Proton Pump Inhibitor Use and Magnesium Concentrations in Hemodialysis Patients: A Cross-Sectional Study.
ABSTRACT: Magnesium concentration is a proven predictor of mortality in hemodialysis patients. Recent reports have indicated that proton pump inhibitor (PPI) use affects serum magnesium levels, however few studies have investigated the relationship between PPI use and magnesium levels in hemodialysis patients. This study aimed to clarify the association between PPI use and serum magnesium levels in hemodialysis patients. We designed this cross sectional study and included 1189 hemodialysis patients in stable condition. Associations between PPI and magnesium-related factors, as well as other possible confounders, were evaluated using a multiple regression model. We defined hypomagnesemia as a value < 2.0 mg/dL, and created comparable logistic regression models to assess the association between PPI use and hypomagnesemia. PPI use is associated with a significantly lower mean serum magnesium level than histamine 2 (H2) receptor antagonists or no acid-suppressive medications (mean [SD] PPI: 2.52 [0.45] mg/dL; H2 receptor antagonist: 2.68 [0.41] mg/dL; no acid suppressive medications: 2.68 [0.46] mg/dL; P = 0.001). Hypomagnesemia remained significantly associated with PPI (adjusted OR, OR: 2.05; 95% CI: 1.14-3.69; P = 0.017). PPI use is associated with an increased risk of hypomagnesemia in hemodialysis patients. Future prospective studies are needed to explore magnesium replacement in PPI users on hemodialysis.
Project description:<h4>Backgrounds</h4>Proton pump inhibitors (PPIs) can be associated with vascular calcification in patients undergoing dialysis through hypomagnesemia. However, only few studies have demonstrated the influence of PPIs on vascular calcification in patients on maintenance hemodialysis (HD). This study aimed to investigate whether the use of PPIs accelerates vascular calcification in patients on HD.<h4>Materials and methods</h4>We retrospectively evaluated 200 HD patients who underwent regular blood tests and computed tomography (CT) between 2016 and 2017. The abdominal aortic calcification index (ACI) was measured using abdominal CT. The difference in the ACI values between 2016 and 2017 was evaluated as ?ACI. Patients were divided into PPI and non-PPI groups, and variables, such as patient background, medication, laboratory data, and ?ACI were compared. Factors independently associated with higher ?ACI progression (? third tertile value of ?ACI in this study) were determined using multivariate logistic regression analysis.<h4>Results</h4>The PPI and non-PPI groups had 112 (56%) and 88 (44%) patients, respectively. Median and third tertile value of ?ACIs were 4.2% and 5.8%, respectively. Serum magnesium was significantly lower in the PPI (2.1 mg/dL) than in the non-PPI (2.3 mg/dL) group (P <0.001). Median ?ACI was significantly higher in the PPI (5.0%) than in the non-PPI (3.8%) group (P = 0.009). A total of 77 (39%) patients had a higher ?ACI. Multivariate analysis revealed that PPIs (odds ratio = 2.23; 95% confidence interval = 1.11-4.49), annual mean calcium phosphorus product, ACI in 2016, baseline serum magnesium levels, and HD vintage were independent factors associated with higher ?ACI progression after adjusting for confounders.<h4>Conclusion</h4>PPI use may accelerate vascular calcification in patients on HD. Further studies are necessary to elucidate their influence on vascular calcification.
Project description:Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored.We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score-matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied.PPI use was associated with hypomagnesemia (Mg <1.8 mg/dl (0.75 mmol/l); odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.38-5.27, P < 0.01). The exposure to PPIs in the full patient cohort was identified as an independent predictor for all-cause mortality in both univariate (HR = 3.16, 95% CI = 1.69-5.90, P < 0.01) and multivariate (HR = 2.70, 95% CI = 1.38-5.27, P < 0.01) Cox regression models. Moreover PPI use was identified as a predictor of CV mortality (HR = 1.51, 95% CI = 1.05-2.20, P = 0.03) Of the 820 patients matched throughout the propensity score analysis, the hazard ratios for all-cause mortality (HR = 1.412, 95% CI = 1.04-1.93, P = 0.03) and CV mortality (HR = 1.67, 95% CI = 1.03-2.71, P = 0.04) were higher among patients on PPIs versus those not on PPIs.The study data suggest that the PPI treatment should be regularly monitored and prescribed only when indicated.
