Hiperfosfatasemia transitoria benigna de la infancia, reporte de un caso / Benign transient hyperphosphatasemia of childhood: a case report

La Hiperfosfatasemia Transitoria Benigna (HTB) es la causa más frecuente de elevación aislada de la Fosfatasa Alcalina (FA) en la población pediátrica. Es relevante tener la sospecha de esta entidad dada su frecuencia, carácter auto limitado y fácil diagnóstico, a pesar de esto, es poco conocida y estudiada en la Pediatría. Su clínica se asocia a niños sanos como a infecciones virales respiratorias, gastrointestinales y al retraso ponderal. El presente trabajo tiene como objetivo reportar un caso clínico y revisar el diagnóstico de la HBT.

Benign Transient Hyperphosphatasemia (BTH) is the most frequent cause of isolated elevation of Alkaline Phosphatase (AF) in the pediatric population. It is relevant to have the suspicion of this entity given its frequency, self limited character and easy diagnosis, despite this, it is little known and studied in Pediatrics. Its symptoms are associated with healthy children, such as viral respiratory, gastrointestinal infections and delayed weight gain. The objective of this work is to report a clinical case and review the diagnosis of HBT.

La alimentación con lactancia materna exclusiva es un factor de riesgo para osteopenia en prematuros menores de 1500 gramos y menores de 32 semanas de gestación en comparacion leche materna fortificada o leche de fórmula / Exclusive breastfeeding is a risk factor for osteopenia in preterm infants under 1500 grams and under 32 weeks of gestation compared to fortified breast milk or formula milk

Contexto: La osteopenia o enfermedad ósea metabólica del prematuro, consiste en una mineralización ósea insuficiente de origen multifactorial que afecta principalmente a recién nacidos pretérminos. Propósito: Determinar si la leche materna exclusiva es un factor de riesgo de osteopenia en prematuros menos de 1500 gramos y menos de 32 semanas de gestación. Material y métodos: Estudio descriptivo, epidemiológico, observacional, transversal de dos cohortes para comparar la osteopenia entre aquellos que consumen leche materna exclusiva versus los que reciben alimentación mixta (leche materna-leche de fórmula). Población 406 casos ingresados en Unidad de cuidados intensivos neonatales del Hospital Docente de Calderón- Hospital Roberto Gilbert Elizalde de Abril - Noviembre 2018. Muestra 209 prematuros. Resultados: Se analizaron 209 prematuros de bajo peso < 1.500 gramos y con edad gestacional < 32 semanas de gestación que fueron alimentados con leche materna o mixta, sexo femenino (n=109; 52,15%) y sexo masculino (n= 100; 47,85%); recibieron leche materna exclusiva (n=99; 47,37%), mientras que el (n=110; 52,63%) recibieron lactancia mixta. Se comparó los parámetros bioquímicos que forman parte del perfil de osteopenia entre los prematuros de bajo peso con lactancia materna versus lactancia mixta; los resultados muestran diferencias significativas para todos los parámetros con p-valor de 0,000; donde para el calcio la media fue de 9,23 mg en lactancia materna y 10,43 mg en mixta; la media del fósforo se ubicó en 2,94 mg en lactancia materna y 4,71 mg en mixta; por último la fosfatasa alcalina presentó promedio de 651,85 UI/L en lactancia materna y 395,51 UI/L en mixta; siendo significativas las diferencias entre estos grupos con p-valor 0,000. Conclusión: Los prematuros que recibieron leche materna exclusiva presentan mayor riesgo de desarrollar osteopenia en relación con los prematuros que recibieron lactancia mixta.

Context: Osteopenia or metabolic bone disease of prematurity, consists of an insufficient bone mineralization of multifactorial origin that mainly affects preterm newborns. Purpose: To determine if exclusive breast milk is a risk factor for osteopenia in premature babies less than 1500 grams and less than 32 weeks of gestation. Material and methods: A descriptive, epidemiological, observational, cross-sectional study of two cohorts to compare osteopenia between those who consume exclusive breast milk versus those who receive mixed feeding (breast milk-formula milk). Population 406 cases admitted to the Neonatal Intensive Care Unit of the Teaching Hospital of Calderón Hospital Roberto Gilbert Elizalde in April - November 2018. It shows 209 premature infants. Results: We analyzed 209 premature infants of low weight <1,500 grams and with gestational age <32 weeks of gestation that were fed with breast milk or mixed, female sex (n = 109, 52.15%) and male sex (n = 100; 47.85%); they received exclusive breast milk (n = 99, 47.37%), while (n = 110, 52.63%) received mixed breastfeeding. We compared the biochemical parameters that are part of the profile of osteopenia among low birth weight premature infants with breastfeeding versus mixed lactation; the results show significant differences for all parameters with p-value of 0.000; where for calcium the average was 9.23 mg in breastfeeding and 10.43 mg in mixed; the average phosphorus was 2.94 mg in breastfeeding and 4.71 mg in mixed; finally, alkaline phosphatase presented an average of 651.85 IU / L in breastfeeding and 395.51 IU / L in mixed; being significant the differences between these groups with p-value 0.000. Conclusion: Preterm infants who received exclusive breast milk presented a higher risk of developing osteopenia in relation to preterm infants who received mixed breastfeeding.

