Nandula Seshagiri Rao, Brichacek Beda, Sen Sabyasachi
Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Metab Syndr Relat Disord. 2025 May;23(4):205-210. doi: 10.1089/met.2024.0199. Epub 2025 Mar 18.
Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, , and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. Urine exosomal podocalyxin levels were significantly high at 10 week ( = 18; = 0.001), 6 month ( = 25; = 0.003) and 12 month ( = 14; = 0.0001) time points. Nephrin levels were also noted to be high at 10 week ( = 18; = 0.001) and 12 month ( = 14; = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）与2019冠状病毒病（COVID-19）的发生有关。COVID-19可能导致内皮细胞功能障碍（ECD），进而引发心脏代谢疾病和足细胞病变。在本研究中，我们探讨了高血糖是否易导致SARS-CoV-2感染，以及COVID-19是否会使个体在急性COVID感染后的长期内面临更高的持续性肾损伤风险。为评估肾损伤，我们检测了蛋白尿和足细胞病变。通过测量急性SARS-CoV-2感染后10天、6个月和12个月时因急性COVID-19入院患者尿液来源外泌体中足细胞特异性蛋白水平来评估足细胞病变。从乔治华盛顿大学COVID数据库获取SARS-CoV-2感染后患者的血液和尿液样本。分离外周血单核细胞和尿液外泌体。从尿液外泌体中鉴定出足细胞特异性蛋白Podocalyxin（PODXL）和Nephrin（NEPH）。在10周（n = 18；p = 0.001）、6个月（n = 25；p = 0.003）和12个月（n = 14；p = 0.0001）时间点，尿液外泌体中Podocalyxin水平显著升高。与从未感染COVID-19的2型糖尿病患者的尿液样本相比，在10周（n = 18；p = 0.001）和12个月（n = 14；p = 0.007）时间点，Nephrin水平也较高。尽管与对照组相比，尿足细胞特异性蛋白水平较高，但两组间尿白蛋白：肌酐比值（UACR）无显著差异。即使在感染COVID后12个月，尿液外泌体中持续高水平的足细胞特异性蛋白也可能导致慢性肾病的发生。
