ROLE OF PARATHYROID HORMONE IN RENAL OSTEODYSTROPHY

描述（由申请人提供）：肾性骨营养不良的频谱已经通过透析患者的骨组织形态测量学得到了很好的表征。然而，只有随着第一代免疫PTH测定（1st PTH- ima）的可用性，这种测量才成为肾性骨营养不良骨骼病变的相对准确的预测指标。然而，间歇性骨化三醇治疗改变了甲状旁腺激素与骨形成的关系。在透析前的慢性肾脏疾病（CKD）儿童中进行类似的研究已有20多年了。

DESCRIPTION (provided by applicant): The spectrum of renal osteodystrophy has been very well characterized by bone histomorphometry in patients treated with dialysis. However, it was only with the availability of the first generation immunometric PTH assay (1st PTH-IMA) that such measurements have emerged as relatively accurate predictors of the skeletal lesion of renal osteodystrphy. However, the relationship between PTH and bone formation was altered by intermittent calcitriol therapy. Similar studies have not been carried out in children with chronic kidney disease (CKD) before dialysis for more than two decades. Despite this lack of data, PTH determinations are commonly used as surrogate markers of bone formation and turnover, and therapy with calcitriol is recommended to those patients to prevent growth retardation and bone deformities. Furthermore, the prediction of bone turnover is further complicated because their interpretation is confounded by the stage of CKD and that it appears likely to reflect progression of the state of skeletal resistance to PTH. It is now known that 1st PTH-IMA detect not only PTH(1-84), but also large amino-terminally truncated PTH fragments, some of which were shown to have hypocalcemic properties in vivo and diminish bone turnover. In contrast, recent developed second generation immunometric PTH (2nd PTH-IMA) that recognize only PTH(1-84), but not naturally occurring fragments of the intact hormone. The current proposal will determine: 1) whether PTH concentrations measured by 2nd PTH-IMA provide a more accurate assessment of bone formation and turnover than 1st PTH-IMA in children, adolescents and young adults with CKD prior to dialysis and those undergoing chronic hemodialysis. 2) To assess the magnitude and progression of renal and skeletal resistance to PTH and to determine whether the abundance of amino-terminally truncated PTH (1-84) fragments contribute to the state of resistance in such patients. Bone formation will be evaluated in cancellous bone by quantitative histomorphometry, renal and skeletal resistance to PTH will be assessed by PTH(1-34) infusions. The results of the study should provide new information on the relationship between PTH and bone formation in CKD and they are likely to have important implications for the diagnosis and treatment of renal osteodystrophy.