Blood Phosphate Research Articles

P0697IDENTIFYING PATIENTS SUITABLE FOR PRIMARY CARE FOLLOW-UP IN A LARGE NON-DIALYSIS CKD COHORT

Abstract Background and Aims Chronic Kidney Disease (CKD) is a growing public health concern, affecting approximately 13.4% of the global population. Due to the rising burden of CKD and its economic cost, there is a pressing need to identify the risk factors which can predict CKD progression and thereby enable us to manage these patients in the community under primary care follow-up. Our study aimed to identify risk factors that can predict outcomes in patients with stable CKD. Method The study was conducted on patients recruited in the Salford Kidney Study, (a large prospective CKD database recruiting patients since 2002). From a total of 2952 recruited between 2002 and the year 2016, 1023 patients with a diagnosis of hypertension, diabetes or pyelonephritis were sampled for this study. Based on the annual rate of progression of estimated glomerular filtration rate (delta eGFR), 140 patients were identified as stable CKD patients (delta eGFR -0.50 and 0.50 ml/min/1.73m2/year). The characteristics of this group was compared with 277 rapid progressors (RP) (delta eGFR<-3) and 212 patients in the improved group (delta eGFR>0.50). Negative predictive value analysis was performed on all patients with an outcome of a GFR < 30ml/min/1.73m2. Results Stable CKD patients had a significantly higher age compared to RP ( 69 vs 62, p<0.001). Further patients in the stable CKD group had a comparatively lower median blood pressure (141.5 vs 137, p<0.001). Other factors which were identified as risk factors for rapid progression included history of diabetes (177 vs 73, p=0.021), low albumin (41 vs 44, p<0.001), raised urine protein creatinine ratio (154.6 vs 18.8, p<0.001) and phosphate (1.24 vs 1.12, p<0.001) (Table-1). Comparing outcomes showed rapid progression reached ESRD (172 vs 18, p<0.001) but no significant difference in mortality (93 vs 55, p=0.25). Characteristics that were statistically different for stable CKD patients in this large cohort were identified: age, systolic blood pressure, diastolic blood pressure, diabetes, albumin, UPCR and phosphate. NPV analysis did not identify reveal any clear predictors for progression in stable CKD patients. Conclusion Several risk factors were identified to distinguish between stable, rapid and improved group. NPV did not identify any predictors in stable group. Further risk prediction models incorporating biomarkers are warranted to identify factors that can guide prognosis thereby stable CKD patients can be managed in the community.

SAT-358 Hypercalcemia-Induced Altered Mental Status as the Primary Manifestation of Classic Hodgkin Lymphoma

Hodgkin lymphomas (HL) are lymphoid neoplasms formed by a conglomerate of malignant Hodgkin/Reed-Sternberg cells with heterogeneous non-neoplastic inflammatory cells. Classic HL (cHL), one of two major subtypes, comprises 90% of all cases. HL typically presents as asymptomatic adenopathy or mass on chest imaging; constitutional symptoms (unintentional weight loss, night sweats, fever) occur in approximately 40% of cases. Though hypercalcemia is not uncommon in HL due to increased production of 1,25(OH)2D or, less commonly, direct bony involvement, it is unusual for severe hypercalcemia and its related symptoms to be the primary reason for presentation such as in our case below.An 87-year-old man was admitted to our institution with three days of increasing agitation and confusion in the context of several weeks of forgetfulness and decline in his daily activities. He previously lived robustly independently. His past medical history included atrial fibrillation, hyperlipidemia, and benign prostatic hyperplasia. His home medications included metoprolol, apixaban, atorvastatin, tamsulosin, finasteride and a multivitamin.Laboratory evaluation revealed serum calcium 17.5 mg/dL and serum creatinine 3.0 mg/dL (eGFR 20 mL/min/1.73m2). Complete blood count, phosphate, magnesium and alkaline phosphatase were normal. Intravenous fluids and later pamidronate improved his calcium to the 11–13 mg/dL range. Endocrinological workup revealed PTH 7 pg/mL (nl 15–65 pg/mL), 25(OH)D 15 ng/mL (nl 20–80 ng/mL), PTHrP 0.8 pmol/L (nl <2.0 pmol/L) and 1,25(OH)2D 57 pg/mL (nl 18–64 pg/mL). Serum protein electrophoresis showed no abnormalities and lactate dehydrogenase was 230 U/L (nl 125–250 U/L)Computed tomography (CT) of his abdomen revealed non-specific prominent mesenteric lymph nodes. Neck CT did not show any abnormal cervical or supraclavicular lymphadenopathy. Chest CT did not show any mediastinal masses, abnormal lymphadenopathy, or findings consistent with silicosis (he had a 15-year history of masonry and brick-laying). Bone scan showed asymmetric uptake in two areas of his femurs, with xrays revealing subcortical scleroic lesions. Patient declined inpatient bone marrow biopsy, and was empirically started on prednisone, with rapid improvement in calcium to 9.6 mg/dL and return to his baseline mental status. He eventually accepted and underwent bone marrow biopsy as an outpatient, which revealed marrow involvement by classic Hodgkin lymphoma. The patient was started on a regimen of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine, with excellent clinical response.This case illustrates an atypical, hypercalcemia-driven initial presentation of Hodgkin’s lymphoma. It also exhibits the hallmark “inappropriate normal” 1,25(OH)2D which, in the context of hypercalcemia and low PTH, suggests extrarenal (i.e. PTH-independent) production of 1,25(OH)2D.

