Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia.

BACKGROUND: Phosphorus levels in the range seen clinically among patients undergoing dialysis have been reported to attenuate calcium receptor activation and modify parathyroid hormone (PTH) release from isolated parathyroid glands in vitro. Some clinicians and providers of dialysis thus have suggested that calcimimetic agents are ineffective and should not be used to manage secondary hyperparathyroidism among those undergoing dialysis when serum phosphorus concentrations exceed certain threshold levels. METHODS: To determine whether hyperphosphatemia diminishes the therapeutic response to calcimimetic agents, we used data from large clinical trials to analyze the effects of etelcalcetide and cinacalcet to lower plasma PTH levels in individuals on hemodialysis who had secondary hyperparathyroidism and varying degrees of hyperphosphatemia. RESULTS: Plasma PTH levels declined progressively during 26 weeks of treatment with either etelcalcetide or cinacalcet without regard to the degree of hyperphosphatemia at baseline. However, with each calcimimetic agent, the decreases in PTH from baseline were less at each interval of follow-up during the trials among participants with serum phosphorus levels above one of three prespecified threshold values compared with those with serum phosphorus levels below these thresholds. CONCLUSIONS: These in vivo findings are the first in humans to support the idea that hyperphosphatemia attenuates calcium receptor activation by calcium ions and by calcimimetic agents. The effect of hyperphosphatemia on the responsiveness to calcimimetic agents appears relatively modest, however, and unlikely to be significant therapeutically. The efficacy of treatment with calcimimetic agents for lowering plasma PTH levels among those with secondary hyperparathyroidism remains robust despite substantial elevations in serum phosphorus.

Association between the initial serum phosphate level and 30-day mortality in blunt trauma patients.

BACKGROUND: Studies on patients with cardiac arrest or sepsis have reported that high initial phosphate levels are associated with poor outcomes. However, no previous study has investigated the association between initial phosphate levels and outcomes in blunt trauma patients. METHODS: This study was a retrospective observational study conducted on blunt trauma patients who had been treated at the single regional trauma center between January 2016 and December 2017. Patients' demographic data, initial vital signs, trauma scores, and laboratory parameters including phosphate levels were collected from the trauma registry. The primary outcome was set to 30-day mortality. The secondary outcomes were the total volume of blood transfused, 30-day hospital-free days, and 30-day intensive care unit-free days. RESULTS: Of the 1,907 included patients, 1,836 were in the survival group, and 71 were in the nonsurvival group. The nonsurvival group had a significantly higher phosphate level than the survival group. Patients in the hyperphosphatemia group had a higher 30-day mortality, fewer 30-day intensive care unit-free days, and higher transfusion volume than those in the other groups. In multivariable logistic regression analysis, hyperphosphatemia was independently associated with 30-day mortality. The receiver operating characteristic curve analysis showed that the area under the curve with the inclusion of phosphate in addition to Injury Severity Score, Revised Trauma Score, and age was 0.911. Area under the curve was also increased when phosphate was simply added to Injury Severity Score and Revised Trauma Score. CONCLUSION: In blunt trauma patients, hyperphosphatemia was associated with an increased 30-day mortality. LEVEL OF EVIDENCE: Prognostic, level III.

Interferences in the measurement of circulating phosphate: a literature review.

Background Inorganic phosphate in blood is currently determined by the reaction with molybdate. This report aims at reviewing conditions underlying spuriously altered levels of circulating inorganic phosphate. Content A systematic search of the Excerpta Medica, the National Library Database and the Web of Science database was conducted without language restriction from the earliest publication date available through January 31, 2020. Summary For the analysis, 80 reports published in English (n = 77), French (n = 1), German (n = 1) and Spanish (n = 1) were retained. Well-documented pseudohyperphosphatemia was observed in individuals exposed to liposomal amphotericin, in patients affected by a gammopathy, in patients with hyperlipidemia and in patients with hyperbilirubinemia. An unexplained elevated inorganic phosphate level sometimes provided a clue to the diagnosis of a gammopathy. Well-documented cases of pseudohypophosphatemia were observed in patients on large amounts of intravenous mannitol. Finally, pseudohypophosphatemia was occasionally observed on treatment with liposomal amphotericin and in patients with a gammopathy. Outlook In order to avoid unnecessary testing and treatment, the phenomenon of spuriously altered inorganic phosphate should be recognized. An unexplained hyperphosphatemia may provide a clue to the diagnosis of a gammopathy or a severe hyperlipidemia.

