The pathogenesis of anemia in patients with chronic renal failure has been greatly attributed to erythropoietin (EPO) deficiency. Recently, however, there has been some thought that uremic inhibitors might suppress the activity of EPO and reduce the maturation of erythropoiesis. Polyamines are well known to be involved in the regulation of cellular proliferation and differentiation. Furthermore, the polyamine levels in the serum or erythrocytes are elevated in chronic hemodialysis patients, and can be lowered immediately by hemodialysis. In the present study, we first measured the polyamines levels (putrescine, spermidine, spermine) by high performance liquid chromatography (HPLC) in 20 chronic hemodialysis patients, and investigated the effects of polyamines on erythropoiesis by in vitro bioassay using fetal mouse liver cells. The direct effects of polyamines in erythroid colony formation in the medium with and without EPO were evaluated. Each polyamine level in chronic hemodialysis patients was higher than in the healthy subjects, and a significant negative correlation was found between polyamines and erythropoiesis. Polyamines inhibited the activity of EPO, but they did not have any direct effect on colony formation of the fetal mouse liver cells. These results suggest that polyamines have inhibitory effects on the proliferation or maturation of erythroid precursor cells and are intimately involved in the pathogenesis of renal anemia in chronic hemodialysis patients.

These results suggest that serum NMP22 is useful parameter of rejection in renal transplantation patients.

Background: Endothelin-1 (ET-1) is involved in some diseases, including renal disease. Recently, the role of ET-1 in postrenal transplantation has been demonstrated in experimental and clinical studies. A new endothelin receptor antagonist, TAK-044, blocks both, ETA and ETB receptors, and was useful in treating acute renal failure in rats. In this study, we evaluated the effect of TAK-044 on autotransplanted kidneys with 18 h of perfusion. Materials and Methods: TAK-044 was injected subcutaneously at 15 mg/kg/day for 2 weeks in one group of dogs, and blood analysis and renal function, were evaluated. A control group was given saline in the same manner as that used for the TAK-044 group. Histopathological examination and immunohistochemistry for ET-1 were performed in the two groups. Results: In the control group, 5 of the 7 dogs died of renal failure within 2 weeks after autotransplantation of the kidney. In the TAK-044 group, 5 of the 7 dogs survived and 2 died of renal failure within the same period. Although the histological changes in the tubules in both groups were severe due to the 18 h of perfusion, TAK-044 ameliorated these changes. Immunohistochemical staining for ET-1 was seen in tubules in the control group. Conclusion: These findings suggest that TAK-044 effectively reduces damage in autotransplanted perfused kidneys in dogs, and may be useful in limiting damage to the kidney by acute tubular necrosis after renal transplantation in humans.

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