Urinary Podocyte-Associated mRNA profile in Various Stages of Diabetic Nephropathy

Abstract

BackgroundPodocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy.MethodsDN patients (N = 51) and healthy controls (N = 13) were enrolled in this study. DN patients were divided into a normoalbuminuria group (UAE<30 mg/g, n = 17), a microalbuminuria group (UAE 30∼300 mg/g, n = 15), and a macroalbuminuria group (UAE>300 mg/g, n = 19), according to their urinary albumin excretion (UAE). Relative mRNA abundance of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.ResultsThe urinary mRNA levels of all genes studied were significantly higher in the DN group compared with controls (p<0.05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and BUN. The expression of podocalyxin, CD2-AP, α-actin4, and podocin mRNA correlated with serum creatinine (r = 0.457, p = 0.001; r = 0.329, p = 0.01; r = 0.286, p = 0.021; r = 0.357, p = 0.006, respectively). Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = −0.349, p = 0.01).ConclusionThe urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

Urinary vimentin mRNA as a potential novel biomarker of renal fibrosis

“…After this report, urinary sediment has become an attractive resource for the development of biomarker candidates for kidney diseases (18 -19, 22). Our previous studies also have indicated the potential application of urinary mRNA detection in the search for diagnostic biomarkers of DN (25)(26). However, these former studies lacked the high efficiency and proper validation processes.…”

Increased Urinary Excretion of Podocyte Markers in Normoalbuminuric Patients with Diabetes

“…The detection of podocytes or podocyte-associated molecules in the urine of patients with DN is also indicative of podocyte damage in DM [15][16][17][18][19][20][21] .…”

Novel Biomarkers for Early Diagnosis and Progression of Diabetic Nephropathy

“…A recent report showed that urinary exosomal Wilms tumor-1 protein (WT-1) level was higher in patients with proteinuria associated with increased urine protein-to-creatinine ratio, serum creatinine and eGFR decline, which suggested that urinary WT-1 upregulation could be useful as early non-invasive marker for DN (Kalani et al 2013). Another study of urinary podocyte-associated mRNA profile in different stages of DN showed that mRNA expression of podocalyxin, CD2-AP, α-actin4 and podocin were upregulated with the progression of DN, suggesting that quantification of urinary podocyte-associated molecules could be useful biomarkers of DN (Zheng et al 2011). In experimental diabetic rats elevated concentrations of Amadori-modified glycated albumin (AGA) were linked with increased nephrin, podocalyxin and βig-h3 protein, test compound treatment can reduce the progression of DN, indicating a new therapeutic target of DN(Cohen and Shearman 2013).…”