Hyperphosphatemic Tumoral Calcinosis: Pathogenesis, Clinical Presentation, and Challenges in Management.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare and disabling disorder of fibroblast growth factor 23 (FGF23) deficiency or resistance. The disorder is manifest by hyperphosphatemia, inappropriately increased tubular reabsorption of phosphate and 1,25-dihydroxy-Vitamin D, and ectopic calcifications. HFTC has been associated with autosomal recessive pathogenic variants in: (1) the gene encoding FGF23; (2) GALNT3, which encodes a protein responsible for FGF23 glycosylation; and (3) KL, the gene encoding KLOTHO, a critical co-receptor for FGF23 signaling. An acquired autoimmune form of hyperphosphatemic tumoral calcinosis has also been reported. Periarticular tumoral calcinosis is the primary cause of disability in HFTC, leading to pain, reduced range-of-motion, and impaired physical function. Inflammatory disease is also prominent, including diaphysitis with cortical hyperostosis. Multiple treatment strategies have attempted to manage blood phosphate, reduce pain and inflammation, and address calcifications and their complications. Unfortunately, efficacy data are limited to case reports and small cohorts, and no clearly effective therapies have been identified. The purpose of this review is to provide a background on pathogenesis and clinical presentation in HFTC, discuss current approaches to clinical management, and outline critical areas of need for future research.

Contribution of Bone Tissue to Regulation of Calcium and Phosphate Metabolism. Role of FGF23 and Klotho Protein.

Bone tissue actively contributes to the regulation of systemic homoeostasis, and particularly the maintenance of calcium-phosphate balance. The parathyroid hormone-vitamin D feedback axis is balanced by the recently discovered bone-FGF23-kidney hormonal axis. An active complex consisting of FGF23, a receptor and Klotho protein blocks phosphate reabsorption in the proximal tubules, increasing urine phosphate levels and decreasing blood phosphate levels. Mutations of the gene mediating FGF23 transcription lead to a number of diseases, examples including autosomal dominant hypophosphataemic rickets. Klotho protein is a cofactor for FGF23 displaying cardio-, vaso- and nephroprotective activity. It increases calcium reabsorption in the kidneys and inhibits phosphate reabsorption. It also exerts antioxidative and anti-insulin effects and inhibits tissue calcification and apoptosis. As an inhibitor of bone resorption, osteoprotegerin becomes an important contributor to bone remodelling, while RANK/RANKL signalling inhibition is used in the treatment of postmenopausal osteoporosis. Osteocalcin plays an important role in energy metabolism in the human body. Sclerostin exerts a strong catabolic effect on bone tissue. Newly identified contributors to the regulation of calcium and phosphate homoeostasis suggest that bone tissue plays a complex role in the systemic metabolism.

Vitamin D and fibroplastic processes in myocardium in spontaneously hypertensive rats with initial kidney dysfunction

