Xu Li, Guo Xiuli, Gan Wen, Yao Linhong, Wang Jianing, Li Qi, Fan Qiuling
Department of Laboratory Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, P.R. China.
Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
Diabetol Metab Syndr. 2025 Jul 16;17(1):272. doi: 10.1186/s13098-025-01856-9.
Podocytic injury and shedding are critical events in the progression and prognosis of diabetic nephropathy (DN). The purpose of our study was to observe heterokaryotic podocytes caused by mitotic catastrophe and the levels of murine double minute gene 2 (MDM2) and synaptopodin (SP) in the urine of patients with diabetic kidney disease (DKD) to explore their value as markers in the early diagnosis of DKD.
We examined urine samples from diabetic patients, determined the presence of urinary podocytes and podocyte mitosis catastrophe (PMC), and analyzed their correlations with numerous indicators. Podocytes in urine sediment were observed and counted using immunofluorescence (IF), and the expression of MDM2 and SP in urine supernatant was detected using enzyme-linked immunosorbent assay (ELISA) kits.
Podocytes might have been damaged in diabetic patients even during the period of normal albuminuria. Urinary SP level was positively correlated with urinary and heterolytic podocyte counts. MDM2 upregulation in urine was consistent with an increase in albuminuria level and heterolytic podocyte count. The sensitivity of urinary MDM2 to creatine (MDM2/Cr) in the diagnosis of DKD was high, as was the specificity of urinary SP to creatinine (SP/Cr). The diagnostic efficacy of combined urinary MDM2/Cr and SP/Cr was higher than that of either one alone.
We observed that PMC and elevated urinary MDM2/Cr levels emerged early in DKD. Additionally, we developed a diagnostic panel combining urinary MDM2/Cr and SP/Cr, which might serve as a predictive tool for early DKD diagnosis and prevention.
足细胞损伤和脱落是糖尿病肾病(DN)进展和预后的关键事件。本研究旨在观察有丝分裂灾难导致的异核足细胞以及糖尿病肾病(DKD)患者尿液中鼠双微体基因2(MDM2)和突触素(SP)的水平,以探讨它们作为DKD早期诊断标志物的价值。
我们检测了糖尿病患者的尿液样本,确定尿足细胞和足细胞有丝分裂灾难(PMC)的存在,并分析它们与众多指标的相关性。使用免疫荧光(IF)观察并计数尿沉渣中的足细胞,使用酶联免疫吸附测定(ELISA)试剂盒检测尿上清液中MDM2和SP的表达。
即使在正常蛋白尿期,糖尿病患者的足细胞也可能已受损。尿SP水平与尿足细胞和异质性足细胞计数呈正相关。尿中MDM2上调与蛋白尿水平和异质性足细胞计数增加一致。尿MDM2对肌酐的比值(MDM2/Cr)在DKD诊断中的敏感性较高,尿SP对肌酐的比值(SP/Cr)的特异性也较高。联合检测尿MDM2/Cr和SP/Cr的诊断效能高于单独检测其中任何一项。
我们观察到DKD早期出现PMC和尿MDM2/Cr水平升高。此外,我们开发了一种结合尿MDM2/Cr和SP/Cr的诊断组合,它可能作为DKD早期诊断和预防的预测工具。