TANYA'S

COMPREHENSIVE GUIDE TO

FELINE CHRONIC KIDNEY DISEASE

 

   

ERYTHROPOIESIS STIMULATING AGENTS (ESAs) FOR SEVERE ANAEMIA

The information here was recommended by Catwatch,

the newsletter of Cornell University College of Veterinary Medicine, May 2011

 

ON THIS PAGE:


What are ESAs


Types of ESAs


Which ESA to Choose


When to Use ESAs


Commonly Used ESAs: Aranesp, Epogen, Procrit, Eprex, NeoRecormon


Usage Guidelines


The Downsides of ESAs


Should I Use an ESA


Feline Erythropoietin


 

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Home > Treatments > Erythropoiesis Stimulating Agents

 


Overview


  • Anaemia means that not enough red blood cells exist in the body. It is relatively common in CKD cats, so it is important to know about it and to be prepared to deal with it.

  • Mild or moderate anaemia may be controlled using various treatments which are discussed on the Anaemia page. This page deals with a form of treatment called erythropoiesis stimulating agents (ESAs), which are used for severe non-regenerative anaemia caused by the CKD.

  • Treating anaemia in a CKD cat with an ESA when appropriate is worthwhile. ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 state "there is evidence that treatment with erythrocyte-stimulating agents (ESAs) may improve quality of life and potentially survival in some cats with CKD."


What are Erythropoiesis Stimulating Agents


 

The kidneys produce a hormone called erythropoietin which stimulates the bone marrow to make red blood cells. This process is known as erythropoiesis.

 

As the kidneys fail in CKD, they cannot produce enough erythropoietin, so the bone marrow is not stimulated, blood cells are not produced, and a particular type of anaemia called non-regenerative anaemia results. Non-regenerative anaemia may have other causes (including other CKD-related problems such as uraemic toxins), as discussed on the Anaemia page, but this is the most common reason for it in CKD cats.

 

Cats with mild anaemia (regenerative or non-regenerative) can be offered various treatments (see the Anaemia page). However, cats with severe non-regenerative anaemia (PCV or HCT below 20%) caused by a lack of erythropoietin often need artificial erythropoietin in order to control their anaemia. The various forms of artificial erythropoietin are collectively known as erythropoiesis stimulating agents (ESAs). They are usually very effective, and in fact one human study, Anemia management and the delay of chronic renal failure progression (2003) Rossert J, Fouqueray B & Boffa JJ Journal of the American Society of Nephrology 14 pp173-177 found that "treatment with epoetin may slow the progression of chronic kidney disease."

 

Unfortunately, after a few months of use, a small percentage of cats may develop a reaction to ESAs (commonly referred to on CKD support groups as the antibody reaction, but which in its worst form is known as pure red cell aplasia or PRCA) which stops them working. However, this is by no means inevitable; with the most commonly used ESA, darbepoetin (Aranesp), it only happens to 10% of cats.

 


Types of Erythropoiesis Stimulating Agents


 

There are two categories of ESA which have been used in CKD cats:

 

Feline Erythropoietin (rfEpo)


Feline erythropoietin has been developed in small quantities for use in clinical trials. There has also been a study into the feline erythropoietin gene. Unfortunately, neither of these treatments is commercially available at present (June 2016), and that is unlikely to change. There is a brief overview of these treatments below, but this page focuses primarily on the treatments which are currently available for you to use, in the form of human erythropoietin.

 

Human Erythropoietin (rhEpo)


Since feline erythropoietin is not commercially available, CKD cats in need of erythropoietin supplementation will be using human erythropoietin to enable their cat's bone marrow to continue to make red blood cells. 

 

There are a number of different types of human erythropoietin available, as follows:


Which Erythropoiesis Stimulating Agent to Choose


The main problem with the use of any human ESA in cats is that a small percentage of cats develop an antibody reaction to the treatment. This is discussed below and is not as gruesome as it sounds, but obviously it is something you want to avoid if at all possible.

 

Epoetin alfa was the subject of the first study into the use of ESAs in cats back in 1998, and has been used in CKD cats for many years (I used it myself for Thomas in 1999). However, these days darbepoetin (Aranesp), which has been the subject of more feline studies, is the treatment of choice at US vet schools, primarily because it is the ESA which is least likely to cause the antibody reaction. ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 state "the use of darbepoetin alfa is preferred over epoetin alfa as it appears significantly less likely to induce PRCA."

 

I think darbepoetin (Aranesp) is the best choice and is what I would choose to use for my own cats. However, if you cannot afford darbepoetin (it costs more upfront) or if your cat's need is urgent and you can obtain one of the other ESAs more quickly, you could consider using one of the other ESAs. You can always switch to darbepoetin later. If you have already started another ESA but would like to switch to darbepoetin, read how to do this here.

 


When to Use Erythropoiesis Stimulating Agents


 

A small number of vets seem to rush to use ESAs as soon as a cat is diagnosed with anaemia, even if the cat is barely anaemic. The majority, however, seem to be reluctant to use ESAs because of the risk of an antibody reaction. In my opinion, neither of these responses is appropriate.

 

Depending upon the severity, type and cause of the anaemia, there are other treatments which may be more suitable for your cat and which are certainly cheaper. See the Anaemia page for more information. In some cases, however, an ESA is an appropriate choice. There are a number of factors to consider:

 

General Criteria


  • The PCV or HCT should not have fallen suddenly, e.g. from 24% one week to 17% the next. Most cats with anaemia caused by CKD become anaemic gradually which means their bodies have had time to adapt to it to some degree. A sudden fall in PCV for a cat in IV fluids is slightly different: PCV may fall quite a lot in cats on IV fluids, who are usually dehydrated when first placed on a drip, which makes the PCV level look artificially high. The PCV level once the cat is properly hydrated is therefore the more accurate reading. However, if your cat develops sudden, severe anaemia but has not been on IV fluids, ask your vet to check for other causes of anaemia. One common cause in such cases is gastrointestinal bleeding.

  • Usually (but not always, particularly in older cats) the CKD will be relatively advanced, with creatinine over 5 mg/dl (US) or 450 µmol/L (international), at least at initial diagnosis. This indicates that the kidney damage is probably more severe, and therefore the kidneys are unlikely to be producing sufficient erythropoietin on their own. Thomas actually needed an ESA regularly when his creatinine level was only 3.57 mg/dl (USA) or 316 µmol/L (international), but his creatinine level had been a lot higher at initial diagnosis.

Severity of Anaemia and Symptoms


Assuming the anaemia is indeed non-regenerative anaemia caused by a lack of erythropoietin, you then need to consider how severe the anaemia is:

  • Some experts believe how the cat is acting and feeling are also important. ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 state "ESA therapy should be considered in cats with persistent CKD-associated anaemia that is symptomatic; or if the PCV is persistently <20%."

Summary


 If your cat has a PCV level below 20% which has not developed suddenly, and/or if your cat has signs of severe anaemia, such as breathlessness, lethargy or severe loss of appetite, you should talk to your vet about starting an ESA.

 

Ideally your vet will have been able to check that your cat has non-regenerative anaemia via a reticulocyte test, but I would not wait the necessary five days to do this if your cat is very sick, especially if your cat's CKD is relatively advanced (creatinine over 5 mg/dl (US) or 450 µmol/L (international)).

 


Using Erythropoiesis Stimulating Agents


There are a number of different types of human erythropoietin available. You can read about the pros and cons of each one and how to measure and dose them under their individual categories. There are also some important usage guidelines applicable to all ESAs, including information on correct storage and possible side effects.


Darbepoetin alfa: Aranesp


 

Since this is the best choice for most cats, I am covering it first.

Darbepoetin Alfa (Aranesp): Overview


Aranesp (darbepoetin alfa). is made by Amgen. It is an erythropoiesis stimulating protein (so it is slightly different to the other ESAs which are all recombinant human erythropoietins or rhEpo), and contains five N-linked oligosaccharide (carbohydrate) chains rather than three. This is supposed to give it greater metabolic stability, and may be why it is less likely to cause the antibody reaction. Darbepoetin alfa: a new therapy for the management of anaemia associated with chronic kidney disease (2002) Lindberg J Expert Opinion on Biological Therapy 2(8) pp977-84 discusses the use of darbepoetin alfa in human patients.

 

In 2005 a number of US veterinary schools, including North Carolina State University, University of Penn, Animal Medical Center in New York, University of California at Davis, and the University of California Veterinary Medical Center (UCVMC), began using darbepoetin alfa on an informal basis.

 

By 2010 darbepoetin had been used on approximately 50-60 cats at UCVMC, with favourable results. As a result, UCVMC now tends to use darbepoetin as a first line treatment for most cats (except when they expect the need for an ESA to be short-lived because the cat is an acute case, in which case they may use epoetin alfa (Epogen) instead since it may show a quicker response time). The Animal Medical Center in NYC also uses darbepoetin as a first line treatment, and has found the antibody rate to be around 10%. Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011 discusses AMC's experiences with darbepoetin.

 

There are two formulations of darbepoetin alfa, one containing human albumin, and one without human albumin and known as HSA-free. The HSA-free form of Eprex (a type of epoetin alfa available in Europe) had a higher antibody reaction rate. I do not know if this is also likely to be true for darbepoetin but it is a possibility. However, some vets feel that ESAs containing albumin may also carry an increased risk of an adverse reaction, since the albumin is a human product. It now appears that the only version which is widely available in the USA is the HSA-free version, because humans apparently had a lower reaction to this, so in practice this is probably what you will be offered. I would not worry too much about this.

 

Although darbepoetin is probably the best choice, certainly from the antibody reaction perspective, there are a few possible downsides to be aware of:

  1. It costs a lot more than epoetin alfa (Epogen or Eprex). It needs to be given less frequently, so the cost should even out over time, but the initial outlay will be much higher, which is a concern for many people.

  2. It may take longer to start taking effect. This is not the case for all cats, but it could be a problem if your cat's anaemia is particularly severe and you want to start making a difference as quickly as you can.

  3. It can be hard to work out the best dose for an individual cat so there are a number of different protocols Some cats respond too well to Aranesp, which carries risks too.

Although I myself used epoetin alfa in the form of Eprex for Thomas, I think overall darbepoetin is the best choice and is what I would choose to use for my cats these days. However, if cost is a factor, or if your cat has critically severe anaemis and you can obtain one of the other ESAs more quickly, then I would consider using that instead.

 

If you have already started another ESA but would like to switch to Aranesp, read how to do this here.

 

Darbepoetin Alfa (Aranesp): What and Where to Buy


Some vets think ESAs cost a fortune and therefore may not bother to prescribe them. However, if you know where to look, it is usually possible to obtain these products at more reasonable prices..

 

Even if you do not need to use ESAs at the moment, I would suggest you read below on how and where to obtain them, especially if your cat is anaemic, so you can obtain one quickly should your cat's anaemia worsen to the point where you need to use one.

 

Darbepoetin is more expensive than epoetin alfa; but since you need to use it less frequently, over time the price difference is not as bad as it appears.

 

Because it is a human medication, there are a number of different strengths of darbepoetin available, so make sure you buy the correct size for your cat (see below). It is sold as a single use human medication, but the single use sizes are routinely used for multiple doses in veterinary medicine.

Darbepoetin Alfa (Aranesp): What and Where to Buy USA


For cats you need the 25mcg/ml vial size. This size of vial contains approximately 6-10 feline doses, depending upon the size of your cat and which dosing regimen you use. However, since it does not need to be administered as frequently as epoetin alfa (Epogen), the cost should work out about the same overall. You will need a prescription from your vet.