Background. Even a moderate decrease in glomerular filtration rate leads to an increased risk of cardiovascular diseases (CVD), which is the leading cause of mortality in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) underlies CVD development in renal dysfunction. The prevalence of LVH in patients with CKD stages 2–4 is 50–70 % and reaches 95 % at the beginning of dialysis, which significantly exceeds the number of cases in general population (15–21 %). Common hemodynamic factors associated with chronic kidney damage —hypertension (HTN), activation of the renin-angiotensin system, anemia, fluid and sodium retention, and others largely explain the high prevalence of LVH among patients with CKD. Nevertheless, the existence of additional non-hemodynamic mechanisms of myocardial remodeling (MR) is evident.Objective. To investigate the associations between the MR physiological/histological characteristics and laboratory parameters of calcium-phosphate metabolism in the initial stages of experimental CKD. Design and methods. Four groups of spontaneously hypertensive rats (SHR) were studied (n = 35): 3/4 nephrectomized rats (Nx) one month exposed after surgery (Nx(1), n = 9), 5/6 Nx two months after surgery (Nx(2), n = 8), sham operated rats one month after surgery (SO(1), n = 9) and two months after surgery (SO(2), n = 9). Myocardial mass index (MMI), systolic blood pressure (BP), proteinuria, creatinine (Cr) concentration, total calcium (Ca) and inorganic phosphate (Pi), 25-OH vitamin D (25OHD) and parathyroid hormone (PTH) in serum, myocardial morphology were studied in all experimental animals.Results. The models corresponded to the 1–3 stages CKD. There were no significant changes in serum total Ca (p = 0,066), Pi (p = 0,051) and PTH (p = 0,015) concentrations, the level of 25OHD was significantly lower in Nx(2) rats vs control (p = 0,015). MMI increased in all nephrectomized rats (p = 0,008). The cardiomyocytes (CM) thickness increased in Nx(1) and Nx(2) animals compared to the corresponding controls (p = 0,010, p = 0,002). A significant increase in interstitial (IF) and perivascular (PF) fibrosis occurred in Nx(2) rats with more damaging influence (p = 0,017, p = 0,004). CM thickness, IF and PF increased with the elevation of BP (r = 0,39, p = 0,038, r = 0,47, p = 0,026, r = 0,49, p = 0,031) and serum Cr (r = 0,68, p = 0,001, r = 0,61, p = 0,003, r = 0,69, p = 0,001), and the decrease in serum 25OHD concentration (r = –0,045, p = 0,047, r = –0,50, p = 0,020, r = –0,52, p = 0,012). Multiple linear regression analysis showed, that 25OHD is an independent predictor of myocardial fibrosis (IF: β = –0,38 ± 0,18, p = 0,047, PF: β = –0,34 ± 0,15, p = 0,032).Conclusions. The initial stages of CKD accompanied with HTN are associated with serum 25OHD concentration decrease CM hypertrophy and myocardial fibrosis. The CM growth is an earlier event in relation to the interstitial fibrosis. The obtained data suggest a possible role of vitamin D deficiency in the development of myocardial fibrotic lesions.

SUN-183 DIURNAL RHYTHMS OF SERUM PHOSPHATE IN HEMODIALYSIS PATIENTS

Hyperphosphatemia is a common complication of chronic kidney disease that associates with increased risks for all-cause and cardiovascular mortality. Phosphate binder therapies are an efficacious strategy to reduce serum phosphate levels. In clinical practice, the decision on binder therapy initiation and dosage is typically determined from the pre-dialysis blood phosphate level. The healthy population exhibits diurnal rhythms in blood phosphate regulation with fluctuations of more than 1 mg/dL throughout the day (Vervloet et al. 2017). Whether such circadian rhythms persist in dialysis patients and whether the fluctuation pattern is different to that of healthy individuals is only partially understood. We profiled the diurnal rhythms of serum phosphate levels in a population of chronic hemodialysis (HD) patients. We used data from adult in-center HD patients (age ≥18 years) with HD vintage >90 days who were treated at a large dialysis organization in the United States in 2018. We computed the mean pre-dialysis blood phosphate levels at the time of the start of each HD treatment in 2-hour periods through 24 hours for the entire population, as well as stratified by phosphate binder use. Time of HD initiation was treated as time-varying exposure, allowing patients to switch time groups if they had pre-dialysis blood draws in multiple time periods of the day. The mean phosphate levels based on the time of the day with 95% confidence limits were plotted and we used a nonparametric smoothing spline model to fit data and calculate the trajectories of phosphate levels throughout the day. A total of 158,156 adult HD patients were included in the analysis. Patients were: mean age 62.8±14.3 years, 57.1% male, 58.2% white race, 15.8% Hispanic ethnicity, 41.9% with diabetes, 19.6% with congestive heart failure, and HD vintage 1509±1288 days. Mean pre-dialysis albumin was 3.8±0.4 g/dL and phosphate was 5.4±1.5 mg/dL for the population. Overall, mean phosphate levels were found to vary remarkably by 0.9 mg/dL throughout the day, with nadir levels from 0900 to 1100 hours (5.3±1.6 mg/dL), followed by a rise to a mid-day peak from 1700 to 1900 hours (5.8±1.8 mg/dL), and the highest levels had a peak time from 2300 to 0100 hours (6.2±2.1 mg/dL) (Figure 1a). Similar fluctuations and phosphate levels were observed among patients using a phosphate binder (n=143,364), however, patients not using a phosphate binder (n=14,792) exhibited absolute values of mean phosphate levels that were consistently about 1 mg/dL lower at every timepoint (Figure 1b). All patients treated with HD from 2300 through 0300 hours (n=315) were taking a phosphate binder. Our results suggest phosphate levels have a diurnal variation of about 1 mg/dL in patients on chronic hemodialysis, characterized by a nadir in the morning, a mid-day peak and a larger nocturnal peak. Further adjusted analyses are needed to confirm these results that account for patient characteristics, phosphate binder dose and duration of use.

Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival

Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transporters are required and whether hormonal changes due to hypophosphatemia contribute to muscle function is unknown. To address these questions we generated a series of conditional knockout mice lacking one or both house-keeping Pi transporters Pit1 and Pit2 in skeletal muscle (sm), using the postnatally expressed human skeletal actin-cre. Simultaneous conditional deletion of both transporters caused skeletal muscle atrophy, resulting in death by postnatal day P13. smPit1−/−, smPit2−/− and three allele mutants are fertile and have normal body weights, suggesting a high degree of redundance for the two transporters in skeletal muscle. However, these mice show a gene-dose dependent reduction in running activity also seen in another hypophosphatemic model (Hyp mice). In contrast to Hyp mice, grip strength is preserved. Further evaluation of the mechanism shows reduced ERK1/2 activation and stimulation of AMP kinase in skeletal muscle from smPit1−/−; smPit2−/− mice consistent with energy-stress. Similarly, C2C12 myoblasts show a reduced oxygen consumption rate mediated by Pi transport-dependent and ERK1/2-dependent metabolic Pi sensing pathways. In conclusion, we here show that Pit1 and Pit2 are essential for normal myofiber function and survival, insights which may improve management of hypophosphatemic myopathy.

Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin D3 [1,25(OH)2D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography-mass spectrometry-based (LC-MS-based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase-mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury.

Vitamin D status of healthy coastal fishermen of Bangladesh

Background and objectives: Vitamin D deficiency is now a global concern. Industrialization, urbanization and the decreasing participation in outdoor activities, with consequent sunlight deprivation, are thought to be the key factors in the increasing prevalence of vitamin D deficiency among general population of many countries. It is presumed that healthy, adequately sun-exposed people should maintain adequate vitamin D levels. However, studies within this population are scarce. Hence, this study was conducted to find out the actual vitamin D status in healthy, adequately sun-exposed population living in coastal district of Bangladesh.&#x0D; Material and Methods: One hundred and forty healthy fishermen living in costal district of Cox’s Bazar (210 25' North, 910 59' East) of Bangladesh were enrolled in this study. Relevant data and blood samples were collected during August 2018, one of the months with lower zenith angle and higher UV index. Chemiluminescent micro-particle immunoassay (CMIA) was used to measure 25-hydroxy vitamin D3. Other relevant biochemical parameters measured were random blood glucose (RBG), serum creatinine, albumin, calcium, phosphate, alkaline phosphatase and intact parathyroid hormone (iPTH).&#x0D; Results: Mean vitamin D level of the study population was 27.04±7.20 ng/ml. Based on the cut off value of Endocrine Society, 70.7% of the study population had low vitamin D levels of which 26 (18.6%) and 73 (52.1%) were in vitamin D deficient (&lt;20ng/ml) and insufficient (20 – 29.99 ng/ml) categories respectively. Vitamin D level was normal in 41 (29.3%) subjects. There was no significant difference in iPTH level between groups with low and normal vitamin D levels (p&gt;.05, 95%CI= -5.68226, 1.21086).&#x0D; Conclusion: The unexpectedly high prevalence of vitamin D deficiency in this healthy and adequately sun-exposed population raises the question regarding the validity of the current cutoff value being used to assess the vitamin D status of Bangladeshi population. Future studies should be carried out to determine nation-specific, local cutoff values for vitamin D sufficiency.&#x0D; Ibrahim Med. Coll. J. 2019; 13(2): 35-39

Bone mineral density and its correlation with serum 25-hydroxyvitamin D levels in patients with hyperthyroidism.

ObjectiveThis study aimed to determine the association between 25-hydroxyvitamin D (25(OH)D) levels and bone mineral density (BMD) in patients with hyperthyroidism after undergoing treatment.MethodsA total of 120 patients with hyperthyroidism were selected as participants. Methimazole tablets were provided to all of the participants, with an initial dose of 20 mg/day and a maintenance dose of 2.5 mg/day for 1 year. Blood calcium, phosphate, parathyroid hormone (PTH), and thyroid hormone levels were assayed using an automatic biochemical analyzer. Levels of 25(OH)D and bone alkaline phosphatase (ALP) in serum were determined by enzyme-linked immunosorbent assay. BMD was measured using dual energy X-ray absorptiometry.ResultsSerum phosphorus, PTH, and 25(OH)D levels in patients with hyperthyroidism were significantly higher, and bone ALP and 24-hour urinary calcium levels were significantly lower after treatment compared with before treatment. BMD in patients with hyperthyroidism was significantly improved after treatment. In logistic regression analysis of BMD-related risk factors, bone ALP, PTH, and 25(OH)D levels were risk factors of BMD.ConclusionTreatment for hyperthyroidism should be supplemented with vitamin D and calcium, which have important clinical significance for adjusting bone metabolism and delaying the process of osteoporosis.

