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.
Highlights
Diabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in patients beginning renal dialysis in the United States, and this trend is extending to developing countries as well [1,2]
We found that all five target genes show significantly higher levels of expression in the experimental groups compared with the control group (p = 0.007 for synaptopodin, p = 0.047 for CD2-AP,p = 0.01 for a-actin4, p = 0.006 for podocalyxin, and p = 0.021 for podocin, respectively, by Mann-Whitney test)
The expression of podocalyxin, CD2-AP, aactin4, and podocin messenger RNA (mRNA) correlated with serum creatinine levels (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)
Summary
Diabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in patients beginning renal dialysis in the United States, and this trend is extending to developing countries as well [1,2]. Recent studies have shown that renal podocyte injury is pathogenically and prognostically important in DN progression. Accumulating evidence suggests that podocyte-associated proteins or genes may correlate with proteinuria and renal function [7,8,9,10]. These findings bring up the interesting possibility that screening for podocyte-related molecules might be a novel strategy in monitoring the progression of DN. Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy
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