Michael S Balzer#, Janina Müller-Deile#, Daniela I Schulze#, Georg Eisenbach, Bernhard MW Schmidt, Hermann Haller and Roland Schmitt*
Division of Nephrology and Hypertension, Department of Medicine, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
Received: 28 October, 2016; Accepted: 29 November; Published: 30 November, 2016
Roland Schmitt, MD, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany, Tel: +49 511 532 6322; Fax: +49 511 600 604 35; E-mail:
Balzer MS, Müller-Deile J, Schulze DI, Eisenbach G, Schmidt BMW, et al. (2016) Potential Impact of Dialysate Magnesium on Intradialytic Hypotension. Arch Renal Dis Manag 2(1): 031-034. DOI: 10.17352/2455-5495.000014
© 2016 Balzer MS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Blood Pressure, Dialysate, Hemodialysis, Intradialytic Hypotension, Magnesium
Numerous beneficial effects on cardiovascular health have been described for magnesium (Mg). Intradialytic hypotension (IDH) is a common complication in hemodialysis patients which contributes to cardiovascular mortality. It has been suggested that higher dialysate Mg (DMg) might reduce the risk of IDH. In this 24-month retrospective observational analysis we studied the incidence of IDH in 45 stable hemodialysis patients who underwent conversion from 0.5 mmol/L DMg to 1.0 mmol/L. Mean serum Mg was 1.12 ± 0.03 mmol/L pre-conversion and changed to 1.35 ± 0.04 mmol/L post-conversion. In parallel, incidence of IDH showed a significant decrease from 1.59 ± 0.34 to 1.08 ± 0.27 % comparing 12 months before and 12 months after DMg conversion. The incidence of muscle cramps and serum calcium showed a trend for reduction while other parameters were unchanged. In conclusion, switching patients from 0.5 mmol/L DMg to 1.0 mmol/L was associated with a significant improvement of IDH incidence without significant changes in other parameters that were analyzed in this study. Further studies are warranted to test the association between DMg and IDH in a prospective randomized fashion.
Worldwide, hemodialysis is the most commonly used treatment modality for patients with end-stage renal disease. Despite technological advances in the delivery of hemodialysis, the mortality rate of patients on long-term hemodialysis remains alarmingly high, with cardiovascular disease being the leading cause of death . One of the most common complications of hemodialysis and an important contributor to cardiovascular mortality is intradialytic hypotension (IDH). While there is no generally accepted definition of IDH, Kidney Disease Outcomes Quality Initiative (K/DOQI) and European Best Practice guidelines define IDH as a decrease in systolic blood pressure of more than 20 mmHg in association with symptoms and/or the need for nursing interventions [2,3]. IDH may occur in up to 25% of treatments and it is assumed that the incidence will continue to increase as a growing number of elderly patients will be developing end-stage renal disease [4,5]. By causing repetitive tissue hypoperfusion, IDH has detrimental effects on several organ systems: IDH leads to a critical shortage of blood supply to the gut and subsequently to increased intestinal permeability, endotoxemia and microinflammation ; furthermore, IDH causes cerebral hypoperfusion and cognitive impairment ; due to recurrent myocardial ischemia IDH aggravates preexisting cardiac disease and promotes heart fibrosis and arrhythmia . The most important trigger for IDH is a rapid decrease in effective blood volume caused by high ultrafiltration rates. However, slowing ultrafiltration as recommended by the European Best Practice guidelines is often difficult to achieve . Cooler dialysate temperature is another strategy against IDH which is currently tested in clinical trials . An additional option to improve intradialytic blood pressure stability is to increase sodium or calcium concentration in the dialysate . A higher sodium level, however, may expand total body water and thereby aggravate ultrafiltration requirements. Higher calcium may lead to calcium loading which enhances the risk of vascular and extravascular calcification. A safer option to counteract IDH could be a higher dialysate magnesium concentration (DMg) as suggested by experimental and clinical data .
