Dysregulated Nephrin in Diabetic Nephropathy of Type 2 Diabetes: A Cross Sectional Study

Abstract

BackgroundPodocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.Methodology/Principal FindingsProtein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = −0.48, p<0.0001) and eGFR (rho = −0.33, p = 0.005).Conclusions/SignificanceThese data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.

Progression after AKI

“…Biomarkers, such as urinary albumin, neutrophil gelatinaseassociated lipocalin, KIM-1, IL-18, L-FABP MCP-1, nephrin, podocalyxin, and podocin, are markers of tubular or glomerular damage. [52][53][54][55] Other biomarkers, such as C-reactive protein and TNF receptor 2, which are general biomarkers of inflammation or endothelial dysfunction, may reflect systemic phenomena relevant to CKD progression, 56 but their predictive value after AKI is unknown.…”

Curcumin attenuates high glucose-induced podocyte apoptosis by regulating functional connections between caveolin-1 phosphorylation and ROS

“…Podocytes are terminally differentiated and highly specialized glomerular visceral epithelial cells that form part of the glomerular filtration barrier, which prevents urinary protein loss [2] . Several recent studies suggested that podocyte damage may play a key role in the pathogenesis of DN [3][4][5] .…”

Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced Diabetes

“…12 This may be due to the cleavage of the extracellular domain of nephrin molecule which becomes undetectable (as all available antibodies recognize only the extracellular domain of nephrin) and/or to the loss of podocytes. Immunostaining of diabetic kidneys for nephrin and podocin in fact showed a reduction in staining area, rather than of staining intensity ( Figure 2B).…”