Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients

Abstract

Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: −0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: −0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43–3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32–4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (Pinteraction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy.

Choice of Acid Suppressant Therapy and Long‐Term Graft Outcomes After Kidney Transplantation

“…Hypomagnesemia is often experienced in the transplant population due to magnesium wasting as a result of tacrolimus use; PPI use has also been associated with hypomagnesemia 9,33 . With significantly higher rates of magnesium supplementation in the PPI arm, this study added to the body of evidence that PPI use significantly increases hypomagnesemia in the transplant population 15,18–20,25 …”

“…9,33 With significantly higher rates of magnesium supplementation in the PPI arm, this study added to the body of evidence that PPI use significantly increases hypomagnesemia in the transplant population. 15,[18][19][20]25 The average time of receipt of PPI or H2RA was several years, despite the majority of patients having no documented GI issues or other compelling reason for therapy posttransplant. At this center, there is a pharmacist present in the outpatient clinic setting but due to high patient volumes not every patient is assessed at every visit by a pharmacist.…”

“…16,17 Other transplant studies have demonstrated associations between PPI use and hypomagnesemia, Clostridium difficile infections, iron deficiency anemia, and increased fracture risk. [18][19][20][21][22][23][24] However, these studies did not compare PPIs to H2RAs [18][19][20][21][22] and included relatively small cohorts. 23,24 Most studies comparing the impact of PPI or H2RA use on renal function posttransplant report outcomes up to a year posttransplant.…”

“…Studies have demonstrated that the formulation of MPA may determine the effect of PPI co‐administration, with mycophenolate mofetil (MMF) exhibiting significantly decreased area under the curve that has not been consistently seen with enteric‐coated mycophenolate sodium (EC‐MPS), although reductions in the active metabolite mycophenolic acid glucuronide have not been shown to consistently be impacted by PPI therapy with either formulation 16,17 . Other transplant studies have demonstrated associations between PPI use and hypomagnesemia, Clostridium difficile infections, iron deficiency anemia, and increased fracture risk 18–24 . However, these studies did not compare PPIs to H2RAs 18–22 and included relatively small cohorts 23,24 .…”

The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study

“…It has been widely documented that PPIs may affect absorption of micronutrients, leading to deficiencies of important electrolytes, including iron and magnesium PLOS MEDICINE [11,14,15]. Indeed, we previously found that PPI use was associated with iron deficiency and hypomagnesemia in KTRs [37,39]. Iron deficiency can in turn lead to iron deficiency anemia, which has been linked to a higher graft failure risk and mortality risk in KTRs [40][41][42].…”