Meowko's Experience with Chronic Kidney Disease Non-regenerative Anemia

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After Meowko was diagnosed with Chronic Kidney Disease,  we had been warned that anemia would someday become a concern. As CKD progresses, a hormone, Erythropoietin, produced by kidney, would likely decrease over time. Erythropoietin however is an important hormone. Bone marrow needs to use Erythropoietin to generate red blood cells. Decreasing supply of Erythropoietin would then cause bone marrow not able to make enough red blood cells -- that's how CKD's non-regenerative anemia comes.

Anemia can be easily detected by blood tests. If a cat's PCV (packed cell volume) or HCT (Hematocrit)(clinically they are used interchangeably) is lower than 20%, the cat is considered sever anemic. If eticulocyte count is low and anemia lasts for more than 5 days, it is identified as non-generative anemia. There are different other things to look for as well; for example, CKD anemia is likely to be normochromic anemia, ie. MCHC is also in the normal range. However, in the range of 10%-20%, most cats can adjust well and do just fine, including Meowko. The cat's situation is like that s/he is living on the top of Himalaya Mt. But when PCV/HCT drops further down to single digit, the cat would show very clear signs: weak, even can't walk, pale, difficulty breathing...etc, generally can't function well at all. Cat's situation would quickly deteriorate since then. It is a very dangerous and fatal situation, and blood transfusion is likely needed to be done immediately. Otherwise death won't be too far.  

• PCV/HCT tests:  If your cat needs to be monitored closely for anemia (but with other conditions stable), you can ask your vet to regularly check your cat's pcv only rather than do complete blood counts (CBC) to save you some money or save cat's precious blood. The cost for pcv ranges from $15-$30 as I had heard of.   

We had a consensus with our original vet that once Meowko's pcv drops to 15% or she starts to show signs of anemia, we would start using Erythropoiesis Stimulating Agents (ESAs), an  artificial erythropoietin. There are actually different kinds of ESAs, including epoetin alfa and beta (brand names: Epogen, Procrit, and Eprex...), and darbepoetin alfa (brand name: Aranesp). Tanya's CKD websites has a very clear explanation about ESAs, which I benefitted a lot from. If you are interested in knowing more about ESAs, please see here:
http://www.felinecrf.org/esas.htm
http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=1728
  
We however didn't see any clear signs of anemia for another year after Meowko was diagnosed CKD, and she had been doing fine on regular exams. Until April 2013 after I returned from a conference trip, I realized something was wrong. We rushed her to emergency, and the blood test confirmed that she was very anemic: pcv 12%. After discussions with vets, Meowko did the first blood transfusion on that day, and we also decided to put Meowko on Darbepoetin alfa (Aranesp), as it apears to have lower anti-body forming rate than both epoetin alfa and epoetin beta. (But keep in mind that Darbepoetin may need longer time to be effective than epoetin, sometimes may take up to 4-5 weeks. Also no matter which kind of ESAs is used, this medication may be a life-long medication, except if anti-body is formed.)  



Darbepoetin alfa (Aranesp)

source: http://ghsrenal.com/ghsfiles/calcs/aranespconv.html

Aranesp is a human injection drug, so you can get this medication also from human pharmacies. You would need a prescription to buy it. Aranesp requires to be refrigerated so it would be best to obtain the medication at your local pharmacy or get it by overnight cool pack shipping. It comes in different size in a vial meant for only one time use (25mcg, 40mcg, 60mcg, 100mcg, 200mcg in 1 ml) but veterinary practices seem to use the vial for multiple draws without problem. 

Temuro U100 syringe 3/100cc

Meowko was on a high dose: 6.25 mcg per week given subcutaneously. We bought 25mcg/1ml vials, and each was good for 4 doses, each dose 0.25ml. And we used the Terumo U-100 insulin 3/100 cc (ie. 0.3ml) syringe with needles to draw the amount out. As the vial is not designed for multiple uses, it would be better you use alcohol cotton ball to wipe the vial's top drawing part before each draw.

• Dosage protocols vary depending on vet's training and the region the vet is at. Details of dosage protocols can be found at Tanya's website. 
• The price range of 25mcg/1ml vial generally ranges from $150-$250. Sometimes local CVS, Walgreens, hospital pharmacies and compounding pharmacies will have some vials stocked in their fridges.  As the price may vary, it would be best to shop around in advance. The best price we got was from Walgreens for $156 after their membership discount (for which you need to register your cat as a member for $20 a year, or $35 for your whole family to include your cat). You can also use higher strength vials if that are what available at your local pharmacies; just remember to do the math carefully. 

Aranesp, 25mcg/1ml

We closely observed Meowko and found an interesting pattern: she seemed to do better for two days after she got the darbepoetin shot. We therefore, under the supervision of our primary vet, separated the dosage to 3.125mcg every 3.5 days. (But I can't find any reports on whether separate smaller doses would be better than just one large amount dose.)  Unfortunately, Meowko didn't response to Darbepoetin well (because she was later diagnosed with aplastic anemia due to Feline Leukemia Virus (FeLV) infection; we will have another post to share our experience about this). During the last two weeks of her life, she received up to 9.375mcg Darbepoetin per week. For a 6 IBs cat, that is a lot. But we didn't see any side effects on her. I actually learned from several people in the feline anemia supporting group that their cats needed 2-3 times of regular dosage in order to "kick off." 

