Abstract: SA-OR036
Colchicine Does Not Affect Anemia or Inflammation in a Mouse Model of CKD
Session Information
- Anemia and Iron Metabolism: Basic Research
November 09, 2019 | Location: 150, Walter E. Washington Convention Center
Abstract Time: 05:30 PM - 05:42 PM
Category: Anemia and Iron Metabolism
- 201 Anemia and Iron Metabolism: Basic
Authors
- Landau, Daniel, Tel Aviv University, Petach Tikva, Israel
- Segev, Yael, Ben Gurion University, Beer-Sheva, Israel
- Shukri, Nehorai, Ben Gurion University, Beer-Sheva, Israel
Background
Previous studies point for a significant role of low grade inflammation mediated by the innate immune system in CKD and its complications. We have recently shown that anemia of CKD is associated with such increased inflammation, which impairs both HIF2-EPO-EPOR signals as well as iron homeostasis. Colchicine is a safe drug for long term use in humans, including children, mainly for the prevention of familial Mediterranean fever attacks, as well in gouty arthritis. In addition, colchicine attenuated both glomerular sclerosis and interstitial fibrosis without affecting systemic blood pressure in a model of CKD by 5/6 nephrectomy (Guan T et al, AJP 2013).
Methods
7-8 wk old C57BL/6 mice were divided into 4 groups (C, C-Col, CKD, CKD-Col). CKD or control states were induced by adenine (0.3-0.2%) or control diet. Colchicine (30ukg/kg/day, IP) or saline were injected for 3 weeks, until sacrifice.
Results
Systemic inflammation (liver CRP, IL6, plasma platelet count) was elevated in CKD animals (140±15%, 151±37% and 239±27% respectively) but was unaffected by colchicine. Serum urea and creatinine were increased by ~ 50% in CKD animals but without differences between CKD-Col and CKD. Kidney IL6 and pSTAT3 were increased in both CKD groups but without differences between them. Anemia developed in this model of CKD (63±5% of C), in association with decreased iron (62±6% of C) and transferrin saturation (55±4% of C), decreased renal EPO (37±5% of C) and renal HIF2 mRNA (55±4% of C) but without differences between the uremic groups.
Conclusion
In this model of CKD associated anemia and inflammation (systemic and renal) colchicine was inefficient in preventing these complications, despite previous reports. Therefore, inflammation control through other pathways (sucj as IL1) may be needed.