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Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder.
Kidney Int. 2018 07; 94(1):102-113.KI

Abstract

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.

Authors+Show Affiliations

Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.Merck KGaA, Darmstadt, Germany.Merck KGaA, Darmstadt, Germany.Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.Unité Institut National de la Santé et de la Recherche Médicale U-1088, Université de Picardie Jules Verne, Amiens, France.Unité Institut National de la Santé et de la Recherche Médicale U-1088, Université de Picardie Jules Verne, Amiens, France.Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. Electronic address: patrick.dhaese@uantwerpen.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29716795

Citation

Neven, Ellen, et al. "Metformin Prevents the Development of Severe Chronic Kidney Disease and Its Associated Mineral and Bone Disorder." Kidney International, vol. 94, no. 1, 2018, pp. 102-113.
Neven E, Vervaet B, Brand K, et al. Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder. Kidney Int. 2018;94(1):102-113.
Neven, E., Vervaet, B., Brand, K., Gottwald-Hostalek, U., Opdebeeck, B., De Maré, A., Verhulst, A., Lalau, J. D., Kamel, S., De Broe, M. E., & D'Haese, P. C. (2018). Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder. Kidney International, 94(1), 102-113. https://doi.org/10.1016/j.kint.2018.01.027
Neven E, et al. Metformin Prevents the Development of Severe Chronic Kidney Disease and Its Associated Mineral and Bone Disorder. Kidney Int. 2018;94(1):102-113. PubMed PMID: 29716795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder. AU - Neven,Ellen, AU - Vervaet,Benjamin, AU - Brand,Kerstin, AU - Gottwald-Hostalek,Ulrike, AU - Opdebeeck,Britt, AU - De Maré,Annelies, AU - Verhulst,Anja, AU - Lalau,Jean-Daniel, AU - Kamel,Said, AU - De Broe,Marc E, AU - D'Haese,Patrick C, Y1 - 2018/04/30/ PY - 2017/06/13/received PY - 2018/01/17/revised PY - 2018/01/25/accepted PY - 2018/5/3/pubmed PY - 2019/8/14/medline PY - 2018/5/3/entrez KW - CKD-MBD KW - chronic kidney disease KW - high bone turnover KW - metformin KW - renal fibrosis KW - vascular calcification SP - 102 EP - 113 JF - Kidney international JO - Kidney Int VL - 94 IS - 1 N2 - 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. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/29716795/Metformin_prevents_the_development_of_severe_chronic_kidney_disease_and_its_associated_mineral_and_bone_disorder_ DB - PRIME DP - Unbound Medicine ER -