Assessment of Renal Functions and Lesions in Dogs with Serological Diagnosis of Canine Visceral Leishmaniasis

Background: Visceral leishmaniasis is a complex vector-borne disease caused by the protozoan Leishmania infantum. In urban centers of South America, where this zoonotic cycle occurs, dogs seem to be the main reservoirs and infection sources. Animals with canine visceral leishmaniasis (CVL) may have a wide clinical spectrum, and dogs are usually classified as asymptomatic, oligosymptomatic, and symptomatic. Several organs are affected in canine CVL, and renal involvement is often a determining factor in dog prognosis. Nevertheless, serum markers are slow to indicate loss of renal function. The aim of this studywas to evaluate kidney impairment in dogs diagnosed with CVL.Material, Methods &amp; Results: Blood and urine samples were collected from 45 dogs from Barra Mansa-RJ, and used for urinalysis, urine protein/creatinine (UPC) ratio, and serum concentrations of urea and creatinine. The animals were classified as symptomatic (42.2%), oligosymptomatic (37.8%), and asymptomatic (20.0%). Some alterations were found in the urine samples; pale-yellow color in 17.8%, low specific gravity in 6.7%, turbidity in 51.1%, proteinuria in 80%, occult blood in 46.7%, bilirubin in 8.89%, and glucose in 6.7% of the samples. According to the UPC ratio, 60% of dogs were proteinuric, and UPC &gt; 2.0 was high in symptomatic dogs. Azotemia was observed only in three dogs with CVL.Discussion: The majority of dogs presented one or more symptoms of CVL, as expected in an endemic area from Brazil. Pale-yellow urine was observed in some samples, and this change, when accompanied by the decreased urine specific gravity in dogs with CVL, suggests some degree of kidney disease. The presence of epithelial and red blood cells, leukocytes, bacteria, suspended mucus, and phosphate crystals that precipitate in alkaline urines could be associated, to some degree, with the urine turbidity found in the present study. The alkaline urine identified in some dogs could be related to the animals’ diet, but renal tubular acidosis (RTA) is another possible cause when referring to animals with CVL. The abnormal presence of bilirubin and glycosuria can be justified by liver damage and glomerular and tubular damage, respectively. Occult blood was found in the urine of almost half of the tested dogs, which occurred because of the presence of red blood cells in the urine sediment and hematuria in some animals, could be caused by tubular and glomerular lesions. The presence of granular and hyaline casts found in the samples reinforce the possibility of tubular injury. We found different levels of proteinuria; it was an important result, possibly caused by immune complex deposition in addition to tubular disease. Most tested dogs, including animals without clinical manifestation, were classified as proteinuric or borderline proteinuric, showing that the renal disease could be the only clinical manifestation of CVL and that it could progress from slight proteinuria to end-stage renal disease, resulting in chronic renal failure, which is the main cause of death. The UPC ratio &gt; 2.0 was significantly the more frequent finding in this study, mainly in symptomatic dogs. This result indicates a glomerular disease in these animals, reinforcing that the progression of renal disease follows the clinical progression of CVL. A few serum samples showed increased urea and creatinine levels, proving that azotemia is an uncommon finding in CVL-infected dogs. In conclusion, urinalysis helped in the early identification of renal injury in CVL-infected dogs, highlighting elements that reinforce the presence of tubular or glomerular lesions, or both, even in non-azotemic dogs. The high frequency of symptomatic dogs with UPC ratio &gt; 2.0 suggests a relationship between the progression of renal disease and the clinical progression of CVL.

Calcium and Phosphate Hormones: Vitamin D, Parathyroid Hormone, and Fibroblast Growth Factor 23.

