Evaluation of a New Automated Routine Measurement for Serum Adjusted Ionized Calcium (at pH 7.4) in Patients Suspected of Calcium Metabolic Disease.

BACKGROUND: Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units. METHODS: Serum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen's kappa (κ). RESULTS: Analytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797-0.917; all P < 0.0001) and in high-throughput settings (r = 0.871; P < 0.0001). The degree of agreement between instruments was moderate to good (κ = 0.52-0.77). In contrast, there was a very poor agreement (κ = -0.14) for total calcium with discrepancy in 53.4% of the samples. CONCLUSIONS: The new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.

Calcium Metabolic Disorders in Pregnancy: Primary Hyperparathyroidism, Pregnancy-Induced Osteoporosis, and Vitamin D Deficiency in Pregnancy.

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes.

Association of klotho gene polymorphism and the regulation of calcium-phosphate metabolism disorders in patients with end-stage renal disease.

BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects. RESULTS: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders. CONCLUSION: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.

Requests of laboratory tests for the diagnosis and management of calcium-phosphate disorders in Spain.

BACKGROUND: Knowledge about the variability in the request of calcium-phosphate metabolism laboratory tests in primary care is important to design strategies to improve health system efficiency. AIM: To compare the inter-practice variability in calcium-phosphate metabolism laboratory tests requested by general practitioners from diverse regions across Spain. MATERIAL AND METHODS: One hundred and forty one clinical laboratories were invited to participate in an observational cross-sectional study. They informed the number of serum calcium, phosphate, parathyroid hormone and 25-hydroxyvitamin D requested by general practitioners. Appropriateness indicators were calculated as number of test requests per 1,000 inhabitants and ratio of related tests requests. The differences according to hospital setting, region and type of management were analyzed. RESULTS: We recruited 76 laboratories (17,679,195 inhabitants). General practitioners requested 3,260,894 calcium-phosphate metabolism tests. The rate of request ranged from 2.97 per 1,000 inhabitants for 25-hydroxyvitamin D to 98.89 per 1,000 inhabitants for calcium. The rates of request for calcium, phosphate, parathyroid hormone in some areas were 30, 100 and 340 times higher than in other areas. Parathyroid hormone and 25-hydroxyvitamin D were highly requested in private management areas. There were also differences in phosphate, parathyroid hormone and 25-hydroxyvitamin D requesting between regions across Spain. CONCLUSIONS: The high variability observed is difficult to explain by differences in patient case mix between regions. Depending on the area, calcium could be under requested to detect primary hyperparathyroidism.

Requests of laboratory tests for the diagnosis and management of calcium-phosphate disorders in Spain / Solicitud de pruebas de laboratorio para el diagnóstico y manejo de los desórdenes del metabolismo fosfocálcico en España

Background: Knowledge about the variability in the request of calcium-phosphate metabolism laboratory tests in primary care is important to design strategies to improve health system efficiency. Aim: To compare the inter-practice variability in calcium-phosphate metabolism laboratory tests requested by general practitioners from diverse regions across Spain. Material and Methods: One hundred and forty one clinical laboratories were invited to participate in an observational cross-sectional study. They informed the number of serum calcium, phosphate, parathyroid hormone and 25-hydroxyvitamin D requested by general practitioners. Appropriateness indicators were calculated as number of test requests per 1,000 inhabitants and ratio of related tests requests. The differences according to hospital setting, region and type of management were analyzed. Results: We recruited 76 laboratories (17,679,195 inhabitants). General practitioners requested 3,260,894 calcium-phosphate metabolism tests. The rate of request ranged from 2.97 per 1,000 inhabitants for 25-hydroxyvitamin D to 98.89 per 1,000 inhabitants for calcium. The rates of request for calcium, phosphate, parathyroid hormone in some areas were 30, 100 and 340 times higher than in other areas. Parathyroid hormone and 25-hydroxyvitamin D were highly requested in private management areas. There were also differences in phosphate, parathyroid hormone and 25-hydroxyvitamin D requesting between regions across Spain. Conclusions: The high variability observed is difficult to explain by differences in patient case mix between regions. Depending on the area, calcium could be under requested to detect primary hyperparathyroidism.

Objetivo: Conocer la variabilidad en la solicitud de pruebas de laboratorio en atención primaria es importante para diseñar estrategias que mejoren la eficiencia del sistema de salud. La propuesta de este estudio fue comparar la variabilidad en la solicitud de pruebas para la evaluación del metabolismo fosfocálcico por médicos de atención primaria de diversas regiones de España. Material y Método: Se invitó a participar a 141 laboratorios clínicos de diversas regiones españolas. Completaron una encuesta con el número de determinaciones de calcio, fósforo, hormona paratiroidea y 25-hidroxivitamina D solicitadas por médicos de atención primaria de sus áreas. Se calcularon las tasas en relación a la población y se construyeron indicadores de adecuación. Los resultados se compararon por características del hospital, región y tipo de gestión. Resultados: Obtuvimos los datos de 76 laboratorios (17.679.195 habitantes). Los médicos de atención primaria solicitaron 3.260.894 pruebas de metabolismo fosfocálcico. La tasa de solicitud varió de 2,97 por 1.000 habitantes de 25-hidroxivitamin D a 98,89 por 1.000 habitantes de calcio. Las tasas de calcio, fósforo, hormona paratiroidea en algunas áreas fue 30, 100 y 340 veces más alta respecto a otras. Hormona paratiroidea y 25-hidroxivitamina D fueron más solicitadas significativamente en hospitales con gestión privada. También hubo diferencias en fósforo, hormona paratiroidea y 25-hidroxivitamina D solicitas entre distintas regiones de España. Discusión: La alta variabilidad observada es difícil de explicar por las diferencias de las características de los pacientes. Dependiendo de la región podría haber una infra solicitud para la detección del hiperparatiroidismo primario.