The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients

Abstract Objectives To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. Material and Methods We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. Results One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. Conclusions High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.

Resultados del tratamiento quirúrgico del hiperparatiroidismo primario en un país en vías de desarrollo / Outcomes of Primary Hyperparathyroidism Surgical Treatment in a Low-Middle Income Country

Introducción: El hiperparatiroidismo primario es una enfermedad común y con una distribución similar en todo el mundo. El propósito del estudio fue establecer si la presentación clínica y bioquímica, así como los resultados de su tratamiento quirúrgico, difieren en un país en vías de desarrollo, que no cuenta con todos los recursos diagnósticos y terapéuticos recomendados actualmente. Metodología: Análisis retrospectivo de pacientes operados por un mismo equipo, entre 1992 y 2015. Se obtuvo información sobre presentación clínica, resultados de estudios preoperatorios, procedimientos quirúrgicos, diagnóstico histopatológico y evolución postoperatoria. Resultados: Se operaron 55 pacientes con edad promedio de 45 años, 78% mujeres. El 65% eran sintomátcos. El valor promedio preoperatorio de calcio sérico fue 11.2 mg/dl, PTH 167.1 pg/ml, fósforo 2.6 mg/ dl, 25-hidroxi vitamina D 17.3 ng/ml y calcio urinario de 24 horas 294.7 mg. Al 59% se realizó estudios de localización preoperatoria. La sensibilidad del ultrasonido fue 57.14% y 75% para centellografa con tecnecio sestamibi. La positividad de los estudios de localización determinó el tipo de exploración quirúrgica (p=0.02). Se practcaron 27 (49%) exploraciones unilaterales y 28 (51%) bilaterales, resecando 47 (85.5%) adenomas solitarios y 3 ½ glándulas en 7 (12.7%) casos de hiperplasias. En 27 (36%) coexista patología tiroidea. Las tasas de curación, persistencia y recurrencia fueron 94.5%, 5.5% y 3.6% respectivamente. Conclusiones: La mayoría de nuestros pacientes operados son jóvenes y sintomátcos. La estrategia quirúrgica fue condicionada por los estudios de localización. Nuestras tasas de curación, persistencia y recurrencia son comparables a las reportadas.

Background: Primary hyperparathyroidism (HPTP) is a common disease with widespread distribution around the world. The aim of this study was to establish if clinical and biochemical disease characteristics and long term results differ in patents with HPTP in a low-middle income country without all recommended diagnostc and therapeutc resources. Methods: Retrospective collection of clinical diagnosis, biochemical, operative details, histology and long term results of all surgically treated patents with HPTP, from 1992 to 2015, by the same surgical team. Results: 55 patents with HPTP were analyzed. Average age is 45 years old with 78% of female patents. Sixty five percent were symptomatic. The mean preoperative serum calcium level was 11.2 mg/dl, PTH 167.1 pg/ml, phosphorus 2.6 mg/ dl, vitamin D 17.3 ng/ml and 24 hour urinary calcium 294.7 mg. Fifty nine percent of the patents had preoperative imaging. Ultrasound and sestamibi scan sensitivity was 57.1% and 75% respectively. Unilateral localization in preoperative imaging determined surgical exploration (p=0.02). Unilateral approach was used in 27 (49%) patents and bilateral in 28 (51%); 47 (85.5%) solitary adenomas and 7 (12.7%) 3 ½ gland resections of hyperplastic glands were performed. Thyroid pathology co-existed in 27 (36%) patients. Cure, persistence and recurrence rates were 94.5%, 5.5% y 3.6% respectively. Conclusions: In this study most of the patents were young and symptomatc. Surgical strategy was determined by preoperatve imaging. Cure, persistence and recurrence rates were comparable to published literature.

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.

Research progress on pharmacotherapy of calcific aortic valve disease / 浙江大学学报·医学版

With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.

Evaluación del metabolismo fosfo-cálcico en el síndrome nefrófico córtico-sensible primario en pediatría / Evaluation of bone and mineral metabolism in primary corticosteroid-sensitive pediatric nephrotic syndrome

