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 A1-containing agents in 55 patients with chronic renal insufficiency (CRI), 37 patients received A1(OH)3 1 tablet 3 times per day (about 302 mg/day of elemental A1) for 3 months and another 18 were used as a control group. The hematological, iron status and A1 data were measured before and after the study. CRI patients who had ingested A1-containing agents for 3 months had significant decreases in hematological parameters and increases in serum A1 and daily urinary A1 excretion. Serum ferritin negatively correlated with serum A1 (r = -0.586, p < 0.0005), and hemoglobin (Hb) positively correlated with renal A1 clearance (r = 0.573, p < 0.0005) and logarithmic transformation of serum A1 (r = -0.437, p < 0.01) in these patients, despite no significant correlations between initially basal hematological and A1 parameters. But there were no significant differences between variables of A1 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 A1 clearance, creatinine clearance (Ccr) and serum iron were the most significant correlation factors with Hb. After Ccr and serum iron had been adjusted, Hb (b = 0.069 +/- 0.02; p < 0.05) still positively correlated with renal A1 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 (Ccr, a higher serum A1 and a lower renal A1 clearance after A1 loading for 3 months. In conclusion, A1 does play a role in the significant reduction of Hb and hematocrit in CRI patients after A1 loading for 3 months, and patients with a lower Ccr may easily develop A1-induced hematologically toxic effects. A1-containing agents should be used with care in long-term therapies of CRI patients.
Lin
J L
JL
Division of Nephrology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Chang Gung Medical College, Taipei, Taiwan, ROC.
Kou
M T
MT
Leu
M L
ML
D000328:Adult; D000368:Aged; D000535:Aluminum / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006403:Hematologic Tests; D006454:Hemoglobins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000628:therapy; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D013997:Time Factors
D006454:Hemoglobins; D000535:Aluminum; D007501:Iron