Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy.
Istituto Oncologico del Mediterraneo, 95029 Viagrande, Italy.
Int J Mol Sci. 2023 May 28;24(11):9412. doi: 10.3390/ijms24119412.
Diabetic kidney disease (DKD) is a complication that strongly increases the risk of end-stage kidney disease and cardiovascular events. The identification of novel, highly sensitive, and specific early biomarkers to identify DKD patients and predict kidney function decline is a pivotal aim of translational medicine. In a previous study, after a high-throughput approach, we identified in 69 diabetic patients 5 serum mitochondrial RNAs (MT-ATP6, MT-ATP8, MT-COX3, MT-ND1, and MT-RNR1) progressively downregulated with increasing eGFR stages. Here, we analyzed the protein serum concentrations of three well-validated biomarkers: TNFRI, TNFRII, and KIM-1. The protein biomarkers were gradually upregulated from G1 to G2 and G3 patients. All protein biomarkers correlated with creatinine, eGFR, and BUN. Performing multilogistic analyses, we found that, with respect to single protein biomarkers, the combination between (I) TNFRI or KIM-1 with each RNA transcript and (II) TNFRII with MT-ATP8, MT-ATP6, MT-COX-3, and MT-ND1 determined an outstanding improvement of the diagnostic performance of G3 versus G2 patient identification, reaching values in most cases above 0.9 or even equal to 1. The improvement of AUC values was also evaluated in normoalbuminuric or microalbuminuric patients considered separately. This study proposes a novel, promising multikind marker panel associated with kidney impairment in DKD.
糖尿病肾病（DKD）是一种严重增加终末期肾病和心血管事件风险的并发症。鉴定新型、高灵敏度、特异性的早期生物标志物以识别 DKD 患者并预测肾功能下降是转化医学的主要目标。在之前的一项研究中，我们采用高通量方法，在 69 名糖尿病患者中鉴定了 5 种血清线粒体 RNA（MT-ATP6、MT-ATP8、MT-COX3、MT-ND1 和 MT-RNR1），这些 RNA 的表达随着 eGFR 阶段的增加而逐渐下调。在这里，我们分析了三种经过充分验证的生物标志物的血清蛋白浓度：TNFRI、TNFRII 和 KIM-1。从 G1 到 G2 和 G3 患者，蛋白生物标志物逐渐上调。所有蛋白生物标志物与肌酐、eGFR 和 BUN 相关。进行多逻辑分析后，我们发现，与单个蛋白生物标志物相比，（I）TNFRI 或 KIM-1 与每个 RNA 转录本的组合和（II）TNFRII 与 MT-ATP8、MT-ATP6、MT-COX-3 和 MT-ND1 的组合可以显著提高 G3 与 G2 患者鉴定的诊断性能，在大多数情况下，其值高于 0.9，甚至等于 1。还分别评估了在正常白蛋白尿或微量白蛋白尿患者中 AUC 值的改善情况。这项研究提出了一个与 DKD 肾脏损害相关的新型、有前途的多种标志物组合。