 

It is usually easier to obtain price quotations if you have the NDC (National Drug Code) for the products you are interested in:

  • Single vial of Aranesp 25mcg/ml: NDC 55513-002-01

  • Pack of four vials of Aranesp 25mcg/ml: NDC 55513-002-04

 

You will usually also need U100 insulin 0.3 or 0.5cc syringes which you use to draw the darbepoetin from the vial in cat-sized doses. You can obtain insulin syringes from your local pharmacy (you will need a prescription).

 

Buying Darbepoetin From Local Pharmacies


You should be able to obtain darbepoetin (Aranesp) for around US$25-50 a week initially, reducing to US$25-50 every 3-4 weeks as your cat stabilises. You could try using a discount card. Sadly not many pharmacies seem to accept discount cards for ESAs, but you can definitely use the Walgreens Prescription Savings Club card, see below. See Cheap Supplies USA for information on other discount cards.

 

Some local pharmacies in the USA can order Aranesp with overnight delivery for around US$220-250 per 25 mcg vial. Hospital pharmacies often have darbepoetin (Aranesp) in stock and may well be prepared to sell it to you with a prescription.

 

Walgreens

Walgreens can usually obtain darbepoetin (Aranesp) for you overnight. The full price is US$255, but if you join their Prescription Savings Club, you should be able to obtain Aranesp for around US$191 a vial plus the cost of club membership the first time you order it. The procedure is as follows:

 

1.    Visit Walgreens. Be sure to use the link given, it will save you time and ensure you are in the correct place.

 

2.   Type Aranesp into the Price Your Drugs box on the left (you will need to allow cookies), then click search. Choose Aranesp 25 MCG/ML vial, 1.0ml package.

 

3.  One vial costs US$190.99 (June 2016). Print the page displaying the price and take it to your local Walgreens along with your cat's prescription.

 

4.   Apply for your cat to join the Walgreens discount scheme, the Prescription Savings Club. This costs US$35 a year for family membership, which includes cats, or US$20 a year for an individual (i.e. your cat). If you are already a member, you should be able to add your cat to your family membership.

 

5.    Ask the pharmacist to order the Aranesp (and suitable syringes, if you need them and have a prescription for them) for you at or near the price on the page you have printed. Some branches will sell at this price, some may occasionally sell it for less, others may argue and try to charge more. You may also find that the branch you try is reluctant to sell one vial only. In such cases, try another branch, or ask to speak to the head pharmacist, or if your need is not urgent, return another day when with luck a more helpful person will be available.

 

6.    Wait for the Aranesp to arrive (it usually arrives the next day) and go and collect it.

 

Buying Darbepoetin Online


It may be cheaper to buy darbepoetin online; the downside is that the cheapest online supplier (Walmart Specialty Pharmacy) may take up to a week to ship the first time you place an order. Also, some online retailers (not those mentioned here) insist you buy at least four vials, which cost US$750 or more.

 

Darbepoetin must be kept cold, so overnight chilled shipping is necessary.

 

Walmart Specialty Pharmacy

Sells darbepoetin (Aranesp) for around US$180-210 per 25mcg/ml vial including overnight refrigerated shipping, syringes and often a sharps container. The website does not show prices so this is the approximate price but for reference, several members of Tanya’s Support Group paid US$194.50 in April 2016 for the Aranesp, overnight shipping and syringes.

 

Note: this is Walmart Specialty Pharmacy, which deals with complex therapies such as ESAs. You must use the link given above or the dedicated phone number (1-877-453-4566) to get these prices, which are not available at the standard online Walmart pharmacy, and are unlikely to be available at your local Walmart Pharmacy.

 

The first time you order it will take around a week to complete the registration process. Walmart will contact you to ask for your preferred delivery date, so you can be sure you are there to receive your order. If you prefer, it can be shipped to your local Walmart pharmacy for you to collect. If you opt for this, ask them to ensure that your local pharmacy will keep it chilled until you can collect it

 

Thriving Pets

Sell darbepoetin (Aranesp) for US$229.95 a vial or US$219.95 per vial if you buy four vials, plus the cost of chilled shipping (around US$15-25 depending upon where you live). They normally ship overnight, but if your need is urgent, call them first to check they have it in stock.

 

Darbepoetin Alfa (Aranesp): What and Where to Buy UK


In the UK you would normally choose the 20mcg/0.5ml prefilled syringes for a cat. You should be able to obtain darbepoetin (Aranesp) for around Ł5-10 a week initially (it depends how big your cat is), reducing to Ł5-10 every 3-4 weeks as your cat stabilises.

 

Unfortunately, UK vets are now allowed to charge to write you a prescription to use elsewhere. My vet charges Ł12.50. If your vet does this, make sure your prescription is a repeat one so you don't have to pay for a new prescription every month or so.

 

Pharmplex Direct

Sells four 20mcg/0.5ml prefilled syringes for Ł170 inc VAT and shipping (I do not know if they ship chilled as they should). Apparently they will also ship to some other EU countries. Check with your vet whether this syringe formulation is suitable.

 

You can also ask your local chemist if they can help (Lloyds Pharmacy was able to order Eprex for me, and I imagine they could order Aranesp too). Your vet may also be able to order it for you. It can also be worth checking with your local hospital pharmacy, which may be able to help more quickly and at a reasonable price.

 

Aranesp must be kept cold, so overnight chilled shipping is necessary.

 

Darbepoetin Alfa (Aranesp): What and Where to Buy Canada


In Canada you would normally choose the 20mcg/0.5ml prefilled syringes or the 25mcg/0.4ml vials for a cat.

 

Walmart in Canada

Apparently sells Aranesp. In November 2008 one person was quoted CA$133 for four vials of the 25 mcg 0.4ml.

 

Benefit RX

Sells Aranesp for US$285.72 for four syringes of the 20mcg 0.5ml. I do not know anybody who has used them yet.

 

You could also ask your vet for a price.

 

Aranesp must be kept cold, so overnight chilled shipping is necessary.

 

Darbepoetin Alfa (Aranesp): Where to Buy Australia and New Zealand


Aranesp is supplied in Australia by Amgen Australia Pty Ltd Level 7, 123 Epping Road, North Ryde. NSW 2113 Tel (02) 9870 1333.

 

Darbepoetin Alfa (Aranesp) Dosages


Please also read the general information on how to give ESAs and what else to be aware of when giving ESAs below.

 

Darbepoetin Alfa (Aranesp): Starting Dosage


There are a number of possible dosing protocols for darbepoetin, as shown below. Remember, darbepoetin is given less frequently than epoetin alfa or epoetin beta, usually only once a week to start with.

 

Because darbepoetin is given less frequently than epoetin alfa or epoetin beta, it may also take longer to take effect for some cats. Therefore, if your cat has very severe anaemia before starting darbepoetin (e.g. PCV below 15%), you may need to consider a blood transfusion to tide your cat over until the darbepoetin begins to work. Some people whose cat's PCV is low (e.g. 15-17%) use epoetin alfa to start with because in principle it takes effect more quickly, and then they switch to darbepoetin later. There is information on this here.

 

Always check PCV before you give the next shot in case your cat is particularly responsive. If your cat's PCV does rise too quickly (more than a 3% increase in PCV or HCT per week), ask your vet about reducing the dose or giving the darbepoetin less frequently. If your cat's PCV does not seem to be rising, click here for tips on what to do.

 

Overall it appears that many cats respond well to darbepoetin, and in some cases their PCV rises too quickly. It may therefore be better to start with a low dose, particularly if your cat is small; but be guided by your vet. It is important to adapt the dosing schedule to what works for your cat.

 

Recommendation

Cat Weight

Source

Dosage

5 lb

2.27 kg

7.5 lbs

3.4 kg

10 lb

4.5 kg

12.5 lbs

5.7kg

Plumb's (2011)1

0.45 mcg per kg* of cat

1.0 mcg

1.5 mcg

2.0 mcg

2.56 mcg

Dr DiBartola

0.25-0.5 mcg per kg of cat

0.57-1.14 mcg

0.85-1.7 mcg

1.125-2.25 mcg

1.425-2.85 mcg

Animal Medical Center, NYC2

1 mcg per kg of cat

2.27 mcg

3.4 mcg

4.5 mcg

5.7 mcg

ISFM3

1 mcg per kg of cat

2.27 mcg

3.4 mcg

4.5 mcg

5.70 mcg

UC Davis4

6.25 mcg per cat

6.25 mcg

6.25mcg

6.25mcg

6.25 mcg

Total Range

0.25-1 mcg

0.57 -6.25 mcg

0.85-6.25 mcg

1.125-6.25 mcg

1.425-6.25 mcg

*A kg is 2.2 lbs

 

1The dose recommended by Plumb's Veterinary Drug Handbook (7th edition) (2011) is the same as the recommended dose for human patients on darbepoetin.

 

2Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 states that this dosage is used at the Animal Medical Center in NYC because 62% of cats in their database responded to this dose when it was given once weekly, whereas only 12% responded to a dose of 0.45 mcg/kg once weekly.

 

3ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 recommend this dose once weekly initially.

 

4Those giving the same dose to every cat regardless of weight, such as the University of California at Davis, usually give 6.25 mcg along with iron in the first week, but then space the Aranesp out as far as possible, usually giving it once every 2-4 weeks. I have heard from a number of people who found their cat's PCV increased too quickly on this dose.

 

I have also heard from a couple of people who gave their cats 5 mcg subcutaneously each week. Again, one of these cats had a PCV that was increasing rather quickly.

 

Personally, I think I would start with the 1 mcg per kg of cat dosing protocol.

 

Remember, these are starting doses. Please read below for maintenance doses. Also see below for how to measure the darbepoetin and how to administer it.

 

Darbepoetin Alfa (Aranesp): How to Measure


Because it is a human medication, darbepoetin needs to be divided into cat-sized doses. If you are giving darbepoetin at home (as many people do), you will need to learn how to do this yourself. It's best to let your vet measure the dose the first time and show you how to do it. They can also show you how to inject it. However, here is a quick guide in case you forget.

 

USA


  • You will normally purchase the 25mcg/ml vial size.

  • In other words, your vial contains one ml of liquid, which contains 25 mcg of darbepoetin.

  • Let's take the example of a 10lb cat who is being given 1 mcg of darbepoetin per kg of cat. If you check the table above, you will see that a 10lb cat weighs 4.5kg, so this cat needs 4.5 mcg each time:

  • Your vial contains 25 mcg, so it contains 5.5 doses altogether (25mcg divided by 4.5mcg).

  • You have one ml of liquid in your vial, so you need to divide this by 5.5 (the number of doses it contains altogether), which results in 0.18 ml. Therefore you need to withdraw a little under 0.20ml (20% or one fifth) of the medication each time you give it.

  • Most people do this using an insulin syringe. Instructions for use is an instruction leaflet from Amgen, the manufacturer of Aranesp, which explains how to draw Aranesp from the vial. You will need syringes to draw and give the medication. Most people use human insulin syringes. These are sold as U100 syringes, which means there are 100 units in 1 ml. They are usually available in three sizes, 1 ml (100 units), 0.5ml (50 units) or 0.3 ml (30 units), and most people use 0.5 or 0.3 ml syringes for cats (see above for sources). Unfortunately, insulin units are not the same as Aranesp units so working out the dose can be confusing. As a general guide, one insulin unit is 0.01ml; so each unit on an insulin syringe is 0.01ml; but the safest thing is to ask your vet to measure out the doses for you and show you how much you need to give.

  • Although the leaflet mentions that Aranesp should only be used once, because cats need tiny doses and Aranesp is expensive, most people re-use the vial with no problems, as long as they store it properly (see below).

UK


  • You will normally purchase the 20mcg/0.5ml size syringe.

