Blog entry by Meguid El Nahas

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by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
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An growing controversy is buidling around the use of steroids in IgA Nephropathy.

Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namley auto-immunity...

http://www.ncbi.nlm.nih.gov/pubmed/25604055

 

 

 

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