Prevalence and outcomes of proton pump inhibitor associated hypomagnesemia in chronic kidney disease

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most widely prescribed medications across the world. PPIs have been associated with significant electrolyte abnormalities including hypomagnesaemia. We explored the prevalence of PPI associated hypomagnesaemia (PPIH) in different Chronic Kidney Disease (CKD) stages, in different PPI agents, and the impact of PPIH on survival in CKD. METHODS: This was a subgroup analysis of the Salford Kidney Study, a prospective, observational, longitudinal study of non-dialysis CKD patients. Patients with outpatient magnesium samples obtained between 2002 and 2013 were included in the analysis. The prevalence hypomagnesaemia based on mean values over 12 months as well as ‘ever’ hypomagnesaemia were investigated. RESULTS: 1,230 patients were included in this analysis, mean age 64.3± 32.3 years and mean eGFR 29.2±15.8 ml/min/1.73m(2). Mean serum magnesium in those on PPI was significantly lower than those not on PPI overall (0.85±0.10 mmolL(-1) versus 0.79±0.12 mmolL(-1) respectively, p<0.001). This finding was maintained at all CKD stages. The adjusted odds ratio (OR) for mean hypomagnesaemia in PPI use was 1.12 (95% CI 1.06–1.18) p = <0. ‘Ever hypomagnesaemia’ had an OR of 1.12 (95% CI 1.07–1.16) p = <0.001. The expected rise in serum magnesium with declining eGFR was not observed in those on a PPI but was seen in those not on PPI. There was no difference in serum magnesium between PPI drugs. Thiazide diuretics were also associated with hypomagnesaemia independent of PPI use. Cox regression analysis demonstrated no reduction in survival in patients with PPI associated hypomagnesaemia. CONCLUSION: No specific PPI drugs show a favourable profile in regards of risk for hypomagnesaemia in CKD. Avoiding concurrent use of PPI and thiazide may be of value in patients with hypomagnesaemia.