Low serum aluminum values in dialysis patients with increased bone aluminum levels

Using an HPLC/ETAAS hybrid speciation technique we previously demonstrated iron to have a multifold effect on the binding of aluminum to transferrin by limiting the number of available binding sites and decreasing the affinity of transferrin for aluminum. Theoretically, at a 60% iron-transferrin saturation the aluminum-transferrin fraction in serum should not exceed 30 microg/l. In the present study previous experimental data were confronted with recent clinical observations in patients with either normal iron status or iron overload.

Serum aluminum levels and iron overload: In 38 dialysis patients with a normal iron status and of whom 63% received Al(OH)3 for phosphate binding 26 (68%) had a serum aluminum level >30 microg/l. On the other hand out of 28 transfusional iron overloaded patients; 68% of them taking Al(OH)3, only 1 subject (4%) had a serum aluminum value in excess of 30 microg/l. Taking patients of both groups receiving Al(OH)3 together a significant (p = 0.001) negative correlation (r = -0.5017) was found between the iron-transferrin saturation and the serum aluminum levels. Iron status and parenteral aluminum loading: Also could a significant (p = 0.001) negative correlation (r = -0.6383) between these parameters be found in an independent group of 44 patients which were acutely intoxicated by the use of aluminum-contaminated dialysis fluids. Since in this population aluminum loading occurred parenterally and not via the gastrointestinal tract, a direct effect of iron on the transferrin binding of aluminum rather than on the element's gastrointestinal absorption must have been responsible for the inverse relationship. Bone aluminum and iron overload: Out of 22 patients with a normal iron status (mean + SD serum ferritin: 216 +/- 245 microg/l; iron-transferrin saturation 20.4 +/- 9.6%), all of them having aluminum overload (bone aluminum level >15 microg/g and/or positive Aluminon staining) none of them presented with a serum aluminum <30 microg/l (mean +/- SD: 82.2 +/- 51.6 microg/l). On the other hand out of 13 iron overloaded patients (serum ferritin >800 microg/l; iron-transferrin saturation 61.4 +/- 17.6%) 10 (77%) presented the proposed criteria of aluminum overload in the presence of a serum aluminum level <30 microg/l.

Our data indicate that in dialysis patients with iron overload (iron-transferrin saturation >60%; serum ferritin >800 microg/l) serum aluminum levels are low (<30 microg/l) despite exposure to aluminum by the intake of Al(OH)3 or the use of aluminum-contaminated dialysis fluids. Low serum aluminum nevertheless may be associated with aluminum overload and even aluminum-related bone disease. An effect of iron on the serum aluminum speciation may at least in part explain our observations. Our findings allow a more accurate interpretation of baseline serum aluminum values.