ROLE OF PTH IN RENAL OSTEODYSTROPHY

描述（由申请人提供）：在接受透析治疗的患者中，通过骨组织形态计量学对肾性骨营养不良的谱进行了很好的表征。然而，它只是与第一代免疫测定PTH测定（1st PTH-IMA）的可用性，这样的测量已经成为相对准确的预测肾性骨病的骨骼病变。然而，PTH和骨形成之间的关系被间歇性骨化三醇治疗改变。类似的研究在透析前的慢性肾脏病（CKD）儿童中进行了二十多年。 尽管缺乏数据，PTH测定通常用作骨形成和骨转换的替代标志物，并建议对这些患者进行骨化三醇治疗，以防止生长迟缓和骨畸形。此外，骨转换的预测更加复杂，因为其解释受到CKD阶段的混淆，并且它似乎可能反映骨骼对PTH抵抗状态的进展。现在已知，1st PTH-IMA不仅检测PTH（1-84），而且还检测大的氨基末端截短的PTH片段，其中一些片段显示出在体内具有低钙特性并减少骨转换。相比之下，最近开发的第二代免疫测定PTH（2nd PTH-IMA）仅识别PTH（1-84），但不识别完整激素的天然存在的片段。 目前的提案将确定：1）在透析前和接受慢性血液透析的CKD儿童、青少年和年轻人中，通过第二次PTH-IMA测量的PTH浓度是否比第一次PTH-IMA更准确地评估骨形成和骨转换。2)评估肾脏和骨骼对PTH的抵抗的程度和进展，并确定氨基末端截短的PTH（1-84）片段的丰度是否有助于此类患者的抵抗状态。将通过定量组织形态测定法评价松质骨中的骨形成，通过PTH（1-34）输注评估肾脏和骨骼对PTH的抵抗力。该研究的结果应提供新的信息PTH和骨形成之间的关系，在CKD，他们可能有重要的意义，诊断和治疗肾性骨营养不良。

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.