Introducción: el tratamiento esteroide del síndrome nefrótico cortico sensible (SNCS) puede causar alteraciones del metabolismo mineral, prevenibles con calcio y vitamina D. Se llevó a cabo un estudio de cohortes de tipo retrospectivo longitudinal a lo largo de 36 meses. Objetivos: 1) evaluar la relación entre la Dosis Acumulativa de corticoides (DAC) con la concentración sérica de 25-OH Vitamina D y con el Contenido Mineral Ëseo (CMO); 2) evaluar la relación entre la DAC y el CMO en la Densitometría Mineral Ësea (DMO). Material y métodos: Incluimos a pacientes entre 2 años y 12 años con síndrome nefrótico primario cortico-sensible (SNCS) (primer episodio o síndrome nefrótico recaedor o síndrome nefrótico cortico-dependiente), normotensos, eutróficos y con FG>90ml/min/1.73m2, los cuales se separaron en 3 grupos: GRUPO A: 3 o 6 años (puntaje Z y CMO), edad ósea, PTHi. Resultados: Evaluamos a 29 pacientes, con una edad media de 4,4 años. La DMO se realizó en 11 pacientes y no hubo diferencias significativas entre los grupos (p=0,08). Tampoco hubo diferencias significativas entre la media de la edad cronológica y la edad ósea media media (p 0,3). La prueba T para evaluar la dosis de 25-OH colecalciferol al aumentar la dosis de Ergocalciferol fue significativa (T:32.4 Q: <0.001). Hubo una correlación significativa entre los tres grupos: entre la dosis de Vitamina D y el dosaje sérico de Vitamina D de 0,9; entre el DAC y la dosis de 25 OH colecalciferol de 0,62 y entre el DAC y el CMO de 0.44. Por último, el aumento promedio en los tres grupos de dosis de vitamina D fue de 1833UI. Conclusiones: Observamos una relación entre la DAC e hipovitaminosis D, corregible al aumentar la dosis de Vitamina D.

Introduction: steroid treatment for corticosteroid-sensitive nephrotic syndrome (CSNS) could cause bone and mineral metabolism alterations, preventable with calcium and Vitamin D. Objectives: We carried out a preliminary retrospective study along 36 months with the following objectives. 1) To evaluate the relationship between Cumulative Corticosteroid Doses (CCD) and 25-0 Vitamin D serum concentration and with Bone Mineral Content (BMC); 2) To evaluate the relationship between CCD and Bone Mineral Densitomety (BMD). Methods: We included patients between 2 and 12 years of age with corticosteroid sensitive primary nephrotic syndrome (CSNS) (first episode, relapsing nephrotic syndrome, corticosteroid dependent nephrotic syndrome) normotensive, eutrophic and FG>:90ml/min/1.73 m2, who were divided into three groups: GROUP A: =3 or 4 relapses/year, GROUP C: CSNS, we measured: a) Quarterly: calcemia, phosphatemia, alkaline phosphatase; b) half-yearly: 25-OH cholecalcipherol levels, CCD; c) annually BMD in children >6 years (score Z and BMC), bone age, PTHi. Results: We evaluated 29 patients, average age: 4.4 years. The BMD was performed on 11 patients and there were no significant differences among the groups (p=0.08). No significant differences were seen between chronologic age and average bone age (p=0.3). Change in 25-OH cholecalcipherol levels due to the increase of ergocalcipherol dose was significant (T:32.4 Q:<0.001). There were significant correlation in the three groups, between Vitamin D dose and Vitamin D serum levels (Pearson correlation R=0.9), between CCD and 25 OH cholecalcipherol dose: (Pearson correlation R=0.62) and between CCD and BMC (Pearson correlation R=0.44). Finally, in these three groups the average increase of vitamin D was: 1833IU. Conclusions: We found a relationship between CCD and hypovitaminosis D, which could be corrected increasing Vitamin D dose.

Trastorno mineral y óseo relacionado a la enfermedad renal crónica en pacientes prevalentes en diálisis crónica en el trienio 2011-2013 en Argentina / Mineral and bone disorder related to chronic renal disease in prevalent chronic dialysis patients in a 3 years period 2011-2013 in Argentina

Introducción: existen pocos datos acerca de la variación en el tiempo de los trastornos del metabolismo mineral y óseo (TMO) relacionado a la IRC en los pacientes prevalentes en diálisis crónica en Argentina. Material y métodos: Tomamos los datos del trienio 2011-2013 del Registro Argentino de Diálisis Crónica SAN-INCUCAI. Se analizaron la demografía, etiología de la IRC y las variables bioquímicas del metabolismo mineral y óseo de los pacientes prevalentes en DC, así como su tratamiento. Resultados: La población prevalente creció desde 26.572 pacientes en el año 2011 hasta 27.966 pacientes en el año 2013. Este aumento de la población prevalente fue debida, fundamentalmente, al crecimiento de los incidentes en DC. La edad promedio de esta población aumentó de 57,2 (±17,0) a 57,5 (±16,9) años entre 2011 y 2013. Aumentó la tasa de prevalentes de 65 o más años de ambos sexos entre 2011 y 2013, pero más en hombres. La nefropatía diabética se constituyó en la primera etiología con el 27,2%. En 2013, se logran valores adecuados de calcemia en el 54,5%, de fosfatemia en el 55% de los pacientes prevalentes en DC. Conclusiones: En el año 2013 el 25,5 % tuvo valores de iPTH entre 150 a 300 pg/ml, el 22,9 % 600 pg/ml. Los valores más bajos de iPTH se obsevan a mayor edad, en varones, en pacientes diabéticos y en los primeros años de DC (nuevos pacientes)...

