Herberth J, Fahrleitner-Pammer A, Obermayer-Pietsch B, Krisper P, Holzer H, Malluche H H, Dobnig H
Division of Nephrology, Bone and Mineral Metabolism, Albert B. Chandler Medical Center, University of Kentucky, 800 Rose Street, MN-564, Lexington, KY 40536, USA.
Clin Nephrol. 2006 May;65(5):328-34. doi: 10.5414/cnp65328.
Loss of renal function is accompanied by progressive increase in serum levels of intact parathyroid hormone (iPTH) in patients with end-stage renal disease (ESRD). There is a paucity of data regarding levels of PTH-(1-84) and its large carboxyl-terminal fragments (large C-PTH fragments) and progressive loss of kidney function in patients with chronic kidney disease (CKD). The current study was undertaken to describe the glomerular filtration rate (GFR)-dependent plasma concentrations of PTH-(1-84) and related large C-PTH fragments in adult patients with CKD by using different commercially available PTH assays.
We studied 80 Caucasian patients with CKD stages 1-5 without renal replacement therapy. Creatinine clearance was calculated by the Modification of Diet in Renal Disease (MDRD) formula. Levels of iPTH were determined by second-generation assays (iPTH Elecsys system, Roche Diagnostics; DUO total iPTH, Scantibodies Laboratory, Inc.; iPTH, Nichols Institute Diagnostics). Third-generation assays were used to measure PTH-(1-84) (CAP (cyclase activating PTH), Scantibodies; Bio-Intact PTH, Nichols). Levels of large C-PTH fragments and ratios of PTH-(1-84)/large C-PTH fragments were calculated and statistical analyses performed.
Levels of iPTH and PTH-(1-84) showed CKD stage-dependent increases. Variations among the assays increased with progressive loss of kidney function. The assay from Scantibodies showed a GFR-dependent decrease of the ratio 1-84 PTH / large C-PTH fragment that was not observed with the Nichols assay.
Increasing variations among the assays with progression of CKD emphasize the fact that the interpretation of measurements must take into consideration the specific assay. We found evidence for a possible preferential increase of the level of large C-PTH fragments over 1-84 PTH in a CKD stage-dependent manner (Scantibodies). The clinical implications of this finding have to be further evaluated by bone biopsy studies.
终末期肾病（ESRD）患者肾功能丧失的同时，血清完整甲状旁腺激素（iPTH）水平会逐渐升高。关于慢性肾脏病（CKD）患者甲状旁腺激素-（1-84）[PTH-（1-84）]及其大的羧基末端片段（大C-PTH片段）水平与肾功能进行性丧失的数据较少。本研究旨在通过使用不同的市售PTH检测方法，描述成年CKD患者中依赖肾小球滤过率（GFR）的PTH-（1-84）及相关大C-PTH片段的血浆浓度。
我们研究了80例未接受肾脏替代治疗的1-5期CKD白人患者。采用肾脏病饮食改良（MDRD）公式计算肌酐清除率。通过第二代检测方法（iPTH Elecsys系统，罗氏诊断公司；DUO总iPTH，Scantibodies实验室；iPTH，Nichols研究所诊断试剂）测定iPTH水平。使用第三代检测方法测量PTH-（1-84）[CAP（环化酶激活型PTH），Scantibodies；生物完整PTH，Nichols]。计算大C-PTH片段水平以及PTH-（1-84）/大C-PTH片段的比值，并进行统计分析。
iPTH和PTH-（1-84）水平随CKD分期增加而升高。随着肾功能的逐渐丧失，各检测方法之间的差异增大。Scantibodies公司的检测方法显示，1-84 PTH/大C-PTH片段的比值随GFR降低，而Nichols公司的检测方法未观察到这种现象。
随着CKD进展，各检测方法之间差异增大，这突出表明测量结果的解读必须考虑特定的检测方法。我们发现有证据表明，大C-PTH片段水平可能以CKD分期依赖的方式优先于1-84 PTH升高（Scantibodies公司检测方法）。这一发现的临床意义必须通过骨活检研究进一步评估。
