Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland, Phone: +48 52 585 40 23, Fax: +48 52 585 40 24.
Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland.
Clin Chem Lab Med. 2018 Jun 27;56(7):1161-1168. doi: 10.1515/cclm-2017-1044.
Midregional proadrenomedullin (MR-proADM) is emerging as a prognostic biomarker for detecting the failure of multiple organs. Establishment of scientifically robust reference intervals facilitates interpretation of laboratory test results. The objectives of this study were (i) to establish reliable reference intervals for plasma MR-proADM using a commercially available automated fluoroimmunoassay in apparently healthy individuals, and (ii) to identify biological determinants of MR-proADM concentrations.
A total of 506 questionnaire-identified apparently healthy adults were enrolled in a single-center, cross-sectional study. A final reference group (n=172) was selected after exclusion of obese individuals, those with increased values of laboratory biomarkers indicating asymptomatic myocardial injury or dysfunction, ongoing inflammation, diabetes, dyslipidemia and renal dysfunction and outliers.
The 2.5th and 97.5th percentile intervals for MR-proADM values in the reference group (90% confidence interval) were 0.21 (0.19-0.23) and 0.57 (0.55-0.59) nmol/L, respectively. Although older age, higher values of HbA1c, C-reactive protein, B-type natriuretic peptide and body mass index, together with a history of smoking and a decreased estimated glomerular filtration rate were significantly associated with increasing concentrations of MR-proADM in both univariate and multivariate analyses, magnitudes of these relationships were modest and did not substantially influence MR-proADM reference intervals. Sex-dependent difference in MR-proADM reference intervals was not detected [0.19 (0.16-0.22)-0.56 (0.54-0.60) nmol/L in females vs. 0.22 (0.20-0.25)-0.58 (0.57-0.63) nmol/L in males].
Our study successfully established robust reference intervals for MR-proADM concentrations in plasma. Considering the negligible influence of potential biological determinants on plasma MR-proADM, we recommend the adoption of single reference intervals for adult population as a whole.
中肾上腺髓质原(proadrenomedullin, MR-proADM) 作为一种预测多种器官衰竭的预后生物标志物而备受关注。建立科学可靠的参考区间有助于解释实验室检测结果。本研究的目的是(i) 使用商业上可获得的自动荧光免疫分析法，在看似健康的个体中建立可靠的血浆 MR-proADM 参考区间，(ii) 确定 MR-proADM 浓度的生物学决定因素。
共纳入了 506 名通过问卷识别的看似健康的成年人，进行了一项单中心、横断面研究。在排除肥胖个体、实验室生物标志物升高值提示无症状心肌损伤或功能障碍、持续炎症、糖尿病、血脂异常和肾功能不全以及离群值后，选择了最终的参考组（n=172）。
参考组（90%置信区间）中 MR-proADM 值的 2.5 百分位和 97.5 百分位区间分别为 0.21（0.19-0.23）和 0.57（0.55-0.59）nmol/L。虽然在单变量和多变量分析中，年龄较大、HbA1c、C 反应蛋白、B 型利钠肽和体重指数较高、吸烟史和估计肾小球滤过率降低与 MR-proADM 浓度的升高显著相关，但这些关系的程度较小，并未显著影响 MR-proADM 的参考区间。未检测到 MR-proADM 参考区间的性别差异[女性 0.19（0.16-0.22）-0.56（0.54-0.60）nmol/L，男性 0.22（0.20-0.25）-0.58（0.57-0.63）nmol/L]。
本研究成功建立了可靠的血浆 MR-proADM 浓度参考区间。鉴于潜在生物学决定因素对血浆 MR-proADM 的影响可以忽略不计，我们建议为整个成年人群采用单一的参考区间。
