Ye Qinglin, Xu Guiling, Yuan Hao, Mi Junhao, Xie Yuli, Li Haoyu, Li Zhejun, Huang Guanwen, Chen Xuesong, Li Wei, Yang Rirong
Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People's Republic of China.
Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People's Republic of China.
Diabetes Metab Syndr Obes. 2023 Dec 27;16:4215-4231. doi: 10.2147/DMSO.S445341. eCollection 2023.
Diabetic kidney disease (DKD) is a chronic renal disease which could eventually develop into renal failure. Though albuminuria and estimated glomerular filtration rate (eGFR) are helpful for the diagnosis of DKD, the lack of specific biomarkers reduces the efficiency of therapeutic interventions.
Based on bulk-seq of 56 urine samples collected at different time points (including 11 acquired from DKD patients and 11 from healthy controls), in corporation of scRNA-seq data of urine samples and snRNA-seq data of renal punctures from DKD patients (retrieved from NCBI GEO Omnibus), urine-kidney specific genes were identified by Multiple Biological Information methods.
Forty urine-kidney specific genes/differentially expressed genes (DEGs) were identified to be highly related to kidney injury and proteinuria for the DKD patients. Most of these genes participate in regulating glucagon and apoptosis, among which, urinary PART1 (mainly derived from distal tubular cells) and PLA2R1 (podocyte cell surface marker) could be used together for the early diagnosis of DKD. Moreover, urinary PART1 was significantly associated with multiple clinical indicators, and remained stable over time in urine.
Urinary PART1 and PLA2R1 could be shed lights on the discovery and development of non-invasive diagnostic method for DKD, especially in early stages.
糖尿病肾病（DKD）是一种慢性肾脏疾病，最终可能发展为肾衰竭。尽管蛋白尿和估算肾小球滤过率（eGFR）有助于DKD的诊断，但缺乏特异性生物标志物降低了治疗干预的效率。
基于对在不同时间点收集的56份尿液样本（包括11份来自DKD患者和11份来自健康对照）的批量测序，结合尿液样本的单细胞RNA测序（scRNA-seq）数据和DKD患者肾穿刺的单细胞核RNA测序（snRNA-seq）数据（从NCBI基因表达综合数据库检索），通过多种生物学信息方法鉴定尿肾特异性基因。
鉴定出40个尿肾特异性基因/差异表达基因（DEG）与DKD患者的肾损伤和蛋白尿高度相关。这些基因大多参与调节胰高血糖素和细胞凋亡，其中，尿PART1（主要来源于远端肾小管细胞）和PLA2R1（足细胞表面标志物）可共同用于DKD的早期诊断。此外，尿PART1与多个临床指标显著相关，且在尿液中随时间保持稳定。
尿PART1和PLA2R1可能为DKD非侵入性诊断方法的发现和开发提供线索，尤其是在早期阶段。
