EPO antibody question

[amanda100wilson]

Does anybody else have antibodies to epo. Injections? We are beginning to suspect that I do, as I am failing to respond to epo injections (I have been on it got many, many years, even before it was licensed for general use in the UK).  If you have, how do they manage your anemia?  Do you continue to have epo. Injections? Does this help maintain you Hgb to some extent?  My Hgb is consistently below 9.0 and seems to be falling despite increasing dose.  As far as I am aware. I am not bleeding anywhere, but should I get a GI investigation just in case?  Would antibodies be specific to one type of epo?  I have recently been switched to Aranesp, and despite more consistent dosing, and no dialysis blood losses (for example, failed rinsebacks which could have accounted for low results in previous months), it still doesn't improve.

[obsidianom]

You might want to bring this to your doctors.


Saudi J Kidney Dis Transpl. 2014 Jan;25(1):73-8.

Evaluation of the effect of pentoxifylline on erythropoietin-resistant anemia in hemodialysis patients.

Mohammadpour AH, Nazemian F1, Khaiat MH, Tafaghodi M, Salari P, Charkazi S, Naghibi M, Shamsara J.

Author information

Abstract

Use of recombinant human erythropoietin (rh-Epo) improves hemoglobin (Hgb) in 90-95% of the cases of anemia of chronic kidney disease (CKD). However, it is known that pro-inflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alfa (TNF-α) and interleukin-1 (IL-1) suppress erythropoiesis, resulting in inadequate response to rh-Epo. Pentoxifylline has been shown to have modulatory effects on the immune system. This prospective study to evaluate the effect of pentoxyphylline on erythropoeisis was performed on 15 (eight males, seven females) clinically stable patients who had been on hemodialysis for at least six months with anemia (Hgb of <10.7 g/dL) unresponsive to rh-Epo despite high doses. They were treated with 400 mg pentoxifylline tablets once daily for 12 weeks. Hgb increased after one and two months of drug administration, but significant changes were observed in eight (53%) patients after three months (P <0.05). Our study illustrates a probable new use for an old medicine. Three months treatment with pentoxifylline was seen to increase Hgb significantly in rh-Epo-resistant patients. More prospective studies with a larger sample size are needed to determine the inhibitory role of cytokines on hematopoiesis and exploring new drugs or new drug indications to overcome anemia in advanced renal failure.

[obsidianom]

Another interesting thought .

Parvovirus B19 (B19) and cytomegalovirus (CMV) infections and anti-erythropoietin (anti-EPO) antibodies in patients on dialysis hyporesponsive to erythropoietin therapy.

Alves MT1, Vilaça SS2, Godoi LC3, Júnior LR3, Carvalho MD4, Silva FS4, Guimarães FL4, Fernandes AP4, Dusse LM4, Gomes KB5.

Author information
Abstract
BACKGROUND:

Approximately 10% of patients receiving recombinant human erythropoietin (rHuEPO) do not respond to the treatment. We evaluated parvovirus B19 (B19) and cytomegalovirus (CMV) infections and anti-erythropoietin (anti-EPO) antibodies as potential causes of anemia in dialyzed patients, hyporesponsive to rHuEPO.

METHODS:

Data from 120 dialyzed patients, receiving rHuEPO alfa, were collected: demographic characteristics, rHuEPO dose, duration of rHuEPO treatment and time on dialysis, etiology of chronic kidney disease and transfusion history. Serology and PCR were performed to address B19 and CMV infection status. An ELISA was developed to detect anti-EPO antibodies.

RESULTS:

rHuEPO resistance correlated with high ferritin levels (p=0.001) and short time on dialysis (p=0.012). B19 DNA was found in 10 (8.3%) dialyzed patients and CMV DNA was detected in 33 (27.5%). There was no significant correlation between B19 infection and anemia, while a tendency of correlation between active CMV infection and hemoglobin or hematocrit levels (p=0.069 and p=0.070, respectively) has been observed. Anti-EPO antibodies were not detected in any patient.

