Abstract: SA-PO738
Disruption of CD40 Attenuates Renal Injury Induced by Acute High Salt Intake in Experimental Hypertensive Renal Disease
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Zhang, Shungang, University of Toledo, Toledo, Ohio, United States
- Khalaf, Fatimah Kareem, University of Toledo, Toledo, Ohio, United States
- Lad, Apurva, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, United States
- Kleinhenz, Andrew, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, United States
- Malhotra, Deepak K., University of Toledo, Toledo, Ohio, United States
- Kennedy, David J., University of Toledo Health Science Campus, Toledo, Ohio, United States
- Haller, Steven T., University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, United States
Background
We have recently shown that circulating levels of the pro-inflammatory receptor CD40 predict progression of renal dysfunction in patients with hypertensive renal disease and the soluble ligand for CD40 (sCD40L) is significantly elevated in this setting. In our CD40 knockout (KO) model developed on a background prone to hypertensive renal disease (Dahl S rat), we demonstrated significantly reduced renal fibrosis and improved renal function following a chronic high salt diet. To test the hypothesis that disruption of CD40 attenuates early indicators of renal injury and reduces inflammation, we performed the following acute high salt study.
Methods
Seven-week old Dahl S wild-type and Dahl S CD40KO male rats (n=8 per group) were given a high salt diet (2% NaCl) for 1 week. Blood pressure, urinary protein excretion (UPE), and plasma creatinine were measured. Kidneys were assessed for evidence of inflammation and injury.
Results
After acute high salt diet, blood pressure and plasma creatinine between wild-type Dahl S rats and Dahl S CD40KO rats were similar. UPE was significantly reduced in the Dahl S CD40KO compared to Dahl S rats (33.7±6.8 mg/24h vs. 106.9±28.6 mg/24h, p<0.05). Renal cortex gene expression of kidney injury molecule-one (KIM-1) (p<0.05), monocyte chemoattractant protein-1 (MCP-1) (p<0.001), and chemokine (C-X-C motif) ligand 2 (CXCL-2) (p<0.05) were significantly lower in Dahl S CD40KO rats compared to Dah S rats as assessed by quantitative PCR.
Conclusion
Disruption of CD40 significantly reduced proteinuria, KIM-1, and markers of inflammation following acute high salt induced renal injury. Our results indicated that CD40 may serve as a therapeutic target to inhibit acute renal injury and prevent the progression of hypertensive renal disease.