Date of Award

Fall 1985

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Patricia A. Pleban

Committee Member

Blair A. Chrenka

Committee Member

Michael J. Solhaug

Committee Member

John D. Van Norman

Call Number for Print

Special Collections LD4331.C45D44

Abstract

Aluminum accumulation in the soft tissues and bone of end stage renal failure patients has been described in the literature. In addition to aluminum normally encountered through ubiquitous sources, these patients are subject to exposures through the dialysate used for hemodialysis and through aluminum-containing phosphate binders. These increased exposures, associated with a decreased ability to excrete aluminum through the kidneys, lead to aluminum accumulation which may result in the onset of an encephalopathy syndrome and/or osteomalacic osteodystrophy. These complications may be very devastating.

Blood serum or plasma aluminum levels do not reflect the total body burden of aluminum. However, they may reflect the extent of active aluminum loading. Furthermore, it has been suggested that that fraction of plasma aluminum which is not protein bound, or is ultrafilterable, may be a reliable indicator of the extent of active aluminum loading and of the effectiveness of chelation therapy. Aluminum which is in the ultrafilterable state may cross a dialysis membrane and be removed from the body.

Aluminum analyses were conducted by polarized Zeeman-effect atomic absorption spectrophotometry. The sensitivity was between 15 and 23 picograms, depending on the quality of the graphite cuvette used in the assay.

A protein precipitation method for determining total plasma aluminum was evaluated. The volume of sample was reduced to 0.5 milliliters from the 1.0 milliliters previously required for the analysis. It was determined that no matrix effects exist when the resulting supernatant is analyzed, and thus it can be compared to an aqueous standard curve. In-run coefficients of variation (CV's) for this method concentrations were of 7.8% 19.4 and and 5.4% 69.0 for mean aluminum micrograms/liter, respectively. Between-run CV's were 12.9% and 9.9% for mean aluminum concentrations of 8.7 and 57.1 micrograms/liter, respectively.

A technique for determining plasma ultrafilterable aluminum was developed. Amicon's MPS-1 micropartitioning system was used with YMT membranes. The membranes required extensive cleaning by soaking in 1.8M HCl and rinsing with 2.4M HCl and deionized water. The membranes were 99.95% effective in excluding serum protein from the ultrafiltrate. The in-run CV for the method was 11.7% for a mean ultrafilterable micrograms/liter.

The duration of sample centrifugation was found to significantly affect ultrafiltrate aluminum concentrations. An inverse relationship was observed between centrifugation duration and ultrafiltrate aluminum concentrations. Additionally, there was a dramatic decrease in the aluminum-binding capacity of serum proteins between pH 7.6 and 7.2.

For the limited number of uremic dialysis patients for whom plasma aluminum analyses were done, the mean (SD) total plasma aluminum, the mean (SD) ultrafilterable aluminum, and the ultrafilterable fraction of the total plasma aluminum was 1 2 5. 6 ( 7 0) micrograms/liter, 3 0. 4 ( 28. 2 ) micrograms/liter, and 27.2 (18.9)%, respectively, for patients not undergoing chelation therapy. For patients undergoing chelation therapy, those values were 384.2 (246.2) micrograms/liter, 149.8 (65.2) micrograms/liter, and 44.9 (17.8)%, respectively. Total plasma aluminum and ultrafilterable aluminum were significantly higher in the chelation therapy patients (two-tailed t-test, p < 0.01 in both cases).

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DOI

10.25777/n5vs-e272

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