Elevated Serum Aluminum Levels in Hemodialysis Patients Associated with Use of Electric Pumps --- Wyoming, 2007

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Aluminum toxicity can cause osteomalacia, anemia, and dementia in hemodialysis patients and has historically been associated with exposure to contaminated water or dialysate preparations or ingestion of aluminum-containing phosphate binders* (1--4). Since 2002, improvements in water treatment methods and use of non--aluminum-containing phosphate binders have resulted in low prevalence (<1%) of aluminum toxicity among hemodialysis patients (1). In the United States, reported cases of aluminum toxicosis are rare, and no outbreak has been reported since 1992 (2). This report describes 10 patients treated at a hemodialysis unit in a Wyoming hospital (hospital A) in 2007 who had elevated serum aluminum levels that were detected through routine serum aluminum screening. An investigation was conducted by the Wyoming Department of Health, which determined that the source of exposure was dialysate acid concentrate that became contaminated with aluminum as it passed through two electric drum pumps. The drum pumps had been used to transfer dialysate acid concentrate from 55-gallon storage drums to 1-gallon jugs for use on individual hemodialysis machines. Removal of the pumps from service resulted in a rapid reduction in patient serum aluminum levels. The findings suggest that regular assessment of machine compatibility with dialysate fluid is needed.

On December 21, 2007, hospital A notified the Wyoming Department of Health of increased serum aluminum levels among patients treated in its hemodialysis unit. Slightly elevated levels had been detected initially in three patients in June 2007 through routine serum aluminum screening, which was conducted for all hemodialysis patients every 6 months. However, after additional increased levels were detected, hospital A increased its testing frequency in September 2007, and began measuring serum aluminum levels as often as every month in certain patients. In December, Wyoming Department of Health investigators conducted a medical record review and environmental assessment. Potential exposures examined included aluminum-containing medications, dialysate preparations, hemodialysis machines, extent of hemodialysis prescription, patient home water supply, and water from the hospital A tap and reverse-osmosis system. Patient surveys and a hospital pharmacy review were conducted to assess aluminum sources in both prescribed and over-the-counter medications. All water and dialysate tests were conducted by two separate laboratories (Spectra Lab, Milpitas, California, and AmeriWater, Dayton, Ohio). Results were compared with Association for the Advancement of Medical Instrumentation aluminum standards for water, which state that levels should not exceed 0.01mg/L (10 µg/L) (5). Patient serum aluminum measurements were interpreted according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI ) guidelines, which state that baseline levels of serum aluminum at the beginning of dialysis should be <20 µg/L, and toxicity can occur at levels >60 µg/L (6). The Wilcoxon rank-sum test was used to compare median serum aluminum levels in patients by period and extent of hemodialysis prescription.

The medical record review of all patients treated in the hemodialysis unit during June 2006--January 2008 indicated a trend toward increasing serum aluminum values beginning in June--September 2007. As of December 2007, 11 patients were receiving hemodialysis at hospital A. One patient had begun hemodialysis in December and was excluded from the analysis because only one baseline serum measurement was available. The remaining 10 patients had been treated in the unit for at least 3 months, and their serum aluminum levels had been measured in December 2007 during at least one other treatment (range: 1--7 treatments) since June 2006. In December 2007, serum aluminum levels for the 10 patients ranged from 16 µg/L to 237 µg/L, and the median was 92 µg/L, compared with a June 2007 range for seven patients of 6 µg/L--41 µg/L with a median of 26 µg/L (p=0.02) (Figure). Abstraction of medical records and interviews with physicians and nursing staff members revealed no signs or symptoms attributable to aluminum toxicosis (e.g., bone or joint pain, erythropoietin-resistant anemia, or dementia).

The serum aluminum levels of the patients of the two nephrologists (doctor A and doctor B) working in the clinic were significantly different, likely because of different hemodialysis prescriptions. In December 2007, the six patients of doctor A had higher serum aluminum levels (range: 43 µg/L--237 µg/L; median: 158 µg/L), compared with the four patients of doctor B (range: 16 µg/L--55 µg/L; median: 34 µg/L) (p=0.05). Doctor A prescribed a dialysate flow rate of 800 mL/min administered over 4 hours, compared with a dialysate flow rate of 500 mL/min administered over 3.5 hours prescribed by doctor B.

No substantial sources of aluminum were found in patient medications, patient home water samples, hemodialysis machines, or water from the hospital A tap and reverse-osmosis system. Dialysate acid concentrate was stored in the original 55-gallon plastic drums and transferred to 1-gallon jugs by using electric drum pumps (Teel model 3P652, Dayton Electric Manufacturing Company, Chicago, Illinois). The jugs were then attached to individual hemodialysis machines where the acid concentrate was suctioned out of the jugs and combined with a bicarbonate and purified water mixture. The resulting fluid (dialysate) was used in the dialyzer. The pump manufacturer provided no indications that the pumps had been designed for use with hemodialysis. Instructions directed only that the pumps be used with nonflammable fluids compatible with pump components, which include some alkalies, acids, chlorines, and photographic chemicals. The same make and model of pump had been used at hospital A since August 2004. However, because of mechanical breakdown, the original pumps had been replaced by the two pumps under investigation. One pump went into service in November 2006 and the other in February 2007.

