ORIGINAL ARTICLE Proton-pump inhibitors do not influence serum magnesium levels in renal transplant recipients Charlotte Van Ende • Steven Van Laecke • Celine Marechal • Francis Verbeke • Nada Kanaan • Eric Goffin • Raymond Vanholder • Michel Jadoul Received: 25 February 2014 / Accepted: 23 April 2014 Ó Italian Society of Nephrology 2014 Abstract Severe hypomagnesemia has been reported with use of proton-pump inhibitors (PPIs). We assessed the effect, if any, of PPI use on serum magnesium level in a cross-sectional analysis of a large published cohort of renal transplant recipients (RTRs). Between February 2004 and February 2006, 512 consecutive prevalent RTRs were enrolled at two university hospitals in Belgium (Brussels and Ghent). Serum creatinine was 1.5 ± 0.7 mg/dl, and estimated glomerular filtration rate (eGFR) 53 ± 19 ml/ min/1.73 m 2 . Mean (and median) magnesium level was 1.91 ± 0.23 mg/dl. PPIs were prescribed in 20 % (n = 101) of cases. At multivariable analysis, PPI use was not an independent predictor of serum magnesium level or hypomagnesemia. The independent predictors of a lower serum magnesium level were the use of tacrolimus, cyclosporin and sirolimus, the absence of use of myco- phenolate mofetil, lower levels of parathyroid hormone and higher eGFR. This study is the first to analyze the potential impact of PPIs on magnesium level in a large, represen- tative cohort of RTR patients. Our results suggest that PPIs may be used without particular fear of favoring hypo- magnesemia-related side effects in RTRs, an important finding in a population at high risk of hypomagnesemia. Keywords Hypomagnesemia Á Kidney transplantation Á Magnesium Á Proton-pump inhibitor Introduction Hypomagnesemia is common, with an estimated preva- lence in the general population ranging from 2.5 to 15 %. It may result from inadequate intake (alcoholism, malnutri- tion, etc.), decreased gastrointestinal absorption, increased renal loss or redistribution from extracellular to intracel- lular space. Proton-pump inhibitors (PPIs) are commonly prescribed for prolonged periods for peptic ulcer disease, gastroduodenitis and gastro-esophageal reflux disease. They have a good safety profile, although severe hypo- magnesemia was reported by Epstein et al. [1] in 2006 for the first time. Approximately 40 cases of hypomagnesemia from PPI use have been reported [1–10]. The mechanism of PPI-induced hypomagnesemia remains unclear [3, 4, 6, 10]. Urinary magnesium (Mg) levels and fractional magnesium excretion are generally low suggesting a defect in intestinal absorption of mag- nesium or increased losses into the gut [1, 4, 5, 7, 9]. In the small intestine, there are two major pathways for magne- sium absorption: a transcellular active transport operating through the transient receptor protein channel family member, TRPM6, and a paracellular passive transport modulated by the tight junction proteins claudin-16 and claudin-19 [4, 14]. In some published cases, hypomagne- semia was partially corrected by high-dose oral magnesium supplements [1, 4]. This suggests that the passive magne- sium transport was intact, and that PPI impaired TRPM6 function, perhaps as a result of the higher pH of the bowel. Another hypothesis is that hypomagnesemia develops in patients heterozygous for mutations in the TRPM6 gene [4, 8]. However, these hypotheses remain unproven. The prevalence and risk factors of PPI-induced hypo- magnesemia are poorly defined [8, 10]. The purpose of our study was thus to assess the effect, if any, of PPI use on C. Van Ende Á C. Marechal Á N. Kanaan Á E. Goffin Á M. Jadoul (&) Department of Nephrology, Cliniques Universitaires Saint-Luc, Universite ´ Catholique de Louvain Medical School, Avenue Hippocrate 10, 1200 Brussels, Belgium e-mail: michel.jadoul@uclouvain.be S. Van Laecke Á F. Verbeke Á R. Vanholder Renal Division, Ghent University Hospital, Ghent, Belgium 123 J Nephrol DOI 10.1007/s40620-014-0105-9