  • In other words, your syringe contains 0.5ml of liquid, which contains 20 mcg of darbepoetin.

  • Let's take the example of a 10lb cat who is being given 1 mcg of darbepoetin per kg of cat. If you check the table above, you will see that a 10lb cat weighs 4.5kg, so this cat needs 4.5 mcg each time.

  • Your syringe contains 20mcg, so it contains around 4.5 doses altogether (20mcg divided by 4.5mcg).

  • You have 0.5 ml of liquid in your syringe, so you need to divide this by 4.5, which results in 0.11 ml. Therefore you need to withdraw a little over 10% or one tenth of your medication each time you give it.

  • Ask your vet for the best way to remove what you need from the syringe. You may need to attach a needle to it and give the required amount, then remove the needle and use a new needle the next time you give it. Alternatively, you may have to transfer the contents into a sterile container, which is not exactly easy. The usual method with Eprex, which also comes in syringes, seems to be to transfer the contents to an empty sterile vial, and measure it from there with a small insulin syringe.

  • Instructions for use is an instruction leaflet from Amgen, the manufacturer of Aranesp, which explains how to draw Aranesp from a vial. You will need syringes to draw and give the medication. Most people use human insulin syringes. These are sold as U100 syringes, which means there are 100 units in 1 ml. They are usually available in three sizes, 1 ml (100 units), 0.5ml (50 units) or 0.3 ml (30 units), and most people use 0.5 or 0.3 ml syringes for cats (see above for sources). Unfortunately, insulin units are not the same as Aranesp units so working out the dose can be confusing. As a general guide, one insulin unit is 0.01ml; so each unit on an insulin syringe is 0.01ml; but the safest thing is to ask your vet to measure out the doses for you and show you how much you need to give.

  • Although the leaflet mentions that Aranesp should only be used once, because cats need tiny doses and Aranesp is expensive, most people re-use the vial with no problems, as long as they store it properly (see below).

Darbepoetin Alfa (Aranesp): Maintenance Dosage


It is very important to check your cat's PCV level before you give a dose of darbepoetin, in case your cat's PCV is rising faster than expected.

 

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 state that once target PCV is reached, the suggested maintenance dose is either the same dose (1 mcg per kg body weight) given every 2-3 weeks or a reduced dose of 0.5 mcg per kg body weight once weekly, depending upon the cat's PCV levels.

 

Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011's recommendation once target PCV is reached is "decreasing the frequency of administration to every two or three weeks." They go on to say "Once an administration frequency of every three weeks is achieved, we lower the dose to 0.45 μg/kg every three weeks or the lowest dose that maintains an adequate PCV."

 

Darbepoetin Alfa (Aranesp): Dosage When Switching From Another ESA


Some people start off by giving epoetin alfa to their cat, because their cat has very severe anaemia and epoetin alfa tends to work faster than darbepoetin. Once their cat's anaemia is less severe, they may wish to switch to darbepoetin.

 

Other people may start with epoetin alfa (Epogen, Procrit or Eprex) because that is what their vet offers or what they can obtain quickly, but they then decide to switch to darbepoetin because they wish to reduce the risk of the antibody reaction. This section explains how do to this. However, if you wish to switch from another ESA to Aranesp because you think your cat has developed the antibody reaction to the other ESA, please read here.

 

In Anemia of chronic kidney disease (2009) CVC in San Diego Proceedings Dr CL Langston states "For patients being converted from rHuEPO therapy, 200 U of rHuEPO is equivalent to 1 µg of darbepoetin." Plumb's Veterinary Drug Handbook (7th edition) (2011) similarly states that you can convert the dosage by dividing the total weekly number of Epogen or Procrit units by 200. This will then give you the equivalent weekly dose of Aranesp.

 

For example, a 10 lb (4.5kg) cat would typically receive 450 units of Epogen three times a week, so the weekly total is 1350. Divide the 1350 by 200 and you get 6.75, so the cat would receive 6.75mcg of Aranesp once a week. If you look at the suggested dosages in the table above, this is a relatively high dose for a 10lb (4.5kg) cat. Be guided by your vet.

 

Darbepoetin Alfa (Aranesp) Usage Guidelines


Please see the additional usage guidelines below which apply to all ESAs.

 


Epoetin Alfa (Epogen, Procrit or Eprex)


Epoetin Alfa (Epogen, Eprex or Procrit): Overview


There are three types of the epoetin alfa variant of recombinant human erythropoietin (rhEpo):

 

Epogen (USA)

Made and sold by Amgen, Epogen is used in the USA for the treatment of anaemia in human CKD patients on dialysis.

 

Procrit (USA)

This is the same product as Epogen and is also made by Amgen, but it is sold by Ortho Biotech in the USA for the treatment of anaemia in human CKD patients who are not on dialysis. It is also commonly used for cancer patients with anaemia caused by chemotherapy.

 

Eprex (UK and other countries)

This is the version of epoetin alfa made by Janssen-Cilag in Europe for the treatment of anaemia in both dialysis and non-dialysis human patients. It is also used for human patients with anaemia from other causes, such as chemotherapy. Whilst Eprex is a form of epoetin alfa, it is not identical to Epogen/Procrit.

 

Epogen and Procrit have been used in CKD cats in the USA for many years. Epogen was the subject of a clinical trial, Use of recombinant human erythropoietin for management of anaemia in dogs and cats with renal failure (1998) Cowgill LD, James KM, Levy JK, Egrie JC, Browne JK, Miller A, Lobinger R Journal of the American Veterinary Medical Association 212 pp521-8), in which 30% of cats developed the antibody reaction.

 

Eprex has been used in CKD cats in the UK for many years - I myself used it for Thomas in 1999 with no problems. Erythropoietin-associated PRCA: still an unsolved mystery (2006) Schellekens H, Jiskoot W Journal of Immunotoxicology 3(3) pp123-130 explains that the currently available HSA-free form of Eprex, which contains polysorbate 80 instead of albumin in order to comply with European regulations, had a higher antibody reaction rate.

 

Epoetin Alfa (Epogen, Procrit or Eprex): What and Where to Buy


Some vets think ESAs cost a fortune and therefore may not bother to prescribe them. However, if you know where to look, it is usually possible to obtain these products at more reasonable prices..

 

Even if you do not need to use ESAs at the moment, I would suggest you read below on how and where to obtain them, especially if your cat is anaemic, so you can obtain one quickly should your cat's anaemia worsen to the point where you need to use one.

 

Epoetin alfa is sold as a single use human medication, but the single use sizes are routinely used for multiple doses in veterinary medicine.

Epoetin Alfa (Epogen or Procrit): What and Where to Buy USA


Most people use the 2,000 iu/Ml strength of Epogen. You may be able to use the 3000 iu/Ml or 4000 iu/Ml strengths at a pinch if your cat is on the bigger side, but you definitely do not want the 10,000 iu/Ml and higher strengths, because it is too difficult to obtain cat-sized doses from these.

 

The 2000 iu/Ml strength vial contains approximately 4-8 feline doses, depending upon the size of your cat. You will need a prescription from your vet.

 

You will usually also need U100 insulin 0.3 or 0.5cc syringes which you use to draw the Epogen or Procrit from the vial in cat-sized doses. You can obtain insulin syringes from your local pharmacy (you will need a prescription).

 

Buying Epogen or Procrit Locally


You should be able to obtain epoetin (Epogen or Procrit) for around US$25-50 a week initially (precise cost depends upon the size of your cat), reducing to US$25-50 every 3-4 weeks as your cat stabilises.

 

You could try using a discount card. Sadly not many pharmacies seem to accept discount cards for ESAs, but you can definitely use the Walgreens Prescription Savings Club card, see below. See Cheap Supplies USA for information on other discount cards.

 

Some local pharmacies in the USA can order Epogen or Procrit with overnight delivery for around US$40 per 2000 iu/Ml vial. Hospital pharmacies often have Aranesp in stock and may well be prepared to sell it to you with a prescription.

 

Walgreens

Walgreens can usually obtain Epogen for you overnight. If you join their Prescription Savings Club, you should be able to obtain it for around US$35-40 a vial plus the cost of club membership the first time you order it. The procedure is as follows:

 

1.   Visit Walgreens. Be sure to use the link given, it will save you time and ensure you are in the correct place.

 

2.   Type Epogen into the Price Your Drugs box on the left (you will need to allow cookies), then click search. Choose Epogen 2,000 units/ml vial, 1.0 ml package. One vial costs US$36.99 (June 2016) and two vials cost US$69.98 (June 2016). Print the page displaying the price and take it to your local Walgreens along with your cat's prescription.

 

3.   Apply for your cat to join the Walgreens discount scheme, the Prescription Savings Club. This costs US$35 a year for family membership, which includes cats, or US$20 a year for an individual (i.e. your cat). If you are already a member, you should be able to add your cat to your family membership.

 

4.    Ask the pharmacist to order the Epogen (and suitable syringes, if you need them) for you at or near the price on the page you have printed. Some branches will sell at this price, some may occasionally sell it for less, others may argue and try to charge more. You may also find that the branch you try is reluctant to sell one vial only. In such cases, try another branch, or ask to speak to the head pharmacist, or if your need is not urgent, return another day when with luck a more helpful person will be available.

 

5.    Wait for the Epogen to arrive at the branch (it usually arrives the next day) and go and collect it.

 

Buying Epogen or Procrit Online


Walmart Specialty Pharmacy

Sells Epogen for around US$50 per 2,000 iu vial, including overnight refrigerated shipping, syringes and often a sharps container. The website does not show prices so this is the approximate price but for reference, a member of Tanya’s Support Group paid US$50 in September 2015 for Epogen, overnight shipping and syringes.

 

Note: this is Walmart Specialty Pharmacy, which deals with complex therapies such as ESAs. You must use the link given above or the dedicated phone number (1-877-453-4566) to get these prices, which are not available at the standard online Walmart pharmacy, and are unlikely to be available at your local Walmart Pharmacy.

 

The only real downside is that it can take around a week to complete the registration process the first time you order. Walmart will contact you to ask for your preferred delivery date, so you can be sure you are there to receive your order. If you prefer, it can be shipped to your local Walmart pharmacy for you to collect. If you opt for this, ask them to ensure that your local pharmacy will keep it chilled.

 

Thriving Pets

Sell Epogen for US$47.95 for a 2000 iu vial or US$45 per vial if you buy five vials or US$30 per vial if you buy ten. You also have to pay the cost of chilled shipping (around US$15-25 depending upon where you live). They normally ship overnight, but if your need is urgent, call them first to check they have it in stock.

 

Epoetin Alfa (Eprex): Where to Buy UK


Eprex is available in various strengths but you do not want the 10,000iu/ml and higher strengths, because it is too hard to obtain cat-sized doses from these.

 

You will usually be offered the 1,000iu/0.5ml strength, which confusingly is the same as the 2,000iu/mL strength, but half the amount. Your vet should be able to advise you on which strength to buy.

 

The 1000 iu/0.5mL strength vial contains approximately 2-4 feline doses, depending upon the size of your cat. You will need a prescription from your vet.

 

Eprex is available from chemists, although you will need a prescription from your vet, and the chemist may have to order it in for you (usually it can be delivered in a day or two). In April 2011 Boots gave me a quote for 12 vials of 1000 iu/0.5mL Eprex of Ł107.51, but needed five working days to get them. Lloyds Pharmacy told me they could only get the 2000 iu/0.5mL strength, for around Ł100 for six vials, but didn't know the timeframe. The best thing to do is to call pharmacies in your neighbourhood to check prices and delivery timeframes. One lady wrote to tell me that she was able to obtain Eprex very quickly from her local hospital pharmacy.