Autosomal dominant hypocalcaemia: identification of two novel variants of CASR gene.

Autosomal dominant hypocalcaemia is a rare aetiology of hypocalcaemia, caused by gain-of-function mutations of the calcium-sensing receptor (CASR) gene. We present two cases of two asymptomatic women (50-year-old-case 1 and 25-year-old-case 2), referred to our endocrinology department for investigation of hypocalcaemia, hyperphosphatemia and inappropriately low parathormone. Both patients had relatives with the same laboratorial findings. At diagnosis, both patients presented basal ganglia calcifications. Genetic analysis was performed, identifying two novel heterozygous CASR variants: c.2269G>A (p.Glu757Lys) and c.2086C>G (p.Leu696Val), respectively, for case 1 and case 2. Affected individuals started oral calcium and vitamin D analogues, aiming to a low-normal calcium level. They remain under observation and are asymptomatic.

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

Clinically-defined preoperative serum phosphorus abnormalities and outcomes of coronary artery bypass grafting: Retrospective analysis using inverse probability weighting adjustment.

BACKGROUND: Serum phosphorus is a well-known marker of vascular calcification, but the effects of serum phosphorus abnormalities defined by clinical criteria on the outcomes of coronary artery bypass grafting (CABG) remain unclear. We aimed to evaluate whether preoperative serum phosphorus abnormalities defined based on clinical criteria are associated with outcomes of CABG using a relatively new statistical technique, inverse probability weighting (IPW) adjustment. METHODS: From January 2001 to December 2014, 4,989 consecutive patients who underwent CABG were stratified into normal (2.5-4.5 mg/dl; n = 4,544), hypophosphatemia (<2.5 mg/dl; n = 238), or hyperphophatemia (>4.5 mg/dl; n = 207) groups depending on preoperative serum phosphorus level. RESULTS: The primary outcome was all-cause death during a median follow-up of 48 months. Secondary outcomes were cardiovascular death, graft failure, myocardial infarction, repeat revascularization, and stroke. In multivariate Cox analysis, preoperative hypophosphatemia was significantly associated with all-cause death (hazard ratio [HR] 1.76; 95% confidence interval [CI] 1.13-2.76; P = 0.01). However, this association varied depending on chronic kidney disease and emergent operation (p for interaction = 0.05 and 0.03, respectively). In addition, analysis after IPW adjustment demonstrated that preoperative serum phosphorus abnormalities were not significantly associated with all-cause death (P = 0.08) or any secondary outcomes except graft failure. Graft failure was significantly associated with preoperative hypophosphatemia (HR 2.51; 95% CI 1.37-4.61; P = 0.003). CONCLUSION: Our study showed that preoperative serum phosphorus abnormalities in clinical criteria were not associated with outcomes after CABG except for graft failure. And, the association of hypophosphatemia with graft failure remains to be evaluated.

Potential interaction of inflammatory hyperemia and hyperphosphatemia in tumorigenesis.

The present article proposes that the association of inflammation with cancer is potentially mediated by the interaction of inflammatory hyperemia and hyperphosphatemia. Hyperemia increases blood flow rate and blood volume, and hyperphosphatemia is caused by elevated serum levels of dysregulated inorganic phosphate. It is hypothesized that the interaction of inflammatory hyperemia and hyperphosphatemia circulates increased amounts of inorganic phosphate to the tumor microenvironment, where increased uptake of inorganic phosphate through sodium-phosphate cotransporters is sequestered in cells. Elevated levels of intracellular phosphorus increase biosynthesis of ribosomal RNA, leading to increased protein synthesis that supports tumor growth. The present article also proposes that the interaction of inflammatory hyperemia and hyperphosphatemia may help explain a chemopreventive mechanism associated with NSAIDs.

