Minimal Change Disease (a second perspective)

Invited commentary by Dr. Sanjeev Sethi

The pathogenesis of minimal change disease has remained enigmatic until recently. With advances in the pathogenesis of membranous nephropathy and focal segmental glomerulosclerosis, it was a matter of time before studies would reveal the underlying mechanism of minimal change disease. Recent studies have shown that primary membranous nephropathy is due to antibodies to phospholipase A2 receptor (anti-PLA2R antibodies), and primary focal segmental glomerulosclerosis may be linked to development of high levels of serum soluble urokinase receptor (suPAR). In the current issue of the American Journal of Kidney Diseases, Chugh et al reviewed recent studies showing that minimal change disease may be related to overproduction of angiopoietin-like 4 (ANGPTL4) by podocytes in mice. Chugh et al reviewed their work showing that overproduction of ANGPTL4 by podocytes results in binding of ANGPTL4 to the glomerular basement membrane with eventual clustering of ANGPTL4 in the sub-epithelial region of the glomerular basement membrane, resulting in podocyte foot process effacement and development of proteinuria. Furthermore, they show that it is the accumulation of a hyposialylated form of ANGPTL4 that results in loss of glomerular basement membrane charge, suggesting that a new form of therapy with sialylating agents maybe be beneficial in minimal change disease. We are living in exciting times with regards to nephrotic syndrome as we elucidate the mechanism of previously idiopathic diseases. It is now time to tailor specific treatment based on the underlying etiology of the nephrotic syndrome.

Sanjeev Sethi, MD, PhD
Associate Professor of Laboratory Medicine and Pathology, Mayo Clinic

Please check out the first post on this AJKD article.

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1 Comment on Minimal Change Disease (a second perspective)

  1. Dr. Paulose Thomas // March 8, 2012 at 11:27 am // Reply

    I think it may be the WOW moment for MCD and may be nephrotic syndrome in general

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