Magnesium Oxide Use and Clinical Outcomes in CKD Patients: Evidence from a Nationwide Population-Based Cohort Study...

Magnesium homeostasis in chronic kidney disease (CKD) is complex, and serum magnesium concentrations reflect only approximately 1% of total body magnesium. Both magnesium deficiency (hypomagnesemia) and excess (hypermagnesemia) have been linked to adverse cardiovascular outcomes, a concern that is particularly relevant in patients with CKD. Magnesium oxide (MgO) is frequently prescribed for dyspepsia and constipation in clinical practice; however, its clinical impact in CKD patients remains uncertain and warrants further investigation.

We included non-dialysis CKD patients identified from the Taipei Medical University Clinical Research Database (TMUCRD) between 1998 and 2021. Adherence to MgO was assessed using the medication possession ratio (MPR). The primary outcomes were acute kidney injury (AKI), acute kidney disease (AKD), hospitalization for AKI, end-stage renal disease (ESRD) requiring dialysis, congestive heart failure with pulmonary edema, cardiac arrhythmia, and acute myocardial infarction. Baseline comorbidities assessed prior to the index date included hypertension, diabetes, hyperlipidemia, ischemic heart disease (IHD), ischemic stroke, congestive heart failure, atrial fibrillation (AF), peripheral arterial disease (PAD), chronic obstructive pulmonary disease (COPD), chronic liver disease (CLD), and dementia. These variables, along with relevant medications, were included as covariates in multivariable models to adjust for potential confounders.

Before matching, 6,105 MgO users and 10,143 non-users were identified; approximately 73% of MgO users had MPR <40%. In the ACE inhibitor (ACEI)/angiotensin receptor blocker (ARB) and pre-end-stage renal disease (pre-ESRD) program cohort, 207 MgO users and 1,401 non-users were included; after matching, 151 MgO users and 302 non-users remained. Dementia was more prevalent among MgO users, whereas diabetes was more common in non-users. MgO use was associated with higher risks of AKI, AKD, ESRD requiring dialysis, cardiac arrhythmia, and myocardial infarction in both unmatched and matched cohorts. In matched CKD patients, adjusted hazard ratios (aHRs) were 37.0 for AKI, 6.26 for AKD, 3.13 for ESRD, 2.06 for cardiac arrhythmia, and 1.86 for acute myocardial infarction. In the matched ACEI/ARB and pre-ESRD cohort, MgO users also demonstrated higher risks of AKI (aHR = 16.1) and AKD (aHR = 2.79). Cumulative incidence analyses consistently showed worse outcomes among MgO users. Among MgO users, advancing CKD stage was associated with progressively higher risks of adverse outcomes, particularly in stages 4-5. Both unmatched and matched analyses demonstrated a dose-response pattern, with the highest hazards observed for dialysis progression and cardiac arrhythmia.

In this large cohort study, MgO use in CKD patients was associated with increased risks of AKI, AKD, ESRD, arrhythmia, and myocardial infarction. The magnitude of risk appeared greater in advanced CKD stages. These findings highlight the importance of careful risk-benefit assessment and close clinical monitoring when prescribing MgO in this high-risk population.