Hyperphosphatemia is required for initiation but not propagation of kidney failure-induced calcific aortic valve disease.

High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uremia-inducing diet, with or without phosphate enrichment, to rats for 7 wk. Forty-two rats were fed with a phosphate-enriched uremic regimen that caused renal insufficiency and hyperphosphatemia. Another 42 rats were fed with a phosphate-depleted uremic regimen, which induces similar severity of renal insufficiency, but without its related mineral disorder. Aortic valves were evaluated at several points during the time of diet administration. In the second part, additional 54 rats were fed a phosphate-enriched diet for various time periods and were then switched to a phosphate-depleted diet to complete 7 wk of uremic diet. Osteoblast-like phenotype, inflammation, and eventually valve calcification were observed only in rats that were fed with a phosphate-enriched regimen. Significant valve calcification was observed only in rats that were fed a phosphate-enriched diet for at least 4 wk. Valve calcification was observed only when the switch to a phosphate-depleted regimen occurred after osteoblast markers and activation of Akt and ERK intracellular signaling pathways had already been found in the valve. Phosphate is essential for the initiation of the calcification process. However, when osteoblast markers are already expressed in valve tissue, phosphate depletion will not halt the disease.NEW & NOTEWORTHY High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease. However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. Our findings indicated that phosphate is essential for the initiation of the process that includes macrophage accumulation and osteoblast phenotype. Furthermore, hyperphosphatemia is dispensable beyond a certain phase of the process, a point of "no return" after which phosphate depletion does not prevent calcification. This point is relatively early in the course of calcification, when no calcification is apparent, but the inflammation, osteoblast markers, and activation of ERK and Akt pathways have already been identified. Our findings emphasize the complexity of the calcification process and suggest that different mediators might be required during different phases and that the role of phosphate precedes the actual calcification.

Sustained Klotho delivery reduces serum phosphate in a model of diabetic nephropathy.

Diabetic nephropathy (DN) is a primary cause of end-stage renal disease and is becoming more prevalent because of the global rise in type 2 diabetes. A model of DN, the db/db uninephrectomized ( db/db-uni) mouse, is characterized by obesity, as well as compromised renal function. This model also manifests defects in mineral metabolism common in DN, including hyperphosphatemia, which leads to severe endocrine disease. The FGF23 coreceptor, α-Klotho, circulates as a soluble, cleaved form (cKL) and may directly influence phosphate handling. Our study sought to test the effects of cKL on mineral metabolism in db/db-uni mice. Mice were placed into either mild or moderate disease groups on the basis of the albumin-to-creatinine ratio (ACR). Body weights of db/db-uni mice were significantly greater across the study compared with lean controls regardless of disease severity. Adeno-associated cKL administration was associated with increased serum Klotho, intact, bioactive FGF23 (iFGF23), and COOH-terminal fragments of FGF23 ( P < 0.05). Blood urea nitrogen was improved after cKL administration, and cKL corrected hyperphosphatemia in the high- and low-ACR db/db-uni groups. Interestingly, 2 wk after cKL delivery, blood glucose levels were significantly reduced in db/db-uni mice with high ACR ( P < 0.05). Interestingly, several genes associated with stabilizing active iFGF23 were also increased in the osteoblastic UMR-106 cell line with cKL treatment. In summary, delivery of cKL to a model of DN normalized blood phosphate levels regardless of disease severity, supporting the concept that targeting cKL-affected pathways could provide future therapeutic avenues in DN. NEW & NOTEWORTHY In this work, systemic and continuous delivery of the "soluble" or "cleaved" form of the FGF23 coreceptor α-Klotho (cKL) via adeno-associated virus to a rodent model of diabetic nephropathy (DN), the db/db uninephrectomized mouse, normalized blood phosphate levels regardless of disease severity. This work supports the concept that targeting cKL-affected pathways could provide future therapeutic avenues for the severe mineral metabolism defects associated with DN.

A practical self-made device in parathyroid autotransplantation for patients with secondary hyperparathyroidism.