Introduction: There are few data concerning variation over time of mineral and bone metabolism disorder (MBD) in prevalent chronic dialysis patients (CD) in Argentina. Methods: 3-years-period time 2011-2013 data from Argentine Registry of Chronic Dialysis was used. Demography, Chronic Renal failure etiology (CRF) and MBD biochemical variables in CD prevalent patients, were analyzed. Results: Prevalent population grew from 26572 to 27966 patients between 2011 and 2013, basically as a consequence of incidents growth. Age increased from 57.2 (± 17.0) to 57.5 (±16.9). In both sexs =65 years old rate increased, more in men. Diabetic Nephropathy is the first etiology (27.2%). Between 2011 and 2013 there is a significant decrease of PTHi (p=0.001) average values. In 2013, 25.5% showed between 150 to 300 pg/ml values, 22.9% 600 pg/ml values. The lowest PTHi values can be observed in elderly, males, diabetic pattiens and in the first years under CD treatment. Conclusions: Average PTHi, as well as patients with over 600 pg/ml percentage decreased, but the adequate range patients percentage (150-300) remained unchanged. Average PTHi decrease is due to the progressive increase of sub-populations less likely to develop hyperparathyroidism: elderlypeople, males, diabetics and new patients...

Metabolismo mineral y óseo: visióngeneral y sus métodos de medición / Bone and mineral metabolism: overview and methods of measurement

Resumen: las concentraciones plasmáticas de calcio, fósforo y magnesio dependen del balance neto del depósito mineral óseo y su resorción, la absorción intestinal y la excreción renal. Estos iones son importantes para muchas funciones biológicas y celulares como la señalización intracelular, la transmisión neural y la contracción muscular. Las principales hormonas que regulan la homeostasis de estos procesos son la hormona paratiroidea (PTH), la calcitonina, la 1,25-dihidroxi vitamina D y el factor de crecimiento fibroblástico-23 (FGF- 23). A través de sus acciones e interacciones sobre el hueso, el riñón y el tracto gastrointestinal las hormonas calciotrópicas (la hormona paratiroidea, la calcitonina y los metabolitos de la vitamina D, especialmente la 1,25-dihidroxi vitamina D) actúan para mantener la calcemia dentro de un rango normal, lo que permite el funcionamiento óptimo de muchos procesos fisiológicos dependientes de calcio. Los avances en las técnicas de análisis de los diferentes componentes del metabolismo mineral y óseo son útiles en la comprensión de su papel en la salud y la enfermedad. En este artículo se ofrece una revisión de los aspectos fisiológicos, clínicos y analíticos de estos protagonistas en el metabolismo óseo y mineral.

Abstract: the plasma concentrations of calcium, phosphate, and magnesium are dependent on the net balance of bone mineral deposition and resorption, intestinal absorption, and renal excretion. These ions are important for many biologic and cellular functions such as intracellular signaling, neural transmission, and muscle contraction. The principal hormones regulating the homeostasis of these processes are parathyroid hormone (PTH), calcitonin, 1.25-dihydroxy vitamin D and fibroblast growth factor-23 (FGF-23). Through their actions on bone, kidney and the gastrointestinal tract, the calciotropic hormones (parathyroid hormone, calcitonin, and vitamin D metabolites, especially the 1.25-dihydroxy vitamin D) act to maintain serum calcium within a normal range, that allows the optimally function of many calcium-requiring physiological functions. The improved procedures for the assays of different components of mineral and bone metabolism are useful in understanding their role in health and disease. This paper provides a review of the physiology, clinical and analytic aspects of these protagonists in bone and mineral metabolism.

Hiperparatiroidismo primario normocalcémico

Presentamos las características clínicas, bioquímicas y densitométricas de 35 pacientes con hiperparatiroidismo primario (HPP) normocalcémico, que se caracteriza por un nivel elevado de hormona paratiroidea intacta (PTHi) con el calcio sérico y iónico persistentemente normales, una vez descartadas posibles causas de hiperparatiroidismo secundario. Del total, 30 fueron mujeres (90%) y 5 varones (10%). Se seleccionó un grupo control de 55 pacientes con hiperparatiroidismo primario hipercalcémico: 51 mujeres (93%) y 4 varones (7%). El promedio de edad al diagnóstico de HPP normocalcémico fue de 61.4 ± 11.7 años y del HPP hipercalcémico de 56.4 ± 11.3 años. Además de las diferencias esperables de la calcemia, el calcio iónico, el fósforo y la calciuria de 24 horas, no encontramos cambios significativos en el resto de las variables bioquímicas. Tampoco encontramos diferencias en los valores densitométricos, la presencia de osteopenia u osteoporosis y el número de fracturas entre ambos tipos de HPP. Sí hubo una diferencia significativa en la presencia de litiasis renal entre el HPP normocalcémico (11.4%) vs el HPP clásico (49.1%), p < 0.0005, en parte vinculada a la presencia de hipercalciuria en el HPP clásico. Dos de los 35 pacientes con HPP normocalcémico evolucionaron al HPP hipercalcémico durante un seguimiento de 4 años. Nuestros resultados apoyan la hipótesis que el HPP normocalcémico podría ser una forma temprana del HPP clásico, teniendo ambos similares repercusiones clínicas a nivel renal y óseo.

