A Copernican Revolution in the Treatment of Renal Anemia
Atsuo Takemasa
Nishinokyo Hospital
I identified six upstream factors for the control of renal anemia. These consist of three cytokines (EPO, TNF-α, leptin) and three transcription factors (hypoxia-inducible factor [HIF], GATA transcription factor [GATA], nuclear factor κB [NF-κB]). These six hematopoietic regulatory factors and the six downstream systems protect the body by maintaining sophisticated crosstalk within cells, between cells, and between organs. In this study, I successfully integrated all these factors into a single comprehensive network, Figure 1. This study reveals that TNF-α plays a central role as an upstream regulator of hematopoiesis and emphasizes the importance of understanding hematopoiesis as a process of blood cell distribution derived from hematopoietic stem cells (HSCs). Many of these factors are essential for physiological function and are neither inherently harmful nor beneficial. Rather, it is an imbalance between these factors that causes pathological conditions.
The conventional ESA-centered approach posits that EPO deficiency is the root cause of renal anemia, and that ESA resistance has other causes. It considers TNF-α, FGF23, and Leptin as "bad" and should be considered separately. While this is a classic analogy, I define this as the geocentric model in renal anemia treatment.
The conventional approach has three major errors, which I have corrected: ① Erythropoiesis needs to be viewed within a larger framework starting with HSCs. ② The balance between infection defense and erythropoiesis is crucial for the body, and there are no factors that are inherently "bad" to the body. ③ The erythropoiesis system, including iron distribution, is a molecular-level network system acquired through constant battles with external bacteria, and large doses of ESA or iron administered intravenously disrupt this network.
Conversely, the heliocentric model in the treatment of renal anemia posits that the body possesses a network that balances hematopoiesis and infection defense, and that all pathological conditions are imbalances in this network. Therefore, compensating for EPO deficiency can be done with physiological amounts, and endogenous EPO is preferable. TNF-α, FGF23, and Leptin are necessary in appropriate amounts for the body. There is no inherent good or bad in any of these factors. While it's impossible to use celestial bodies as a metaphor for everything, we can consider HSCs to be equivalent to the sun. A symbolic image created using AI is shown in Figure 2. Hematopoietic stem cells cannot survive or differentiate without the help of TNF-α, Leptin, and HIF-1.