EFFECT OF CHRONIC-RENAL-FAILURE ON THE EXPRESSION OF ERYTHROPOIETIN MESSAGE IN A MURINE MODEL

The anemia of chronic renal failure (CRF) is largely due to decreased production of erythropoietin (EPO) by the kidney. A small amount of EP O also originates from extra-renal sources, and this would be expected to assume a more important role in maintaining erythropoiesis when re nal production is impaired. In this study, we examined the production of EPO mRNA by RT-PCR in kidney, liver, and bone marrow tissues isolat ed from normal mice, mice rendered acutely anemic by phlebotomy, and f rom mice with surgically induced CRF. The induction of acute anemia re sults in an expected increase in the expression of EPO mRNA in renal a nd hepatic tissue. In contrast, while the expression of EPO mRNA was e xpectedly reduced in the kidney from CRF mice, it was completely absen t in the liver of these same animals. EPO mRNA expression was also abs ent in the bone marrow in both states of acute anemia and CRF. These r esults show that CRF can directly or indirectly can suppress the extra renal production of EPO by the liver and that this effect may further aggravate the anemia of CRF.