 

Epoetin Alfa (Eprex): Where to Buy Canada


Eprex is available in various strengths but you do not want the 10,000 iu/ml and higher strengths, because it is too hard to obtain cat-sized doses from these.

 

You will usually be offered the 1,000 iu/0.5mL strength, which confusingly is the same as the 2,000iu/mL strength, but half the amount. Your vet should be able to advise you on which strength to buy.

 

Walmart in Canada

Sells six vials of 1000 iu/0.5mL strength Eprex for around CA$110 (2015).

 

Eprex should also be available from local pharmacies, particularly hospital pharmacies. In November 2011, one person in the Toronto area was able to obtain six vials 1000 iu/0.5mL strength Eprex from her local pharmacy for CAN$119. In November 2014 one person was able to obtain six vials of the 4000 iu strength for CAN$400.

 

Epoetin alfa (Eprex): Where to Buy Australia


Your best bet is probably a hospital pharmacy, with a prescription from your vet.

 

Epoetin alfa (Epogen, Procrit or Eprex) Dosages


 

Epoetin Alfa (Epogen, Procrit or Eprex) Starting Dosage


It is generally accepted that the usual starting dose is 100 iu per kg of cat, given subcutaneously three times a week. Therapeutic implications of recent findings in feline renal insufficiency - proceedings (2009) Scherk M CVC in Kansas City Proceedings recommends this dosage. Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) Chew D A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference also gives this dosage.

 

Plumb's Veterinary Drug Handbook used to recommend a higher starting dose for cats with severe anaemia, i.e. for cats with a PCV level below 14%, the 2008 edition of Plumb's suggested using up to 145 units per kg (2.2lbs) of bodyweight subcutaneously three times a week.

 

Plumb's also used to suggest that a lower dose of 48.4 units per kg (2.2lbs) of cat, given subcutaneously three times a week, might be advisable for cats with hypertension (high blood pressure) before starting epoetin alfa, or if hypertension appears after starting. Neither of these recommendations appear in the 2011 edition of Plumb's. Talk to your vet about the best approach for your cat.

 

When giving the ESA three times a week, I would simply give it every other day with one day left over e.g. Mon/Wed/Fri or Tue/Thur/Sat. It is very important to check your cat's PCV once each week and before you give that day's dose, in case your cat's PCV is rising faster than expected.

 

The exact amount to be given depends upon the strength which you are using. These medications are sold in varying strengths, but the larger sizes (10,000iu/mL upwards) are impossible to give in cat-sized amounts, so try to use nothing larger than the 3000iu/mL strength.

 

Most people in the USA use the 2000iu/1ml strength, whilst most people in the UK use the 1000iu/0.5mL strength. 

 
 

If Standard Dosage of 100 units per kg in Weight is Prescribed

 

Cat Weight

 

5 lb

2.27 kg

7.5 lb

3.4 kg

10 lb

4.5 kg

12 lb

5.45kg

Epoetin alfa Strength

Needs

227 units

Needs

340 units

Needs

450 units

Needs

545 units

1000 iu/0.5 ml*

0.113 ml

0.1835 ml

0.225 ml

0.273 ml

2000 iu/1ml*

0.113 ml

0.1835 ml

0.225 ml

0.273 ml

3000 iu/1ml

0.075 ml

0.122 ml

0.15 ml

0.18 ml

4000 iu/1ml

0.056 ml

0.09 ml

0.1125 ml

0.137 ml

*The 1000iu strength contains 1000iu but in 0.5mL so it is the same strength as the 2000iu/mL

Remember, these are starting doses. Please read below for maintenance dosages.

 

Also see below for how to measure the epoetin and how to administer it.

 

Epoetin Alfa (Epogen, Eprex or Procrit): How to Measure


Because it is a human medication, epoetin needs to be divided into cat-sized doses. If you are giving epoetin at home (as many people do), you will need to learn how to do this yourself.

 

Calculating how much to use can be very confusing! Normally you will be told how many units to give, based on your cat's weight. 1 cc of the 3000iu/mL strength contains 3000 units of medication; 1 cc of the 2000iu/mL strength contains 2000 units; and so on. We used the 1000iu strength of Eprex, which (just to confuse matters) is slightly different: it contains 1000iu but in 0.5mL so it is the same strength as the 2000iu/mL although it sounds different. Whichever you use is less important than giving the correct amount.

It's best to let your vet measure the dose the first time and show you how to do it. They can also show you how to inject it. However, here is a quick guide in case you forget.

 

As you can see, the dosages are pretty precise, but your vet will probably want to round the dose up or down so as to make it easier for you to measure it.

 

USA


  • You will normally purchase the 2000iu/ml strength.

  • In other words, your vial contains one ml of liquid, which contains 2000 units of epoetin.

  • Let's take the example of a 10lb cat who is being given the standard epoetin starting dose of 100 units per kg of cat. If you check the table above, you will see that a 10lb cat weighs 4.5kg, so this cat needs 450 units (100 x 4.5) of epoetin each time (normally three times a week to start with).

  • Your vial contains 2000 iu/ml, so it contains 4.4 doses altogether (2000 iu divided by 450).

  • You have one ml of liquid in your vial, so you need to divide this by 4.4 (the number of doses it contains altogether), which results in 0.225 ml. Therefore you need to withdraw a little over 0.20ml ( a little over 20% or one fifth) of the medication each time you give it.

  • Instructions for use is an instruction leaflet from Amgen, the manufacturer of Aranesp, which explains how to draw Aranesp from the vial. The procedure is probably similar for Epogen, but be guided by your vet. You will need syringes to draw and give the medication. Most people use human insulin syringes. These are sold as U100 syringes, which means there are 100 units in 1 ml. They are usually available in three sizes, 1 ml (100 units), 0.5ml (50 units) or 0.3 ml (30 units), and most people use 0.5 or 0.3 ml syringes for cats (see above for sources). Unfortunately, insulin units are not the same as Epogen units so working out the dose can be confusing. As a general guide, one insulin unit is 0.01ml; so each unit on an insulin syringe is 0.01ml; but the safest thing is to ask your vet to measure out the doses for you and show you how much you need to give.

     

    Although the leaflet mentions that Aranesp should only be used once, because cats need tiny doses and ESAs are expensive, most people re-use their ESA vial with no problems, as long as they store it properly (see below).

UK


  • You will normally purchase the 1000iu/0.5ml strength

  • In other words, your syringe contains 0.5ml of liquid, which contains 1000 units of epoetin.

  • Let's take the example of a 10lb cat who is being given the standard epoetin starting dose of 100 units per kg of cat. If you check the table above, you will see that a 10lb cat weighs 4.5kg, so this cat needs 450 units (100 x 4.5) of epoetin each time (normally three times a week to start with).

  • Your vial contains 1000 iu/0.5ml, so it contains 2.22 doses altogether (1000 iu divided by 450).

  • You have half a ml (0.5ml) of liquid in your vial, so you need to divide this by 2.2 (the number of doses it contains altogether), which results in 0.225 ml. Therefore you need to withdraw a 0.225ml, or a little under half, of the 0.5ml of medication each time you give it.

  • When we used Eprex, we used the syringe and needle in which the Eprex came, giving half the vial each time. However, I am told that these days the 1,000 iu/0.5ml strength Eprex comes with safety syringes, which only work once. Therefore, if you want to re-use the vial, you have to transfer the contents into a sterile container, which is not exactly easy. The usual method seems to be to transfer the contents to an empty sterile vial, and measure it from there with a small insulin syringe. Unfortunately this often means you end up losing some of the Eprex, but it still works out cheaper than only using a vial once.

     

  •  Instructions for use is an instruction leaflet from Amgen, the manufacturer of Aranesp, which explains how to draw Aranesp from a vial. The procedure is probably similar for Eprex if you decant it into a vial, but be guided by your vet. You will need syringes to draw and give the medication. Most people use human insulin syringes. These are sold as U100 syringes, which means there are 100 units in 1 ml. They are usually available in three sizes, 1 ml (100 units), 0.5ml (50 units) or 0.3 ml (30 units), and most people use 0.5 or 0.3 ml syringes for cats (see above for sources). Unfortunately, insulin units are not the same as Epogen units so working out the dose can be confusing. As a general guide, one insulin unit is 0.01ml; so each unit on an insulin syringe is 0.01ml; but the safest thing is to ask your vet to measure out the doses for you and show you how much you need to give.

Epoetin Alfa (Epogen, Procrit, Eprex) Usage Guidelines


Please see the additional usage guidelines below which apply to all ESAs.

 

Epoetin Alfa (Epogen, Procrit or Eprex) Maintenance Dosage


Many vets reduce dosing frequency to twice a week initially, but may then reduce to once a week or eventually to once every 10-14 days. You may also be able to reduce the amount given to 50-75 units per kg bodyweight. If the anaemia begins to recur at these lower levels or frequencies, you will usually need to increase the amount and/or frequency of the injections (though you should also check for other possible causes, see below).

 

It is very important to check your cat's PCV once each week and before you give that day's dose, in case your cat's PCV is rising faster than expected.

 

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 recommend "50-100 U/kg SC 1-2 times weekly based on PCV."

 

Therapeutic implications of recent findings in feline renal insufficiency - proceedings (2009) Scherk M CVC in Kansas City Proceedings recommends "reduce dose and frequency to 50-75 U/kg SC 2 times/week" for epoetin alfa.

 

In Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference, Dr D Chew states "frequency of administration is reduced to twice a week."

 

Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011 states "Once the target range is attained, an average maintenance dose of 50 to 100 U/kg once or twice weekly is adjusted based on PCV monitoring."

 


Epoetin Beta: NeoRecormon


 

Hoffmann LaRoche make a form of recombinant human erythropoietin (rhEpo) called NeoRecormon. This is epoetin beta, rather than epoetin alfa (Epogen, Eprex or Procrit are all epoetin alfa). As far as I know, NeoRecormon is not available in the USA, but it may be offered to you if you are in Europe.

 

I am not aware of any research into the use of NeoRecormon in cats, but my vet has used it quite often for CKD cats.

 

Epoetin Beta (NeoRecormon): Where to Buy UK


My vet's wholesaler (Dunlops) can get this for them quite quickly, so this might be the quickest way to obtain it.

 

If your vet can't help, you would have to call around your local pharmacies as outlined above for epoetin alfa (Eprex) in the UK. In 2015, one member of my support group paid Ł256 for five vials.

 

Dosage and Usage Guidelines for NeoRecormon


I have only heard from a few people using NeoRecormon. Most people seem to be using it in similar fashion to epoetin alfa, giving it three times a week, but they usually give and 50-100iu per kg of body weight (usually 100iu per kg of bodyweight is used for epoetin alfa).

 

I did find one reference about using it, Veterinary Pharmacology, which suggests the above dose but which also recommends that PCV should increase by 1% a day for the first month (!), which seems inappropriate to me - I would recommend the more usual target increase of 2% a week would be a more suitable goal.

 

Please see the additional usage guidelines below which apply to all ESAs.

 


Giving an ESA: Usage Guidelines


 

Here are the basic guidelines to help you use your chosen ESA as safely and effectively as possible.

How to Give ESAs


These treatments are administered by way of subcutaneous injection, i.e injecting under the skin. Your vet can teach you how to do this so you can give the ESA to your cat yourself at home - most on Tanya's Support Group do this. I used to give Thomas his ESA shot after his sub-Q fluids, a short distance away from the sub-Q shot. ESAs may sting, although Thomas did not react too badly.

 

I am sometimes asked if it is possible to add the ESA to the sub-Q fluids so the cat only has to be injected once. This is not recommended, because it may dilute these extremely important and expensive medications.