1. Lisa Underland, DO* 2. Morri Markowitz, MD* 3. Robert Gensure, MD, PhD† 1. *Children’s Hospital at Montefiore, the University Hospital for Albert Einstein College of Medicine, Bronx, NY 2. †Tufts Medical Center, Tufts University School of Medicine, Boston, MA * 1,25-D: : 1,25-dihydroxyvitamin D 25-D: : 25-hydroxyvitamin D CaSR: : calcium-sensing receptor DMP1: : dentin matrix acidic phosphoprotein 1 FDA: : Food and Drug Administration FGF23: : fibroblast growth factor PTH: : parathyroid hormone PTHrP: : parathyroid hormone–related peptide Disorders of vitamin D, parathyroid hormone, and fibroblast growth factor 23 encompass both very rare and fairly common patient presentations in the pediatric population, and so understanding the differential diagnosis is important. After completing this article, readers should be able to: 1. Understand the basic interplay among vitamin D, parathyroid hormone, and fibroblast growth factor 23 in the maintenance of optimal calcium and phosphorous levels and bone health. 2. Understand the differential diagnosis and basic evaluation of hormonal disorders resulting in low calcium and/or phosphorous levels. 3. Understand the basics of presentation, pathophysiology, and treatment of these hormone disorders. Plasma calcium and phosphorous concentrations are regulated by 3 major players: hormonal vitamin D, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23). Understanding the interplay among them is essential for assessing calcium and phosphorous levels in children. This is especially important for pediatricians as they care for patients during the crucial times in bone formation and accrual as well as growth. This review focuses on the normal physiology as well as evaluation and treatment of the diseases associated with dysfunctions that result in too little calcium or phosphate in blood. ### Physiology: Vitamin D Production and Action Vitamin D is a precursor molecule to a critical hormone, calcitriol, involved in calcium and, to a lesser extent, phosphorus metabolism. It is not actually a vitamin because it can be produced in skin from 7-dehydrocholesterol by UV-B radiation. The product of this transformation is termed cholecalciferol or vitamin D3. This process is self-regulating, preventing vitamin D intoxication even in the setting of large amounts of sunlight exposure. A very similar compound, ergocalciferol (also called vitamin D2) is derived …

Metastatic Calcinosis Cutis Secondary to Selective Fibroblast Growth Factor Receptor Inhibitor: Rapid and Complete Regression after Blood Phosphate Normalization and Drug Withdrawal

Metastatic Calcinosis Cutis Secondary to Selective Fibroblast Growth Factor Receptor Inhibitor: Rapid and Complete Regression after Blood Phosphate Normalization and Drug Withdrawal

Occurrence regularity and risk factors of new-onset atrial fibrillation in early stage after brain and spinal surgery

Objective To explore the occurrence regularity and risk factors of new-onset atrial fibrillation in early stage after brain and spinal surgery of Neurosurgery Department so as to provide a basis for carrying out predictive nursing for high-risk population. Methods From March to June 2019, we selected 107 patients with brain or spinal surgery of Neurosurgery Department at a Class Ⅲ Grade A hospital in Beijing by convenience sampling. Data were collected including electrocardiogram of patients 12 hours after surgery, general information and clinical data. We analyzed the incidence and characteristics of atrial fibrillation, hospital stay as well as incidences of complications. Logistic regression model was used to analyze the risk factors. Results A total of 107 patients were included. The incidences of new-onset atrial fibrillation in early stage after surgery and persistent atrial fibrillation were 16.80% (18/107) and 1.87% (2/107) respectively. The average onset time of new-onset atrial fibrillation after surgery was 261.00 (87.00, 419.00) min after surgery. The incidence (50.00%) of atrial fibrillation within 4 h after surgery was the highest, and decreased progressively after that. The average duration of atrial fibrillation every time was 3.00 (1.50, 8.30) min, and the total duration was 5.50 (3.00, 11.25) min. The risk factors of new-onset atrial fibrillation after surgery of Neurosurgery Department included the high levels of blood phosphate and lymphocyte percentage before surgery, lesion located in brainstem or insular lobe as well as a low level of fasting blood glucose after surgery (P<0.05) . Conclusions New-onset atrial fibrillation after brain and spinal surgery of Neurosurgery Department mostly occurred within 8h after surgery. Pay attention to heart rhythm after surgery of patients with high levels of blood phosphate and lymphocyte percentage before surgery, lesion located in brainstem or insular lobe as well as a low level of fasting blood glucose after surgery. Key words: Neurosurgery; Brain surgery; Spinal surgery; Postoperative atrial fibrillation

Fetal Hemoglobin, Serum Total Cholesterol, Plasma Phosphate and Serum Calcium Levels in Patients with Leukemia and Lymphoma

