Hemoglobin or Epo Dose: Which Poses Heart Risk?
Hemoglobin or Epo Dose: Which Poses Heart Risk?
Dr. Bakris: That makes sense and I would agree with that position myself. The last question that I am going to ask you is to speculate, because we have very few data on this, except in rodents. A whole new class of agents is on the horizon, called the hypoxia-inducible factor (HIF) agents. These are totally separate from the erythropoietin or erythropoietin-stimulating drugs, working through the liver and not requiring iron. It is like the dabigatran-to-Coumadin analogy. They are probably not going to be ready for prime time before 2016, but if you had to look down the road over the next 5 years, do you think we are still going to be using EPO agents if these do pan out to be as good in 2018?
Dr. McCullough: There are clearly advances in this area of hematology and nephrology. About 90% of EPO is produced by the kidneys. The major physiologic stimulus is hypoxia. But 10%, as you pointed out, is produced by the liver. The gene that produces EPO and the factors that regulate that gene clearly are inducible. That is, a liver can be revved up to respond to stimuli and start to pick up the load and produce endogenous EPO. Endogenous EPO, as far as we can tell, is probably not toxic at all. It's the exogenous, very supraphysiologic doses that are the problem. Endogenous production of EPO could be a solution, and the HIF drugs are a terrific approach.
Don't forget the iron reutilization defect. When the human body gets sick, the liver produces hepcidin-25. Hepcidin-25 blocks the ferroportin receptor and basically puts a lock on iron utilization and transfer across the body, particularly in the bone marrow. The agents that allow normal iron trafficking between cells -- and, in a sense, take out hepcidin-25 -- are probably going to have a huge impact. Right now we are pouring in EPO because the kidneys aren't making enough, the liver is not picking up the load, and the body is resistant to it.
Then we are pouring in iron because we have a defect that blocks iron utilization. These are blunt tools, if you will. When we have more sophisticated tools, we will get the erythron in patients with CKD back up to the normal levels, and the patients should feel much better and enjoy better outcomes.
Dr. Bakris: Thank you very much, Peter. It has been enjoyable to have this cardio-renal moment with you. Thank you very much for enlightening us on this. So, for Peter McCullough, I'm George Bakris. Thank you and have a good day.
Future Oral Erythropoietin Inducers
Dr. Bakris: That makes sense and I would agree with that position myself. The last question that I am going to ask you is to speculate, because we have very few data on this, except in rodents. A whole new class of agents is on the horizon, called the hypoxia-inducible factor (HIF) agents. These are totally separate from the erythropoietin or erythropoietin-stimulating drugs, working through the liver and not requiring iron. It is like the dabigatran-to-Coumadin analogy. They are probably not going to be ready for prime time before 2016, but if you had to look down the road over the next 5 years, do you think we are still going to be using EPO agents if these do pan out to be as good in 2018?
Dr. McCullough: There are clearly advances in this area of hematology and nephrology. About 90% of EPO is produced by the kidneys. The major physiologic stimulus is hypoxia. But 10%, as you pointed out, is produced by the liver. The gene that produces EPO and the factors that regulate that gene clearly are inducible. That is, a liver can be revved up to respond to stimuli and start to pick up the load and produce endogenous EPO. Endogenous EPO, as far as we can tell, is probably not toxic at all. It's the exogenous, very supraphysiologic doses that are the problem. Endogenous production of EPO could be a solution, and the HIF drugs are a terrific approach.
Don't forget the iron reutilization defect. When the human body gets sick, the liver produces hepcidin-25. Hepcidin-25 blocks the ferroportin receptor and basically puts a lock on iron utilization and transfer across the body, particularly in the bone marrow. The agents that allow normal iron trafficking between cells -- and, in a sense, take out hepcidin-25 -- are probably going to have a huge impact. Right now we are pouring in EPO because the kidneys aren't making enough, the liver is not picking up the load, and the body is resistant to it.
Then we are pouring in iron because we have a defect that blocks iron utilization. These are blunt tools, if you will. When we have more sophisticated tools, we will get the erythron in patients with CKD back up to the normal levels, and the patients should feel much better and enjoy better outcomes.
Dr. Bakris: Thank you very much, Peter. It has been enjoyable to have this cardio-renal moment with you. Thank you very much for enlightening us on this. So, for Peter McCullough, I'm George Bakris. Thank you and have a good day.
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