Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular
calcification and renal osteodystrophy, an entity called ‘CKD–Mineral and Bone Disorder’
(CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable
effects on progressive, severe CKD and concomitant mineral metabolism disturbances.
Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with
200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe,
stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these
rats which led to arterial calcification and high bone turnover disease. Metformin
protected from development toward severe CKD. Metformin-treated rats did not develop
hyperphosphatemia or hypocalcemia and this prevented the development of vascular calcification
and inhibited the progression toward high bone turnover disease. Kidneys of the metformin
group showed significantly less cellular infiltration, fibrosis and inflammation.
To study a possible direct effect of metformin on the development of vascular calcification,
independent of its effect on renal function, metformin (200 mg/kg/day) or vehicle
was dosed for ten weeks to rats with warfarin-induced vascular calcification. The
drug did not reduce aorta or small vessel calcification in this animal model. Thus,
metformin protected against the development of severe CKD and preserved calcium phosphorus
homeostasis. As a result of its beneficial impact on renal function, associated comorbidities
such as vascular calcification and high bone turnover disease were also prevented.
Keywords
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Article Info
Publication History
Published online: April 28, 2018
Accepted:
January 25,
2018
Received in revised form:
January 17,
2018
Received:
June 13,
2017
Identification
Copyright
© 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