In this study, fetal hemoglobin (HbF), blood total cholesterol, phosphate and calcium levels of leukemia and lymphoma cases in Mandalay were determined. It was a cross-sectional, comparative study. Thirty adult cases of leukemia and lymphoma and equal number of control subjects of comparable age (14 to 80 yrs) and sex were studied. Mean HbF of leukemia group (n=9), acute myeloid leukemia (AML) subgroup (n=6) and controls (n=30) were 2.72±0.47%, 3.17±0.69% and 1.39±0.25% of total Hb, respectively. The HbF levels of leukemia group and AML were significantly higher than that of controls (p&lt;0.02). Mean serum total cholesterol levels of leukemia group, AML subgroup and controls were found to be 126.5±17.38 mg%, 137.96±24.66 mg% and 177.18±7.68 mg%, respectively. Cholesterol levels of leukemia group and AML were lower than that of controls. Mean plasma phosphate levels of leukemia and lymphoma cases (n=30), leukemia group (n=9) and lymphoma group (n=21) were 1.21±0.07 mmol/l, 1.33±0.17 mmol/l and 1.15±0.06 mmol/l, respectively. Mean phosphate level of controls was 0.94 mmol/l. Plasma phosphate levels of the whole cases and individual case groups were significantly higher than that of controls (p&lt;0.001). Mean serum calcium levels of the whole cases, leukemia group and lymphoma group were 10.16±0.36 mg%, 10.03±0.75 mg% and 10.21±0.45 mg%, respectively. Mean serum calcium level of controls was 8.55±0.14 mg%. Serum calcium levels of the whole cases and individual case groups were found to be significantly higher than that of controls (p&lt;0.01). The study showed that not only raised HbF but also hypocholesterolaemia might be the diagnostic clues in leukemia cases. Recognition of blood phosphate and calcium changes leads to appropriate therapy and a reduction of morbidity.

Ergocalciferol improves endothelial vasodilatory and vasoconstrictor function in an in vivo model of mild uraemia.

Endothelial dysfunction and vitamin D deficiency are prevalent in patients with cardiovascular disease (CVD) and chronic kidney disease (CKD). Both are risk factors for cardiovascular events in patients with CKD. No studies have investigated the effect of nutritional forms of vitamin D on endothelial function in earlier stages of CKD, when vascular endothelium may be more amenable to this therapy. We studied the effect of ergocalciferol in a pre-clinical model of mild uraemia.Male Wistar rats underwent either a 5/6th nephrectomy or sham surgery. Four weeks after the final stage of the surgery, these two groups were randomly allocated to placebo or an oral dose of 1000 iu of ergocalcfierol at day 7 and 2 pre sacrifice. Vascular responses to acetylcholine, Spermine NONOate and phenylephrine were determined in aortic rings. Blood pressure, calcium, phosphate and parathyroid hormone were measured in all groups.Ergocalciferol significantly improved the endothelium-dependent responses to acetylcholine and overcame the blunting of the contractile response to phenylephrine seen in uraemic animals. Ergocalciferol improved the contractile response to potassium chloride in uraemic, but not sham animals. All effects occurred independently of changes to calcium, phosphate, parathyroid hormone and systolic blood pressure. There were no differences in endothelium-independent relaxation to Spermine NONOate.In summary, in a model of mild uraemia, ergocalciferol improved vasodilator and vasoconstrictor tone independently of blood pressure and bone mineral parameters suggesting a direct effect of ergocalciferol on the endothelium.

Moxibustion therapy for treating patients with primary osteoporosis: A systematic review and meta-analysis protocol.

Background:Primary osteoporosis (POP) is a common disease among elderly, which increase the risk of fracture and impact to the quality of life. As a Chinese traditional therapy, moxibustion has been commonly applied in treating chronic musculoskeletal diseases in China. Many trails have shown that moxibustion therapy is effective in treating primary osteoporosis. The protocol aims to present the methods used to access the effectiveness and safety of moxibustion therapy for patients with primary osteoporosis.Methods:The following databases will be searched from their inception: the Cochrane Central Register of Controlled Trails(CENTRAL), Pubmed, EMBASE, China National Knowledge Infrastructure(CNKI), Chinese Biomedical Literature Database(CBM), Chinese Scientific Journal Database (VIP database), and Wan-Fang Database. Clinical randomized controlled trials related to moxibustion therapy for treating primary osteoporosis will be included, regardless of publication status and languages. Study selection, data collection, and quality assessment will be independently conducted by 2 researchers. We will select the fixed-effects or random-effects model according to the heterogeneity assessment for data synthesis. Bone mineral density(BMD) will be the primary outcomes. Visual analogue scale(VAS), response rate, TCM Syndrome scale(TCMSS), bone gla protein(BGP), alkaline phosphatase(BALP), blood calcium(Ca), blood phosphate(P), quality of life(QOL) will be the second outcomes. If it is appropriate for meta-analysis, RevMan V.5.3 statistical software will be used. Otherwise, a systematic narrative synthesis will be conducted. The results will be presented as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and weight mean difference(WMD) or standard mean difference (SMD) 95% CIs for continuous data.Trial registration number:PROSPERO CRD42019129507

Teriparatide (rhPTH 1-34) treatment in the pediatric age: long-term efficacy and safety data in a cohort with genetic hypoparathyroidism.

