Emerging Data on Iron Management: Clinical Implications

ASN Renal Week, Official Symposium, October, 2004

Panel Discussion

Panel Discussion

Dr. Coyne
Dr. Warady
Dr. Kalantar-Zadeh
Dr. Nissenson
Question index:
Questions received during this symposium have been paraphrased
and the answers submitted by the panelists are presented.


In that first quartile of patients with the high mortality rate, you demonstrated low measurements of iron. Did you look at iron administration in those patients? Did it match or was it lower than the other 3 quartiles or was it the same?
I wanted to know if somebody could comment on the recent paper which came out on iron, and this showed increase in interstitial fibrosis, I believe, a in rat model after giving intravenous iron.

Panelist Responses
(Back to question index) In that first quartile of patients with the high mortality rate, you demonstrated low measurements of iron. Did you look at iron administration in those patients? Did it match or was it lower than the other 3 quartiles or was it the same?

Dr. Zadeh: The question is if iron administration played a role in essentially determining where your patients' iron status is - I believe that is what you are asking or something to that end. We did adjust for the amount of administered iron to these patients. We did not find any association, first of all, between the amount of iron that was given to the patients and the mortality. Also, there was some association, but somewhat weak, between the amount of iron given to the patients and serum iron. However, as you have noticed, almost half of the patients in that core, they did not receive any iron during the first 3 months of the study. I guess, we can answer hopefully your question using the 50,000 database at some point.

Panel: I think it is an important question because if the hepcidin story is correct, these patients could be sequestering the iron in the RE system and the liver especially, and you will never see it and it is really a marker. It really, rather than being an indication that you are not getting enough iron, could be an indication that these are patients that are scheduled to die because of other reasons.

Zadeh: I completely agree, but as I said, there was no association between mortality and the amount of iron, but I completely agree that that could be the case too.


(Back to question index) I wanted to know if somebody could comment on the recent paper which came out on iron, and this showed increase in interstitial fibrosis, I believe, in a rat model after giving intravenous iron.

Panel: I am not entirely certain what article you are referring to. If you are referring to a study in patients in KI recently, there was a paper by Rajiv Agarwal and others that looked at administration of iron sucrose to CKD patients. The patients had standard indications for getting IV iron, and he looked at administration of 100 mg of iron sucrose to the CKD patients, and it did cause temporary proteinuria, enzymuria, and oxidative stress, which peaked within 15 minutes, and all parameters returned to normal within 24 hours.

Audience:
This is a different paper. In that, they compared the highest risk is with iron sucrose and the least was with iron dextran, and this was in a rat model

Dr. Zadeh: That is Zager's paper in animals. It is an interesting study.

Audience:
My question is do you place any relevance to this? Should anything be changed right now or should you just leave it for CKD patients regarding iron?

Panel: I think differences between IV iron as far as injury to cells is provocative and, as I mentioned, Rajiv Agarwal's paper in CKD patients showed there is the potential for injury. What we do not have yet is discrimination between agents and humans. So, from the standpoint of Zager's several studies comparing all of the agents that we have available - he has done a great service to us to compare them - but we have to take them to the next step and understand what the risks are in patients - what the comparative risks between drugs is, and how to use these agents as safely as possible, because - as my talk was about most of these patients are going to need IV iron for the foreseeable future until we can come up with some way to get them to absorb iron in the GI fashion.

Dr. Nissenson: I think maybe what you are getting at is - for CKD patients the patients who are on hemodialysis, in particular, who have residual renal function. I think these sorts of studies need to be replicated in larger numbers of patients - but are concerning. I mean, anyone needs to be worried about this sort of data. So, I think that emphasizes to an even greater extent the fact that you need to really work hard on achieving iron repletion with oral iron in CKD patients, which you can achieve in a large fraction of patients, and really do that aggressively before you go to IV iron, and also remember that if someone fails oral iron - a CKD patient - and needs IV iron, that does not mean they will never respond to oral iron. The next time, you should go back to oral iron or once they are replete, then it may be easier to maintain repletion with oral iron. That is the message I have got right now. I am trying to be very conservative about IV iron in CKD patients until this is clarified a little bit better.

Panel: I want to reiterate what you said as I walked forward you started to say what I was going to say. There probably are 3 major categories in the CKD population. The iron-deficient population has been totally underestimated. These are people with high hepcidin, poor absorption, GI blood losses, and that group probably never was estimated correctly, but may exceed at least a third and then the individuals with functional iron deficiency - we do not know how to count them either. As we start to treat these patients with erythropoietin and other stimulating proteins, we are going to uncover this tremendous lot of individuals who have both iron deficiency and functional deficiency, and we are going to provoke these deficiencies with the erythropoietin activity. After some generation of increased reticulocytosis, we are going to see this falloff, and we are going to recognize as we are following patients with GFR of 60, 50, 40 - if they are progressive or if they hang at stable levels - that their anemias are going to become very significant longstanding issues, and I do agree with the comment that you just made I am not sure everyone heard it - these patients need to be studied in large enough numbers so that we can assess exactly what the percentage of iron deficiency is and what happens when we give them oral iron - if in fact it is an adequately absorbed substance, to give them a red cell production if necessary to prevent the cardiovascular adverse outcomes. I would recommend, and I am sure you do as well, that that type of study be undertaken.



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