Project description:BACKGROUND: Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. METHODS AND FINDINGS: We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients. CONCLUSIONS: PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.
Project description:Case series suggest that long-term use of proton pump inhibitors (PPIs) is associated with hypomagnesemia, but the current literature lacks systematically collected data. Our aim was to examine whether hypomagnesemia at the time of hospital admission is associated with out-of-hospital use of PPIs.Nested case-control study matched for age and sex.Data were collected retrospectively from a tertiary acute-care facility. Eligible cases consisted of 402 adults with hypomagnesemia (serum magnesium <1.4 mEq/L) at the time of hospital admission to medical services, age- and sex-matched with 402 control individuals with normal serum magnesium levels (1.4-2.0 mEq/L).Out-of-hospital PPI use was identified in the hospital record. An omeprazole equivalent dose was calculated when possible. Covariates included the Charlson-Deyo comorbidity index, diabetes, diuretic use, estimated glomerular filtration rate, and gastroesophageal reflux.Multivariable conditional logistic regression analyses were used to examine the association of PPI use with hypomagnesemia at the time of hospital admission.PPI use was not associated with hypomagnesemia (adjusted OR, 0.82; 95% CI, 0.61-1.11). Neither PPI type nor omeprazole equivalent daily dose was associated with hypomagnesemia. Sensitivity analyses of PPI use restricted to patients with esophageal disorders (adjusted OR, 1.00; 95% CI, 0.69-1.45), severe hypomagnesemia (magnesium, ?1.0 mEq/L; adjusted OR, 0.78; 95% CI, 0.13-4.61), or estimated glomerular filtration rate ?60 mL/min/1.73 m(2) (adjusted OR, 0.84; 95% CI, 0.53-1.34) were unrevealing.Exposure misclassification; hospitalized patients on medical services may not be representative of a broader ambulatory-based population.In a hospital-based adult population, out-of-hospital PPI use is not associated with hypomagnesemia at the time of hospital admission to medical services. In light of these inconclusive results, prospective cohort studies are needed to address this rare potential medication-related adverse effect.
Project description:<h4>Background</h4>Hypomagnesemia is known to impede hypocalcemia correction. This prospective observational study aimed to evaluate the impact of serum magnesium levels on the development of refractory hypocalcemia, which remains a concerning problem after total thyroidectomy (TT).<h4>Subjects and methods</h4>Consecutive subjects (<i>n</i> = 312; mean age = 38.4 [range: 13-83] years; M:F = 62:250) undergoing TT for benign or malignant thyroid diseases were evaluated for serum corrected-calcium (8.4-10.4 mg/dL), magnesium (1.7-2.4 mg/dL), intact parathormone (iPTH), and 25-hydroxycholecalciferol (25OHD) levels preoperatively, at 48-h and 6-month post-TT.<h4>Results</h4>Postoperatively, 98 subjects (31.4%) exhibited transient hypocalcemia, 96 (30.8%) had hypomagnesemia, and 52 (16.7%) had refractory hypocalcemia. Preoperatively, 38 subjects (12.2%) had asymptomatic hypocalcemia and 77 (24.7%) had hypomagnesemia. In multivariate logistic regression analysis, independent risk factors of transient hypocalcemia were hyperthyroidism (odd's ratio [OR]: 5.6), 48-h iPTH (OR: 3.2), 48-h magnesium (OR: 2.7), preoperative 25OHD (OR: 0.96), and preoperative calcium (OR: 0.5; each <i>P</i> < 0.01). In receiver-operating characteristic analysis, percent calcium decline and 48-h magnesium reliably predicted transient hypocalcemia with a threshold of 10.5% and 1.9 mg/dL, respectively. Area under curve, sensitivity, and specificity were 0.822, 82.7%, and 72.9%; and 0.649 (each <i>P</i> < 0.001), 68.4%, and 63.1%, respectively.<h4>Conclusion</h4>Serum magnesium below 1.9 mg/dL had 2.7 times higher odds of developing transient hypocalcemia post-TT. Hypomagnesemia and percent calcium decline >10.5% within 48-h post-TT are associated with refractory hypocalcemia, which necessitates correction of both the deficiencies for prompt resolution of symptoms.
Project description:Purpose of review:Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps. Sources of information:Peer-reviewed articles. Methods:We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist. Key findings:The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ?0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia. Limitations:Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.
