Regulación del calcio por SERC-A antes de la enfermedad de Alzheimer y durante la misma / Calcium regulation by SERC-A before and during Alzheimer disease

Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos / Pseudohypoparathyroidism: report of two cases of late presentation

Pseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyperphosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth's Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting, they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroidism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder / Reversão da calcinose tumoral urêmica pela otimização do tratamento clínico da desordem do metabolismo ósseo e mineral

Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Resumo A calcinose tumoral é um tipo raro de calcificação extraóssea caracterizada por grandes massas císticas e elásticas contendo depósitos de fosfato de cálcio. A condição é mais prevalente no tecido periarticular e preserva estruturas osteoarticulares. A elevação do produtos cálcio-fósforo e o hiperparatireoidismo secundário grave estão presentes na maioria dos pacientes com calcinose tumoral urêmica (UTC). O relato de caso em questão refere-se a um homem de 22 anos, branco, obeso, com doença renal crônica secundária à glomerulonefrite crônica, em diálise peritoneal ambulatorial contínua (CAPD), que apresentou aparecimento de tumores indolores na face medial do quinto quirodáctilio e braço esquerdo. A calcinose tumoral foi confirmada por biópsia do bíceps esquerdo. O paciente apresentava baixa adesão à CAPD. Foi transferido para a modalidade de diálise peritoneal e depois iniciou tratamento por hemodiálise. Apesar da persistência do hiperparatireoidismo grave, houve redução progressiva da UTC, com resolução próxima do seu desaparecimento completo. Há 1 ano o paciente foi submetido a transplante renal, doador falecido, e apresentou melhora do hiperparatiroidismo secundário. A UTC deve ser incluída na elucidação de calcificação periarticular de pacientes em diálise. Os achados laboratoriais relevantes, tais como hiperparatiroidismo secundário e elevação dos produtos cálcio-fósforo na presença de calcificação periarticular, devem chamar a atenção para o diagnóstico da UTC.

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.

Comparison of on -line hemodiafiltration and high -flux hemodialysis for correcting calcium and phosphate metabolic disorder in uremia patients / 中国基层医药

Objective To compare the effect on correcting calcium and phosphate metabolic disorder and the impact on quality of life in uremia patients between on -line hemodiafiltration and high -flux hemodialysis.Methods 90 patients with uremia,digital watches were randomly divided into QL -HDF group and HFHD group,Ca2 +,P3 +, serum parathyroid hormone(PTH)level were measured before and after dialysis blood.The survival quality of patients were evaluated by the KDQOL -SFTM1.3 scale.The incidence of adverse reactions were collected.The similarities and differences of two groups were compared.Results The comparison of Ca2 + levels in the two groups before and after dialysis showed no significant difference(P >0.05);Of the QL -HDF group after treatment,P3 + was (1.82 ± 0.19)mmol/L,PTH was (401.6 ±16.7)pg/L,which were significantly lower than those of QL -HDF group[P3 +(2.14 ±0.22)mmol/L,PTH(425.0 ±17.2)pg/L](t =24.256,21.059,all P 0.05 );6 cases of adverse reactions was in the QL -HDF group (13.33%),14 cases of adverse reactions was in the HFHD group(31.11%),there was significant difference between the two groups(χ2 =5.361,P <0.05).Conclusion The two methods can improve the metabolic disorders of calcium and phosphorus in patients with uremia,and QL -HDF showed stronger ability to remove the ability,and the quality of life is higher,it is worth promoting in clinical practice.

