Safety and Efficacy of Amiloride in Reducing the Need for Magnesium Supplementation in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Calcineurin Inhibitors (2016)

Calcineurin inhibitors (CI) cause renal tubular injury resulting in magnesium (Mg) loss. Amiloride, a potassium (K)-sparing diuretic, has been shown to mitigate K and Mg loss in patients receiving amphotericin B. To our knowledge, amiloride use to reduce Mg loss caused by CI has not been described. We have prescribed amiloride to select allogeneic hematopoietic stem cell transplant (aHSCT) patients receiving CI to reduce the need for oral/intravenous (IV) Mg supplementation. We sought to assess the benefits and risks of this intervention. We included adult patients receiving concomitant CI and amiloride, who underwent aHSCT at our center from 1/1/08 to 5/31/15. Patients on foscarnet or amphotericin were excluded. Patterns of amiloride use and electrolyte supplementation were summarized from review of inpatient medication administration records and/or outpatient medication lists. Oral and IV forms of K were considered bioequivalent; oral Mg supplements were estimated to be 33% bioavailable. Due to variability in the timing of the first amiloride dose (day 0), supplement use on day 0 was not included in the analysis. Paired t-tests were used to compare the average daily Mg and K supplement use as well as serum Mg, creatinine (Cr) and K in the 5-days preceding amiloride to that of days 1-5 and days 6-10 post-amiloride. Thirty-three patients were included; median age 52 years (range 18 to 69), 18 (55%) were male. The median amiloride dose was 5 mg/day (range 2.5 to 10); median duration of use was 21 days (interquartile range 6-75), with 2 patients on amiloride at time of last follow-up. The most common reason for amiloride discontinuation was hyperkalemia (n = 10), which prompted electrocardiograms in 6 patients and sodium polystyrene sulfonate use in 4. Figures 1, 2, and 3 describe total Mg supplementation, IV Mg supplementation, and serum Mg levels, respectively. Compared to the 5-day pre-amiloride period: 1) total K supplement use decreased by 12 mmol/day (3.7-21, p < 0.001) in days 1-5 post-amiloride, and by 21 mmol/day (9.8-32, p < 0.001) in days 6-10; 2) the serum K level increased by 0.49 mmol/L (0.33-0.64, p < 0.001) in days 1-5 and by 0.72 mmol/L (0.44-0.99, p < 0.001) in days 6-10; 3) serum Cr was not significantly changed in days 1-5, but increased by 0.16 mg/dL (0.06-0.26, p = 0.004) in days 6-10. Amiloride use was associated with a reduction in K supplementation, but not with a decrease in total Mg supplementation in aHSCT patients on CI. The decrease in IV Mg use and increase in Mg serum levels during the latter third of the observation period suggests a possible delayed Mg-sparing effect. Amiloride use in this setting appears to confer a significant risk of hyperkalemia, and the routine use of amiloride to reduce Mg supplementation in aHSCT patients on CI cannot be recommended. Future prospective study is needed.Figure 2IV Magnesium Supplementation: Data points represent mean daily IV magnesium supplementation for each patient within the three 5-day periods, with day 0 being I ho day of amiloride initiation. Dosage is expressed as elemental magnesium. Days -5 to -1 and day 1 to 5 include available data for all patients (n = 33) Days 6 to 10 include available data for patients receiving amiloride for al least 7 days (n = 29). P-values reflect paired t-test comparisons of each post-amiloride time period with the pre-amiloride time period (differences relative to the pre-amiloride time period and 95% confidence intervals are shown if statistically significant).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Serum Magnesium Level: Data points represent mean serum magnesium level for each patient within the three 5-day periods, with day 0 being the day of amiloride initiation. Days -5 to -1 and days 1 to 5 include available data for all patients (n = 33). Days 6 to 10 include available data for patients receiving amiloride for at least 7 days (n = 29). P-values reflect paired t-test comparisons of each post-amiloride time period with the pre-amiloride time period (differences relative to the pre-amiloride time period and 95% confidence intervals are shown if statistically significant).View Large Image Figure ViewerDownload Hi-res image Download (PPT)