Key result
Unilateral ureteral obstruction increased cortical renin mRNA and protein levels by 35% and 28%, respectively, and decreased medullary (pro)renin receptor levels compared to sham surgery.
Why the study?
It remained unknown whether intrarenal renin-angiotensin system (iRAS) is activated in early stages of chronic kidney disease.
p-value: p=<0.05
In a mouse model of unilateral ureteral obstruction, intrarenal RAS components are differentially modulated depending on renal localization, with cortical renin upregulation and medullary (pro)renin receptor downregulation.
Differential RAS modulation in obstructive models may guide targeted therapies; leaves open human relevance and clinical translation.
Chronic kidney disease (CKD) is characterized by renal dysfunction, which is a common feature of other major diseases, such as hypertension and diabetes. Unilateral ureteral obstruction (UUO) has been used as a model of CKD in experimental animals and consists of total obstruction of one kidney ureter. The UUO decreases renal blood flow, which promotes the synthesis of renin in the juxtaglomerular apparatus, the first step in renin-angiotensin system (RAS) cascade. RAS induces inflammation and remodeling, along with reduced renal function. However, it remains unknown whether intrarenal RAS (iRAS) is activated in early stages of CKD. Our objective was to characterize different iRAS components in the renal cortex and in the medulla in an early phase of UUO. Male C57BL/6 mice (8-12 weeks old) were subjected to UUO in the left kidney, or to sham surgery, and were euthanized after 7 days (n=5/group). Renal function, renal inflammatory/remodeling processes, and iRAS expression were evaluated. UUO increased plasma creatinine, right renal hypertrophy (9.08 ± 0.31, P<0.05 vs. Sham) and tubular dilatation in the left kidney cortex (42.42 ± 8.19µm, P<0.05 vs. Sham). This correlated with the increased mRNA of IL-1β (1.73 ± 0.14, P<0.01 vs. Sham, a pro-inflammatory cytokine) and TGF-β1 (1.76 ± 0.10, P<0.001 vs. Sham, a pro-fibrotic marker). In the renal cortex of the left kidney, UUO increased the mRNA and protein levels of renin (in 35% and 28%, respectively, P<0.05 vs. Sham). UUO decreased mRNA and protein levels for the (pro)renin receptor in the renal medulla (0.67 ± 0.036 and 0.88 ± 0.028, respectively. P<0.05 vs. Sham). Our results suggest that modulation of iRAS components depends on renal localization and occurs in parallel with remodeling and pro-inflammatory/pro-fibrotic mechanisms.
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Figueroa et al. (2019) studied Chronic kidney disease (Unilateral ureteral obstruction model) (n=10). Unilateral ureteral obstruction vs. Sham surgery was evaluated on Cortical renin mRNA levels (p=<0.05). Unilateral ureteral obstruction increased cortical renin mRNA and protein levels by 35% and 28%, respectively, and decreased medullary (pro)renin receptor levels compared to sham surgery.
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