Journal Article

Protective effects of PPARγ agonist in acute nephrotic syndrome

Yiqin Zuo, Hai-Chun Yang, Sebastian A. Potthoff, Behzad Najafian, Valentina Kon, Li-Jun Ma and Agnes B. Fogo

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 1, pages 174-181
Published in print January 2012 | ISSN: 0931-0509
Published online May 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr240
Protective effects of PPARγ agonist in acute nephrotic syndrome

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Background.

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have beneficial effects on renal structure and function in models of diabetes and chronic kidney diseases. However, the increased incidence of weight gain and edema potentially limits their usefulness. We studied an acute minimal-change disease-like nephrotic syndrome model to assess effects of PPARγ agonist on acute podocyte injury and effects on fluid homeostasis.

Methods.

Acute podocyte injury and nephrotic syndrome were induced by puromycin aminonucleoside (PAN) injection in rats.

Results.

PPARγ agonist, given at the time or after, but not before PAN, reduced proteinuria, restored synaptopodin, decreased desmin and trended to improve foot process effacement. There was no significant difference in glomerular filtration, effective circulating volume, blood pressure or fractional sodium excretion. PAN-injured podocytes had decreased PPARγ, less nephrin and α-actinin-4, more apoptosis and reduced phosphorylated Akt. In PAN-injured cultured podocytes, PPARγ agonist also reversed abnormalities only when given simultaneously or after injury.

Conclusions.

These results show that PPARγ agonist has protective effects on podocytes in acute nephrotic syndrome without deleterious effects on fluid homeostasis. PPARγ agonist-induced decrease in proteinuria in acute nephrotic syndrome is dependent at least partially on regulation of peroxisome proliferator-response element-sensitive gene expression such as α-actinin-4 and nephrin and the restoration of podocyte structure.

Keywords: nephrotic syndrome; podocytes; PPARγ; puromycin aminonucleoside

Journal Article.  4971 words.  Illustrated.

Subjects: Nephrology

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