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在透析前慢性肾脏病(CKD)中,完整的甲状旁腺激素(PTH)与生物完整的 PTH(1-84)与骨和矿物质代谢之间的关系。

The relationship between intact PTH and biointact PTH (1-84) with bone and mineral metabolism in pre-dialysis chronic kidney disease (CKD).

机构信息

Department of Clinical Chemistry, GSTS Pathology, St Thomas' Hospital, London SE1 7EH, UK.

出版信息

Clin Biochem. 2013 Oct;46(15):1405-9. doi: 10.1016/j.clinbiochem.2013.06.023. Epub 2013 Jul 2.

Abstract

OBJECTIVES

Abnormalities in PTH are implicated in the pathogenesis of bone abnormalities in chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD). PTH concentrations are important in clinical decision and management. This emphasises the importance of providing an assay which measures biologically active PTH. We compared concentrations of intact PTH with biointact PTH (1-84) in CKD and end stage renal disease (ESRD) and investigated the relationship between the 2 PTH assays with bone and mineral laboratory parameters and bone mineral density (BMD) in CKD.

DESIGN AND METHODS

We assessed 140 patients (61 in ESRD and 79 with CKD stages 1-4) in this cross-sectional study. We measured biointact PTH (1-84) as well as routine biochemical parameters on all subjects. In the CKD cohort, bone turnover markers; bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase (TRACP)-5b and bone mineral density (BMD) were also determined.

RESULTS

In ESRD, intact PTH concentration was significantly higher compared to biointact PTH (1-84) (422 [443] v/s 266 [251] pg/mL, (p<0.001) with an average bias of 60%. In CKD, intact PTH concentration was also higher compared to biointact PTH (1-84) (79[55] v/s 68[49] pg/mL p<0.001) with an average bias of 18%. Only the biointact PTH (1-84) assay showed any significant correlation with serum calcium concentrations (r=-0.26, p<0.05) and phosphate (r=0.25, p<0.05) in CKD. Following multilinear regression analysis and adjustment for all significant co-variables, only eGFR, BAP and 25 (OH)vitamin remained significantly associated with intact PTH and biointact PTH (1-84). The strength of association was stronger between BAP and biointact PTH (1-84) (biointact PTH (1-84): p=0.007, intact PTH: p=0.01). In adjusted analyses, only biointact PTH (1-84) was significantly associated with BMD at the fore-arm (FARM) (p=0.049).

CONCLUSIONS

The study confirms the differences between intact PTH and biointact PTH (1-84) in ESRD. Whilst there may be similarities in the diagnostic ability of both intact and biointact PTH (1-84), our data suggest that biointact PTH (1-84) assay may better reflect bone metabolism and BMD in CKD. Further longitudinal studies are needed.

摘要

目的

甲状旁腺激素(PTH)的异常与慢性肾脏病(CKD)-矿物质骨代谢紊乱(CKD-MBD)中的骨异常发病机制有关。PTH 浓度在临床决策和管理中很重要。这强调了提供测量生物活性 PTH 的检测方法的重要性。我们比较了 CKD 和终末期肾病(ESRD)患者中完整 PTH 与生物活性 PTH(1-84)的浓度,并研究了这两种 PTH 检测方法与 CKD 中骨和矿物质实验室参数以及骨矿物质密度(BMD)之间的关系。

设计和方法

我们在这项横断面研究中评估了 140 名患者(ESRD 患者 61 名,CKD 1-4 期患者 79 名)。我们对所有受试者进行了生物活性 PTH(1-84)以及常规生化参数的检测。在 CKD 队列中,还测定了骨转换标志物;骨碱性磷酸酶(BAP)和抗酒石酸酸性磷酸酶 5b(TRACP-5b)和骨矿物质密度(BMD)。

结果

在 ESRD 中,完整 PTH 浓度明显高于生物活性 PTH(1-84)(422[443]比 266[251]pg/ml,(p<0.001),平均偏差为 60%。在 CKD 中,完整 PTH 浓度也高于生物活性 PTH(1-84)(79[55]比 68[49]pg/ml,p<0.001),平均偏差为 18%。只有生物活性 PTH(1-84)检测与 CKD 患者血清钙浓度(r=-0.26,p<0.05)和磷酸盐(r=0.25,p<0.05)有显著相关性。经多元线性回归分析和对所有显著协变量进行调整后,仅 eGFR、BAP 和 25(OH)维生素与完整 PTH 和生物活性 PTH(1-84)仍有显著相关性。BAP 与生物活性 PTH(1-84)之间的相关性更强(生物活性 PTH(1-84):p=0.007,完整 PTH:p=0.01)。在调整分析中,只有生物活性 PTH(1-84)与前臂(FARM)的 BMD 显著相关(p=0.049)。

结论

该研究证实了 ESRD 中完整 PTH 和生物活性 PTH(1-84)之间的差异。虽然完整 PTH 和生物活性 PTH(1-84)的诊断能力可能存在相似之处,但我们的数据表明,生物活性 PTH(1-84)检测可能更好地反映 CKD 中的骨代谢和 BMD。需要进一步的纵向研究。

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