This report shows our conclusions on the clinical, biochemical and densitometry characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients. This condition is defined by a high level of intact parathyroid hormone (iPTHI) with persistently normal serum and ionized calcium in the absence of secondary hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%). The control group of 55 hypercalcemic patients with primary hyperparathyroidism included 51 women (93%) and 4 men (7%). The average age at diagnosis of normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic PHPT. Besides the expected differences in serum calcium, ionized calcium, phosphorus and 24 h urinary calcium, we found no significant changes in other biochemical variables, and no differences in densitometry evaluations such as the presence of osteopenia or osteoporosis and the number of fractures in the two types of PHPT. But there was a significant difference in the presence of renal lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005, to some extent associated to the presence of hypercalciuria in classic PHPT. Two of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over a 4 year follow-up period. Our findings support the hypothesis that the normocalcemic PHPT could be an early stage of the classic PHPT, both having similar clinical effects to metabolic renal and bone levels.

KDIGO CKD-MBD Discussion forum: the Brazilian perspective / Fórum nacional de discussão das diretrizes do KDIGO para o distúrbio mineral e ósseo da doença renal crônica (DMO-DRC): uma análise crítica frente à relidade Brasileira

No dia 14 de novembro de 2009, a Sociedade Brasileira de Nefrologia promoveu um fórum de discussão das novas diretrizes do KDIGO (Kidney Disease: Improving Global Outcomes). O objetivo desse encontro, onde estiveram presentes 64 participantes, foi discutir estas novas diretrizes diante da realidade brasileira. Esse encontro teve o patrocínio da Empresa de Biotecnologia Genzyme, que não teve acesso à sala de discussão e tampouco aos temas tratados durante o evento. Este artigo traz um resumo das diretrizes do KDIGO e das discussões realizadas pelos participantes.

On November 14th, 2009, the Brazilian Society of Nephrology coordinated the Brazilian Discussion Meeting on the new KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. The purpose of this meeting, which was attended by 64 nephrologists, was to discuss these new guidelines from the Brazilian perspective. This meeting was supported by an unrestricted grant of the biotechnology company Genzyme, which did not have access to the meeting room or to the discussion sections. This article brings a summary of the KDIGO guidelines and of the discussions by the attendees.

Osteomalacia tumoral / Tumoral osteomalacia

La osteomalacia tumoral (OT) u osteomalacia oncogénica es un síndrome paraneoplásico producido por una pérdida renal de fosfato. Es una enfermedad rara, con aproximadamente 130 casos publicados. Recientemente, se han descrito varios factores de origen óseo que participarían en el mantenimiento de la homeostasis del fósforo; en conjunto se los denomina ?fosfatoninas?, y el más conocido es el Factor de Crecimiento Fibroblástico 23 (FGF-23). Ésta es una hormona proteica detectable en el suero de sujetos sanos y ha sido relacionado con la fisiopatología de tres tipos de raquitismo/osteomalacia con hipofosfatemia: dos enfermedades hereditarias (raquitismo u osteomalacia hipofosfatémicos asociado/a al cromosoma X [XLH], y raquitismo u osteomalacia autosómicos dominantes [ADHR]), y la OT. Los tumores asociados a la OT son de origen mesenquimático, de crecimiento lento, complejos y polimórficos. En general estos tumores son benignos, de tamaño pequeño, asintomáticos y de localización incierta; también se ha descrito el cuadro en asociación con neoplasias malignas. El diagnóstico presuntivo requiere la documentación de hipofosfatemia y de una disminución marcada en la reabsorción tubular de fósforo. Deben registrarse los antecedentes familiares, y proceder a estudios de localización del tumor: la TC y la RNM son de poca utilidad, y recientemente se ha visto la sensibilidad de centellogramas con análogos de somatostatina y del PET scan con fluorodesoxiglucosa. El diagnóstico de certeza se obtiene si se logra la reversión de la hipofosfatemia con la extracción del tumor. El tratamiento médico requiere dosis altas de fosfatos y calcitriol por vía oral, no siempre bien tolerados. Se han usado también el octreotide y el calcimimético cinacalcet. El tratamiento curativo es la remoción quirúrgica del tumor causante.

Rosiglitazona, agonista do PPAR-y "Peroxisome Proliferator-Activated Receptor-y" reverte a nefrotoxicidade induzida pelo tenofovir-DF / The peroxisome proliferator-activated receptor-y agonist rosiglitazone reverses tenofovir-induced nephrotoxicity

