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Kidney Week

Abstract: FR-PO388

Progression of Established CKD Is Halted by Metformin Treatment in Rats

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Corremans, Raphaëlle, University of Antwerp, Antwerp, Belgium
  • Vervaet, Benjamin Arthur, University of Antwerp, Antwerp, Belgium
  • D'Haese, Patrick C., University of Antwerp, Antwerp, Belgium
  • Verhulst, Anja, University of Antwerp, Antwerp, Belgium
Background

Metformin, the first-line drug for type-2 diabetes mellitus, also exerts multiple benign pleiotropic actions on different organs. Recent preclinical and clinical data point towards a beneficial impact of metformin on the kidney. Chronic kidney disease (CKD) is a worldwide recognized public health problem and represents a progressive loss of renal function over a period of months or years. Current treatment strategies for CKD mainly focus on controlling important risk factors. To date, effective treatment directly targeting the kidney is lacking. Here, the efficacy of metformin to attenuate progression of already established CKD was investigated.

Methods

A rat model of adenine-induced CKD (n=64) was used. Metformin (200 mg/kg) or vehicle (1% carboxymethylcellulose) treatment, by daily oral gavage (7 days/week), was initiated after 4 and 5 weeks of adenine (0.25%) administration; i.e. after CKD had developed. Treatment was continued during 4 weeks until the end of the study (i.e. week 8 and 9, respectively). A constant dose volume of 10 mL/kg was used. The effect of metformin on renal function and histopathology was studied.

Results

Serum creatinine levels dramatically rose in vehicle-treated CKD rats: from 0.6 ± 0.1 mg/dL (week 0) to 1.3 ± 0.2 mg/dL (week 4) and 2.6 ± 1.2 mg/dL (week 5) and further to 5.7 ± 0.6 mg/dL (week 8) and 4.8 ± 1.1 mg/dL (week 9). This increase from week 4 and 5, respectively, was almost completely prevented by metformin treatment as indicated by serum creatinine levels after 8 (2.0 ± 0.5 mg/dL) and 9 (2.9 ± 0.5 mg/dL) weeks respectively (p<0.05 vs. vehicle). Histological examination of periodic acid–Schiff-stained renal sections revealed less tubular dilation, epithelial flattening, brush border loss and, basement membrane thickening in metformin-treated rats in comparison to vehicle-treated animals. The renal tubulointerstitial area percentage, consisting of both extracellular matrix and infiltrating cells, in metformin treated CKD rats, was significantly lower, as compared to vehicle treatment (33% and 23% lower in rats receiving metformin from week 4 and 5, respectively, as compared to vehicle).

Conclusion

Metformin is able to attenuate the progression of pre-existing adenine-induced CKD in rats.

Funding

  • Government Support - Non-U.S.