Darbepoetin appears to be a very safe drug for cats. The biggest concern is the anti-body reaction, for which Tanya's website also has a very clear explanation for owners. Darbepoitin's other side effects mostly come from too quick increase of red blood cells, which may lead to hypertension and blood clots, and complications associated to hypertension and blood clots. You can check Aranesp's own website for adverse effects on human patients that mostly apply to cats as well. It would therefore be better to monitor cat's pcv/hct every week, and adjust the dosage accordingly. The best result should be about 2% gradual increase in pcv/hct per week. Also be reminded that it is suggested to supplement additional iron, vitamin B9 and B12 when a cat is on Darbepoetin so that the cat can have enough iron and B vitamins to produce red blood cells. 

• Iron supplement is preferred to be given orally to prevent iron toxicity. The iron injection usually is only considered when sever iron-insufficient anemia is diagnosed. Meowko used oral supplement, NutriVed, which contains iron and B vitamins. We bought it from Amazon for $12. Meowko unfortunately hated the taste of this supplement to death. Alternitively, cooked chicken or beef liver can also be fed to increase iron intake, 1 tea spoon, twice a week. Be careful not to fee too much as liver contains high level vitamin A and D, over intake of which would cause toxicity. However, if it is sometimes hard to find fresh chicken or beef liver in the grocery stores, liver freeze dried liver treats can certainly be a substitute. We used to give Meowko Whole Life Pet Freeze dried beef live, 1 piece per day.  
• We also tried a supplement called lactoferrin. Lactoferrin is a kind of protein that helps regulate and bind free iron in the blood to build red blood cells. There has been many medical reports on using lactoferrin in conjunction with ESAs to treat certain types of anemia in human patients. Lactoferrin in the form of apo-lactoferrin may be particularilly helpful. Meowko was on 150mg daily. We got our apo-lactoferrin from Life Extension.   
• B12 can be given orally or subcutaneously. But it is believed that subcutaneous injection is better absorbed than oral supplement, especially for cat with inflammatory bowel diease, like Meowko. Meowko was on 250mcg subcutaneous injection weekly and oral B12 500mcg daily. You can actually get B12 injection (in the form of cyanocobalamin) from human pharmacies (prescription needed): we got a 1000mcg/1ml vial manufactured by APP Pharmaceuticals for $2 dollars from Walgreens. But this B12 injections contains aluminum that can be toxic if its accumulation reaches certain level. So we later turned to Vetco's B12 injectable, 100ml at 1000mcg/1ml strength for $4.97. For the oral B12, we used the Doctor's Best B12 1500mcg caps (in the form of Methylcobalamin) by separating each original cap into three gel caps and fed Meowko one cap daily. 
• For more information about B12, please visit Tanya's website.  

Blood transfusion

Meowko after her 1st blood transfusion

If a cat is too anemic, s/he will need blood transfusions to get through the time before ESAs start to work. Blood transfusion is actually not a complicated procedure. In most situations, it is just to slowly inject red blood cells collected from a compatible donor cat via IV into your cat. But other components of blood, platelets and plasma, can also be transfused. Cats, like human, have different blood types: A, B and AB; there is also another blood type called Mik positive and negative, which has not been well researched so far as I understand. A compatible donor is crucial to make the transfusion last longer.

Generally, most vet hospitals will have their own hospital cats ready to donate blood for transfusion. But if for some reasons a donor cat is not available, there are animal blood banks that can provide you with cat blood through overnight shipping, even shipping internationally. I learned that red blood cells can hardly be stored for too long,  but platelets and plasma can be stored for longer. I however once heard from an animal bank claimed that their blood have 30 shelf life and is willing to sale those for lower prices --- I doubt the correctness of this information, but I am not an expert of vet science, so do check with your vet if any blood bank tells you that. In some occasions, Oxyglobin, a substitute of red blood cell, can also be considered. 

The transfusion itself generally takes 4-5 hours to complete, but it would be a good idea if the cat can stay longer for observation in case anti-body reaction happens. It is recommended to give antihistamine each time before the transfusion to lower the risk of forming anti-body reaction. 

• As far as I know, a blood transfusion costs about $500-700, which includes antihistamine, the cost of blood cross-match, matched blood and one day hospitalization fee. 

Unfortunately, as said our vets, transfusion is just a band-aid, not a cure. A good transfusion can probably last for 4-5 weeks, and sometimes multiple transfusions are needed. Sadly for Meowko, her first transfusion only lasted for no more than 2 days, and she got the second transfusion without having any improvement on pcv.

International Cat Care has a blood transfusion guide for vets, which can also provide owners a clear sense about how exactly a blood transfusion process is supposed to be done.



What else can you do?

heating pad

Taking care of an anemic cat is challenging. Since an anemic cat would suffer from lack of oxygen and therefore become very weak, the first thing we did for Meowko was to provide a cozy space, with food, water, and litter nearby on one surface so that she didn't have to move too far or jump to get to her basic needs. Also anemic cat tends to have lower body temperature. We used electronic heating pad that I use for my period to keep Meowko warm (you can get one on amazon for $13). Being more extreme, you can consider using oxygen cylinders to build an oxygen tent to temporarily help your cat feel better. I did this several years ago for a foster cat, but I didn't have a chance to do so for Meowko... 

Recommendations

• If you are reading this post because you have an anemic CKD cat, please definitely visit http://www.felinecrf.org/anaemia.htm, and also consider joining its supporting group http://pets.groups.yahoo.com/group/tanyas-ckd-support/ This group helped Meowko and me get through the most difficult times, and we learned a lot from both the website and the group! 
• Please also consider joining the feline anemia supporting group where Meowko and myself had benefited a lot: http://pets.groups.yahoo.com/group/Feline_Anemia/?yguid=506681762