Analysis by Spectra Lab of the dialysate acid in the 55-gallon drums revealed aluminum concentrations of <8 µg/L. Measurements after the acid had been passed once through the pumps ranged from 123 µg/L to 166 µg/L. Results from AmeriWater Laboratory revealed concentrations of 53 µg/L--144 µg/L in the drums and 223 µg/L--240 µg/L after the acid had been passed through the pumps.

On December 26, 2007, both pumps in the hemodialysis unit were removed from service because they were suspected of causing aluminum contamination of the dialysate. Follow-up patient samples from January 23, 2008, showed substantially lower levels in serum aluminum levels in all 10 patients (range: 9 µg/L--53 µg/L; median: 20 µg/L). This trend was observed in patients treated by both doctor A (range: 12 µg/L--53 µg/L; median: 29 µg/L) and doctor B (range: 9 µg/L--21 µg/L; median: 16 µg/L).

In May 2008, investigators dismantled one of the two pumps in the hemodialysis unit. Five internal components suspected of containing aluminum were sent to St. Louis Testing Laboratories (St. Louis, Missouri) for metallurgic analysis by inductively coupled plasma-atomic emission spectroscopy. All five components were contained in a region of the pump that sat above the 55-gallon storage drum and did not appear to be in the direct fluid transfer pathway. However, all the components appeared to have varying degrees of corrosion, likely indicating they had come into contact with the acid concentrate. One of the five components had two severely corroded metal pieces that were composed of 76% aluminum oxides; however, the precise origin of the aluminum toxicity could not be determined.

Reported by: TP Ryan, PhD, LL McElwain, TD Murphy, MD, Wyoming Dept of Health. MJ Arduino, DrPH, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases; SA Anderson, DVM, EIS Officer, CDC.

Editorial Note:

Worldwide, the last outbreak of aluminum toxicosis was reported in 2001 in Curaçao and was associated with a cement mortar water distribution pipe (3). Before the cluster of elevated serum aluminum levels described in this report, the last reported U.S. outbreak of aluminum toxicity associated with use of an electric pump in hemodialysis occurred in 1992 (2). Results of that investigation led to release of a Food and Drug Administration safety alert warning of the potential corrosive effects of low pH solutions on metals used in the components of hemodialysis systems. The pumps implicated in the 1992 outbreak were found to contain aluminum casings and impellers (2,4). Manufacturer specifications for the two pumps described in this report do not mention suitability for use in hemodialysis or that the pumps contained aluminum components. However, the presence of aluminum oxides on two pieces of one component suggests corrosion of an aluminum alloy. Although the precise origin of the contamination could not be determined, spectroscopy results showed aluminum was present, which likely contaminated the acid concentrate as it passed through each pump. As further evidence, when the two pumps were removed from service, the result was an immediate reduction in serum aluminum levels in all 10 patients.

A dose-response effect appeared likely by prescribing practice. With a higher dialysate flowrate, a larger volume of dialysate enters the dialyzer over time, causing larger amounts of solutes (e.g., electrolytes or glucose) from the dialysate to diffuse into the patient's blood. Patients of doctor A received a higher dialysate flowrate, were exposed to a larger volume of contaminated dialysate over a longer period, and had higher levels of serum aluminum than patients of doctor B.

The findings in this report are subject to at least two limitations. First, opinions differ on the definition of toxic serum aluminum levels (1). NKF-KDOQI provides a recommended baseline level of <20 µg/L and a level potentially associated with toxicity of >60 µg/L. Although only five of the 10 hemodialysis patients at hospital A experienced serum aluminum levels >60 µg/L during the study period, the levels trended upward in late 2007 and declined in all 10 patients once the suspect pumps were removed from service. Second, serum aluminum values are a poor predictor of aluminum concentrations in tissues outside of the blood compartment (7). Although the patients were asymptomatic, no further diagnostics such as bone biopsy, deferoxamine stimulation, or advanced cognitive tests were performed on the patients to determine whether their aluminum exposure had resulted in any subclinical ill effects.

Since the 1992 outbreak, improvements in hemodialysis technologies and patient care have virtually eliminated occurrences of aluminum toxicosis. The low prevalence of aluminum toxicity among hemodialysis patients has raised debate among some in the dialysis community regarding the value of patient serum aluminum screening, which some hemodialysis units conduct routinely (1,8). NKF-KDOQI guidelines recommend serum aluminum testing at least annually in all hemodialysis patients and every 3 months in those who receive aluminum-containing medications (6); others propose routine serum aluminum testing only in patients with known aluminum exposure or manifestations of toxicity (1). As illustrated in this report, routine monitoring can detect elevated serum aluminum levels with the potential to produce serious illness in hemodialysis patients. Hemodialysis units should consider routine monitoring of aluminum in the water system and regular assessment of equipment compatibility with dialysate fluids (1,2). Dialysis unit operators should consider asking dialysate acid concentrate manufacturers for recommendations of appropriate devices (e.g., pumps or delivery systems) that are compatible with their dialysate fluids.

This report is based, in part, on contributions from P Tilton, MD, N Nwaba, PharmD, Center for Devices and Radiologic Health, Food and Drug Admin; R Sinn, St. Louis Testing Laboratories, Missouri; and P Patel, MD, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases, CDC.

References

* Oral medications used to bind excess serum phosphorous in patients with chronic renal failure. Some older phosphate binders contained aluminum, but such medications are uncommon today.

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