Project description:Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics.Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df?=?7, P<0.001, I2?=?98.0%).PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.
Project description:In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown.We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures.9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011.Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ?2.4mg/dL).All-cause mortality.2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0mg/dL were 1.39 (95% CI, 1.23-1.58; P<0.001) and 1.20 (95% CI, 1.06-1.36; P=0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5g/dL) and magnesium level < 2.0mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P=0.004), whereas patients with high serum albumin levels (?3.5g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 [P?0.001] for magnesium < 2.0 and ?2.0mg/dL, respectively; reference: albumin < 3.5g/dL and magnesium ? 2.0mg/dL).Causality cannot be determined, and residual confounding cannot be excluded given the observational study design.Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.
Project description:Prior studies have shown the association of low serum magnesium levels with adverse health outcomes in patients undergoing hemodialysis. There is a paucity of such studies in patients undergoing peritoneal dialysis (PD).Cohort study.10,692 patients treated with PD from January 1, 2007, through December 31, 2011, in facilities operated by a single large dialysis organization in the United States.Baseline serum magnesium levels, examined as 5 categories (<1.8, 1.8-<2.0, 2.0-<2.2 [reference], 2.2-<2.4, and ?2.4mg/dL).Time to first hospitalization and time to death using competing-risks regression models.The distribution of baseline serum magnesium levels in the cohort was <1.8mg/dL, 1,928 (18%); 1.8 to <2.0mg/dL, 2,204 (21%); 2.0 to <2.2mg/dL, 2,765 (26%); 2.2 to <2.4mg/dL, 1,765 (16%); and ?2.4mg/dL, 2,030 (19%). Of 10,692 patients, 6,465 (60%) were hospitalized at least once and 1,392 (13%) died during follow-up (median, 13; IQR, 7-23 months). Baseline serum magnesium level < 1.8mg/dL was associated with higher risk for hospitalization and all-cause mortality after adjustment for demographic and clinical characteristics (adjusted HRs of 1.23 [95% CI, 1.14-1.33] and 1.21 [95% CI, 1.03-1.42], respectively). The higher risk for hospitalization persisted upon adjustment for laboratory variables, whereas that for all-cause mortality was attenuated to a nonsignificant level. The greatest risk for hospitalization was in patients with low serum albumin levels (<3.5g/dL; P for interaction < 0.001).Possibility of residual confounding by unmeasured variables cannot be excluded.Lower serum magnesium levels may be associated with higher risk for hospitalization in incident PD patients, particularly those with hypoalbuminemia. Additional studies are needed to confirm these findings and investigate whether correction of hypomagnesemia reduces these risks.
Project description:Background: Torsades de pointes (TdP) is a life-threatening ventricular tachycardia occurring in long QT-syndrome patients. It usually develops when multiple QT-prolonging factors are concomitantly present, more frequently drugs and electrolyte imbalances. Since proton-pump inhibitors (PPIs)-associated hypomagnesemia is an increasingly recognized adverse event, PPIs were recently included in the list of drugs with conditional risk of TdP, despite only few cases of TdP in PPI users have been reported so far. Objectives: Aim of the present study is to evaluate whether PPI-induced hypomagnesemia actually has a significant clinical impact on the risk of TdP in the general population. Methods: Forty-eight unselected patients who experienced TdP were consecutively enrolled (2008-2017). Shortly after the first TdP episode, in those patients who did not receive magnesium sulfate and/or potassium or calcium replacement therapy, serum electrolytes were measured and their relationship with PPI usage analyzed. Results: Many patients (28/48, 58%) were under current PPI treatment when TdP occurred. Among TdP patients in whom serum electrolyte determinations were obtained before replacement therapy (27/48), those taking PPIs had significantly lower serum magnesium levels than those who did not. Hypomagnesemia occurred in ~40% of patients receiving PPIs (6/14), in all cases after an extended treatment (>2 weeks). In patients taking PPIs the mean QT-prolonging risk factor number was significantly higher than in those who did not, a difference which was mainly driven by lower magnesium levels. Conclusions: In unselected TdP patients, PPI-induced hypomagnesemia was common and significantly contributed to their cumulative arrhythmic risk. By providing clinical support to current recommendations, our data confirm that more awareness is needed when a PPI is prescribed, specifically as regards the risk of life-threatening arrhythmias.