A NOVEL ANTI -IL-1 β ANTIBODY IMPROVES CHRONIC KIDNEY DISEASE (CKD) RELATED ANEMIA THROUGH HIF/EPO-R PATHWAYS

Background: Anemia, a common feature of CKD, is associated with poor outcomes. We have previously shown that exacerbated inflammation through IL-1 leads to worsening renal damage and anemia in a mouse model of CKD. Inhibition of IL-1β has been shown to be beneficial in many low-grade inflammation conditions, but its role in CKD and its effects on anemia are unknown.

Methods: CKD or control states were induced in 7-8 wk old C57BL/6 mice by adenine or control diet. CKD-Ab mice were also injected intraperitoneally with 5 mg/kg of P2D7KK, a novel anti-IL1 Ab, twice a week, and were sacrificed after 2 weeks.

Results: Administration of P2D7KK to CKD mice resulted in a lower grade of systemic and kidney inflammation (liver CRP, kidney IL6). The elevation of serum urea and creatinine and histological fibrosis were blunted in CKD-Ab Vs CKD. Hematocrit levels were decreased in CKD animals but improved by 31% in CKD-Ab Vs CKD. Renal HIF2 and bone marrow erythropoietin receptor mRNA levels were significantly decreased in both CKD groups but were higher in CKD-Ab Vs CKD. Bone marrow transferrin receptor mRNA levels were significantly increased in CKD-Ab compared to all other groups.

Conclusions: Inflammation (through IL1) plays a key role in CKD complications. Novel treatments to reduce inflammation, such as P2D7KK, may attenuate the anemic state or increase the response to exogenous EPO.