Update on clinical trials with cinacalcet in secondary hyperparathyroidism due to chronic kidney disease / Atualização sobre os Ensaios clínicos com cinacalcete no hiperparatireoidismo secundário associado à doença renal crônica

Data from several recent clinical trials reaffirm the efficacy of treatment with cinacalcet for controlling plasma PTH levels among dialysis patients with established secondary HPT. In contrast to results reported previously from studies where cinacalcet was used together with relatively large but constant doses of vitamin D sterols, plasma PTH levels can be reduced effectively during treatment with cinacalcet among patients receiving lower doses of vitamin Dsterols. Compared to conventional treatment with vitamin D sterols, serum calcium and phosphorus levels are better controlled with this therapeuticapproach, and a larger proportion of patients are able to achieve serum calcium and phosphorus concentrations and values for Ca x P with the ranges recommended in current practice guidelines. Additional prospective clinical trials are needed, however, to determine whether the use of cinacalcet among dialysis patients with secondary HPT affects other important and clinically relevant outcomes such bone morphology, bone mass and/or bone density, skeletal fracture rates, and the need for parathyroidectomy.

Dados de vários ensaios clínicos recentes reafirmam a eficácia do tratamento com cinacalcete para controlar o nível plasmático do PTH em pacientes em diálise com hiperparatireoidismo secundário estabelecido. Em contraste com resultados previamente relatados, derivados de estudos onde cinacalcete era usado junto com doses relativamente altas porém constantes de vitamina D ou derivados, os níveis plasmáticos de PTH podem ser efetivamente reduzidospor cinacalcet em pacientes recebendo doses mais baixas de esteróides da vitamina D. Em comparação ao tratamento convencional com esteróides da vitamina D, os níveis séricos de cálcio e fósforo são melhor controlados com esta abordagem terapêutica e uma maior proporção de pacientes podealcançar concentrações séricas de cálcio e fósforo e valores do produto Ca x P dentro das faixas recomendadas pelas diretrizes atuais. Entretanto, ensaiosclínicos prospectivos adicionais são necessários para determinar se o uso de cinacalcete em pacientes em diálise com hiperparatireoidismo secundárioafeta outras variáveis importantes e clinicamente relevantes como, por exemplo, a morfologia do osso, a massa e/ou a densidade óssea, a taxa de fraturas, e a necessidade de paratireoidectomia.

A comparative study of p53 immunoexpression in parathyroid hyperplasias secondary to uremia, primary hyperplasias, adenomas and carcinomas.

OBJECTIVE: To investigate immunoexpression of p53 in parathyroid tumors and hyperplasias and correlate it with the histopathological diagnosis and severity of hyperparathyroidism. DESIGN: A total of 102 parathyroid tissues from archival paraffin-embedded specimens or obtained at surgery between 1988 and 1997 from 65 consecutive individuals with hyperparathyroidism were studied. METHODS: p53 immunoexpression, gland mass, preoperative serum calcium and intact parathyroid hormone (PTH) were analyzed; 14 normal parathyroid glands were used as controls. RESULTS: The histopathological findings were: adenomas (n = 28), primary hyperplasias (n = 12), secondary nodular and diffuse hyperplasias (patients with uremia, n = 57), carcinomas (n = 4) and carcinomatous metastatic tissue (n = 1). Nuclear p53 was detected in 36% of the adenomas, 42% of the primary hyperplastic glands, 72% of the diffuse hyperplasias, 44% of nodular hyperplasias and 40% of the carcinomatous tissues, and was absent from normal glands. p53 expression was significantly more frequent in diffuse hyperplasias than in adenomas (P = 0.037). Serum ionized calcium tended to be higher in p53-positive glands in all histopathological groups; however, the difference was only significant in nodular hyperplasias (P = 0.018). The same trend was observed for serum intact PTH levels of adenomas and nodular hyperplastic glands. Gland mass was not significantly different according to p53 staining. CONCLUSIONS: p53 immunoexpression was not useful in differentiating between the histopathological parathyroid subgroups. p53 immunodetection was particularly frequent in secondary hyperplastic glands of uremic patients. Our study suggests that p53, whether wild-type or mutant, is regulated in parathyroid tumors and hyperplasias. Changes in wild-type p53 may be part of a cellular response to a hyperproliferative condition.