Abstract
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—LYZ, C3, FKBP5, and G6PC—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 vs. tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85–32.87, p < 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.
Highlights
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) globally, including in Korea [1]
Baseline renal function and the amount of proteinuria were comparable between patients with DKD and those with combined non-diabetic renal disease (NDRD) and DKD
Utilizing public gene expression omnibus (GEO) datasets, we extracted 30 mRNAs as biomarker candidates; we observed that levels of 17 mRNAs were significantly altered in the urine of patients with DKD, compared to those of healthy controls
Summary
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) globally, including in Korea [1]. A large epidemiological study has revealed the decreasing prevalence of albuminuria and increasing prevalence of eGFR in DKD over the last 3 decades [5]. Urinary mRNAs in Diabetic Kidney Disease clinically diagnosed DKD may have associated NDRD [6,7,8,9,10]. Identifying patients in whom DKD diagnosis has been confirmed through kidney biopsy is an essential prerequisite for the successful discovery of relevant biomarkers. This approach has rarely been used in the field of DKD research, partially justifying the reason for the validation failure of previously identified DKD biomarkers [11]. The incidence of biopsy-proven DKD has been increasing over the past decades [12]
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