Introdução: A nefrotoxicidade dos antiretrovirais constituem atualmente fator importante na morbidade e mortalidade de pacientes com HIV. O tenofovir DF (TDF) se enquadra em um dos antiretrovirais mais lesivos ao rim. Conhecer seu mecanismo de nefrotoxicidade e estudar medidas protetoras podem melhorar seu uso clínico. Material e Métodos: Ratos foram tratados durante 30 dias com uma de duas doses de TDF (50 ou 300mg/Kg de dieta), sendo que um grupo teve adicionado em sua dieta maleato de rosiglitazona (RSG) na dose de 92mg/Kg de dieta nos últimos 15 dias. Após esse período, os ratos foram colocados em gaiola metabólica e sacrificados. Foram estudados parâmetros bioquímicos, fluxo sanguíneo renal e os rins extraídos para expressão semiquantitativa dos transportadores epiteliais tubulares. Resultados: Os animais que receberam TDF em dose alta apresentaram insuficiência renal severa acompanhada de redução da expressão da oxido-nítrico sintase endotelial e vasoconstricção renal intensa. Todos esses parâmetros foram parcialmente revertidos pela administração de RSG. Baixas doses de TDF não causou alteração significativa do ritmo de filtração glomerular, porém induziu fosfatúria, acidose tubular proximal, poliúria e redução da capacidade de concentração urinária. Essas alterações foram associadas a redução da expressão de alguns transportadores epiteliais (cotransportador sódio-fosforo, contratransportador sódio-hidrogênio tipo 3 e aquaporina tipo 2). Não foi caracterizado síndrome de Fanconi, pois não houve proteinúria ou glicosúria. O tratamento com RSG reverteu todos os parâmetros de nefrotoxicidade estudados, normalizando as alterações bioquímicas urinárias e a expressão dos transportadores de membrana. Conclusões: Os achados desses experimentos tem potencial aplicação clínica em pacientes com nefrotoxicidade induzida pelo TDF, especialmente naqueles com hipofosfatemia e/ou redução do ritmo de filtração glomerular.

Objective: To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)- induced nephrotoxicity and the protective effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-y agonist. Methods: Rats were treated for 30 days with one of two TDF doses (50 or 300 mg/kg of food), to which RSG (92 mg/kg of food) was added for the last 15 days. Biochemical parameters were measured, and renal tissue was extracted for immunoblotting. Results: Mean daily ingestion was comparable among all the treated groups. Highdose TDF induced severe renal failure accompanied by reduced expression of endothelial nitric-oxide synthase and intense renal vasoconstriction. All of these features were ameliorated by RSG administration. Low-dose TDF did not alter the glomerular filtration rate but induced significant phosphaturia, proximal tubular acidosis and polyuria, as well as reducing urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. No Fanconi's syndrome was identified (proteinuria was normal and there was no glycosuria). Treatment with RSG reversed TDF-induced tubular nephrotoxicity, normalizing urinary biochemical parameters and membrane transporter protein expression. Conclusion: These findings have potential clinical applications in patients presenting with TFV-induced nephrotoxicity, especially in those presenting with hypophosphatemia or a reduction in glomerular filtration rate.

Calcinosis tumoral en pediatría: reporte de un caso clínico y revisión de la literatura / Tumoral calcinosis in young children: report of a case and literature review

We report a case of tumoral calcinosis in young girl, a quite infrecuent condition, caused by a hereditary dysfunction of phosphate regulation. Our aims are to review imaging signs (plain radiography ultrasound, Computed Tomography and nuclear medicine) and clinical and laboratory findings as well. Finally we made a literature search, oriented to help in diagnosing this disease, specially regarding images.

Presentamos el caso de una niña preescolar portadora de calcinosis tumoral, entidad infrecuente, causada por una disfunción hereditaria en la regulación de la excreción de fosfatos. Damos a conocer los hallazgos radiológicos (radiografía simple, ultrasonografía, tomografia computada y cintigrafía ósea), así como también hallazgos clínicos y laboratorio del caso, además de revisar la literatura para una breve actualización de esta condición, especialmente en lo que respecta al diagnóstico y las imágenes.

Raquitismos e metabolismo ósseo / Rickets and bone metabolism / Raquitismos y metabolismo ósseo

Objetivo: atualizar o conhecimento do metabolismo ósseo e da fisiopatogenia, diagnóstico e tratamento dos raquitismos. Fontes pesquisadas:artigos localizados na base MEDLINE publicados entre 1997 e 2007, com as palavras chave “deficiência de vitamina D”, “raquitismo”, e “metabolismoósseo”, além de outros artigos relevantes publicados antes, e as publicações da American Society for Bone and Mineral Research entre 2003e 2008. Síntese dos dados: os conhecimentos relativos ao metabolismo ósseo ampliaram-se, destacando o receptor-sensor de cálcio (RSCa),fundamental no controle da secreção do PTH e da calciúria, e o FGF-23 (fator de crescimento dos fibroblastos-23), importante no controle da fosfatemia através da inibição do co-transportadorde sódio e fosfato tipo II (NPT-II) no túbulo proximal, além de inibir a 1α-hidroxilase e a formação da vitamina D ativa (calcitriol). Foi elucidado o sistema RANKL-RANK-OPG na atividadeosteoclástica. A homeostase do cálcio e fósforo no osso depende da ação integrada do calcitriol, PTH, RSCa e FGF-23. Os distúrbios dessa homeostasepodem causar raquitismo, caracterizadopela inadequada mineralização da placa de crescimento. A deficiência da vitamina D ainda constitui a principal causa, em especial nas populaçõesem desenvolvimento. Em crianças eadolescentes com doenças crônicas o raquitismo pode decorrer de deficiência da vitamina D ou de alterações no seu metabolismo. Novas etiologiasgenéticas de raquitismo hipofosfatêmico foram descritas, relacionadas às alterações da secreção ou ação do FGF-23, ou da ação do NPT-II. Conclusões:o conhecimento da fisiologia óssea pelopediatra permite que o raquitismo seja adequadamente suspeitado e investigado nas crianças com crescimento deficiente ou deformidades e naquelas com doenças crônicas.

