonic dystrophy (DM1) have a higher incidence of hypercalcaemia compared with the general population. The nature and effects of dysregulated calcium metabolism underpinning this phenomenon have not been fully characterised. To determine the characteristics of dysregulated calcium metabolism in patients with DM1 and its association with bone mineral density. A retrospective review of medical records of patients with DM1 attending a DM clinic at Logan Hospital, Brisbane, Queensland, between 2005 and 2018 and who had concurrent serum assays performed of corrected serum calcium, 25 hydroxyvitamin D, parathyroid hormone (PTH) and phosphate and for whom results were available for estimated glomerular filtration rate, bone mineral densitometry tests and urinary calcium clearance to creatinine clearance ratio (UCCR). Forty-four patients with DM1 (22 females, 22 males) were reviewed of whom 14 (32%) had elevated corrected serum calcium and inappropriate PTH. Another 10 patients (23%) had raised PTH with normocalcaemia. Eighteen of 19 (94.7%) patients with hypercalcaemia or high PTH level completed 24-h urinary calcium. All had UCCR ≤0.02. Twelve patients had UCCR <0.01. Seven of 44 (16%) had low 25 hydroxy vitamin D. All patients had normal estimated glomerular filtration rate. None was osteoporotic. One in three patients with DM1 was hypercalcaemic with unsuppressed PTH. Their clinical features and biochemical pictures resemble those of familial hypocalciuric hypercalcaemia (FHH) and raises the possibility that impaired activity of calcium-sensing receptors, due to abnormal splicing of the calcium-sensing receptor messenger RNA in DM1, causes a FHH-like syndrome ('pseudo-FHH of DM1').

The relationship between estimated glomerular filtration rate and urine m/creatinine ratio and parathyroid hormone in elderly Koreans.

This study aimed to assess the relationship between estimated glomerular filtration rate (eGFR), urine microalbumin/creatinine ratio (uACR), and parathyroid hormone (PTH) levels in elderly Korean men and women. Data were analyzed from 2880 adults (1262 men and 1618 women) aged ≥ 50years from the Fifth Korean National Health and Nutrition Examination Survey V-2 (KNHANES V-2). In men, after adjusting for related variables, the odds ratios (ORs) of the high PTH levels (PTH > 78.0ng/L) were significantly higher in the decreased eGFR group [eGFR < 60ml/min/1.73m2; 1.353 (95% confidence interval [CI], 0.989-1.851)], elevated uACR group [uACR ≥ 30mg/g; 1.804 (95% CI, 1.004-3.239)], and decreased eGFR plus elevated uACR group [eGFR < 60ml/min/1.73m2 and uACR ≥ 30mg/g; 2.158 (95% CI, 1.208-3.858)] relative to the normal group (eGFR ≥ 60ml/min/1.73m2 and uACR < 30mg/g). In women, after adjusting for related variables, the ORs of the high PTH levels were significantly higher in the decreased eGFR group [1.585 (95% CI, 0.911-2.760)], elevated uACR group [1.645 (95% CI, 1.127-2.400)], and decreased eGFR plus elevated uACR group [2.934 (95% CI, 1.267-6.795)] relative to the normal group. In conclusion, PTH was positively associated with an increase in uACR in elderly Korean men and women but was not associated with a decrease in eGFR. In addition, PTH increased greatly when both a decrease in eGFR and increase in uACR appeared simultaneously.