Proton-Pump Inhibitor and Tacrolimus use is Associated with Hypomagnesemia in Connective Tissue Disease: A Potential Pathogenic Link with Renal Deterioration and Recurrent Infections

Abstract Background: Low levels of serum magnesium (Mg) perturb renal tubular cell function and, lymphocyte resulting in renal deterioration and an imbalance in mononuclear cells. Here, we investigated the influence of hypomagnesaemia in patients with connective tissue disease (CTD). Methods: We retrospectively evaluated CTD patients who visited our hospital during 2019 with available serum Mg levels. Patients were divided into two groups, those with or without hypomagnesemia (<1.8 mg/dL) and compared by rate of hospitalization for severe infection and cumulative renal deterioration. They were also compared by fractions of lymphocytes, and natural killer (NK) and dendritic cell (DC) subsets as measured by fluorescence-activated cell sorting (FACS) analysis.Results: Among 284 patients, hypomagnesemia was detected in 63 (22.2%). Multivariate analysis revealed that use of proton-pump inhibitors (PPIs) (OR 1.48, p=0.01) and tacrolimus (TAC) (OR 6.14, p<0.01) was independently associated with hypomagnesaemia. Renal deterioration rate was significantly higher in TAC and/or PPI users with hypomagnesemia (p=0.01). Hospitalization rate for severe infection was also higher in patients with hypomagnesaemia (p=0.04). FACS analysis showed lower counts for CD8+ T cells, CD19+ B cells, NK cells, and DC in hypomagnesaemia (p=0.03, p=0.02, p=0.02, and p=0.03, respectively). Conclusions: Use of TAC and PPIs may be associated with hypomagnesaemia and lead to poor renal outcomes and severe infection in CTD.