[Disorders of calcium metabolism]. / Störungen des Kalziumstoffwechsels.

The majority of clinical complaints derive from disorders of calcium metabolism and are associated with a wide variety of clinical symptoms caused by numerous diseases with entirely different types of pathophysiology. The prognosis varies from favorable to fatal depending on the pathophysiology of the underlying disorder of calcium metabolism; therefore, the diagnostic work-up aims to quickly identify the underlying disease causing the disturbance in calcium homeostasis. Every clinical situation with a diminished state of calcium absorption is treated with calcium and vitamin D in varying doses whereas every disorder with an increased calcium absorptive or resorptive state is treated with improved diuresis in addition to antiresorptive drugs, such as bisphosphonates. In many situations the management of a disturbed calcium balance requires an interdisciplinary approach in order to treat the underlying disease in parallel with correction of the calcium homeostasis.

How to diagnose and manage difficult problems of calcium metabolism in sarcoidosis: an evidence-based review.

PURPOSE OF REVIEW: Calcium metabolism impairments have long been recognized as a complication of sarcoidosis. For more than six decades physicians and investigators have been trying to elucidate this severe problem; nevertheless it seems puzzlingly new for both readers and researchers. RECENT FINDINGS: This review highlights the problems of calcium metabolism in sarcoidosis in relation to vitamin D synthesis, which is definitely altered by granulomatous inflammation. Increasing evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. As calcium homeostasis is primary controlled by levels of vitamin D, parathyroid hormone (PTH) and calcitonin, this literature review emphasizes the role of general immunomodulating properties of vitamin D and the correlation with calcium metabolism impairments, with the special accent on already known interactions with sarcoidosis. SUMMARY: Granuloma formation has been related to a failure of the innate immune system. One of the possible explanations is a vitamin D deficiency. The evidence-based findings on calcium metabolism impairments and the interactions with vitamin D might help both clinicians and researchers in developing new strategies.

Hipercalcemia como urgencia médica / Hypercalcemia as a medical emergency

La hipercalcemia es una alteración del metabolismo del calcio que, producida bruscamente o por encima de 14,5 mg/dl, puede provocar complicaciones sistémicas que comprometan la vida del paciente. Es una urgencia médica que se presenta con mayor frecuencia en la enfermedad tumoral avanzada, generalmente a través de la activación de la proteína relacionada con la hormona paratiroidea. Se debe iniciar un tratamiento inmediato, siendo la sueroterapia intensiva y los bifosfonatos intravenosos las claves para conseguir una restauración metabólica rápida. Zolendronato se considera actualmente el bifosfonato más eficaz para la hipercalcemia aguda(AU)

Hypercalcemia is a metabolic disorder of calcium that may cause systemic complications when is produced suddenly or above 14.5 mg/dl. It is considered as a medical emergency that appears more frequently at advanced malignant disease, usually through the activation of parathyroid hormone-related protein. It should be treated promptly and an intensive therapy with fluids and intravenous bisphosphonates are the keys to achieve metabolic restoration. At present, zoledronic acid is considered the most effective bisphosphonate for acute hypercalcemia(AU)

Desconocimiento de las guías K/DOQITM sobre la alteración del metabolismo óseo-mineral asociadaa la enfermedad renal crónica no en diálisis: resultados de la encuesta en el estudio multicéntrico español OSERCE / No disponible

Desde su publicación en el 2003, las guías K/DOQITM sobre metabolismo y enfermedad ósea en la enfermedad renal crónica(ERC) han sido referencia internacional. El objetivo de este estudio fue analizar el grado de conocimiento de las mismas en pacientes con ERC estadios 3, 4 y 5 no en diálisis mediante una encuesta a 32 nefrólogos españoles que participaron en el estudio OSERCE. De este análisis se deduce quela frecuencia teórica de medición de parámetros bioquímicos es habitualmente menor a la recomendada, excepto en el estadio3. Los objetivos terapéuticos para la PTH intacta fueron inadecuadamente reportados por el 59% de los nefrólogos encuestados para estadios 3 y 4, mientras que para el estadio5 sólo por el 22%. Los objetivos para el fósforo fueron inadecuadamente reportados en el 50 % de los casos (estadios 3 y4) y 60% (estadio 5). Para el calcio fueron del 70%, 73,3% y65,5% en los estadios 3, 4 y 5 respectivamente. Un calcio plasmático corregido entre 9,5 y 10,2 mg/dl fue todavía considerado apropiado en el 31% de las respuestas. Hasta un87% de los nefrólogos consultados manifestaron no medir sistemáticamente los niveles plasmáticos de calcidiol. En general, estos resultados demuestran que existe un alto grado de desconocimiento de las guías K/DOQITM en los pacientes con ERC no en diálisis. Por consiguiente, la falta de implementación de las mismas no sólo ha sido debido a la menor disponibilidad de agentes terapéuticos prediálisis, la dificultad de cumplimiento de objetivos o la propia incertidumbre de las guías sino también a su desconocimiento. Sería pues recomendable que próximas guías como las K-DIGO vinieran acompañadas también de intervenciones de carácter educativo en el diagnóstico y tratamiento precoz de las alteraciones del metabolismo óseo-mineral asociado a la ERC (AU)