Metabolismo mineral óseo en pacientes con enfermedad renal crónica: Revisión sobre su fisiopatología y morbimortalidad / Bone mineral metabolism in patients with chronic kidney disease: review of its pathophysiology and morbimortality

La enfermedad mineral ósea (EMO) es un término amplio que incluye a las alteraciones séricas del calcio, fósforo, vitamina D, paratohormona, anormalidades en el crecimiento, mineralización ósea y/o a las calcificaciones extraesqueléticas que acompañan al paciente con enfermedad renal crónica (ERC). Está presente en casi la totalidad de pacientes en diálisis y con el trasplante renal puede no siempre mejorar. Se han identificado nuevos factores y hormonas; como klotho y factor de crecimiento de fibroblastos-23 (FGF-23) que interactúan con la vitamina D y con la paratohormona en el manejo renal del calcio y fósforo. Ciertos reportes indican que son marcadores precoces del desarrollo de EMO, incluso cuando la función renal está levemente disminuida y los niveles de paratohormona son normales. La EMO ha sido asociada con mayor mortalidad, principalmente por su vinculación con la calcificación vascular. Este proceso conlleva a un incremento de eventos cardiovasculares que constituyen la principal causa de morbimortalidad en pacientes con ERC, sobre todo aquellos que se encuentran en diálisis, independientemente de la modalidad que los pacientes sigan. La forma de presentación de la EMO puede ser de alto o bajo recambio. Aunque no está completamente definido qué es lo que determina que se exprese una en particular, se ha encontrado que la enfermedad de bajo recambio se relaciona con malnutrición, uso inadecuado de calcitriol y diálisis ineficiente. El conocimiento de la EMO es relevante por su asociación con las complicaciones mencionadas y porque constituye un parámetro para evaluar la terapia instalada.

Mineral Bone Disorder (MBD) is a broad term that includes abnormal serum calcium, phosphorus, vitamin D, parathyroid hormone, growth abnormalities, bone mineralization and/or extraskeletal calcifications in patients with chronic kidney disease (CKD ). It is present in almost all patients on dialysis and may not always improve with a kidney transplant. New factors and hormones have been identified, such as Klotho and fibroblast growth factor-23 (FGF-23) that interact with vitamin D and the parathyroid hormone in the renal management of calcium and phosphorus. Some reports indicate that they are early markers of the development of MBD, even when kidney function is slightly decreased and parathyroid hormone levels are normal. MBD has been associated with higher mortality, mainly because of its link with vascular calcification. This process leads to an increase in cardiovascular events which are the leading cause of morbidity and mortality in CKD patients, especially those who are on dialysis, regardless of the modality that the patients follow. The presentation of the BMD can be of high or low turnover. Although it is not completely defined what determines that a particular form of presentation is expressed, it has been found that the low turnover disease is related to malnutrition, inappropriate use of calcitriol and inefficient dialysis. Knowledge of BMD is relevant for its association with the complications mentioned above and because it constitutes a parameter for assessing the instituted therapy.

Study on the related factors for mineral metabolism in elderly patients with maintenance hemodialysis / 中华老年医学杂志

Objective To investigate the present state of mineral metabolism and its related factors in elderly patients with maintenance hemodialysis (MHD),in order to improve the quality of life and survival rate in elderly patients with MHD in Xinxiang.Methods Clinical data of 466 patients with treatment of MHD for over 3 months in 4 hospitals in Xinxiang district were enrolled from January 2012 to August 2013 in this study,and the patients were divided into the elderly group (n=159,aged ≥ 60 years) and the non-elderly group (n =307,aged ＜ 60 years).The evaluation indexes for mineral metabolism were determinated,such as serum levels of calcium,phosphorus,intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP).The present state of mineral metabolism and its relationships with anemia,dialysis ages,adequacy of dialysis,malnutrition and inflammatory factors were analyzed in elderly patients with MHD.Results Among 466 patients,the serum levels of calcium,phosphorus and iPTH in MHD patients were (1.95 ± 0.34) mmol/L,(2.54±1.38) mmol/L and (409.5±345.6) ng/L respectively,and their control rates were 34.3％,20.4％ and 25.5％ respectively.And in patients with hemodialysis three times a week,the control rates were 50.8％,31.4％ and 32.2％ respectively.The serum levels of phosphorus,iPTH,ALP,albumin and transferrin saturation were lower in elderly group than in non-elderly group (all P＜0.01),and the serum levels of pre-albumin,hemoglobin and feritin were lower in elderly group than in non-elderly group (all P＜0.05).But the serum levels of calcium and C-reactive protein (CRP)were higher in elderly group than in non-elderly group (all P＜0.05).Conclusions The elderly patients with MHD exhibit unique clinical manifestations of abnormal mineral metabolism,and low bone transformation osteopathy is the main manifestation.The micro-inflammation,malnutrition and anemia are more severe in elderly patients than in non elderly patients.

