Podocyte and endothelial cell injury lead to nephrotic syndrome in proliferative lupus nephritis

Aims Nephrotic syndrome ( NS ) is a major manifestation of lupus nephritis ( LN ). The dysregulation of podocytes, the glomerular basement membrane ( GBM ) and endothelial cells ( EC s) results in proteinuria in glomerular diseases. The aim of our study was to clarify whether the dysregulation of these barriers is associated with NS in proliferative LN and membranous LN . Methods and results Fifty‐six patients with NS , including minimal change NS in 15, primary membranous nephropathy ( PMN ) in 13, class III / IV LN in 15, and class V LN in 13, were enrolled in this study. Subjects with idiopathic haematuria were assigned as controls. Glomerular expression of Wilms tumour protein 1 ( WT 1), nephrin, synaptopodin and podocalyxin was evaluated by immunohistochemistry ( IHC ) and real‐time quantitative reverse transcription polymerase chain reaction. EC injury was evaluated by CD 31 immunostaining and electron microscopy ( EM ). Reduced expression of WT 1, nephrin and synaptopodin was found in PMN , class III / IV LN and class V LN as compared with controls by IHC and mRNA analysis. Reduced expression of these molecules was not different between class III / IV LN and class V LN . Reduced numbers of CD 31‐positive EC s were found in class III / IV LN as compared with class V LN . EC injury showing subendothelial widening on EM was apparent in class III / IV LN as compared with class V LN . Foot process effacement was found only along the GBM showing EC injury in class III / IV LN . Conclusions Our study suggests that coexistence of podocyte and EC injury may lead to NS in proliferative LN . Podocyte damage alone leads to NS in membranous LN .