Objective: up-to-date the knowledge about bone mineral metabolism and the physiopathology, diagnosis and treatment of rickets. Data source: articles published between 1997-2007 were selected from MEDLINE. Relevant articles published previously to this period and publications from “The American Society for Bone and Mineral Research” from 2003 to 2008 were also examined. Data synthesis: the knowledge about bone mineral physiology has been changed with emphasis on the calcium sensing-receptor (CaSR), that acts to regulate the PTH secretion and the calciuria, and on the FGF-23 (fibroblast growth factor-23), that controls phosphatemiainhibiting the sodium-phosphate co-transporter type II (NPT-II) on proximal tubule, and that also reduces the 1α-hydroxylase activity and the formation of active vitamin D (calcitriol). The role of RANKL-RANK-OPG system on osteoclasts was clarified. The calcium and phosphorus homeostasis depends on the integrated action of calcitriol, PTH,CaSR and FGF-23. Disturbances affecting this homeostasis may cause rickets, characterized by inadequatemineralization of the growth plate. Vitamin D deficiency is still considered an important cause of rickets in Africa, Asia and in populational groupsfrom other countries. Children and adolescents with chronic diseases may have rickets due to deficiencyof vitamin D or to alterations of its metabolism. New etiologies of hypophosphatemic genetic ricketshave been described related to disturbances affecting the secretion or the action of FGF-23 or the actionof NPT-II. Conclusions: the knowledge of bone mineral physiology by pediatricians allows that rickets be adequately suspected and investigatedin children with deficient growth or deformities or with chronic diseases.

Objetivo: actualizar el conocimiento del metabolismo óseo y de la fisiopatogenia, diagnostico y tratamiento de los raquitismos. Fuentes pesquisadas:artículos localIzados en la base de datos MEDLINE publicados entre 1997 y 2007, utilizando las palabras claves “deficiencia de vitamina D”,“raquitismo”, y “metabolismo óseo”, además de otros artículos importantes publicados antes, y las publicaciones de la American Society for Bone andMineral Research entre 2003 y 2008. Síntesis de los datos: los conocimientos relativos al metabolismo óseo se ampliaron, destacando el del receptor-sensor de calcio (RSCa), fundamental en el control de la secreción de PTH y de calciuria, y el FGF-23 (factorde crecimiento de los fibroblastos-23), importante en el control de la fosfatemia a través de su acción renal. Fue elucidado el sistema RANKL-RANKOPGen la actividad osteoclastica. La homeostasis del calcio y fósforo en el hueso depende de la acción integrada del calcitriol, PTH, RSCa y FGF-23. Losdisturbios de esa homeostasis pueden causar raquitismo, caracterizado por la mineralización inadecuada de la placa de crecimiento. La deficiencia devitamina D todavía constituye la causa principal, en especial en las poblaciones en desarrollo. En niños y adolescentes con enfermedades crónicas el raquitismopuede decorrer de la deficiencia de vitamina D o de alteraciones en su metabolismo. Nuevas etiologías genéticas del raquitismo hipofosfatemicofueron descritas, relacionadas a las alteraciones de la secreción o acción del FGF-23, o de la acción del NPT-II. Conclusiones: el conocimiento de la fisiología ósea por el pediatra permite que el raquitismo sea adecuadamente sospechado e investigado en losniños con crecimiento deficiente o deformedades e en aquellos con enfermedades crónicas.

Impacto de um programa de educação nutricional no controle da hiperfosfatemia de pacientes em hemodiálise / The impact of a nutrition educational program on the control of the hyperphosphatemia in hemodialysis patients