 

You will need to draw the correct dose for your cat from the vial or syringe before you inject it. See above for dosages for darbepoetin and epoetin, and for tips on how to measure the dose for darbepoetin and for epoetin.

 

Even if you give the ESA at home, you will still have to visit the vet at regular intervals (once a week initially), in order to monitor your cat's PCV level and blood pressure; but once the cat is on a maintenance dose, less frequent checks are required (every 4-6 weeks). See below for more on monitoring.

 

Building Blocks


In order to maximise the chances of your chosen ESA working properly, you need to add a couple of building blocks:

 

Iron Supplements


Iron is important for CKD cats. This is because, according to Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40, "Iron deficiency is present in 25–38% of anemic people with CKD", and Iron status of cats with chronic kidney disease (2015) Gest J, Langston C & Eatroff A Journal of Veterinary Internal Medicine 29 pp1488-1493 found "Total iron binding capacity in this population of cats with chronic kidney disease was significantly lower than in this population of healthy cats."

 

Even if your cat is not iron deficient, an iron supplement is usually given to cats receiving ESAs. This is because the cat's body will try to produce a lot of red blood cells when you start giving an ESA, but it needs sufficient iron in order to complete the process; so an iron supplement helps ensure that your cat has the iron it needs to enable the ESA to do its work. The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369 states "Iron is a necessary component of hemoglobin formation. Iron deficiency can not only impair adequate erythropoiesis but also impair the ability of an ESA to function properly."

 

Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 says "Iron is necessary for hemoglobin formation and RBC function, and should be administered to all cats receiving ESAs." Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011 recommends:

  • "50 to 100 mg/day for cats (10 to 20 mg of elemental iron)" if you are giving oral iron; or

  • "Intramuscular iron dextran given every three or four weeks may be a better alternative. Dosages are typically 50 mg/cat."

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 state "iron supplementation is generally recommended to ensure iron deficiency does not contribute to the anaemia." They recommend either:

  • 50mg of iron dextran injected intramuscularly once at the start of ESA therapy and repeated monthly (this is the preferred treatment); or

  • 50-100mg of ferrous sulfate given by mouth daily.

Use of erythropoietin and calcitriol for chronic renal failure in dogs and cats (2005) Sanderson S Presentation to the World Small Animal Veterinary Association World Congress explains more about when and how to supplement iron when using ESAs.

 

You can read more about iron supplementation on the Anaemia page.

 

B Vitamins


It is also a wise idea to give any anaemic cat B vitamins, particularly vitamin B12, because a lack of vitamin B can actually cause or contribute to non-regenerative anaemia. Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 says "Several B vitamins are necessary for erythropoiesis, including cobalamin (B12), folic acid (B9), niacin (B3) and pyridoxine (B6). Deficiencies of these vitamins may exacerbate anemia and increase erythropoietin resistance."

 

They go on to say "Although there is a paucity of data on whether CKD patients commonly develop deficiencies of these vitamins, supplementation of these water soluble vitamins is unlikely to cause harm, but they are not effective as sole therapies for anemia."

 

I would give B vitamins myself, because they will not harm but they certainly seem to help some cats feel better.

 

Target PCV or HCT Level


How high should the PCV or HCT be? This is a tricky question these days, to which there is no simple answer.

 

Although all laboratories have different ranges for normal values, as a rough guide a normal PCV in a healthy cat would be in the 29-45% range. When I was giving Thomas an ESA back in 1999/2000, it was usually recommended to aim for a PCV of 35-40%, so the cat was no longer anaemic, but firmly in the middle to high end of the normal range.

 

Over time the recommended target began to fall, and people were advised not to go above 35% because higher levels increase the chances of thrombosis and associated heart problems (though very few cats I heard about seemed to have a problem with a PCV or HCT of 35%). This target may have become popular because it tied in with the general recommendations for humans using ESAs.

 

In June 2011 the FDA recommended that a goal for PCV or HCT levels should no longer be set for human patients on ESAs (see below). Instead, it states that the lowest dose sufficient to "reduce the need" for blood transfusions should be used.

 

Perhaps because of this, gradually the recommendations for target PCV for cats on ESAs have reduced, mainly in order to reduce the risks associated with ESAs:

  • University of California at Davis recommends a target range of 28-33%.

 

So what should be your goal? Let's consider the Animal Medical Center recommendation of a PCV of 25%. With some laboratories, this would actually mean that the cat was still anaemic or barely out of anaemic range (the PCV range for some laboratories starts at 24%, but at 29% for others). I believe this would be the case at AMC itself - when my cat had blood tested there, the lab range began at 29%, although it is possible that the range has changed since then. If your cat remains in the anaemic range, s/he might still be experiencing some of the effects of anaemia.

 

A low target like this also gives you little room for manoeuvre should your cat suddenly become more anaemic (perhaps because of sudden blood loss or infection). It is relatively easy to arrange a blood transfusion for a human whose anaemia suddenly worsens, with blood banks easily accessible almost everywhere, but it is a lot harder (though not always impossible) for a cat.

 

You might decide not to aim for an exact target, but to monitor your cat and alter your ESA dosing once the PCV is approaching normal range, as long as the symptoms of anaemia have gone. If your cat is still showing signs of anaemia, however, you may wish to cautiously aim for a higher PCV or HCT level. Generally speaking, a range of around 25-30%, depending upon your laboratory's reference levels (25% if your laboratory's range starts at 24%, or 30% if your laboratory's range starts at 29%), might be reasonable, but aiming for 30-35%, as I have seen many people do successfully, might also be appropriate, at least if your laboratory's range begins at 29%.

 

It's not easy, is it? When we made the decision to use an ESA for Thomas, we decided to make sure he was no longer anaemic. Despite all the increased knowledge about the use of ESAs in cats today, I think I personally would still have the same goal today, in which case I would aim for an HCT of around 30. Discuss with your vet what would be most appropriate for your cat, but whatever you do, monitor blood pressure carefully.

 

Monitoring PCV Levels


Your vet should check PCV and blood pressure a week after starting treatment, and continue to check these weekly until target PCV is reached and maintained for 3-4 weeks. Regular checks should then continue every two weeks until the level is stable. Therapeutic implications of recent findings in feline renal insufficiency - proceedings (2009) Scherk M CVC in Kansas City Proceedings states "It is important to monitor PCV every 2 weeks for the first 60-90 days to check for development of anti-epo antibodies", but don't forget, you are also monitoring blood pressure, so you should visit the vet once a week initially.

 

Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 recommends also performing a reticulocyte count each week until target PCV is reached, and thereafter doing this monthly, but mentions that the reticulocyte count does not always increase in cats receiving darbepoetin.

 

In Anemia of chronic kidney disease (2009) CVC in San Diego Proceedings Dr CL Langston suggests that "Monthly monitoring is usually sufficient once the PCV has been stabilized. A complete blood count should be checked monthly to bimonthly for the duration of therapy." It also recommends checking iron measurements before starting an ESA and then every 1-2 months thereafter.

 

If you are due to check your cat's PCV  level, always do it before administering the next dose of an ESA, because you only want a rise of around 2% a week (if it rises faster, it may increase the risk of hypertension and other problems). If it is rising faster than this, apart from in the first week (see below), then speak to your vet about whether you should adjust your dosing regimen.

 

Unfortunately checking PCV frequently can be a bit problematic with anaemic cats. Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011 states "The frequent blood sampling of hospitalized patients, especially small pets, can contribute to anemia." Fortunately, if you only need to test PCV, it is not necessary to draw a lot of blood - a tiny drop taken from the ear may be sufficient. See Anaemia for more on testing blood, including home testing machines.

 

Speed and Nature of Response


In Anemia of chronic kidney disease (2009) CVC in San Diego Proceedings Dr CL Langston says "Hematocrit generally starts to increase within 1 to 2 weeks of starting ESA therapy. The desired PCV typically takes 4 to 12 weeks to achieve."

 

Of course, it does depend upon your starting point (the more severe the anaemia, the longer it will take to reach target range) and whether, for example, your cat has received a blood transfusion before starting the ESA. However, the typical cat will not need a full twelve weeks. In Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 Dr Langston says "On average, the target packed cell volume (>25%) is reached within 3–4 weeks of ESA therapy."

 

Speed of Response: Darbepoetin Alfa (Aranesp)


Generally speaking, you will see a slower response with darbepoetin compared to epoetin alfa. Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats (2013) Polzin DJ Journal of Veterinary Emergency and Critical Care 23(2) pp 205–215 states "Typically an increase in PCV occurs within 2-3 weeks." In one study, The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369, the median time for the cats to reach target PCV level was only three weeks, but this was the median and some cats needed longer (5-6 weeks). However, it does appear that darbepoetin may work faster than was previously thought for some cats, and it is certainly safer from the antibody reaction perspective.

 

Speed of Response: Epoetin Alfa or Epoetin Beta


It usually takes around 1-2 weeks for these ESAs to start showing an effect, with PCV or HCT usually rising around 2% a week. When I say by 2%, I mean, for example, a rise from 15% to 17%, not 2% of the original  level (15% in this example).

 

Although these ESAs may start to show an effect more quickly, they may take longer than darbepoetin to reach the PCV target. Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011 states that "a response is usually seen within three or four weeks."  By response, they mean reaching the target PCV level of 25%. In Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference, Dr D Chew states "Depending upon the severity of anemia, it may require 3-4 weeks for the PCV to enter the target range."

 

Nature of Response


You normally want an increase in PCV of around 2% a week, though 1-3% is an acceptable range according to Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40.

 

Whichever ESA is used, some cats will show an abrupt increase in PCV in the first week of use, perhaps as much as a 10% increase. This is more likely to happen in cats with less severe anaemia (and in fact some of them perhaps are starting the medication a little prematurely, before PCV or HCT is below 20%), and/or in cats with less severe CKD (creatinine under 5 ml/dl US or 450 µmol/L international) whose kidneys may still be able to make a little erythropoietin on their own.

 

One analogy used is that if a fire has not gone out completely, it is easier to fire it up again than if it has virtually gone out. An abrupt increase of this nature in the first week is probably not cause for concern as long as your cat's blood pressure is under control, but if PCV continues to rise faster than 4% in two weeks, you should ask your vet about reducing the amount given, because rises in excess of this level have been associated with an increased risk of hypertension and stroke in human patients.

 

Very occasionally, it is possible to stop giving ESAs completely. This might be the case, for example, with a cat who has acute kidney injury rather than CKD and whose anaemia improves as the kidneys start functioning again. The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369 reports on a cat with acute on chronic kidney disease who was able to manage without an ESA once he was stable. However, in a cat with CKD it is unlikely that you will be able to stop the ESA completely, and stopping and starting is not recommended (see below).

 

If PCV Does Not Rise


If your cat's PCV level does not rise, or if it rises and then begins to fall, do not panic. You need to address all possible causes before assuming it is the antibody reaction causing the problem. Managing anemia in patients with chronic kidney disease (2011) Chalhoub S, Langston CE Veterinary Medicine May 2011 states "Failure to reach the target PCV with ESA treatment can be caused by a number of factors, such as iron deficiency, anemia of chronic inflammation, concurrent illnesses, infections, hemorrhage from gastrointestinal erosions or ulcers, bone marrow failure or fibrosis, and pure red cell aplasia." The link has a helpful table (in a pop up window halfway down the page) entitled "algorithm to troubleshoot persistent anemia (below PCV range) while using darbepoetin" which your vet can use as a checklist if PCV is not rising as you would expect.

