Neither the initiating factors nor the proximate causes of injury that produce
proteinuria in
nephrotic syndrome have been clearly defined. Immune mechanisms have been postulated in
minimal-change nephrotic syndrome (MCNS), focal segmental glomerular
sclerosis (FSGS), and glomerular
sclerosis associated with human immunodeficiency virus (
HIV) infection. Circulating factors have been proposed in MCNS and FSGS, although no specific mediator has been identified. Prompt remission of
proteinuria following
steroid treatment and the presence of altered immune responsiveness in patients with MCNS have been used to support the participation of an immune mechanism in the pathogenesis of MCNS. Both FSGS and
HIV-related nephropathy are usually
steroid-resistant. Immune mechanisms are postulated in FSGS because of early recurrence after
transplantation, and in
HIV-related nephropathy because of the numerous associated immune abnormalities. Experimental models of
nephrotic syndrome based on neutralization of glomerular charge, toxic injury to podocytes, injection of
antibodies to glomerular components, or abnormalities in transgenic mice have been used to define mechanisms of glomerular injury. This review summarizes physiologic and immunologic abnormalities in MCNS, FSGS, and
HIV-associated nephropathy and in several experimental models of
nephrotic syndrome, and outlines the immunologic mechanisms and cellular reactions that may be responsible for glomerular dysfunction in these entities.