Five years results after intrafamilial kidney post-transplant in a case of familial hypomagnesemia due to a claudin-19 mutation / Resultado cinco anos pós-transplante renal intrafamiliar em um caso de hipomagnesemia familiar devido a mutação da claudina-19

Introduction: Familial Hypomagnesaemia with hypercalciuria and nephrocalcinosis, with severe ocular impairment secondary to claudin-19 mutation, is a rare recessive autossomic disorder. Its spectrum includes renal Mg2+ wasting, medullary nephrocalcinosis and progressive chronic renal failure in young people. Objective: To report a case of kidney transplantation father to daughter in a familial occurrence of severe bilateral nephrocalcinosis associated with ocular impairment in a non-consanguineous Brazilian family, in which two daughters had nephrocalcinosis and severe retinopathy. Methods: The index case, a 19 years-old female, had long-lasting past medical history of recurrent urinary tract infections, and the abdominal X-ray revealed bilateral multiple renal calcifications as well as ureteral lithiasis, and she was under haemodialysis. She had the diagnosis of retinitis pigmentosa in the early neonatal period. The other daughter (13 years-old) had also nephrocalcinosis with preserved kidney function, retinopathy with severe visual impairment, and in addition, she exhibited hypomagnesaemia = 0.5 mg/dL and hypercalciuria. The other family members (mother, father and son) had no clinical disease manifestation. Mutation analysis at claudin-19 revealed two heterozygous missense mutations (P28L and G20D) in both affected daughters. The other family members exhibited mutant monoallelic status. In despite of that, the index case underwent intrafamilial living donor kidney transplantation (father). Conclusion: In conclusion, the disease was characterized by an autosomal recessive compound heterozygous status and, after five years of donation the renal graft function remained stable without recurrence of metabolic disturbances or nephrocalcinosis. Besides, donor single kidney Mg2+ and Ca2+ homeostasis associated to monoallelic status did not affect the safety and the usual living donor post-transplant clinical course. .

Introdução: Hipomagnesemia familiar com hipercalciúria e nefrocalcinose, com grave envolvimento ocular, por mutação no gene da claudina-19, é uma doença rara autossômica recessiva. Seu espectro inclui perda renal de magnésio, nefrocalcinose medular e doença renal progressiva em crianças e adolescentes. Objetivo: Relatar um caso de transplante renal pai para filha em uma ocorrência familiar de nefrocalcinose bilateral grave associada com comprometimento ocular em uma família brasileira não consangüínea, na qual duas filhas apresentavam nefrocalcinose e retinopatia severa. Métodos: O caso índice, uma mulher de 19 anos de idade, tinha longa história pregressa de infecção urinária de repetição, o raio-X abdominal revelava calcificações renais múltiplas bilaterais, bem como litíase ureteral, e estava sob hemodiálise. Havia um diagnóstico prévio de retinite pigmentosa no período neonatal precoce. A outra filha (13 anos de idade) também apresentava nefrocalcinose com função renal preservada, retinopatia com grave deficiência visual, e além disso, ela exibia hipomagnesemia = 0,5 mg/dL e hipercalciúria. Os outros membros da família (mãe, pai e filho) não tinham nenhuma manifestação clínica da doença. A análise mutacional no gene da claudin-19 revelou duas mutações heterozigotas (P28L e G20D) em ambas as filhas afetadas. Os outros membros da família apresentavam estado mutante monoalélico. Apesar disso, o caso índice foi submetido a transplante de rim com doador vivo intrafamiliar (pai). Conclusão: Em conclusão, a doença foi caracterizada por um estado heterozigoto recessivo composto autossômico e após cinco anos de doação a função do enxerto ...

