Original Investigation Concentrations of Trace Elements in Hemodialysis Patients: A Prospective Cohort Study Marcello Tonelli, MD, SM, 1 Natasha Wiebe, MMath, PStat, 2 Aminu Bello, MD, PhD, 2 Catherine J. Field, RD, PhD, 3 John S. Gill, MD, MS, 4 Brenda R. Hemmelgarn, MD, PhD, 1 Daniel T. Holmes, MD, 5 Kailash Jindal, MBBS, 2 Scott W. Klarenbach, MD, MSc, 2 Braden J. Manns, MD, MSc, 1 Ravi Thadhani, MD, MPH, 6 and David Kinniburgh, PhD, 7 on behalf of the Alberta Kidney Disease Network* Background: Low concentrations and excessive concentrations of trace elements have been commonly reported in hemodialysis patients, but available studies have several important limitations. Study Design: Random sample of patients drawn from a prospective cohort. Setting & Participants: 198 incident hemodialysis patients treated in 3 Canadian centers. Measurements: We used mass spectrometry to measure plasma concentrations of the 25 elements at baseline, 6 months, 1 year, and 2 years following enrollment in the cohort. We focused on low concentrations of zinc, selenium, and manganese and excessive concentrations of lead, arsenic, and mercury; low and excessive concentrations of the other 19 trace elements were treated as exploratory analyses. Low and excessive concentrations were based on the 5th and 95th percentile plasma concentrations from healthy reference populations. Results: At all 4 occasions, low zinc, selenium, and manganese concentrations were uncommon in study participants (#5.1%, #1.8%, and #0.9% for zinc, selenium, and manganese, respectively) and a substantial proportion of participants had concentrations that exceeded the 95th percentile ($65.2%, $74.2%, and $19.7%, respectively). Almost all participants had plasma lead concentrations above the 95th percentile at all time points. The proportion of participants with plasma arsenic concentrations exceeding the 95th percentile was relatively constant over time (9.1%-9.8%); the proportion with plasma mercury concentrations that exceeded the 95th percentile varied between 15.2% and 29.3%. Low arsenic, platinum, tungsten, and beryllium concentrations were common (.50%), as were excessive cobalt, manganese, zinc, vanadium, cadmium, selenium, barium, antimony, nickel, molybdenum, lead, and chromium concentrations. Conclusions: There was no evidence that low zinc, selenium, or manganese concentrations exist in most contemporary Canadian hemodialysis patients. Some patients have excessive plasma arsenic and mercury concentrations, and excessive lead concentrations were common. These findings require further investigation. Am J Kidney Dis. -(-):---. ª 2017 by the National Kidney Foundation, Inc. INDEX WORDS: Hemodialysis; trace elements; toxicity; low levels; arsenic; mercury; lead; plasma concentration; end-stage renal disease (ESRD). B iological fluids or tissues contain trace elements in parts per billion (micrograms per liter) or low parts per million (milligrams per liter). 1 When substances are not protein bound, they tend to be removed by hemodialysis (HD) when they are present in lower concentrations in dialysate than in blood. Although this is appropriate in the case of uremic toxins, biologically essential substances might become depleted, especially those for which low concentra- tions are not easily identified by available laboratory tests. In addition to this possible ongoing removal of trace elements, HD patients are at risk for low dietary intake of these types of substances because of uremia- related anorexia and dietary restrictions. 1 At the same time, because HD patients are exposed to high volumes (.120 L/wk) of dialysate, even tiny concentration gradients between blood and dialysate can result in clinically relevant toxicity, as exemplified by aluminum. 2-6 Although concentrations of various trace elements are monitored in HD source water, body From the 1 Department of Medicine, University of Calgary, Calgary; Departments of 2 Medicine and 3 Agricultural, Food & Nutritional Science, University of Alberta, Edmonton; Departments of 4 Medicine and 5 Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; 6 Department of Medicine, Harvard University, Boston, MA; and 7 Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada. * A list of the members of the Alberta Kidney Disease Network is available at www.akdn.info. Received December 22, 2016. Accepted in revised form June 22, 2017. No paper or electronic reprints will be available. Address correspondence to Marcello Tonelli, MD, SM, Uni- versity of Calgary, 7th Floor, TRW Building, 3280 Hospital Drive NW, Calgary, Alberta, Canada T2N 4Z6. E-mail: tonelli.admin@ ucalgary.ca Ó 2017 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2017.06.029 Am J Kidney Dis. 2017;-(-):--- 1