title: Magnesium modifies the association between serum phosphate and the risk of progression to end-stage kidney disease in patients with non-diabetic chronic kidney disease.
abstract: It is known that magnesium antagonizes phosphate-induced apoptosis of vascular smooth muscle cells and prevents vascular calcification. Here we tested whether magnesium can also counteract other pathological conditions where phosphate toxicity is involved, such as progression of chronic kidney disease (CKD). We explored how the link between the risk of CKD progression and hyperphosphatemia is modified by magnesium status. A post hoc analysis was run in 311 non-diabetic CKD patients who were divided into four groups according to the median values of serum magnesium and phosphate. During a median follow-up of 44 months, 135 patients developed end-stage kidney disease (ESKD). After adjustment for relevant clinical factors, patients in the lower magnesium-higher phosphate group were at a 2.07-fold (95% CI: 1.23-3.48) risk for incident ESKD and had a significantly faster decline in estimated glomerular filtration rate compared with those in the higher magnesium-higher phosphate group. There were no significant differences in the risk of these renal outcomes among the higher magnesium-higher phosphate group and both lower phosphate groups. Incubation of tubular epithelial cells in high phosphate and low magnesium medium in vitro increased apoptosis and the expression levels of profibrotic and proinflammatory cytokine; these changes were significantly suppressed by increasing magnesium concentration. Thus, magnesium may act protectively against phosphate-induced kidney injury.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakaguchi
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Iwatani
authors.affiliation: Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
authors.affiliation: Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan.
authors.forename: Kodo
authors.initials: K
authors.lastname: Tomida
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawabata
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kusunoki
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shimomura
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui
authors.affiliation: Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008274:Magnesium / Q000097:blood*; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D010710:Phosphates / Q000097:blood* / Q000633:toxicity; D065840:Protective Factors; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D010710:Phosphates; D008278:Magnesium Sulfate; D008274:Magnesium; C018279:sodium phosphate