Chronic Use of Proton-Pump Inhibitors is Associated with Lower Magnesium and Iron Status and Excess Mortality in Renal Transplant Recipients

E. van den Berg, R.M. Douwes, A.W. Gomes Neto, M.F. Eisenga, R.O.B. Gans, G.J. Navis, H. Blokzijl, S.J.L. Bakker

Friday 16 march 2018

10:40 - 10:50h at Van Rijck/Ruys Zaal

Categories: Clinical, Session (parallel)

Parallel session: Parallel session 15: Clinical

Background and objectives

Chronic use of proton-pump inhibitors (PPI) is very common in renal transplant recipients (RTR). However, chronic PPI use may induce magnesium and iron deficiencies and increase the risk of mortality. We investigated the association of PPI use with mortality and magnesium and iron status in a large single-center cohort of stable RTR.

Methods

We included 707 RTR with a functioning graft ≥ 1 year. RTR with missing data on PPI dosage (n=4) were excluded, leaving 703 RTR eligible for analysis. Plasma magnesium, serum ferritin, and 24-h urinary magnesium excretion were measured with standard methods. Associations of PPI use with magnesium and iron status were analyzed by linear regression. The association of PPI use with all-cause and cardiovascular mortality were analyzed by Cox regression.

Results At baseline, RTR were at a median of 5.4 [1.9-12.0] years after transplantation, mean age was 53±13 years, 57% were male and 53% used PPI. Plasma magnesium was 0.95 ± 0.12 mmol/L, serum ferritin 118 [55-222] mmol/L and magnesium excretion was 3.4 ± 1.6 mmol/24h. PPI use was inversely associated with plasma magnesium (β:-0.02, P=0.04), serum ferritin (β:-70.6, P<0.001) and magnesium excretion (β:-0.62, P<0.001), all independent of potential confounders, including age, gender, BMI, eGFR, proteinuria, hs-CRP, leukocytes, physical activity score, smoking behavior, alcohol use, 24-h urinary sodium and potassium excretion and immunosuppressive medication use. During median follow-up of 5.4 [4.8-6.1] years, 151 RTR died, of which 61 due to cardiovascular disease. PPI use was associated with higher risk of all-cause mortality (HR 2.01; 95%CI 1.43-2.83, P<0.001) and cardiovascular mortality (HR 2.28; 95%CI 1.32-3.95, P=0.003). Adjustment for potential confounders did not materially alter the association (all-cause mortality: HR 1.81; 95%CI 1.26-2.61, P=0.001, cardiovascular mortality: HR 1.96; 95%CI 1.09-3.51, P=0.02).

Conclusions

PPI use is associated with lower magnesium and iron status, together indicating impaired gastro-intestinal absorption, potentially related to the reduced gastric acid secretion. Moreover, PPI use is associated with increased risk of all-cause mortality and cardiovascular mortality in RTR, suggesting PPI use is not without danger in RTR and treatment indication may need to be revisited.

Keywords: proton-pump inhibitors, magnesium, iron, all-cause mortality, renal transplantation.