 

Here are some of the possible causes of the problem:

 

Dehydration


Some cats' PCV may not rise, and in fact may fall in the first couple of weeks of use of an ESA. This is quite common if your cat is dehydrated when you first begin the treatment. As mentioned in Hemoglobin and Hematocrit (1990) Billett HH in Clinical methods: the history, physical and laboratory examinations, Third Edition, Eds. Walker HK, Hall WD & Hurst JW chapter 151, dehydration inflates the PCV value, so if your cat is dehydrated when PCV is tested, the value will appear higher than it actually is. For example, if your cat has a  PCV level of, say, 20%, but is dehydrated when the test is run, the level may appear lower (say, 18%) once the dehydration has been brought under control. The severity of the fall would depend upon the level of dehydration at the first check.

 

It may be that your cat is not dehydrated but PCV has fallen or not risen. I know when this happens, some vets immediately say it is the antibody reaction. That is unlikely because the earliest I have ever heard of the antibody reaction occurring was after five weeks (one case only). There are many other possible reasons for the PCV not increasing, so you need to look at these first.

 

Building Blocks


You need to ensure all the building blocks to enable the ESA to work are in place, such as B vitamins.

 

A cat who appears not to be responding to the ESA often needs more iron. Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 states that "Lack of available iron for erythropoiesis is recognised as the leading cause of treatment failure in humans on ESA therapy." If you have not been supplementing iron, therefore, you should consider this possibility before fearing the worst. See above for dosage guidelines. Even if you have been supplementing iron, a lack of iron may still be a factor because cats in the study who were receiving both an ESA and oral iron supplements still had decreased iron levels.

 

Dosage


You need to review the dosage because you may not have measured it correctly, or your cat may actually need more ESA than you have been giving. Some vets give too small a dose in the mistaken belief that this may reduce the risk of the antibody reaction. Plus some cats simply need more ESA than others - Thomas's PCV went up and down in the first few weeks of treatment so we were very worried, but we simply gave him more of the ESA rather than less, and his PCV then rose steadily. A cat whose CKD is advancing may also need more ESA than s/he previously needed. Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 states "In some cases, the ESA dose may be too low for the patient or be incorrectly administered. A higher ESA dose may partially overcome ESA resistance, although doses higher than 500IU/kg a week for epoetin or1.5–2.0μg/kg a week of darbepoetin are rarely used by the authors."

 

Viability of the ESA


You need to consider whether your ESA is still viable. Perhaps it was not shipped to you chilled, or it was left out of the fridge overnight. Perhaps you have had the vial open for a long time and it is no longer potent. If for some reason you are using the 10,000 iu/ml strength of epoetin alfa (which is not recommended in cats), or if you are giving darbepoetin (Aranesp) only every 3-4 weeks, the drug may lose its potency before you get a chance to finish the vial. This can lead you to incorrectly suspect that your cat is developing the antibody reaction.

 

One thing that may not occur to you is the way your pharmacy stores your ESA before you receive it. One member of Tanya's CKD Support Group who went to collect her ESA happened to see that it was up on the rack with all the standard medications - the person who had unpacked it hadn't known it needed to be refrigerated.

 

Infection or Inflammation


In Anemia of chronic kidney disease (2009) CVC in San Diego Proceedings Dr CL Langston says that over 75% of human patients whose anaemia does not improve on an ESA have an infection or inflammation. She states "In a retrospective study of cats, 25 per cent of patients did not reach the target haematocrit and were suspected of having infection or inflammation (unpublished data, Langston and Kittrell, 2006). Higher doses of rHuEPO do not overcome the resistance; control of the infection or inflammatory state is necessary."

 

Review Other Medications


Make sure your cat's phosphorus levels are under control, because high phosphorus levels may reduce your cat's response to ESAs.

 

On the other hand, if you are using an aluminium hydroxide phosphorus binder, this may be a possible factor (though this is rare). Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 states that other reasons for a low response should be considered, such as "aluminum toxicity."

 

If you are giving an ACE inhibitor or ARB such as benazepril (e.g. Fortekor), these might be a factor. Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 states "Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers are suspected to decrease angiotensin II-induced release of erythropoietin, as well as prevent pluripotent hemopoietic stem cell recruitment."

 

Other Issues


Other possible causes for a failure to respond to ESAs include hidden blood loss (e.g. from gastrointestinal bleeding) or cancer. Ensure your vet checks for and treats all other causes of anaemia.

 

Try not to panic. Use the checklist in the above link and keep going. If you do all this, you should with luck start to see an improvement after 2-3 weeks. In the meantime, depending upon how severe your cat's anaemia is, you may have to consider a blood transfusion to tide your cat over until the ESA begins to work.

 

In some cases, the ESA will not fully resolve the anaemia. In one study, The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369, 76% of cats did respond to the use of ESAs, but this meant 24% did not respond. Of those who did respond, 20% failed to maintain their response over time. Some of these cats were suspected of having persistent gastrointestinal bleeding and one was thought to have FIP.

 

If PCV Increases Too Far


This is uncommon but it can happen occasionally, especially if you give a dose of ESA without checking your cat's PCV level first. This actually happened to Thomas, when a vet who was unfamiliar with ESAs gave him a shot when he went in for a blood pressure check without checking his PCV level first, and without realising I was actually giving the shots myself at home. Thomas's PCV went up to, wait for it, 55%!

 

I have also heard of a couple of cats whose PCV rose too high because their vet recommended the wrong dose or the pharmacy accidentally dispensed the wrong strength of ESA.

 

The main risk here is that the blood thickens - my vet said Thomas had raspberry jam running through his veins - which can increase the risk of stroke and seizures. In such cases you need to monitor blood pressure carefully and may need to place the cat on IV fluids to thin the blood. And of course, definitely do not give any more ESA until the level is down to a safe level. Fortunately Thomas was OK and had no problems.

 

So in the starting phase, please be sure not to give darbepoetin without checking PCV levels first; do not give epoetin alfa or epoetin beta more than three times without checking PCV levels first; and double check the dosage prescribed by your vet and the ESA strength dispensed by the pharmacy.

 

Storage and Lifespan of ESAs


These medications usually contain no preservatives, so MUST be kept in the refrigerator inbetween treatments, but since the vials should not be shaken, do not keep them in the fridge door. It is fine to leave the vial out at room temperature for 20-30 minutes before administering it so it is not too cold when you inject your cat.

 

You should not shake the vial, though it is acceptable to roll it gently in your hand to warm it a little before giving it to your cat.

 

Some pharmacists tell people they can only use a vial once and then must throw it away; whilst this is true for human patients, it is standard to re-use these products for cats. It is unlikely that any problems will arise from doing so, as long as you keep the vial or syringe sterile and do not use the medication past its "use by" date.

 

Having said that, since maintenance doses of darbepoetin (Aranesp) tend to only be given once every few weeks, you may need to be more cautious if you are using an opened vial or syringe. A couple of my group members found that their cats' PCV began to fall and they feared they were seeing the antibody reaction; however, when they switched to a new vial of darbepoetin, their cats' PCV began to climb again. I would not keep an opened vial or syringe for longer than 2-3 months. If you can afford it, it might be wise to ditch it after around six weeks. Talk to your vet about the best approach.

 

ESAs: Side Effects and Interactions


The antibody reaction is discussed below, but that is not normally seen (if it occurs at all) until the cat has been on an ESA for 4-5 months. This section focuses on the risks to be aware of as soon as you start using an ESA.

 

Most CKD cats do not seem to have problems when using ESAs, but possible side effects include vomiting, fever, hair loss, diarrhoea and occasionally seizures. The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369 discusses the use of darbepoetin and possible side effects. In this study, four cats had seizures, but three of them also had hypertension, which itself can cause seizures.

 

In fact hypertension is really the major concern when using an ESA, because in the worst case hypertension may cause heart problems or a stroke. The use of erythropoietin (2003) Langston CE, Reine NJ & Kittrell D Veterinary Clinics of North America Small Animal Practice 33(6) pp1245-1260 found that 40-50% of cats on ESAs develop hypertension, so blood pressure should always be monitored while your cat is on an ESA, particularly when you first begin treatment.

 

Since CKD cats are prone to hypertension anyway, ideally you should have started monitoring blood pressure as soon as your cat was diagnosed with CKD; but if you have not been doing this, do try to ensure that blood pressure is monitored once you begin the ESA. If your cat's blood pressure rises to an unacceptable level (see hypertension for information on target blood pressure levels) and your cat is not yet on blood pressure medication, you will probably need to start it. If you are already giving blood pressure medication, you may need to increase the dose. You may also need to decrease the amount and/or frequency of the ESA, at least until blood pressure is under control. Be guided by your vet as to the best course of action in your cat's case.

 

There is some debate as to whether ACE inhibitors may exacerbate anaemia and/or induce some resistance to the use of human erythropoietin in humans. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin (1999) MacDougall IC Nephrology Dialysis Transplantation 14(8) pp1836-1841 reports on the evidence for and against this concern in humans, and Anaemia of renal disease: what is it, what to do and what's new (2011) Chalhoub S, Langston C & Eatroff A Journal of Feline Medicine & Surgery 13(9) pp629-40 mentions it as a possible reason for a cat responding poorly to ESAs.

 


Possible Problems with ESAs


 

See above for the side effects and interactions section.

 

The main concern with the use of ESAs in cats is that in a small number of cases (around 10% if you are using darbepoetin, around 30% if you are using epoetin), an antibody reaction may occur. In the worst case this will develop into pure red cell aplasia (PRCA).

 


The Antibody Reaction


What is the Antibody Reaction


ESAs are effective medications for most cats, but there is one potential major disadvantage to using them. Epoetin alfa and epoetin beta are recombinant human erythropoietins or rhEpo. Darbepoetin alfa is slightly different (it is manufactured using recombinant human DNA erythropoiesis stimulating protein). With any of these medications (though it is less likely to happen with darbepoetin alfa), some cats will eventually produce an antibody reaction because their bodies consider the ESA to be a foreign body. These antibodies then neutralise the ESA (i.e. stop it working to produce red blood cells), so the anaemia returns. In this site I refer to this as the antibody reaction, but elsewhere you may see this referred to as PRCA, which is the most extreme form of the antibody reaction. Because of the risk of the antibody reaction, it is usually recommended that cats should not be placed on ESAs until the benefits of using them outweigh the risks (see above). 

 

It is not known for certain how many cats go on to develop this antibody reaction because it is hard to test for it. Some sites refer to a rate of around 70% but in the only clinical trial to date on the use of an ESA in cats, Use of recombinant human erythropoietin for management of anaemia in dogs and cats with renal failure (1998) Cowgill LD, James KM, Levy JK, Egrie JC, Browne JK, Miller A & Lobinger R Journal of the American Veterinary Medical Association 212 pp521-8, the number of cats who developed the reaction to epoetin alfa in the form of Epogen was around 30%. In Anemia of chronic kidney disease (2009) CVC in San Diego Proceedings Dr CL Langston says that the rate seen at the Animal Medical Center in NYC is around 21% for Epogen.

 

It appears that darbepoetin alfa (Aranesp) may be less likely to cause the antibody reaction. There has been one suspected case of the antibody reaction in a dog at UCMVC but this was never confirmed. I haven't heard of any confirmed cases in cats as at June 2016, though they probably exist. In Anemia of chronic kidney disease (2009) CVC in San Diego Proceedings Dr CL Langston says that the rate seen at the Animal Medical Center in NYC is around 10% for darbepoetin (this figure includes two confirmed cases in dogs). The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369 states "Of the 11 nonresponders, PRCA was not clinically suspected in 9 cats because other conditions were present that adequately explained the poor response. PRCA was considered possible but unlikely in 2 cats. Neither cat was documented to have reached the target PCV, but insufficient information was available to determine if other conditions were present."

