Abstract
BackgroundPodocyte injury is an early feature of diabetic nephropathy (DN). Recently, urinary exosomal Wilm's tumor-1 protein (WT1), shed by renal epithelial cells, has been proposed as a novel biomarker for podocyte injury. However, its usefulness as biomarker for early diabetic nephropathy has not been verified yet. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline.MethodsThe expression of WT1 protein in urinary exosomes from spot urine samples of type-1 diabetes mellitus patients (n = 48) and healthy controls (n = 25) were analyzed. Patients were divided based on their urinary albumin excretion, ACR (mg/g creatinine) into non- proteinuria group (ACR<30 mg/g, n = 30) and proteinuria group (ACR>30 mg/g, n = 18). Regression analysis was used to assess the association between urinary exosomal levels of WT1 with parameters for renal function. Receiver Operating Characteristic (ROC) curve analysis was used to determine the diagnostic performance of exosomal WT-1.ResultsWT1 protein was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The levels of urinary exosomal WT1 protein is significantly higher (p = 0.001) in patients with proteinuria than in those without proteinuria. In addition, all the patients with proteinuria but only half of the patients without proteinuria were positive for exosomal WT1. We found that the level of exosomal WT1 were associated with a significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR. Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased renal function compared to WT1-negative patients. ROC analysis shows that WT-1 effectively predict GFR<60 ml. min-1/1.73 m2.ConclusionThe predominant presence of WT1 protein in urinary exosomes of diabetic patients and increase in its expression level with decline in renal function suggest that it could be useful as early non-invasive marker for diabetic nephropathy.
Highlights
Diabetic nephropathy (DN) is a major cause of end stage renal disease affecting millions of people worldwide [1]
Predominant expression of Wilm’s tumor-1 protein (WT1) protein in Urinary exosomes of diabetic patients compared to healthy controls
Using regression analysis we found that WT1 protein band density associated with increase in urine protein excretion as indicated by its significant association with albumin-to-creatinine ratio (ACR) (r = 0.89, p,0.001) and with protein-to-creatinine ratio, UPC (r = 0.91, p,0.001) in type-1 diabetic patients (Figure 2)
Summary
Diabetic nephropathy (DN) is a major cause of end stage renal disease affecting millions of people worldwide [1]. The onset and course of diabetic nephropathy can be ameliorated to a very significant degree by several interventions, if instituted at a point very early in the course of the development of this complication. This advocates an urgent need for early detection of nephropathy. Its presence is appropriate in patients with advanced diabetic nephropathy, it has limited ability to predict the earliest stages of DN [3]. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline
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