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Abstract: SA-PO983

Increased Severity of CKD in Response to High Potassium Intake Depends on Mineralocorticoid Receptor Activation

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Olivier, Valerie, Universite de Geneve, Geneve, GE, Switzerland
  • Feraille, Eric, Universite de Geneve, Geneve, GE, Switzerland

Group or Team Name

  • PHYME
Background

Dietary treatment is seminal for the management of chronic kidney disease (CKD). The effects of potassium intake on CKD progression are controversial. The aim of the project was to assess the effects of potassium intake on CKD progression.

Methods

We used 2 mouse models of CKD to analyze the effects of potassium diet on kidney injury: the unilateral ureteral obstruction (UUO) performed in wild type mouse, as an obstructive CKD model, and the POD-ATTAC mouse, as a glomerular CKD model. The POD-ATTAC mouse model displays a podocyte-specific apoptosis after the administration of a chemical inducer. We also studied the role of the mineralocorticoid receptor (MR) using the MR antagonist spironolactone in POD-ATTAC mice and UUO in kidney tubule epithelial cell-specific MR KO mice.

Results

In UUO and POD-ATTAC mice, high potassium diet increased interstitial fibrosis quantified by Sirius red staining of kidney slices (Fig.1). High potassium diet also increased the abundance of the extracellular matrix protein fibronectin and decreased the expression levels of the epithelial marker Na+-K+ ATPase, assessed by Western blot. Consistently, POD-ATTAC mice fed with high potassium diet displayed lower glomerular filtration rate (Fig.1) and decreased peritubular capillary network assessed by CD34 staining. Spironolactone decreased fibrosis induced by high potassium diet in POD-ATTAC mice. However, tubular-specific MR knockdown did not improve the fibrotic lesions induced by UUO under normal or high potassium diet. High potassium diet led to enhanced kidney inflammation and to a proinflammatory macrophage phenotype, which were reversed under spironolactone.

Conclusion

High potassium intake induces enhanced inflammation and accelerated fibrosis leading to decreased kidney function in 2 mouse models of CKD. Non-tubular MR plays a pivotal role in potassium-induced fibrosis. The effect of reducing potassium intake, as a way to slowdown CKD progression should be assessed in future clinical trials.

Funding

  • Private Foundation Support