Sodium ferrous citrate does not cause aluminum retention in rats with experimentally induced renal failure

Accumulation of aluminum (Al) in the brain and bone has been implicated in the development of encephalopathy and osteodystrophy in patients with renal failure, and it has been reported that citric acid enhances Al absorption and retention. Oral iron supplementation is usually carried out with recombinant human erythropoietin (rHuEPO) therapy in end-stage renal disease (ESRD) patients. Accordingly, there is a possibility that Ferromia (sodium ferrous citrate, tetrasodium biscitrato iron (II), E0708), which is used for the treatment of iron deficiency anemia, might accelerate Al absorption and retention. To investigate this possibility, we administered oral aluminum hydroxide [Al(OH)3] [50mg Al/kg body weight (BW)] with or without E0708 (48mg/kg BW or 480mg/kg BW) to 5/6-nephrectomized rats (n = 27) five times per week for 16 weeks, and determined the Al content of the serum, liver, cerebral cortex, and femoral bone by flameless atomic absorption spectroscopy. The low dose of E0708 corresponded approximately to the clinical dose, and its low and high doses contained 34.5mg/kg BW and 345.0mg/kg BW, respectively, of citric acid. In addition, we gave 5/6-nephrectomized rats Al(OH)3 with citric acid at 35mg/kg BW, which was identical to the citric acid dose of the low-dose regimen of E0708. The weight gain, serum urea nitrogen, and creatinine levels indicated that the rats developed mild to moderate renal failure. There was no significant increase of the Al content in the serum or organs of the Al(OH)3, + E0708-treated rats when compared with the Al(OH)3-treated rats and Al(OH)3 + citric acid-treated rats. These findings suggest that the usual clinical dose of E0708 does not promote Al retention in rats with mild to moderate renal failure or normal rats.