Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA141

Poster Communications

Altered expression of the renal prostaglandin E2 signaling system in kidney tissue from patients suffering from hydronephrosis and renal fibrosis

S. S. Tofteng1, A. K. Mogensen1, A. Toft3, B. L. Jensen1, K. Madsen1,2

1. Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark. 2. Department of Pathology, Odense University Hospital, Odense, Denmark. 3. Department of Urology, Odense University Hospital, Odense, Denmark.


Renal fibrosis is the final common pathway in chronic kidney diseases (CKD). The mechanisms leading to renal fibrosis are only partly understood. Increased prostaglandin E2-EP4 receptor signaling through increased EP4 receptor expression has been suggested to attenuate renal fibrogenesis in mice using the unilateral ureteral obstruction (UUO) model of CKD. It is currently unknown if patients suffering from 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. 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 controls. Kidney tissue was collected within 60 minutes of removal from the patient and divided into cortex, outer and inner medulla. Tissue sections were Periodic Acid Schiff (PAS) stained and the percentage of the cortical region affected by interstitial fibrosis was scored according to Sethi et al. (Kidney Int 91:787-797,2017). Expression of the renal prostaglandin E2 signaling system was determined by quantitative PCR. The study was approved by the Regional Committees on Health Research Ethics. Mean age of the patients was 54 years [range 26-78 years] in the hydronephrosis group and 55 years [range 28-78 years] in the control group. Male:female ratio was 1:1. In the control group, all patients showed minimal or no signs of renal fibrosis (less than 10%). In the hydronephrosis group, 4 patients showed mild (10-25%), 3 patients moderate (26-50%) and 2 patients a severe degree of fibrosis (>50%), whereas 3 patients showed minimal or no signs of renal fibrosis. No significant changes in COX-2, COX-1 or prostaglandin E2 synthase mRNA abundance was detected in in kidney regions. In kidney cortex, a significant upregulation of EP2 receptor mRNA abundance 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. 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.

Where applicable, experiments conform with Society ethical requirements