Urinary vimentin mRNA as a potential novel biomarker of renal fibrosis

Abstract

Renal fibrosis is a histological outcome of chronic kidney disease (CKD) progression. However, the noninvasive detection of renal fibrosis remains a challenge. Here we constructed a renal fibrosis target mRNA array and used it to detect urinary mRNAs of CKD patients for investigating potential noninvasive biomarkers of renal fibrosis. We collected urine samples from 39 biopsy-proven CKD patients and 11 healthy controls in the training set. Urinary mRNA profiles of 86 genes showed a total of 21 mRNAs that were differentially expressed between CKD patients and controls ( P < 0.05), and vimentin (VIM) mRNA demonstrated the highest change fold of 9.99 in CKD vs. controls with robust correlations with decline of renal function and severity of tubulointerstitial fibrosis. Additionally, VIM mRNA further differentiated patients with moderate-to-severe fibrosis from none-to-mild fibrosis group with an area of the curve of 0.796 ( P = 0.008). A verification of VIM mRNA in the urine of an additional 96 patients and 20 controls showed that VIM is not only well correlated with renal function parameters but also correlated with proteinuria and renal fibrosis scores. Multiple logistic regression and receiver-operating characteristics analysis further showed that urine VIM mRNA is the best predictive parameter of renal fibrosis compared with estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen. In addition, there is no improved predictive performance for the composite biomarkers to predict renal fibrosis severity compared with a single gene of VIM. Overall, urinary VIM mRNA might serve as a novel independent noninvasive biomarker to monitor the progression of kidney fibrosis.

Feature selection and classification of urinary mRNA microarray data by iterative random forest to diagnose renal fibrosis: a two-stage study

“…Recent findings have implied that TEC, MMP-9, and TIMP-2 expression can be upregulated by TGF-β in disease models2223. We previously reported that the expression of MMP9 mRNA was strongly correlated with kidney function parameters9. Here, we further showed that these two mRNAs could serve as TIF biomarkers.…”

“…Moreover, these markers reveal limited information regarding the underlying molecular mechanism. Recent data have shown that measuring transcriptional differences in urine sediment from patients with CKD may provide a novel means for early and sensitive diagnosis789.…”

“…Recently, microarrays have been used as a high-throughput screening platform to discover potential mRNA biomarkers. Using targeted microarrays, our previous study showed that urinary vimentin mRNA was significantly upregulated in moderate-to-severe fibrosis9. However, whether urinary mRNAs can efficiently identify patients with renal fibrosis in the context of CKD has not been investigated yet.…”

Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

“…2a–e). Opn , a marker for vascular calcification23, Vim , a marker for kidney fibrosis24, and Ngal and Kim-1 , markers for tubular damage25, increased significantly in the CKD model mice compared with the control mice. αKlotho , another marker for kidney damage26, also decreased significantly in the CKD mice.…”

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

“…3 Renal fibrosis is the common pathological changes of CKD. 4 The development of epithelial-to-mesenchymal transition (EMT) of mature tubular epithelial cells leads to the accumulation and deposition of extracellular matrix (ECM), 5 which results in tissue fibrosis. Transforming growth factor beta1 (TGF-b1), a fibrosis-promoting cytokine, is involved in the process of EMT and ECM production.…”