Effect of long-term low-dose aluminum-containing agents on hemoglobin synthesis in patients with chronic renal insufficiency

To investigate the possible toxic effects of long-term low-dose exposure to Al-containing agents in 55 patients with chronic renal insufficiency (CRI), 37 patients received Al(OH)3 1 tablet 3 times per day (about 302 mg/day of elemental Al) for 3 months and another 18 were used as a control group. The hematological, iron status and Al data were measured before and after the study. CRI patients who had ingested Al-containing agents for 3 months had significant decreases in hematological parameters and increases in serum Al and daily urinary Al excretion. Serum ferritin negatively correlated with serum Al (r = -0.586, p < 0.0005), and hemoglobin (Hb) positively correlated with renal Al clearance (r = 0.573, p < 0.0005) and logarithmic transformation of serum Al (r = -0.437, p < 0.01) in these patients, despite no significant correlations between initially basal hematological and Al parameters. But there were no significant differences between variables of Al and hematological parameters before and after 3 months of follow-up in the control group. All factors correlating with Hb were measured with stepwise regression analysis; renal Al clearance, creatinine clearance (C_cr) and serum iron were the most significant correlation factors with Hb. After C_cr and serum iron had been adjusted, Hb (b = 0.069 ± 0.02; p < 0.05) still positively correlated with renal Al clearance. Comparing patients who had reduced Hb (at least 0.5 g/dl) and those who did not, the response group had a lower basal (C_cr, a higher serum Al and a lower renal Al clearance after Al loading for 3 months. In conclusion, Al does play a role in the significant reduction of Hb and hematocrit in CRI patients after Al loading for 3 months, and patients with a lower C_cr may easily develop Al-induced hematologically toxic effects. Al-containing agents should be used with care in long-term therapies of CRI patients.