Since its publication in 2003, the K/DOQITM clinical practice guidelines for bone metabolism and disease in chronic kidney disease(CKD) have become a worldwide reference. The aim of this study was to analyze the observance to these guidelines in patients with a glomerular filtration rate < 60 ml/min/1.73m2 not yet included indialysis in a Spanish multicenter cohort. A questionnaire by investigator/centre was completed by 32 different nephrologists participating in the OSERCE study and representing the overall Spanish public health net. We observed that biochemical parameters were measured less frequently than recommended, except in CKD stage3. The therapeutic goals for intact PTH were not properly reported by 59% of the consulted nephrologists for stages 3 and 4, whereas only 22% did not report them properly for stage 5. The goals for phosphorus were not adequately reported in 50% of cases (stages3 y 4) and 60% (stage 5). For calcium, these values were 70 %,73.3% and 65.5% for stages 3, 4 and 5, respectively. A corrected plasma calcium between 9.5 and 10.2 mg/dl is still considered adequate for 31%. As much as 87% nephrologists stated that they did not sistematically measure calcidiol plasma levels. In general, these results demonstrate that there is a great degree of unawareness of K/DOQITM predialysis guidelines. Thus, their poor implementation is probably not only due to the lower availability of approved therapeutic agents, the difficult achievement of goals or the disbelief on current recommendations. It would be desirable that forthcoming guidelines such as the KDIGO could also consider the need of educational efforts for CKD-Mineral and Bone Disorder (AU)

Disorders of calcium metabolism.

Hypocalcaemia not associated with hypoalbuminaemia or 25(OH)-Vitamin D deficiency is rare and should be referred to a specialist clinic. 25(OH)-Vitamin D deficiency can often be treated safely by GPs, unless it is associated with renal impairment and secondary hyperparathyroidism, in which case a nephrology referral is required. An endocrine referral is required if deficiency is associated with pregnancy, co-existent primary hyperparathyroidism or the patient is receiving warfarin. The key role of the GP in managing hypercalcaemia is to distinguish between malignant and parathyroid causes in order to make the appropriate specialist referral (oncology, endocrine or renal). Severe hypercalcaemia (greater than 3.5 mmol/L or hypercalcaemia with dehydration, abdominal pain or reduced consciousness is a medical emergency.

Medical evaluation and treatment of urolithiasis.

Nephrolithiasis is responsible for 1 in 1000 to 1 in 7600 pediatric hospital admissions annually throughout the United States. Seventy-five percent of children with nephrolithiasis have an identifiable predisposition to stone formation. This article reviews the different causes and disease states associated with nephrolithiasis in the pediatric population. The initial evaluation and the metabolic evaluation of children with nephrolithiasis are reviewed. Treatment modalities for the different stone types are also described.

Fatty acids and idiopathic calcium nephrolithiasis.

Clinical and experimental investigations seem to underline the important role of fatty acids in the pathogenesis of hypercalciuria, a well-known risk factor for lithogenesis. To evaluate the relationships between the previously reported increase in plasma phospholipid arachidonic acid level and the factors responsible for calcium metabolism in idiopathic calcium nephrolithiasis, a best-fit model was constructed. This new statistical application shows a causal relationship between plasma phospholipid arachidonic acid content, intestinal calcium absorption, biochemical markers of bone turnover, urinary calcium excretion and bone mineral density at the lumbar spine. This model suggests that a defect in the phospholipid fatty acid composition could represent the primary event responsible for the mosaic of metabolic and clinical alterations that are distinctive features of renal stone formers, such as kidney, intestine, and bone calcium metabolism, and several forms of idiopathic hypercalciuria.

Increased gastrin and calcitonin secretion after oral calcium or peptones administration in patients with hypercalciuria: a clue to an alteration in calcium-sensing receptor activity.

The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH (30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration (1 g calcium gluconate) and, on a separate occasion, after peptone loading test (protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration (P < 0.01) and peptone loading (P < 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule (where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.

Endocrine disorders in the neonate.

There is a significant amount of knowledge that has been gained in recent years in the study of endocrine disorders in the newborn. The explosion of genetic data shedding light on the origins of endocrine disease has expanded the level of diagnostic evaluation and management of these infants. This article provides a general review of endocrine disorders as they present in a newborn.