建立新的 LC-MS/MS 方法测量血浆 BH4 作为糖尿病肾损伤的预测生物标志物。
Newly established LC-MS/MS method for measurement of plasma BH4 as a predictive biomarker for kidney injury in diabetes.
机构信息
Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, China.
Department of Clinic Laboratory, Renmin Hospital of Wuhan University, China.
出版信息
Free Radic Biol Med. 2022 Jan;178:1-6. doi: 10.1016/j.freeradbiomed.2021.11.021. Epub 2021 Nov 20.
OBJECTIVE
The clinical research on BH4 is limited because of the difficulties on its measurement. In this study, we used our own established LC-MS/MS method to examine the plasma BH4 levels in diabetes to determine whether it could be used as a biomarker for the prediction of kidney injury in those patients.
METHODS
Hospitalized diabetes patients in Renmin Hospital of Wuhan University from Jan to Aug 2021 were recruited. To assess the association between plasma BH4 with ACR or eGFR in diabetes, a total of 142 patients with type 2 diabetes (T2DM) were enrolled. They were divided into three groups by albuminuria levels: normoalbuminuria (n = 68), microalbuminuria (n = 48), and macroalbuminuria (n = 26) according to ACR; or into two groups by eGFR: eGFR≥90 or eGFR<90 ml/min for correlation and logistic regression analysis. Plasma BH4 level was measured by LC-MS/MS along with other biochemical indices.
RESULTS
Plasma BH4 concentrations were decreased as ACR progressed. BH4 (r = -0.55, P < 0.001) and 2h C-Peptide (CP-2h) (r = -0.248, P = 0.003) levels were negatively correlated with ACR. Moreover, multivariable logistic regression analysis showed BH4 concentrations (B = -0.468, P < 0.001) and CP-2h (B = -0.257, P = 0.028) were independently associated with ACR progression. ROC curve showed that BH4 level has a predictive value on ACR (95%CI 0.686-0.841, sensitivity 69.1%, specificity 73%). Moreover, in diabetes patients with eGFR≥90 ml/min, plasma BH4 level (P = 0.008) is higher than those in diabetes with eGFR<90 ml/min and BH4 was remained independently associated with eGFR after multivariable logistic regression analysis (B = -0.193, P = 0.048).
CONCLUSION
Our established LC-MS/MS method could be used on human plasma BH4 measurements and our data suggested that BH4 level can be used as a biomarker for kidney injury in diabetes indicated by its association with ACR progression and early renal function decline.
目的
由于 BH4 测量困难，其临床研究受到限制。本研究采用我们自行建立的 LC-MS/MS 方法检测糖尿病患者的血浆 BH4 水平，以确定其是否可作为预测此类患者肾损伤的生物标志物。
方法
本研究纳入 2021 年 1 月至 8 月在武汉大学人民医院住院的糖尿病患者。为评估血浆 BH4 与糖尿病患者 ACR 或 eGFR 的相关性，共纳入 142 例 2 型糖尿病（T2DM）患者。根据 ACR 将其分为三组：正常白蛋白尿组（n=68）、微量白蛋白尿组（n=48）和大量白蛋白尿组（n=26）；根据 eGFR 将其分为两组：eGFR≥90 或 eGFR<90 ml/min 用于相关性和逻辑回归分析。采用 LC-MS/MS 测定血浆 BH4 水平及其他生化指标。
结果
随着 ACR 的进展，血浆 BH4 浓度降低。BH4（r=-0.55，P<0.001）和 2h C-肽（CP-2h）（r=-0.248，P=0.003）水平与 ACR 呈负相关。此外，多元逻辑回归分析显示，BH4 浓度（B=-0.468，P<0.001）和 CP-2h（B=-0.257，P=0.028）与 ACR 进展独立相关。ROC 曲线显示 BH4 水平对 ACR 具有预测价值（95%CI 0.686-0.841，敏感性 69.1%，特异性 73%）。此外，在 eGFR≥90 ml/min 的糖尿病患者中，血浆 BH4 水平（P=0.008）高于 eGFR<90 ml/min 的患者，且经多元逻辑回归分析后 BH4 仍与 eGFR 独立相关（B=-0.193，P=0.048）。
结论
本研究建立的 LC-MS/MS 方法可用于人血浆 BH4 的检测，数据表明 BH4 水平可作为糖尿病患者肾损伤的生物标志物，其与 ACR 进展和早期肾功能下降相关。
Zotero 插件