CONCLUSIONS:

B19 infection is a rare complication in dialyzed patients and should be investigated after exclusion of other common causes, while CMV infection is rather common. The role of CMV infection in the hyporesponsiveness in dialyzed patients should be further evaluated in other studies. Our data suggest that anti-EPO antibodies are not involved in rHuEPO resistance in this population.

Copyright © 2014. Published by Elsevier B.V.

[obsidianom]

Anti EPO antibodies are in fact RARE.

Clin Nephrol. 2013 Feb 8. [Epub ahead of print]

A simple screening test for the detection of erythropoietin antibodies.

Meran S, Wonnacott A, Davies M, Ellis R, Phillips A.

Abstract

Antibody-mediated pure red cell aplasia (PRCA) is a rare complication of erythropoietin (EPO) therapy. Identification and demonstration of functional activity of EPO antibodies required to diagnose this condition is difficult and only performed in selected laboratories worldwide. In this article we report a recent cluster of three cases of antibody-mediated PRCA over a 16-month period in a single center associated with EPREX use. We also describe the use of a simple low-cost inhibitor assay that can be used to screen for PRCA in local laboratories

[obsidianom]

If you do in fact have antibodies, here is a treatment protocol.


Int J Hematol. 2013 Feb;97(2):272-4. doi: 10.1007/s12185-013-1258-3. Epub 2013 Jan 26.

Successful treatment of anti-erythropoietin antibody-mediated pure red cell aplasia with low-dose prednisolone.

Aoki K1, Ono Y, Tabata S, Matsushita A, Ishikawa T.

Author information

Abstract

The standard therapy for anti-erythropoietin (EPO) antibody-mediated pure red cell aplasia (PRCA) is cyclosporine (CyA) or prednisolone (PSL) 0.5-1.0 mg/kg. However, many patients with severe chronic kidney disease (CKD) and chronic heart failure cannot tolerate such an immunosuppressive regimen. An 86-year-old man with anemia related to CKD and chronic heart failure, who had received recombinant human erythropoietin subcutaneously, developed anti-EPO antibody-mediated PRCA. The patient was treated with CyA followed by PSL (1.0 mg/kg); however, he was unable to tolerate this drug regimen. The PSL dose was reduced to 0.2 mg/kg. Surprisingly, his reticulocyte count increased 3 months later, and RBC transfusion was no longer required. Low-dose PSL is a treatment option for patients with anti-EPO antibody-mediated PRCA who cannot tolerate CyA and PSL (0.5-1.0 mg/kg).

[dialysisuser82]

I too no longer respond to Epo injection.

For a period of 8 months my Hemoglobin was below 10. Out of the 8 months, the Hgb was idle in 8 range for 5 months. Within this period my neph raised the EPO dosage without result.

I refused to get blood transfusion.

I decided to experiment with different type of foods.  My Hemoglobin started to climb and three time the Hgb was above 12.

Unfortunately, I did not keep a dairy of special food intake. So for the past 3 month, my Hgb is down to 10 range.

My current research is to get the Hgb up. It is a matter of getting the right food combination. 

The Epo injection is optional, often I simply refuse it- unless my neph would nag.

[obsidianom]

How about iron? How is your iron and Tsat? that can also cause anemia.
Also if a male you shoud have your testosterone checked as kidney disease can lower it. Testosterone can raise hemoglobin levels .

[dialysisuser82]

 Obsidianom, thank you for your suggestion.

I do not respond to Iron injection. My % sat is 21.

There are a few obstacles for long term kidney patient on dialysis and the solutions are out there.
 
I am female so no Testosterone 

I will trouble shoot this Hemoglobin issue as I have done before.  Challenges makes one's stronger.


------------------------------
In-center hemodialysis since 1982--32 YEARS on April, 2014
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
No interest in transplant.

3 hours   3x/wk
800 dialysate flow (Qd)    400 blood pump (Qb)
Gambro- Polyflux Revaclear (1.4m2)
Arteriovenous Fistula  32 years- intact
Parathyroidectomy 2002
Diagnosis: Glomerulnephristis- High Blood Pressure 1982
----------------

[obsidianom]

 Obsidianom, thank you for your suggestion.