Mg, which is the fourth most abundant cation in the human body, has direct effects on many physiological variables, e.g. blood pressure, myocardial contractility, bone mineralization and parathyroid function . Mg stabilizes enzymes in ATP generating reactions; it is important for cell adhesion and membrane transport and modulates insulin signaling . About 99% of total Mg is located in bone, muscles and non-muscular soft tissue. In the general population, several studies have indicated an association between low serum Mg and ischemic heart disease, diabetes mellitus, metabolic syndrome, coronary artery disease and atherosclerosis [10,11]. Mg homeostasis is determined by dietary Mg intake, intestinal absorption and renal excretion. In hemodialysis patients this normal balance is lost and Mg homeostasis becomes majorly dependent on Mg removal during hemodialysis. As current hemodialysis guidelines do not recommend specific dialysate Mg concentrations, common standard compositions vary from 0.25 to 1.00 mmol/L Mg . Correlative studies in hemodialysis cohorts suggest that higher dialysate Mg concentrations might be advantageous for cardiovascular disease and for preventing IDH [13,14]. The goal of our retrospective study was to examine the effects of increased DMg on the occurrence of IDH in an outpatient hemodialysis center in which standard treatment had been changed from 0.5 mmol/L to 1.0 mmol/L DMg.
Materials and Methods
The study was performed as a retrospective, longitudinal single-center study at Kuratorium für Dialyse und Nierentransplantation, a non-profit dialysis provider associated with Hannover Medical School. For evaluating the impact of doubling DMg from 0.5 to 1.0 mmol/L, a period of 12 months before and 12 months after dialysate conversion was analyzed. 45 patients met the inclusion criteria (age above 18 years, chronic hemodialysis for at least 3 months before study period, completion of 24 months study period, hemodialysis using the central dialysate supply system, no episodes longer than 3 weeks outside the center due to hospitalization or vacation). Patient baseline characteristics are shown in Table 1. All patients underwent three standard weekly hemodialysis treatments of 4-5 hours. According to the local standard maximum ultrafiltration rates were ≤ 13ml/kg/hour in all patients throughout the study period. Blood and dialysate flow was standardized to 300 mL/min (Qb) and 500 mL/min (Qd), respectively. Hemodialysis was performed with high-flux polysulfone filters using individualized bicarbonate levels ranging from 30-36 mmol/L. Dialysate calcium was standardized to 1.25 mmol/L. The study had been approved by the institutional ethics board of Hannover Medical School and by Kuratorium für Dialyse und Nierentransplantation.
The frequency of IDH and muscle cramps was analyzed by evaluating routine patient records. IDH was defined as a drop in systolic blood pressure of more than 20 mmHg and concurrent requirement of volume expansion by nurse intervention. Muscle cramps were defined as localized, painful contractions requiring nurse intervention (generally injection of hypertonic saline). Archived treatment and laboratory data were analyzed for intradialytic weight loss by ultrafiltration, changes in calcium (Ca), phosphate (PO4) and intact parathyroid hormone (iPTH).
For comparison of paired dichotomous data, McNemar test was applied and for comparison of paired continuous variables statistical analyses comprised two-tailed paired t-tests. Analyses were performed using a web-based McNemar test and IBM SPSS Statistics 22. Results are given as means with standard error of the mean (SEM), unless otherwise stated. Changes were considered statistically significant for p < 0.05 (two-sided).
Patient characteristics and impact of DMg conversion on serum Mg
Baseline characteristics of the 45 study patients are summarized in Table 1. Their mean age was 57.9 ± 17.6 years, and a total of 31 patients were male. The median duration of dialysis was 10.5 ± 8.0 years. Mean serum Mg at baseline was 1.12 ± 0.03 mmol/L, which was at the upper limit of normal (0.70-1.10 mmol/L). Conversion from standard (0.5 mmol/L) to high (1.0 mmol/L) DMg caused a significant increase in mean pre-dialysis serum Mg levels to 1.35 ± 0.04 mmol/L (p < 0.0001). Dialysate composition differed only by Mg content while all other components were not altered. The number of patients that took oral magnesium supplements were lower under high DMg compared to lower DMg (Table 2). Mg containing phosphate binders were not used during the time of the study (p < 0.0001). (Figure 1).
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