Hypoparathyroidism is characterized by the absence or inadequately low circulating concentrations of the parathyroid hormone, resulting in hypocalcemia, hyperphosphatemia, and elevated fractional excretion of calcium in the urine. The use of activated vitamin D analogs and calcium supplements represent conventional therapy. Subcutaneous recombinant human parathormone [rhPTH(1-34)] has been proposed as a substitutive treatment, even to avoid side effects of vitamin D and calcium. To assess the long-term safety and efficacy of rhPTH(1-34) in a pediatric cohort of patients with genetic hypoparathyroidism. The study is a 9.2-year self-controlled study of six pediatric patients (four males and two females, aged 9.4 ± 5.2) with DiGeorge, hypoparathyroidism-deafness-renal dysplasia (HDR) or autoimmune-candidiasis-polyendocrinopathy-ectodermal-dysplasia (APECED) syndrome, associated with autoimmune intestinal malabsorption in a patient. The presence of clinical signs of hypocalcemia and biochemical parameters, such as calcium, phosphate, alkaline phosphatase in the blood and calcium-creatinine ratio in urine, were compared during conventional treatment and rhPTH(1-34) (teriparatide, 12.5 μg twice daily). The rhPTH(1-34) treatment allowed a reduction, although not always a complete suspension, of calcium supplementation and a slight reduction of calcitriol therapy. The number of tetanic episodes was reduced in four patients during the rhPTH(1-34) treatment. Mean blood calcium, alkaline phosphatase, and phosphate did not significantly change, while a significant reduction of the urinary calcium-to-creatinine ratio (0.55 ± 0.32 vs 0.16 ± 0.09, p = 0.03) was obtained. Renal ultrasound examination showed a worsening in three patients, while it did not change in the remaining three subjects during the follow-up. In children with syndromic hypoparathyroidism presented here, replacement therapy with rhPTH(1-34) allowed to maintain adequate levels of the calcium and phosphate in the blood, normalize urinary calcium excretion, and reduce tetanic episodes. In patients with low compliance to conventional therapy or intestinal malabsorption, the use of rhPTH(1-34) could be considered, also to reduce the side effects of treatment with vitamin D and calcium.

Detection of Phosphate in Human Blood Based on a Catalytic Hydrogen Wave at a Molybdenum Phosphide Modified Electrode.

Detection of inorganic phosphate is very important in environmental and health care applications. In this work, we found that phenomenon similar to "catalytic hydrogen wave" occurred on a molybdenum phosphide (MoP) modified electrode in the presence of phosphate, that is, a new wave of catalytic hydrogen evolution appeared before the normal hydrogen evolution reaction. The catalytic hydrogen wave arose from a structure similar to phosphomolybdic acid (noted as MoPO), which was formed by the interaction between phosphate and molybdenum oxides on the surface of the MoP modified electrode, resulting in the altered surface structure and adjusted interface catalytic activity. A novel phosphate electrochemical sensor was constructed based on this phenomenon with a linear range from 0.10 to 20.0 mmol·L-1, an actually determined minimum concentration of 0.030 mmol·L-1, and recoveries of 94%-107%, and this sensor was successfully applied to the detection of phosphate in human blood. Furthermore, this work proposes a new sensing method based on catalytic hydrogen waves on the modified electrodes.

Good long-term renal graft survival and low incidence of cardiac pathology in adults after short dialysis period and renal transplantation in early childhood - a cohort study.

Over the past 30years, there has been an improvement in both patient and graft survival after pediatric renal transplantation (RTX). Despite this success, these patients still carry an elevated risk for untimely death, partly through premature aging of the vasculature. The aim of this study was thus to investigate the long-term outcome of individuals with RTX in childhood, as well as to explore the cardiovascular health of these adults more than a decade later. We studied 131 individuals who had undergone a RTX between the years 1979 and 2005. Furthermore, left ventricular hypertrophy (LVH), coronary artery calcifications (CAC), and related metabolic factors were investigated in a cross-sectional study including 52 individuals as part of the initial cohort. The mortality rate (n=131) was 12.2%. The median estimated graft survival was 17.5years (95% CI 13.6-21.3), being significantly better in children transplanted below the age of 5years (18.6 vs. 14.3years, P<0.01) compared with older ones. CAC were found in 9.8% and LVH in 13% of the patients. Those with cardiac calcifications had longer dialysis vintage and higher values of parathyroid hormone (PTH) during dialysis. Left ventricular mass correlated positively with systolic blood pressure, PTH, and phosphate measured at the time of the study.