OBJECTIVE: Secondary hyperparathyroidism (sHPT) is one of the most serious complications in patients on long-term hemodialysis. These patients may suffer from metabolic bone diseases, severe atherosclerosis, and undesirable cardiovascular events. Endoscopic parathyroidectomy with autotransplantation is a treatment option for those who do not respond to clinical management. This study aimed to investigate practical use of a self-made device in parathyroid autotransplantation for patients with sHPT, and to compare this device with ordinary surgical scissors. METHODS: A total of 15 patients with sHPT were treated with endoscopic parathyroidectomy and autotransplantation. Pieces of parathyroid tissue were squeezed in our self-made device and injected into the brachioradialis muscle. Sixteen patients with sHPT who were treated with traditional parathyroid transplantation served as controls. Serum levels of parathyroid hormone, alkaline phosphatase, calcium, phosphorus and intact parathyroid hormone were measured before and after surgery. RESULTS: Preoperative symptoms were alleviated, and serum parathyroid hormone and alkaline phosphatase levels, hyperphosphatemia, and hypercalcemia were improved or normalized in all of the patients in both groups. Pathological examinations showed that parathyroid cells remained active. CONCLUSION: Application of our squeezing device is an economic, effective, and safe method in endoscopic parathyroidectomy and autotransplantation for patients with sHPT.

MicroRNA-21 mediates high phosphate-induced endothelial cell apoptosis.

Hyperphosphatemia, the elevated level of inorganic phosphate (Pi) in serum, is associated with increased cardiovascular morbidities and mortality. The effects of high Pi on endothelial cells are not well studied. This study investigated high Pi-induced endothelial cell apoptosis and the role of microRNA-21. Mouse myocardial endothelial cells (MEC) were cultured in normal (1 mM) and high (5 mM) Pi conditions. Apoptosis was detected by TUNEL staining and flow cytometry. MicroRNA profiles of MEC response to changes in Pi concentration were obtained using gene expression arrays. Expression levels of the microRNA-21 target genes, programmed cell death gene 4 ( PDCD4), poly(ADP-ribose) polymerase ( PARP), and phosphatase and tensin homolog ( PTEN), as well as NF-κB were measured by Western blotting and RT-PCR. MicroRNA-21-specific inhibitors and mimics were used to study effects of microRNA-21 on MEC apoptosis and gene expression regulations. High Pi induced MEC apoptosis and upregulated microRNA-21 expression. MicroRNA-21-specific mimics reproduced high Pi-induced apoptosis in normal Pi medium, and microRNA-21 inhibitors ameliorated the high Pi induction of apoptosis, suggesting that microRNA-21 mediated high Pi-induced MEC apoptosis. The microRNA-21 targets PDCD4, PTEN, PARP, and NF-κB were significantly downregulated in high Pi conditions. High Pi-induced downregulation of PDCD4 was abolished by microRNA-21 inhibitors and selective ERK inhibitor (selumetinib) and was reproduced by microRNA-21 mimics. Inhibitors and mimics of microRNA-21 did not have effects on high Pi-induced NF-κB downregulation. Selumetinib blocked high Pi-induced NF-κB downregulation. MicroRNA-21 mediates high Pi-induced endothelial cell apoptosis, which involves an ERK1/2/microRNA-21/PDCD4 pathway. High Pi-induced downregulation of NF-κB expression is mediated by an ERK1/2 signaling-dependent but microRNA-21-independent mechanism.

Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies.

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment.

Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κB.

Background The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear.Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD.Results In cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO4 increased the abundance of zinc-finger protein TNF-α-induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO4 supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO4 ameliorated the osteoinductive effects of uremic serum in VSMCs.Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.

Hyperphosphatemic tumoral calcinosis caused by FGF23 compound heterozygous mutations: what are the therapeutic options for a better control of phosphatemia?

