Preferred monitoring for aluminum toxicity in patients undergoing dialysis
Preferred test for routine aluminum screening
Monitoring metallic prosthetic implant wear
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Under normal physiologic conditions, the usual daily dietary intake of aluminum (5-10 mg) is completely eliminated. Excretion is accomplished by avid filtration of aluminum from the blood by the glomeruli of the kidney. Patients in renal failure (RF) lose the ability to clear aluminum and are candidates for aluminum toxicity. Many factors increase the incidence of aluminum toxicity in RF patients:
-Aluminum-laden dialysis water can expose dialysis patients to aluminum.
-Aluminum-laden albumin can expose patients to an aluminum burden they cannot eliminate.
-The dialysis process is not highly effective at eliminating aluminum.
-Aluminum-based phosphate binder gels are administered orally to minimize phosphate accumulation; a small fraction of this aluminum may be absorbed and accumulated.
If it is not removed by renal filtration, aluminum accumulates in the blood, where it binds to proteins such as albumin and is rapidly distributed through the body. Aluminum overload leads to accumulation of aluminum at 2 sites: brain and bone. Brain deposition has been implicated as a cause of dialysis dementia. In bone, aluminum replaces calcium at the mineralization front, disrupting normal osteoid formation.
Deposition of aluminum in bone also interrupts normal calcium exchange. The calcium in bone becomes unavailable for resorption back into blood under the physiologic control of parathyroid hormone (PTH) and results in secondary hyperparathyroidism. While PTH is typically quite elevated in RF, 2 different processes may occur: 1) High-turnover bone disease associated with high PTH (>150 pg/mL) and relatively low aluminum (<20 ng/mL), or 2) low-turnover bone disease with lower PTH (<50 pg/mL) and high aluminum (>60 ng/mL). Low-turnover bone disease indicates aluminum intoxication.
Serum aluminum concentrations are likely to be increased above the reference range in patients with metallic joint prosthesis. Prosthetic devices produced by Zimmer Company and Johnson and Johnson typically are made of aluminum, vanadium, and titanium. Prosthetic devices produced by Depuy Company, Dow Corning, Howmedica, LCS, PCA, Osteonics, Richards Company, Tricon, and Whiteside, typically are made of chromium, cobalt, and molybdenum. This list of products is incomplete, and these products change occasionally; see prosthesis product information for each device for composition details.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-6 ng/mL (all ages)
<60 ng/mL (dialysis patients-all ages)
Patients in renal failure not receiving dialysis therapy invariably have serum aluminum levels above the 60 ng/mL range.
McCarthy(1) and Hernandez(2) describe a biochemical profile that is characteristic of aluminum overload disease in dialysis patients:
-Patients in renal failure with no signs or symptoms of osteomalacia or encephalopathy usually had serum aluminum <20 ng/mL and parathyroid hormone (PTH) concentrations >150 pg/mL, which is typical of secondary hyperparathyroidism.
-Patients with signs and symptoms of osteomalacia or encephalopathy had serum aluminum >60 ng/mL and PTH concentrations <50 pg/mL (PTH above the reference range, but low for secondary hyperparathyroidism).
-Patients who had serum aluminum >60 ng/mL and <100 ng/mL were identified as candidates for later onset of aluminum overload disease that required aggressive efforts to reduce their daily aluminum exposure. This was done by switching them from aluminum-containing phosphate binders to calcium-containing phosphate binders, by ensuring that their dialysis water had <10 ng/mL of aluminum, and ensuring the albumin used during postdialysis therapy was aluminum-free.
Prosthesis wear is known to result in increased circulating concentration of metal ions.(3) Modest increase (6-10 ng/mL) in serum aluminum concentration is likely to be associated with a prosthetic device in good condition. Serum concentrations >10 ng/mL in a patient with an aluminum-based implant not undergoing dialysis suggest significant prosthesis wear. Increased serum trace element concentrations in the absence of corroborating clinical information do not independently predict prosthesis wear or failure.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Failure to pay attention to proper specimen collection procedures can cause abnormal results due to specimen contamination, which can lead to misinterpretation and misdiagnosis:
-Special evacuated blood collection tubes are required for aluminum testing.(4) These tubes are readily available (Mayo Medical Laboratories Supply T184) and should always be used.
-Most of the common evacuated blood collection devices have rubber stoppers that are comprised of aluminum-silicate. Simple puncture of the rubber stopper for blood collection is sufficient to contaminate the specimen with aluminum. Typically, blood drawn in standard evacuated blood tubes will be contaminated by 20 to 60 ng/mL aluminum.
-The use of wooden applicator sticks or pipette tips during specimen aliquoting can cause abnormal results due to contamination.
High concentrations of gadolinium and iodine are known to interfere with most metals tests. If either gadolinium- or iodine-containing contrast media has been administered, a specimen should not be collected for 96 hours.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. McCarthy JT, Milliner DS, Kurtz SB, et al: Interpretation of serum aluminum values in dialysis patients. Am J Clin Pathol 1986;86:629-636
2. Hernandez JD, Wesseling K, Salusky IB: Role of parathyroid hormone and therapy with active vitamin D sterols in renal osteodystrophy. Sem Dialysis 2005;18:290-295
3. Liu TK, Liu SH, Chang CH, Yang RS: Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty. Tohoku J Exp Med 1998;185:253-262
4. Schwarz C, Sulzbacher R, Oberbauer R: Diagnosis of renal osteodystrophy. Eur J Clin Invest 2006;36:13-22