Syndromes néphrotiques idiopathiques. Physiopathologie et prise en charge thérapeutique spécifique chez l'adulte

Idiopathic nephrotic syndrome is the most frequent glomerular disease in children and in young adults. While genetic analyses have provided new insights into disease pathogenesis through the discovery of several podocyte genes mutated in distinct forms of inherited nephrotic syndrome, the molecular bases of minimal change nephrotic syndrome and focal and segmental glomerulosclerosis with relapses remain unclear. Although immune cell disorders, which may involve both innate and adaptive immunity, appear to play a role in the pathogenesis of steroid sensitive minimal change nephrotic syndrome, the mechanisms by which they induce podocyte dysfunction remain unresolved. It was postulated that podocyte injury results from a circulating factor secreted by abnormal T cells, but the possibility that bipolarity of the disease results from a functional disorder shared by both immune cells and the podocytes is not excluded. Minimal change nephrotic syndrome relapses are associated with an expansion of T and B cell compartments and production of growth factors as well as many cytokines. Dysfunction of T cells is supported by several findings including, inhibition of a type IV hypersensitivity reaction and unclassical T helper polarization, resulting from transcriptional interference between Th1 and Th2 transcriptional factors. A low serum level of some IgG fractions is frequently observed suggesting a defect in T-B cell cooperation, which remains to be explored. In this review, we discuss recent advances in the pathogenesis and the therapy of idiopathic nephrotic syndrome.