Abstract: PO0644
Metformin Therapy Is Able to Halt the Progression of Established CKD in Rats
Session Information
- CKD Mechanisms - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Corremans, Raphaëlle, Universiteit Antwerpen, Antwerpen, Belgium
- Neven, Ellen, Universiteit Antwerpen, Antwerpen, Belgium
- D'Haese, Patrick, Universiteit Antwerpen, Antwerpen, Belgium
- Vervaet, Benjamin Arthur, Universiteit Antwerpen, Antwerpen, Belgium
- Verhulst, Anja, Universiteit Antwerpen, Antwerpen, Belgium
Background
Metformin, first-line drug for type-2 diabetes, exerts benign pleiotropic actions beyond its prescribed use and emerging data show protective effects against the development/progression of renal impairment. Current treatment strategies for chronic kidney disease (CKD) mainly focus on controlling important risk factors, while effective treatment directly targeting the kidney is lacking. However, in 2019, the FDA approved the use of the sodium-glucose co-transporter-2 (SGLT2) inhibitor, canagliflozin, to treat diabetic nephropathy. Here, the ability of metformin to attenuate the progression of established, non-diabetic CKD was investigated and compared to canagliflozin.
Methods
Adenine-induced CKD rats (n=86) were assigned to different treatment groups to receive 200 mg/kg metformin, 4 or 5 weeks after the start of the adenine diet (0.25%), i.e. after CKD had developed, or 25 mg/kg canagliflozin 4 weeks after the start of the diet, by daily oral gavage, during 4 weeks. Each treatment group was compared to a vehicle (1% carboxymethylcellulose) group.
Results
Serum creatinine levels dramatically rose in vehicle-treated CKD rats: from 0.7 ± 0.1 mg/dL (week 0) to 1.5 ± 0.1 mg/dL (week 4), 2.6 ± 1.2 mg/dL (week 5) and further to 6.2 ± 0.3 mg/dL (week 8) and 4.8 ± 1.1 mg/dL (week 9). Canagliflozin treatment did not alter the increase in serum creatinine as indicated by serum creatinine levels at week 8 (5.8 ± 0.4 mg/dL). In contrast, metformin treatment almost completely prevented the increase from week 4 or 5 on, as indicated by the serum creatinine levels after 8 (2.0 ± 0.5 mg/dL) and 9 (2.9 ± 0.5 mg/dL) weeks (p<0.05 vs. vehicle).
Canagliflozin treatment did not alter the tubulointerstitial area percentage, while this parameter was 33% lower at week 8 and 23% lower at week 9 in metformin-treated CKD rats compared to vehicle treatment (p<0.05 vs. vehicle). Further histological examination revealed more tubular proliferation (PCNA positive cells) and less interstitial inflammation (CD45 positive cells) in metformin-treated rats compared to vehicle-treated animals.
Conclusion
In conclusion, metformin is able to attenuate the progression of pre-existing adenine-induced CKD in rats. Our data do not present evidence for a beneficial effect of canagliflozin on progression of non-diabetic CKD.