Tuberculose associada a nefrocalcinose em um lactente / Tuberculosis associated with nephrocalcinosis in an infant

Objetivos: Relatar um caso clínico de tuberculose de apresentação não usual.Descrição do caso: Uma lactente de oito meses, sem infecção pelo vírus de imunodeficiência humana (HIV), filha de mãe seropositiva para HIV e com tuberculose pulmonar, foi internada por febre com 15 dias de evolução, sem outra sintomatologia. A radiografia de tórax revelou múltiplos focos de hipotransparência bilateralmente e a prova de tuberculina 8 mm. A doente não havia recebido a vacina BCG. Realizou broncofibroscopia que evidenciou compressão extrínseca da árvore traqueobrônquica, causada por múltiplas adenopatias, confirmadas por ressonância magnética nuclear do mediastino. Na ecografia abdominal foram encontrados aspectos sugestivos de nefrocalcinose. Os estudos do metabolismo cálcio-fósforo e da função renal não revelaram alterações. Iniciou terapêutica antibacilar tripla e corticoterapia. Foi isolado Mycobacterium tuberculosis no lavado bronco-alveolar. Verificou-se boa evolução clínica, tendo alta com 27 dias de terapêutica antibacilar.Conclusões: Este caso clínico destaca-se pela forma incomum de apresentação da tuberculose, com a presença de nefrocalcinose. As perturbações do metabolismo do cálcio associadas à tuberculose são raras, mas têm implicação no seguimento e no prognóstico.

Aims: To report a case of tuberculosis with unusual presentation.Case description: An eight months old infant without infection by the human immunodeficiency virus (HIV), born of an HIV-positive mother with pulmonary tuberculosis, was hospitalized for fever lasting 15 days, with no other symptoms. Chest radiography revealed multiple bilateral nodular opacities and the tuberculin test was 8 mm. The patient had not received BCG vaccination. Bronchoscopy showed extrinsic compression of the tracheobronchial tree, caused by multiple adenopathies, confirmed by nuclear magnetic resonance imaging of the mediastinum. Abdominal ultrasound was suggestive of nephrocalcinosis. Phospho-calcium metabolism and renal function studies showed no alterations. Triple antituberculous therapy and corticosteroid were started. Mycobacterium tuberculosis was isolated in bronchoalveolar lavage. There was good clinical outcome and the patient was discharged with 27 days of antituberculosis therapy.Conclusions : This case stands out for its unusual presentation , with the presence of nephrocalcinosis. Disturbances of calcium metabolism associated with tuberculosis are rare, but have implications for the follow-up and prognosis.

Calciphylaxis, a diagnostic and therapeutic challenge: report of a successful case / Calcifilaxia, desafio diagnóstico e terapêutico: relato de um caso bem sucedido

Calciphylaxis, also known as calcific uremic arteriolopathy, is a severe complication often observed in patients with hyperparathyroidism secondary to chronic renal failure, which occurs mainly in women. It is characterized by ischemic tissue loss secondary to progressive vascular compromise. This is a rare and severe condition and its pathogenesis is unclear. The best treatment is prevention, especially in order to maintain adequate levels of calcium and phosphorus. We describe a case of this disease in a patient with hyperparathyroidism secondary to chronic renal failure who underwent medical treatment, surgical debridement and total skin autografts, with resolution of symptoms after 6 months.

A Calcifilaxia, também conhecida como arteriolopatia urêmica calcificante, é uma complicação freqüentemente observada nos pacientes com hiperparatireoidismo secundário à insuficiência renal crônica, ocorrendo principalmente em mulheres. Caracteriza-se por necrose isquêmica cutânea, de instalação aguda e progressiva, secundária à calcificação de vasos sanguíneos de pequeno ou de médio calibre. Trata-se de uma afecção rara e grave, cuja patogênese é obscura, e o melhor tratamento é a prevenção, especialmente visando manter os níveis adequados de cálcio e de fósforo. Descrevese um caso desta moléstia em paciente portadora de hiperparatireoidismo secundário à insuficiência renal crônica, submetida a tratamento clínico, desbridamento cirúrgico e enxertos autólogos de pele total, com resolução completa do quadro após 6 meses.