Establishment of a Rat Model for Renal Anemia Based on 5/6 Nephrectomized Rats

抄録

Chronic kidney disease (CKD) progresses to renal fibrosis and anemia, ultimately leading to chronic renal failure (CRF). Renal anemia, primarily caused by impaired erythropoietin (EPO) production and dysregulated iron metabolism, reduces QOL and increases cardiovascular risk. To establish an experimental model of CRF-associated anemia, male Wistar rats underwent 5/6 nephrectomy (Nx). In a subset of Nx rats, tacrolimus (TAC, 1 mg/kg, subcutaneously every other day for two weeks starting at week 4) was administered to exacerbate renal injury. Renal function, hematological parameters, iron-related indices, and fibrotic changes were evaluated at defined postoperative time points. The Nx rats developed progressive renal dysfunction and interstitial fibrosis, accompanied by declining hematocrit and reduced plasma EPO levels and attenuation of renal hypoxia-inducible factor-2α expression. TAC administration further aggravated renal injury and anemia and resulted in a lower hematocrit despite detectable circulating EPO levels. This pattern may suggest a relative inadequacy of erythropoietic response under aggravated renal injury conditions rather than absolute EPO deficiency. These findings indicate that the Nx model reproducibly recapitulates key features of CKD-associated anemia. The addition of TAC accelerates pathological progression within this established model and facilitates the induction of advanced renal injury. This experimental system provides a practical preclinical platform for investigating the molecular mechanisms underlying CKD/CRF-related anemia and for evaluating therapeutic strategies targeting fibrosis, iron metabolism, or impaired erythropoietic response.