RESUMO
BACKGROUND: Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. METHODS: Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. RESULTS: Treatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. CONCLUSIONS: In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds.
Assuntos
Calcimiméticos/uso terapêutico , Cinacalcete/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Diálise Renal , Cálcio , Humanos , Hormônio Paratireóideo , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Expression of the calcium-sensing receptor (CaSR) has previously been demonstrated in human circulating monocytes (HCM). The present study was designed to measure CaSR expression in HCM and to examine its potential modulation by pro-inflammatory cytokines, Ca2+, vitamin D sterols in U937 cell line. Twenty healthy volunteers underwent blood sampling with subsequent isolation of peripheral blood mononuclear cells (PBMC) at 3 visits. Flow cytometry analysis (FACS) was performed initially (V1) and 19 days later (V2) to examine intra- and intersubject fluctuations of total and surface CaSR expression in HCM and 15 weeks later (V3) to study the effect of vitamin D supplementation. In vitro experiments were conducted to assess the effects of pro-inflammatory cytokines, calcidiol, calcitriol and Ca2+ on CaSR expression in U937 cell line. By FACS analysis, more than 95% of HCM exhibited cell surface CaSR staining. In contrast, CaSR staining failed to detect surface CaSR expression in other PBMC. After cell permeabilization, total CaSR expression was observed in more than 95% of all types of PBMC. Both total and surface CaSR expression in HCM showed a high degree of intra-assay reproducibility (<3%) and a moderate intersubject fluctuation. In response to vitamin D supplementation, there was no significant change for both total and surface CaSR expression. In the in vitro study, U937 cells showed strong total and surface CaSR expression, and both were moderately increased in response to calcitriol exposure. Neither total nor surface CaSR expression was modified by increasing Ca2+ concentrations. Total CaSR expression was concentration dependently decreased by TNFα exposure. In conclusion, CaSR expression can be easily measured by flow cytometry in human circulating monocytes. In the in vitro study, total and surface CaSR expression in the U937 cell line were increased by calcitriol but total CaSR expression was decreased by TNFα stimulation.
Assuntos
Regulação da Expressão Gênica , Monócitos/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Adolescente , Adulto , Idoso , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Receptores de Detecção de Cálcio/sangue , Fator de Necrose Tumoral alfa/farmacologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/metabolismo , Adulto JovemRESUMO
The recent history of French and Brazilian medicine goes back to the first decades of the xixth century. As regards nephrology, the first links were established starting in the 1950s of the xxth century. Over the past 60 years, the scientific production of the Franco-Brazilian school of nephrology totalized more than a thousand scientific papers and created a new generation of more than two hundred disciples, formed in Brazil by nephrologists who had completed their studies in France. In this article, we would like to memorize the successive exchanges between French and Brazilian physicians, mainly in the field of nephrology.
Assuntos
Intercâmbio Educacional Internacional/história , Nefrologia/história , Brasil , França , História do Século XIX , História do Século XX , Hospitais/história , Humanos , Editoração/história , Editoração/estatística & dados numéricos , Faculdades de Medicina/história , Sociedades Médicas/históriaRESUMO
Antecedentes: El inicio y la discontinuación del tratamiento antiparatiroideo son decisiones importantes en los pacientes en hemodiálisis crónica (HD) en los que la carga de pastillas es con frecuencia excesiva. El objetivo de este estudio es describir de tratamiento del hiperparatiroidismo secundario (sHPT) en pacientes en HD. Métodos: Estudio de cohorte, observacional retrospectivo de pacientes europeos incidentes en HD con sHPT a quienes se prescribió calcitriol o alfacalcidol (calcitriol-alfa), paricalcitol o cinacalcet. Resultados: Se incluyeron en el análisis pacientes que recibieron por primera vez calcitriol-alfa (N=2259), paricalcitol (N=1689) y cinacalcet (N=1245). Los valores sericos de hormona paratiroidea intacta (iPTH) disminuyeron tras iniciación con todos los tratamientos; los valores de calcio y fosforo serico se elevaron en respuesta al tratamiento con activadores de vitamina D pero disminuyeron con cinacalcet. Aproximadamente un tercio de los pacientes que recibieron calcitriol alfa y paricalcitol, y menos de una cuarta parte de los de cinacalcet discontinuaron el tratamiento. Aunque los tres grupos tuvieron descensos comparables de iPTH al momento de la interrupción del tratamiento, sin embargo difirieron en los valores de calcio y fosforo serico. Tras la interrupción, la evolución de los parámetros de laboratorio fué diferente según la modalidad de tratamiento: mientras que la iPTH se elevó en las tres modalidades, el calcio y fosforo sericos disminuyeron en los pacientes que estaban siendo tratados con calcitriol-alfa y paricalcitol en el momento de la interrupción y aumentaron en los que lo hacían con cinacalcet. Conclusiones: En condiciones clínicas que representan la práctica diaria, alcanzar y mantener los valores recomendados para el control del sHPT se consigue más frecuentemente con cinacalcet que con compuestos activos de vitamina D (AU)
Background: Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. Methods: Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. Results: Treatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. Conclusions: In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds (AU)