I do not respond to Iron injection. My % sat is 21.

There are a few obstacles for long term kidney patient on dialysis and the solutions are out there.
 
I am female so no Testosterone 

I will trouble shoot this Hemoglobin issue as I have done before.  Challenges makes one's stronger.


------------------------------
In-center hemodialysis since 1982--32 YEARS on April, 2014
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
No interest in transplant.

3 hours   3x/wk
800 dialysate flow (Qd)    400 blood pump (Qb)
Gambro- Polyflux Revaclear (1.4m2)
Arteriovenous Fistula  32 years- intact
Parathyroidectomy 2002
Diagnosis: Glomerulnephristis- High Blood Pressure 1982
----------------

Actully even females can use lower dose testosterone . It is out of the box but I have seen articles in the past about it. Women after menopause also produce less testosterone . Women have been given it at doses about 1/4 of male doses (around 25mg/week) for sexual issues but it also increases red cell production as it also brings in more iron absorbtion etc. You can ask your doctor about it. It is unorthodox but if you are really having trouble it may be worth looking into. (it will also increase muscle mass a bit which can help also. )

[dialysisuser82]

Obsidianom, thank's for your great suggestion.

I will definitely look into it if my researches come up empty.

It is good to have another solution.

[JW77]

You say you recently switched to Aranesp..  Were you more responsive to your previous EPO?

There are 2 main types of EPO under various brands, Aranesp being an EPO Alpha. Others like NeoRecormon being an EPO beta.

Might be another factor to look into.  I think a lot of UK hospitals have switched overall to Aranesp as in theory its lower dosage and thus saves money. After 2 doses with very nasty reactions each time, I went back to NeoRecormon (an Epobeta.

[kristina]

Does anybody else have antibodies to epo. Injections? We are beginning to suspect that I do, as I am failing to respond to epo injections (I have been on it got many, many years, even before it was licensed for general use in the UK).  If you have, how do they manage your anemia?  Do you continue to have epo. Injections? Does this help maintain you Hgb to some extent?  My Hgb is consistently below 9.0 and seems to be falling despite increasing dose.  As far as I am aware. I am not bleeding anywhere, but should I get a GI investigation just in case?  Would antibodies be specific to one type of epo?  I have recently been switched to Aranesp, and despite more consistent dosing, and no dialysis blood losses (for example, failed rinsebacks which could have accounted for low results in previous months), it still doesn't improve.

Hello Amanda,

I am sorry about your recent EPO experiences and I am wondering how you are doing?

I know from my own experiences how devastating and isolating an allergy and drug-intolerance can become
and I have been wondering whether it might be a good idea for you to talk to the chemist of the Epo company
and ask them whether anything has been changed recently? Have they been sold? Have they changed some ingredients?

I wonder, because I took for a few years a medication against SLE-flare-ups and it worked extremely well.
This  (antimalarial) medication gave me no problems with drug intolerance or allergies for a few years,
but all of a sudden I became very unwell and bedridden.
After going through a very long process to eliminate certain foods, vegetables etc
in an effort to find out what it was I had become allergic to,
I finally realized that it must be the (antimalarial) medicine I was taking every day against SLE flare-ups.
This seemed a contradiction, because I had tolerated it so well for quite a few years...
Nevertheless, I located the number of the company, phoned them and finally was able to talk to the chemist there.
He told me, that the company had been sold  a few months ago to another company
and they now produced the same medicine a little different:
in order to save more money, they had exchanged the formerly (more expensive) natural sugar coating of each tablet
with artificial sugar-coating ... and my body happens to react allergic to artificial sugar coating & artificial colouring ... and that was that.
It was a very sad ending to a formerly very successful treatment, but I had to give this medicine a miss
because of my any allergies and drug-intolerance. My bad luck was that in this particular case there was no alternative treatment left for me...

Could it be a similar case with you? Could it be that your formerly successful Epo is being produced slightly different now
and you have become allergic to some of these different ingredients ?
Or has the Epo-producing company been sold to another company ? After all, your body did tolerate these Epo injections before?

Best wishes and good luck from Kristina.