Abstract P178: Mineralocorticoid Receptor Antagonism Improved the Metabolic Function in a Mouse Model With Chronic Kidney Disease and Obesity

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 74; no. Suppl_1
• Main Authors: Palacios Ramirez, Roberto, Bonnard, Benjamin, Jaisser, Frederic
• Format: Journal Article
• Language: English
• Published: 01-09-2019
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.74.suppl_1.P178

Abstract only
Introduction:
Chronic kidney disease (CKD) is associated to cardiovascular and metabolic comorbidities. Several studies reported beneficial effects of mineralocorticoid receptor antagonists (MRA) in CKD.
Objective:
We investigated the metabolic alterations associated to CKD in a context of obesity and explored the effect of MR antagonism.
Methods:
5/6 nephrectomy was applied to C57BL6j mice to induce CKD . One month later they were randomized in 3 groups with similar renal failure: CKD + chow diet (CKD), CKD + High Fat Diet (CKD HFD) and CKD HFD treated with canrenoate (30mg/kg/day) (CKD HFD CAN). Analysis was done one month later. Glucose tolerance test (ipGTT) and insulin tolerance test (ipITT) were performed. Gene expression in Epididymal Visceral Adipose Tissue (EVAT) was analyzed by RT-PCR: Adipokines and markers of fibrosis and inflammation were evaluated. The comparison was performed by one way ANOVA (n=7-9) and two way ANOVA for the insulin and glucose tests (n=7-9). Results were considered significant with p<0.05.
Results:
The CKD HFD mice showed body and EVAT weight higher than the CKD, these effects were prevented by canrenoate (eith no improvement of renal function). Glucose tolerance was impaired in CKD HFD mice and canrenoate improved it. The MRA also improved insulin sensitivity. The adipokine leptin was increased by HFD and canrenoate normalized its levels while the expression of PPARα were reduced in both CKD HFD and CKD HFD CAN. The expression of the pro-fibrotic marker TGFβ as well as the pro-inflammatory marker TLR4 was reduced in CKD HFD CAN compared to CKD HFD.
Conclusion:
MRA might be useful in the management of metabolic comorbidities associated to CKD.