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Kidney Week

Abstract: TH-PO898

Altered Expression of the Renal Prostaglandin E2 Signaling System in Kidney Tissue from Patients with Hydronephrosis and Renal Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Madsen, Kirsten, University of Southern Denmark, Odense C, Denmark
  • Tofteng, Signe Skou, University of Southern Denmark, Odense C, Denmark
  • Kamstrup mogensen, Amalie, Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark,, Odense, Denmark
  • Jensen, Boye, University of Southern Denmark, Odense C, Denmark
Background

Renal fibrosis is the final common pathway in chronic kidney diseases (CKD). Increased prostaglandin E2-EP4 receptor signaling through increased EP4 receptor expression has been suggested to attenuate renal fibrosis in mice using the unilateral ureteral obstruction (UUO) model. It is unknown if patients with hydronephrosis and renal fibrosis show similar regulation of the renal prostaglandin E2 signaling system. We tested the hypothesis that hydronephrosis and renal fibrosis is associated with increased renal COX-2 and EP4 receptor expression in humans.

Methods

Kidney tissue was collected from patients diagnosed with hydronephrosis undergoing unilateral nephrectomy (n=12) at the Dept. of Urology, Odense University Hospital. Normal appearing kidney tissue from age- and gender matched subjects undergoing nephrectomy due to renal cell carcinoma (n=12) was used as control. The percentage of the cortical region affected by interstitial fibrosis was scored and expression of the prostaglandin E2 signaling system was determined by qPCR.

Results

Mean age was 54 years [range 26-78 years] in the hydronephrosis group and 55 years [range 28-78 years] in the control group. All patients in the control group showed minimal or no signs of renal fibrosis (0-10%). In the hydronephrosis group, 4 patients showed mild (10-25%), 3 patients moderate (26-50%) and 2 patients severe fibrosis (50-100%). 3 patients showed minimal or no signs of renal fibrosis. No significant changes in COX-2, COX-1 or PTGES mRNA was detected. In kidney cortex, a significant upregulation of EP2 receptor mRNA was detected in the hydronephrosis group compared to controls and a concomitant downregulation of the EP3 receptor mRNA level. No significant changes in EP1 or EP4 receptor mRNAs were seen. In outer medulla, a significantly reduced expression of the EP3 receptor was seen in the hydronephrosis group. No changes in EP receptor expression were seen in the inner medulla.

Conclusion

In conclusion, hydronephrosis and renal fibrosis in humans is associated with altered renal EP2 and EP3 receptor expression. No changes were detected in COX-2 and EP4 receptor expression as has been described in mice. Results suggest the EP2 and not the EP4 receptor to be dominant in PGE2 receptor signaling during renal fibrogenesis in humans.

Funding

  • Private Foundation Support