慢性腎不全患者におけるアルミニウムに関する研究 ： 造血能への影響

Abstract

Among several inhibitory factors proposed in refractory anemia for rHuEPO, Aluminium (Al) is of most importance in the clinical setting, ruling out an iron deficiency. So, an evaluation of Al accumulation in the patient with chronic renal failure and an inhibitory effect by Al in erythropoiesis have been investigated in this study to infer some aspect of the pathogenesis of Al-induced anemia. An inhibitory effect by Al in erythropoiesis was assessed by in vitro culture method of CFU-E colony formation using fetal mouse liver cells. 1) Evaluation of Al accumulation : RBC-Al content in patients was apparently higher than that in healthy subjects and disclosed clear correlation with ΔAl(r=0.540, p<0.05). In addition, comparative analysis between RBC-Al and Hb concentration also showed significant correlation (r=-0.400, p<0.001) and RBC-Al value corresponding to Hb concentration of as low as 6 g/dl was to be 65 μg/10¹³ cells or so. 2) In vitro study of CFU-E : CFU-E colony count was significantly reduced by application of Al in all experimental conditions. Furthermore, inhibitory effect found in Al application preceding the addition of EPO was to be about double the degree found in other experiments. 3) Erythropoietic activity : CFU-E/logEPO of each patient correlated significantly with RBC-Al value (r=-0.486, p<0.05). Based upon the above three studies, the following conclusions could be proposed, which may substantially contribute to protecting patients with chronic renal failure from Al-intoxication more safely. Conclusions : RBC-Al content is a precise parameter for prediction of Al-intoxication ; 2) RBC-Al measured in patients showed that a patient on maintenance dialysis having a risk of Al is not uncommon, irrespective of current widely expanded prophylaxis measures ; 3) Al inhibitory effect on CFU-E formation is confirmed by in vitro study as well as in vivo study ; 4) RBC-Al value of 65 μg/10¹³ cells is proposed as the critical value to predict the risk of Al intoxication ; 5) in the rHuEPO therapy of patients having an RBC-Al level higher than this level, removal therapy of Al should be considered.