Proteinuria-associated renal magnesium wasting leads to hypomagnesemia: a common electrolyte abnormality in chronic kidney disease.

Abstract

BACKGROUND:

Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain.

METHODS:

In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year.

RESULTS:

In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2-4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001).

CONCLUSIONS:

Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD.

• Authors: Tatsufumi Oka, Takayuki Hamano, Yusuke Sakaguchi, Satoshi Yamaguchi, Keiichi Kubota, Masamitsu Senda, Sayoko Yonemoto, Karin Shimada, Ayumi Matsumoto, Nobuhiro Hashimoto, Daisuke Mori, Chikako Monden, Atsushi Takahashi, Yoshitsugu Obi, Ryohei Yamamoto, Yoshitsugu Takabatake, Jun-Ya Kaimori, Toshiki Moriyama, Masaru Horio, Isao Matsui, Yoshitaka Isaka
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 34 Issue 7 Pg. 1154-1162 (07 01 2019) ISSN: 1460-2385 [Electronic] England
• PMID: 29796601 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Biomarkers
• Electrolytes
• Magnesium Oxide
• Magnesium

Topics

• Adult
• Biomarkers (blood, urine)
• Cross-Sectional Studies
• Disease Progression
• Electrolytes (metabolism)
• Female
• Follow-Up Studies
• Humans
• Japan (epidemiology)
• Kidney Function Tests
• Magnesium (metabolism)
• Magnesium Oxide (therapeutic use)
• Male
• Middle Aged
• Outpatients
• Prevalence
• Proteinuria (complications, drug therapy, metabolism)
• Renal Insufficiency, Chronic (complications, drug therapy, metabolism)
• Renal Tubular Transport, Inborn Errors (epidemiology, etiology, prevention & control)
• Retrospective Studies