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Kidney Week

Abstract: PO2520

Angiotensin II Type 2 Receptor Agonist C21 Acutely Prevents the Loss of Megalin in the Kidney Cortex and the Onset of Proteinuria in Obese Zucker Rats Fed with High-Sodium Diet

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms


  • Kulkarni, Kalyani, University of Houston System, Houston, Texas, United States
  • Hussain, Tahir, University of Houston System, Houston, Texas, United States
  • Patel, Sanket Niranjanbhai, University of Houston System, Houston, Texas, United States

The appearance of protein in the urine (i.e. proteinuria) is a function of the glomerular filtration rate of protein and the reabsorption of protein from the post-glomerular filtrate by the endocytic receptors, megalin and cubilin, localized in the renal proximal tubules. We have shown that treatment with the angiotensin-II type 2 receptor (AT2R) agonist C21 for 2 weeks reduces proteinuria in obese Zucker rats (OZR) fed HSD. The consumption of sodium-rich diet (HSD) can acutely precipitate proteinuria which is a risk factor and indicator of kidney injury. Therefore, the objective of this study was to identify the acute and chronic mechanism that may have been involved in proteinuria upon consumption of HSD and to identify the anti-proteinuric mechanism upon AT2R activation in obesity.


Male OZR were treated acutely (2 days) or chronically (14 days) without or with AT2R agonist C21 (1mg/kg/day) while fed with normal salt diet NSD (0.4%) or HSD (4%).


The effects of HSD feeding on the expression of endocytic receptor megalin was biphasic. The HSD feeding for 2 days decreased, but for 14 days, increased megalin expression (p<0.05 vs. OZR). However, at 2- and 14-days, HSD feeding caused significant proteinuria (p<0.05 vs. OZR). The expression of cubilin remain unaffected. The AT2R agonist treatment significantly prevented the HSD-associated changes in the expression of megalin at 2-days and 14-days, and prevented the onset of proteinuria. The expression of glomerular proteins, nephrin and podocin, which are part of the renal filtration apparatus, in the kidney cortex remains unaffected at 2-days, which suggest that glomerular filtration of protein due to the loss of these glomerular proteins, per se, is not affected by HSD intake and that altered tubular reabsorption is involved in the initiation of proteinuric injury.


Collectively, these data suggest that AT2R activation protects against HSD induced proteinuria in obese rats by preventing the early loss of endocytic receptor megalin.


  • NIDDK Support