 

In my experience over the last sixteen years of monitoring a number of CKD-related online groups, the frequency of the antibody reaction in practice appears to be far lower than 25-30% even when using epoetin alfa, perhaps closer to 5-10%. See below for a possible explanation of this discrepancy.

 

It is impossible to predict which cats will develop the antibody reaction, although epoetin alfa in the form of Eprex appears to carry a higher risk of the antibody reaction for humans than either epoetin alfa in the form of Epogen or Procrit, particularly if the HSA-free form of Eprex (which contains polysorbate 80 instead of albumin, in order to comply with European requirements) is used. Erythropoietin-associated PRCA: still an unsolved mystery  (2006) Schellekens H & Jiskoot W Journal of Immunotoxicology 3(3) pp123-130 has more information about this.

 

The antibody reaction does not usually occur in the first month of use, and if it is going to occur it tends to be around 4-5 months after commencing treatment (only rarely does it happen much earlier or later than this). There is no definitive test to show that the cat has developed the antibody reaction; a bone marrow aspiration (biopsy) would provide some information in the form of a very high myeloid to erythroid ratio (M:E ratio), but this does not happen in every case. Bone marrow aspiration is invasive and unlikely to be worthwhile for most cats. Pet Place explains more about bone marrow and bone marrow biopsy. Skills laboratory: how to collect diagnostic bone marrow samples (2005) Young KM & Friedrichs KR Veterinary Medicine has some information on how this procedure is performed.

 

From a practical perspective, the main sign of an antibody reaction is that the cat's PCV value will steadily drop by approximately 2% a week, despite the use of adequate amounts of an ESA. Large drops in PCV in the space of a few days or a week are unlikely to be caused by the antibody reaction, and other possible causes such as gastrointestinal bleeding should be investigated. Rapid falls may occasionally be a sign of PRCA, but this is rare.

 

Please also read above about possible causes for PCV not increasing - many of these may also be factors in PCV actually falling too.

 

What Happens During the Antibody Reaction


Whilst nobody wants their cat to experience the antibody reaction, it must be stressed that it is not as awful as it sounds. Some people think it is akin to anaphylactic shock but it is nothing like that at all!

 

What normally happens is that the PCV gradually falls at a rate of around 2% a week (any larger fall and you should search for another cause, such as gastrointestinal bleeding), despite the cat being on an ESA. If the cat is still producing a little erythropoietin naturally, the antibodies may also neutralise the cat's own erythropoietin as well, at least for a while, and this further worsens the anemia. In the worst case, a condition called PRCA can occur.

 

But, and most importantly, even in those cats who develop the antibody reaction, the erythropoietin antibodies will not always neutralise the effects of the ESA. In other words, some cats may have the antibody reaction but you would never know it because the ESA continues to work and the cat does not become anaemic again. This may explain why it is often claimed that 30% of cats receiving epoetin alfa develop the antibody reaction, yet in practice on the online support groups, the percentage appears to be much lower, around 5-10%.

 

If your cat does develop the antibody reaction to an ESA, since the resulting anaemia will eventually kill the cat, the only remedy is to stop using the ESA. It takes the cat's body 3-4 months until the antibodies wear off, and during that period it is often necessary to keep the anaemia under control via blood transfusions. You cannot start using the ESA again, even after the antibodies wear off, so depending upon the level at which your cat's anaemia stabilises, you may need to use blood transfusions indefinitely. Some vet schools have been investigating using darbepoetin in cats who have developed an antibody reaction to epoetin alfa, you can read more about this here.

 

In most cases the cat was suffering from severe anaemia, otherwise an ESA would not have been started in the first place. So in the worst case, using an ESA will have bought you an extra few months with your cat; and in the best case, using an ESA could control your cat's anaemia indefinitely. 

 

Pure Red Cell Aplasia (PRCA)


In the worst case, the antibodies to an ESA which some cats develop may cause the cat not only to neutralise his or her own erythropoietin but also to develop a condition called pure red cell aplasia (PRCA), which also kills off existing red blood cells. In such a case, the cat develops a sudden loss of response to the ESA, the PCV level falls suddenly, and the reticulocyte count will be extremely low. The cat will often be very lethargic and short of breath.

 

Many vets believe that the antibody reaction to ESAs is identical to PRCA. They therefore fear that the chance of this happening is around 30%, and consider that any cat who suddenly becomes more anaemic despite being on an ESA must be developing PRCA.

 

I see it more as a question of degree. Whereas some cats develop the antibody reaction mildly (so the ESA keeps on working for them, see above), those cats who develop PRCA are exhibiting a reaction at the opposite end of the spectrum, which also affects their existing red blood cells. In Pure red cell aplasia clinical presentation (2009), Dr Paul Schick states that "The development of pure red cell aplasia may represent the extreme end of the spectrum of EPO-induced immunological suppression of RBC production."

 

PRCA is thought to be an autoimmune condition, and developing it as a result of using an ESA is rare - humans on ESAs have a rate of PRCA of less than 1%. Most cases in humans on ESAs occurred in people using Eprex prior to 2003, and cases tended to be concentrated within certain countries such as the UK and France, whereas Germany had hardly any. The cases that were seen coincided with a change to the formulation of Eprex. The currently available HSA-free form of Eprex, which contains polysorbate 80 instead of albumin in order to comply with European regulations, had a higher PRCA rate; and it was also thought that the way the drug was administered may have been a factor (subcutaneous administration appeared to increase the risk). Erythropoietin-associated PRCA: still an unsolved mystery (2006) Schellekens H, Jiskoot W Journal of Immunotoxicology 3(3) pp123-130 reports further on this issue. Following prescribing changes in December 2002, even though the same type of Eprex was being used, the number of human cases of PRCA fell dramatically. Epoetin-associated pure red cell aplasia: past, present and future considerations (2008) McKoy JM, Stonecash RE, Cournoyer D, Rossert J, Nissenson AR, Raisch DW, Casadevall N & Bennett CL Transfusion 48(8) pp1754-62 explains more about the numbers involved.

 

PRCA appears to be more common in cats than in humans, though it is hard to know exactly how many cats develop it because many vets do not differentiate between PRCA and the less severe form of antibody reaction. It is also fairly common for vets to assume a cat is developing PRCA when PCV falls without addressing other posssible (and more likely) causes of the falling PCV, such as infection or gastro-intestinal bleeding. PRCA usually does not occur until the patient has been on an ESA for three months. As far as cats are concerned, The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases (2012) Chalhoub S, Langston C & Farrelly J Journal of Veterinary Internal Medicine 23(2) pp363-369 states "PRCA, one of the most serious complications of epoetin, has been reported to occur after 5–38 weeks of treatment, with a median of 14.5 weeks." In theory therefore, you should be safe for the first few weeks of using epoetin alfa (Dr Katherine James, one of the researchers into the use of epoetin alfa in CKD cats, has stated that many cats do not have problems for 4-5 months); and don't forget, even in the worst case scenario, your cat has a 70% chance of never having this problem. If you are using darbepoetin (Aranesp), your chances of being safe are really very high - your cat has a 90% chance of never developing problems.

 

If your cat's PCV or HCT suddenly falls, whether during or after the first three months of use, consider other causes before fearing the worst. You can read above about possible causes for PCV not increasing - many of these may also be factors in PCV actually falling too.

 

If, however, your cat really does develop the antibody reaction so severely that PRCA results, you must immediately stop using the ESA. You might need to arrange a blood transfusion for your cat. It takes the cat's body 8-10 months until the antibodies wear off, and during that period it is often necessary to keep the anaemia under control via regular blood transfusions. You cannot start using the ESA again, so depending upon the level at which your cat's anaemia stabilises, you may need to use blood transfusions indefinitely. Although this is a big commitment and expense, I do know of people who have done this successfully. Some vet schools have been investigating using darbepoetin in cats who have developed an antibody reaction to epoetin alfa, you can read more about this here. It is possible that stem cell transplants may also help.

 

Please don't feel guilty if your cat develops PRCA. Your cat was most probably suffering from severe anaemia, otherwise an ESA would not have been started in the first place. So in the worst case, using an ESA will have bought you an extra few months with your cat; and in the best case, using an ESA could control your cat's anaemia indefinitely. 

 

The cat of one of my support group members did experience PRCA following the use of epoetin (Epogen), which was confirmed as far as it can be via a bone marrow aspiration and by ruling out possible other causes. The PCV began falling after six weeks of treatment, eventually plummeting over a 24 hour period. Her vet began a treatment protocol which involved stopping the Epogen for a few weeks, giving the cat prednisolone (a corticosteroid) along with regular blood transfusions, and later switching her to darbepoetin (Aranesp). Unfortunately her cat developed antibodies to the blood transfusions, but this method did buy her a few more months, and my group member did not regret trying an ESA, but she wished she had started with darbepoetin (Aranesp).

 

FDA Warnings


As mentioned above, there can be other risks using ESAs, such as high blood pressure, seizures, heart problems and strokes (although controlling blood pressure does help reduce the risk of many of these issues). Various warnings relating to these concerns have been issued by the US Food & Drug Administration over the years regarding the use of ESAs in humans. The 2007 FDA warning recommended aiming for lower target haemoglobin levels than many doctors originally aimed for, because this reduced the risks of serious side effects. Previously many doctors aimed for a haemoglobin (Hb) level over 12, but the 2007 warning recommended aiming for an Hb level of between 10 and 12.

 

Targets for human ESA patients are measured in haemoglobin, but in haematocrit (HCT) or packed cell volume (PCV) for cats. To convert Hb into HCT, you multiply by approximately three. If the advice for humans was extrapolated to cats, this would have meant that your target HCT (based on the maximum Hb level of 12) should be no higher than 36. Since it had long been recommended that people aim for a conservative HCT or PCV level of no more than 35% in cats using these products, this warning did not raise any additional concerns when it was issued.

 

The 2011 FDA warning, issued in June 2011, states that humans on ESAs are considered to be at greater risk of adverse events if they target an Hb level of 11. The FDA now suggests considering starting an ESA when Hb level falls below 10, but declines to state exactly when humans should start ESAs or what level of Hb they should aim for. Instead it recommends individualised dosing and states that the lowest dose sufficient to reduce the need for blood transfusions should be used.

 

I discuss the implications of these warnings for cats above.

 

Why Stopping and Starting ESAs is a Bad Idea


Very occasionally, it is possible to stop giving ESAs completely. In fact, if your cat has acute kidney injury rather than CKD, you may not need to start them in the first place - although cats with AKI tend to have high bloodwork results generally, they often are not anaemic, or, if they are, the anaemia resolves itself naturally as the kidneys begin working again.

 

However, I have heard that some vets have a policy for every CKD cat they treat of using an ESA short-term until the anaemia is resolved, then stopping it and starting it again later when the cat has become anaemic again, in the mistaken belief that this may reduce the risk of the antibody reaction.

 

This is really not a good idea. Dr Katherine James, who participated in the Epogen trial in cats mentioned above (the trial that has many vets worried about the antibody reaction in the first place) has stated that there is no evidence either way, but she suspects that doing this might actually increase the risk of the antibody reaction occurring. She also believes that the resulting fluctuations in PCV could cause problems with blood pressure control.

 

On the most basic level, I really do not see the point of allowing a cat to become anaemic again, with all the strains on the body and effects on the cat's quality of life which that entails. Most scarily, I have heard from two people whose vets insisted on this approach and their cats died of anaemia during one of their anaemic phases. If you decide to use an ESA, I'd recommend making a commitment to using it fully in order to keep your cat free of anaemia, and in most cases this will mean using the ESA for life, though of course as a maintenance dose.

