Urinary mRNA Signatures as Predictors of Renal Function Decline in Patients With Biopsy-Proven Diabetic Kidney Disease

• Published in: Frontiers in endocrinology (Lausanne) 2021-11, Vol.12, p.774436-774436
• Main Authors: Lee, Yu Ho, Seo, Jung-Woo, Kim, Miji, Tae, Donghyun, Seok, Junhee, Kim, Yang Gyun, Lee, Sang-Ho, Kim, Jin Sug, Hwang, Hyeon Seok, Jeong, Kyung-Hwan, Moon, Ju-Young
• Format: Article
• Language: English
• Subjects: Adult; Aged; biomarker; Biomarkers - urine; Biopsy; Case-Control Studies; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - urine; diabetic kidney disease; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - genetics; Diabetic Nephropathies - pathology; Diabetic Nephropathies - urine; Disease Progression; Endocrinology; Female; Glomerular Filtration Rate; Humans; Kidney - metabolism; Kidney - pathology; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - genetics; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - urine; Kidney Function Tests - methods; Male; Middle Aged; mRNA; Prognosis; renal pathology; Republic of Korea; RNA, Messenger - urine; Transcriptome; urine
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2021.774436

The clinical manifestations of diabetic kidney disease (DKD) are more heterogeneous than those previously reported, and these observations mandate the need for the recruitment of patients with biopsy-proven DKD in biomarker research. In this study, using the public gene expression omnibus (GEO) repository, we aimed to identify urinary mRNA biomarkers that can predict histological severity and disease progression in patients with DKD in whom the diagnosis and histologic grade has been confirmed by kidney biopsy. We identified 30 DKD-specific mRNA candidates based on the analysis of the GEO datasets. Among these, there were significant alterations in the urinary levels of 17 mRNAs in patients with DKD, compared with healthy controls. Four urinary mRNAs- , and -reflected tubulointerstitial inflammation and fibrosis in kidney biopsy and could predict rapid progression to end-stage kidney disease independently of the baseline eGFR (tertile 1 . tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85-32.87, < 0.001). In conclusion, we demonstrated that urinary mRNA signatures have a potential to indicate the pathologic status and predict adverse renal outcomes in patients with DKD.