Introdução: O controle do fósforo sérico é um desafio no tratamento de pacientes em hemodiálise. O emprego de estratégias educativas poderia contribuirpara melhorar a adesão destes pacientes ao tratamento. Assim, o objetivo deste estudo foi avaliar o impacto de um programa de educação nutricional sobreo conhecimento a respeito do fósforo e sobre a fosfatemia de pacientes em hemodiálise. Métodos: Foram incluídos 147 pacientes [85homens/62mulheres,idade= 50,5±15,7 anos, tempo em diálise = 32 (1-205) meses] que estavam no programa de hemodiálise durante o período de agosto a dezembro de 2006.O material educacional incluiu um questionário de avaliação de conhecimentos, uma palestra, jogos e livretos educativos. Foram medidas as concentraçõesséricas de fósforo e uréia, e a eficiência da diálise foi avaliada por meio do Kt/V. Resultados: Após a aplicação do programa educacional, houve umaumento da pontuação do questionário de conhecimentos (5,7±1,1 para 6,6±0,7;P<0,01) e uma redução do fósforo sérico (5,5±1,6 para 5,2±1,6mg/dl;P<0,01). A uréia sérica se manteve e o Kt/V aumentou (1,34±0,28 para 1,43±0,31;P<0,01). Quando os pacientes foram divididos de acordo com aconcentração sérica de fósforo do início do programa, foi observado que, no grupo normofosfatêmico (fósforo sérico ³5,5mg/dl, n=81), não houve alteraçõesno fósforo sérico após a aplicação do programa (4,4±0,7 para 4,6±1,6 mg/dl;P=0,12). Já no grupo hiperfosfatêmico (fósforo sérico ³5,5mg/dl, n=66),observou-se uma redução da concentração sérica de fósforo (6,9±1,2 para 5,8±1,6mg/dl;P<0,01), uréia (173±33 para 167±36mg/dl;P=0,02) e um aumentodo Kt/V (1,26±0,28 para 1,38±0,22;P<0,01). A variação do fósforo sérico neste grupo correlacionou-se positivamente com a variação da uréia sérica(r=0,29; P=0,02), mas não com a variação do Kt/V. A redução da concentração sérica de fósforo para valores inferiores a 5,5mg/dl ocorreu em 39,4.

Hiperparatiroidismo secundario en diálisis / Secondary hyperparathyroidism in dialysis

El hiperparatiroidismo secundario es uno de los principales problemas que afectan al paciente con Insuficiencia Renal Crónica. Objetivos: Determinar la prevalencia del hiperparatiroidismo secundario y el tiempo aproximado de diálisis transcurrido hasta el momento de su diagnóstico. Material y método: Estudio prospectivo, transversal, realizado en el hospital “Luis Vernaza” desde septiembre a diciembre de 2003, con un total de 48 pacientes atendidos en el área de Nefrología. Para el Diagnóstico de hiperparatiroidismo secundario se determinó en sangre niveles de calcio, fósforo, fosfatasa alcalina y hormona paratiroidea. Se procedió a diagnosticar con hiperparatiroidismo a aquellos que presentaron niveles de PTH >250pg/ml. Resultados: La prevalencia de hiperparatiroidismo secundario en diálisis es de un 46, específicamente de un 45 para los pacientes sometidos a Hemodiálisis y de un 46 para los pacientes sometidos a diálisis peritoneal. Solo en un 5 (n=1) se evidenció un probable riesgo de calcifilaxia. El Tiempo de diálisis promedio de los pacientes con Hiperparatiroidismo secundario es de 3,38 años para los pacientes sometidos a Hemodiálisis y de un 2,05 años para los pacientes sometidos a DPCA. Conclusión: Todos los pacientes sometidos a Diálisis están en igual riesgo de desarrollar hiperparatiroidismo secundario. Los pacientes en Hemodiálisis no tienen un mayor riesgo de desarrollar Hiperparatiroidismo secundario que aquellos que están sometidos a DPCA. La prevalencia de hiperparatiroidismo secundario fue igual en ambos sexos. Los pacientes sometidos a hemodiálisis manejan niveles más altos de PTH.

Secondary hyperparathyroidism is one of the most common problems that affect patients with chronic renal failure. Objectives: Determine the prevalence of secondary hyperparathyroidism and determine the time that exists between the last dialysis and being diagnosed with secondary hyperparathyroidism. Method and materials: It is a prospective, transversal study done at “Luis Vernaza” Hospital during the period of September to December 2003 with a total of 48 patients that were treated at the Nefrology department. To diagnose Secondary hyperparathyroidism we determined serum levels of calcium, phosphorus, alkaline fosfatase and parathyroid hormone. Patients that had a level of parathyroid hormone of >250pg/ml was diagnosed with hyperparathyroidism. Results: The prevalence of secondary hyperparathyroidism in dialysis is 46. Patients undergoing hemodialysis the prevalence was of 45 and 46 for patients undergoing peritoneal dialysis. The amount of time that the patients with secondary hyperparathyroidism have been undergoing hemodialysis is approximately of 3.83 years. Conclusions: All of the patients in dialysis have the same risk to develop secondary hyperparathyroidism. Patients undergoing hemodialysis do not have a higher risk of developing secondary hyperparathyroidism. The prevalence of secondary hyperparathyroidism was the same in both sexes. The patients that underwent hemodialysis had a higher PTH.

Tumoral calcinosis with hyperphosphatemia.

Tumoral calcinosis is a rare disorder of mineral metabolism among adolescents and young adults characterized by deposition of calcific masses around large joints. It is less commonly reported in pediatric population and commonly mistaken for bone tumors. Typical lab parameters include hyperphosphatemia with normal levels of serum calcium, parathyroid hormone (PTH) and alkaline phosphatase. A ten-year-old boy with typical features of tumoral calcinosis is presented.