BACKGROUND: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disease caused by mutations in genes encoding FGF23 or its regulators, and leading to functional deficiency or resistance to fibroblast growth factor 23 (FGF23). Subsequent biochemical features include hyperphosphatemia due to increased renal phosphate reabsorption, and increased or inappropriately normal 1,25-dihydroxyvitamin D (1,25-D) levels. CASE-DIAGNOSIS/TREATMENT: A 15-year-old girl was referred for a 1.2-kg-calcified mass of the thigh, with hyperphosphatemia (2.8 mmol/L); vascular impairment and soft tissue calcifications were already present. DNA sequencing identified compound heterozygous mutations in the FGF23 gene. Management with phosphate dietary restriction, phosphate binders (sevelamer, aluminum, nicotinamide), and acetazolamide moderately decreased serum phosphate levels; oral ketoconazole was secondary administered, leading to significantly decreased 1,25-D levels albeit only moderate additionally decreased phosphate levels. However, therapeutic compliance was questionable. Serum phosphate levels always remained far above the upper normal limit for age. The patient presented with two relapses of the thigh mass, requiring further surgery. CONCLUSIONS: We suggest that control of phosphate metabolism is crucial to prevent recurrences and vascular complications in HFTC; however, the medical management remains challenging.

A service review to assess if innovative intensive phosphate dietary education can help reduce phosphate levels to the recommended range in a hemodialysis population.

INTRODUCTION: Studies suggest that hemodialysis (HD) patients are less likely to adhere to phosphate dietary restriction than to potassium, sodium, or fluid restriction. It is particularly important that dietary education is provided appropriately, consistently, and reinforced regularly to encourage compliance with diet and phosphate-binder regimens. Patient awareness of the consequences of a chronically raised phosphate and its treatment is associated with lower serum phosphate levels. OBJECTIVE: The aim of this study was to assess the impact of a structured educational program on patient knowledge and control of serum phosphate in a maintenance HD population. METHODS: Thirty-six patients with a phosphate level >1.7 mmol/L for the previous 3 months were assessed. A phosphate knowledge questionnaire was devised by the authors and completed by the patient group. This focused on patient knowledge of dietary sources of phosphate and complications of high phosphate levels. The education program was divided into three modules and was based around diet, phosphate additives, and complications of hyperphosphatemia. Visual aids, oral, and written information were provided to each patient throughout the sessions. Seventeen patients completed the education sessions. The knowledge and food frequency questionnaire were repeated at the end of the modules to assess change. RESULTS: Phosphate levels dropped from an average of 2.12-1.73 mmol/L over the education period with a significance level of P = 0.000481 (significant if P < 0.001). This average falls in line with recommended guidelines. Knowledge questionnaire results improved overall. CONCLUSION: This education program displayed excellent outcomes with an overall reduction in phosphate levels and an improved phosphate knowledge among our sampled HD population. This education program shows that discovering novel ways of education is crucial to enhancing dietetic practice with renal dietitians best placed to deliver patient specific phosphate education.

Hypoparathyroidism.

Hypoparathyroidism is a disease characterized by inadequately low circulating concentrations of parathyroid hormone (PTH) resulting in low calcium levels and increased phosphate levels in the blood. Symptoms of the disease result from increased neuromuscular irritability caused by hypocalcaemia and include tingling, muscle cramps and seizures. The most common cause of the disease is inadvertent removal of, or injury to, the parathyroid glands during neck surgery, followed by genetic, idiopathic and autoimmune aetiologies. Conventional treatment includes activated vitamin D and/or calcium supplements, but this treatment does not fully replace the functions of PTH and can lead to short-term problems (such as hypocalcaemia, hypercalcaemia and increased urinary calcium excretion) and long-term complications (which include nephrocalcinosis, kidney stones and brain calcifications). PTH replacement has emerged as a new treatment option. Clinical trials using human PTH(1-34) and PTH(1-84) showed that this treatment was safe and effective in studies lasting up to 6 years. Recombinant human PTH(1-84) has been approved in the United States and Europe for the management of hypoparathyroidism; however, its effect on long-term complications is still being evaluated. Clinical practice guidelines, which describe the consensus of experts in the field, have been published and recognize the need for more research to optimize care. In this Primer, we summarize current knowledge of the prevalence, pathophysiology, clinical presentation and management of hypoparathyroidism.