Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome

Abstract

The pathogenesis of proteinuria in idiopathic minimal lesion nephrotic syndrome (IMLNS) remains to be elucidated. The most-accepted hypothesis is that the increased glomerular permeability to plasma proteins results from the effect of circulating factors on glomerular capillaries. This report critically reviews the current studies that have attempted to isolate and characterize this putative factor(s). Products released from hepatocyte or peripheral blood mononuclear cells or isolated by chromatography from serum or plasma have been tested in rats for their role in inducing proteinuria. These factors have been infused into the isolated kidney preparation or into the intact animal as a single venous injection, or continuously by pump for a period of 4 h to 7 days. Several of these isolated factors have been shown to induce proteinuria in rats. However, their exclusive pathogenetic role is questionable since none is always present in all IMLNS patients during relapse. Therefore, the increase in proteinuria in these patients may result from a single or a variety of factors as yet to be identified.

Induction of Podocyte VEGF164 Overexpression at Different Stages of Development Causes Congenital Nephrosis or Steroid-Resistant Nephrotic Syndrome

“…17 This response has been interpreted as a consequence of the immunosuppressive effect of glucocorticosteroids. 46 However, the cell and molecular mechanism(s) mediating the effect of glucocorticosteroids on foot process effacement are poorly understood. In cultured podocytes dexamethasone induces activation of nephrin transcription.…”

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

“…A potential candidate for a permeability factor is IL-8/CXCL8. Most studies that assessed this chemokine in INS found increased serum levels in patients during relapse, and normal concentrations in remission (7,8,38). IL-8/CXCL8 was also found to have effects on the metabolism of the glomerular basement membrane, possibly increasing glomerular permeability (7).…”

“…More recently, it has been proposed that alterations in the cytokine and chemokine profile of INS patients might contribute to proteinuria and glomerular damage (7,8). Cytokines are a group of proteins produced by several kinds of cells that function as soluble mediators with intercellular signaling functions (4).…”

“…Studies have found increased levels of MCP-1/CCL2 and RANTES/CCL5 in progressive glomerular diseases, allograft rejection and interstitial nephritis (18,19). Another mediator of interest when studying the INS pathogenesis is IL-8 (IL-8/CXCL8), a chemokine produced by endothelial cells and macrophages that attracts neutrophils and lymphocytes to the inflammation site (17,18), and may be involved in the pathogenesis of proteinuria in INS (7,20).…”

MicroRNAs in Idiopathic Childhood Nephrotic Syndrome

“…Childhood nephrotic syndrome (NS) 3 is associated with an increase in the permeability across the glomerular filtration barrier due to processes that affect the dynamics and permselectivity of the glomerular filtration barrier. This increased permeability leads to an inability to restrict the loss of protein to Ͻ100 mg/m 2 body surface per day (1 ).…”