 


Using Darbepoetin in Cats Who Have Developed the Antibody Reaction to Epoetin


 

It is not recommended to use any form of ESA in a patient who has reacted to another form (in other words, if you have developed the antibody reaction to epoetin alfa in the form of Epogen, it is not advisable to use darbepoetin alfa in the form of Aranesp instead). Since there are some differences between epoetin alfa and darbepoetin alfa, some US vet schools have tried to maintain cats who have developed the antibody reaction to epoetin alfa by using blood transfusions for several (6-8) weeks, and then starting them on darbepoetin, in the hope that the cats will not also develop an antibody reaction to darbepoetin. Apparently there is anecdotal evidence that this approach worked for one cat but it did not work for any others. Sometimes prednisone, a corticosteroid, is used in the interim period before starting treatment with darbepoetin.

 

One person whose cat may have developed the antibody reaction to epoetin alfa (this person's vet had recommended a stop/start approach, which is not advisable because it may increase the risk of the antibody reaction) tried to switch to darbepoetin. He found that using darbepoetin alone or darbepoetin and prednisone did not help his cat, but using it in conjunction with both prednisone and chlorambucil (Leukeran), an immunosuppressive drug commonly used in the treatment of cancer, did help for a while. This regimen was based on the successful treatment plan for a woman who also developed the antibody reaction. However, chloramucil can itself cause anaemia.

 

Feline non-regenerative immune-mediated anaemia: features and outcome in 15 cases (2016) Black V, Adamantos S, Barfield D & Tasker S Journal of Feline Medicine & Surgery 18(8) pp597-602 surveys the treatment of anaemic cats including cats with PRCA. Of the seven PRCA cats in the study, two died. Of the five surviving cats, most required blood transfusions initially. Two of the cats with PRCA were treated with prednisone and three were treated with prednisone and chlorambucil. All five of these cats went into remisson after a maximum of six weeks and all of them were still alive at follow up. The cause of the PRCA in the cats in this study is not stated, but most of these cats were young so it was probably not related to the use of ESAs.

 

Pure red cell aplasia secondary to epoetin alfa responding to darbepoetin alfa in a patient on peritoneal dialysis (2004) Asari A R Gokal R Journal of the American Society of Nephrology 15 pp2202-7 reports on the case of a human patient who developed the antibody reaction to Epogen who was successfully switched to Aranesp.

Successful reintroduction of a different erythropoiesis stimulating agent after pure red blood cell aplasia: relapse after successful therapy with prednisone (2005) Andrade J, Taylor PA, Love JM, Levin A Nephrology Dialysis Transplantation 20 pp2548-51 discusses the case of a woman who developed the antibody reaction and who was helped by prednisone.

Erythropoietin, cure or nightmare (2004) Chan SK, Chan CK, Chow CC is a Presentation to the Hong Kong Society of Nephrology Interhospital Meeting about a woman who developed the antibody reaction and who was helped by prednisone and chlorambucil.

Mar Vista Vet has some information about chlorambucil (Leukeran).

 


Should I Use an ESA?


 

I know it is not easy making the decision to use an ESA, and your head is probably spinning after reading this page (I've tried to make it as clear and simple as I can, but I'm afraid it's a complicated subject). Please discuss the pros and cons with your vet before making your decision. Remember, you should not normally need to use an ESA if the cat's PCV or HCT is 20% or higher. The criteria for knowing if it is time to consider using an ESA are here.

 

If your cat does have severe CKD-related anaemia caused by a lack of erythropoietin, then to some extent there is no real decision to make, because the only real alternative to starting an ESA is to watch your cat die of anaemia.

 

I discuss above when it is usually recommended to start using an ESA. We decided to use an ESA for the following reasons:

  • It was quite obvious that if we did not do so, the anaemia would kill Thomas long before the CKD would (he was extremely  weak, had no appetite and was breathless).

  • We felt the odds were in our favour with at least a two to one chance that it would work for us. We used epoetin alfa; the odds are much better with darbepoetin.

  • Even if he were to develop the antibody reaction, it should buy him up to 4-5 months of additional time and thus postpone having to say goodbye.

  • In the best possible scenario, once the ESA had done its work, we would never have to worry about CKD-related anaemia caused by a lack of erythropoietin again.

Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) Chew D A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference states "Treated animals demonstrate resolution of anemia, weight gain, improved appetite, improved haircoat, increased alertness, and increased activity."

 

Therapeutic implications of recent findings in feline renal insufficiency - proceedings (2009) Scherk M CVC in Kansas City Proceedings states "While there is a risk of Ab developing, the majority of cats will enjoy the benefits of an improved hemogram."

 

If you are considering the use of an ESA, don't take too long to make your decision, because if you do, your cat may die of the anaemia before the ESA has a chance to take effect (it may take up to three weeks to see an improvement after starting to use an ESA, and the anaemia should only improve gradually). If your cat has a low PCV level but is acting relatively well, don't be lulled into a false sense of security. Because non-regenerative anaemia caused by CKD tends to develop and worsen gradually, many cats' bodies do adapt to the anaemia so they may not seem desperately ill, but they could still suddenly hit crisis point. If necessary, a blood transfusion might help your cat through a critical period while you wait for the ESA to take effect.

 

Personally I would never let PCV fall below 15% before starting an ESA, and if my cat was showing symptoms of anaemia with a PCV of 16-19%, I would start it earlier. We began it as soon as Thomas was diagnosed following his crash, when his PCV was 18% (though it was probably lower, since he was severely dehydrated at the time - as mentioned in Hemoglobin and Hematocrit (1990) Billett HH in Clinical methods: the history, physical and laboratory examinations, Third Edition, Eds. Walker HK, Hall WD & Hurst JW chapter 151, dehydration makes PCV look higher than it really is. When Thomas died seven months later, his anaemia was completely under control. If we had not used the ESA, he would have only managed a month at most.

 

So, to summarise:

  • I discuss research into possible new anaemia treatments for CKD cats here, but at the present time (June 2016) there are no alternatives to ESAs for the treatment of severe CKD-related non-regenerative anaemia. Milder anaemia may be treated via the methods outlined here.

  • if you do not use an ESA for severe CKD-related non-regenerative anaemia, your cat will die of anaemia.

  • the antibody reaction is rare. Even going by the worst case statistics, your cat has less than a 1 in 3 chance of developing the antibody reaction whilst on epoetin alfa, or only a 10% chance while on darbepoetin. That's a 90% chance in your favour! Based on what I've seen over sixteen years of online support groups, your cat has more like a 1 in 10 to 1 in 20 chance of developing the antibody reaction.

  • if your cat does develop the antibody reaction, it will not usually be for 4-5 months, during which time your cat will have no problems at all with anaemia.

  • if the antibody reaction occurs, your cat will normally become anaemic again gradually, which simply means you will be back where you started 4-5 months earlier when you first decided to use erythropoietin.

  • if the antibody reaction occurs, you will see a fall in PCV/HCT of around 2% a week. A larger fall may indicate PRCA, but may also indicate some other cause, such as gastrointestinal bleeding.

  • if your cat develops the antibody reaction, you will probably have to use blood transfusions to control the anaemia instead. At the present time I know of no other treatment, except possibly switching to darbepoetin if you are currently using another ESA.

  • if your cat, as is most likely, does not develop the antibody reaction, s/he may well have no problems with anaemia and all its attendant side effects in the future.

Ultimately it is your decision whether to use an ESA. There have been trials into feline alternatives (see below) but, according to the researchers involved, none of these studies is expected to result in the commercial availability of alternative treatments in the foreseeable future. 

 

If you do decide to use an ESA, darbepoetin alfa (Aranesp) is usually the best choice.

 

I know people find this all overwhelming, and I am sometimes asked to make it simple. Well, making the decision to use an ESA isn't simple, but once you've made the decision and sourced your medication, it is less complicated. If I were faced with anaemia in a CKD cat, I would

  • give darbepoetin (Aranesp) using the 1mcg/kg per week dosage regimen.

  • begin using it once my cat had a PCV below 20% with non-regenerative anaemia caused by CKD and was showing symptoms of anaemia. If my cat was not showing symptoms but PCV fell to 18%, I would use darbepoetin regardless.

  • I would give my cat iron and B vitamins to help the ESA work properly.

  • I would monitor my cat's blood pressure

 


Feline Erythropoietin (rfEpo)


 

I am only covering these treatments briefly here because neither is commercially available at the moment (2016), nor likely to be in the immediate future.

 

Feline Erythropoietin (rfEpo)


Feline erythropoietin is not commercially available currently, but was developed in small quantities for use in two feline trials, one in 2010 at Colorado State University and one in 2002 at Cornell.

 

CSU Feline Erythropoietin Trial (2010)


The sponsor of this study at the Veterinary Teaching Hospital at Colorado State University engineered a new feline erythropoietin (rfEpo). In 2010 this was administered to 18 healthy cats at varying doses and on average, raised the red blood cell count 25% or more with no side-effects and the effect lasted more than one month.

 

Cornell Feline Erythropoietin Trial (2002)


A new synthetic form of feline erythropoietin was developed at Cornell University in the USA, and a one year trial for CKD cats was completed there in November 2002.

 

Expression, bioactivity and clinical assessment of recombinant feline erythropoietin (2004) Randolph JF, Scarlett JM, Stokol T, Saunders KM and McLeod JN American Journal of Veterinary Research 65(10) pp 1311-1450 explains the outcome of the study. Unfortunately, whilst the rfEpo was effective at curing anaemia in the study cats, even in those cats who had previously had an antibody reaction to human erythropoietin, 26% of the cats receiving feline erythropoietin (and who had never used human erythropoietin) developed an antibody reaction to the feline erythropoietin.

 

Feline Erythropoietin Gene Studies


 

2011 University of California at Davis


The Winn Feline Foundation gave a grant in 2011 to the University of California at Davis College of Veterinary Medicine to create a feline erythropoietin gene, with a view to using this later in clinical trials. Lentiviral gene therapy strategy for the in vitro production of feline erythropoietin (2012)  Vapniarsky N, Lame M, McDonnel S & Murphy B PLoS One 7(9) e45099 discusses the outcome of the research.

 

2000 Ohio State University


A 2000 study at Ohio State University College of Veterinary Medicine investigated the development of a feline erythropoietin gene. The gene that makes feline erythropoietin was implanted into the leg or back muscle by an intramuscular injection similar to a vaccination. Tests conducted on healthy cats showed that this increased PCV levels over a seven week period following the injection.  

 

Results were mixed with some cats responding extremely well and others less well, but overall the trials were encouraging. Once the gene is implanted, the cat should produce erythropoietin on its own, and in the trials responsive cats had been doing so for up to one year. Further trials may be conducted in due course.

 

Transfer of the feline erythropoietin gene to cats using a recombinant adeno-associated virus vector (2000) Beall CJ, Phipps AJ, Mathes LE, Stromberg P, Johnson PR Gene Therapy 7 (6) pp 534-539 describes the beginning of the trial.

 

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This page last updated: 25 June 2016

 

Links on this page last checked: 20 June 2016

   

*****

 

TREATING YOUR CAT WITHOUT VETERINARY ADVICE CAN BE EXTREMELY DANGEROUS.

 

I have tried very hard to ensure that the information provided in this website is accurate, but I am NOT a vet, just an ordinary person who has lived through CKD with three cats. This website is for educational purposes only, and is not intended to be used to diagnose or treat any cat. Before trying any of the treatments described herein, you MUST consult a qualified veterinarian and obtain professional advice on the correct regimen for your cat and his or her particular requirements; and you should only use any treatments described here with the full knowledge and approval of your vet. No responsibility can be accepted.

 

If your cat appears to be in pain or distress, do not waste time on the internet, contact your vet immediately.

 

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