Digital pathology evaluation of complement C4d component deposition in the kidney allograft biopsies is a useful tool to improve reproducibility of the scoring

Complement C4d component deposition in kidney allograft biopsies is an established marker of antibody-mediated rejection. In the Banff 07 classification of renal allograft pathology, semi-quantitative evaluation of the proportion of C4d-positive peritubular capilaries (PTC) is used. We aimed to explore the potential of digital pathology tools to obtain quantitative and reproducible measure of C4d deposition in the renal allograft tissue

MicroRNAs in Diabetic Nephropathy: From Biomarkers to Therapy

Recent estimates suggest that 1 in 12 of the global population suffers from diabetes mellitus. Approximately 40 % of those affected will go on to develop diabetes-related chronic kidney disease or diabetic nephropathy (DN). DN is a major cause of disability and premature death. Existing tests for prognostic purposes are limited and can be invasive, and interventions to delay progression are challenging. MicroRNAs (miRNAs) are a recently described class of molecular regulators found ubiquitously in human tissues and bodily fluids, where they are highly stable. Alterations in miRNA expression profiles have been observed in numerous diseases. Blood and tissue miRNAs are already established cancer biomarkers, and cardiovascular, metabolic and immune disease miRNA biomarkers are under development. Urinary miRNAs represent a potential novel source of non-invasive biomarkers for kidney diseases, including DN. In addition, recent data suggest that miRNAs may have therapeutic applications. Here, we review the utility of miRNAs as biomarkers for the early detection and progression of DN, assess emerging data on miRNAs implicated in DN pathology and discuss how the data from both fields may contribute to the development of novel therapeutic agents

Glomerular permselectivity in proteinuric patients after kidney transplantation.

To characterize the defect in glomerular permselectivity responsible for proteinuria after renal transplantation, we studied 10 patients with moderate proteinuria (median 0.37 g/d, range 0.20-0.79), 16 patients with the nephrotic syndrome (6.73 g/d, 3.9-14.6), 8 living related donor transplant recipients without any history of rejection (median proteinuria 0.26 g/d, 0.06-0.58), and 12 healthy volunteers. The fractional clearance of neutral dextrans > 54 A was significantly higher in nephrotic patients, demonstrating a defect in glomerular size selectivity. Using a log-normal model of glomerular pore size distribution, r*(5%) and r*(1%), indices for the presence of large pores, were increased in the nephrotic patients. The fractional clearance of negatively charged dextran sulfate was significantly higher in all patient groups, indicating a loss of glomerular charge selectivity. Biopsy findings showed more prominent glomerular lesions in the nephrotic group compared with the moderately proteinuric group. We conclude that mild proteinuria late after renal transplantation is associated with a defect in glomerular charge selectivity. The development of nephrotic range proteinuria is associated also with a defect of glomerular size selectivity, which correlates with prominent glomerular pathology