TANYA'S

COMPREHENSIVE GUIDE TO

FELINE CHRONIC KIDNEY DISEASE

 
 

MISCELLANEOUS TREATMENTS

 

ON THIS PAGE:


ACE Inhibitors: benazepril (Fortekor or Lotensin) or enalapril (Enacard), and Angiotensin II Receptor Antagonists: telmisartan (Semintra)

Stem Cell Transplants


Steroids


Kidney Transplants


 

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Home > Treatments > Miscellaneous Treatments

 


Overview


  • This page covers treatments that don't fit neatly into any of the other treatment pages.

  • ACE inhibitors, particularly benazepril (Fortekor) are commonly prescribed for CKD cats in Europe, Canada and Australasia.

  • Stem cell transplants are a promising new treatment currently available in the USA and Australia.

  • Steroids are not a routine part of CKD treatment, but may be necessary in some cases.

  • Kidney transplants are not widely available and are extremely expensive, but are covered briefly below.


ACE Inhibitors and Angiotensin II Receptor Antagonists                         Back to Page Index


What are ACE Inhibitors?


ACE inhibitors are heart medications. They work by preventing the conversion of a hormone called angiotensin I into another hormone called angiotensin II, the role of which is to constrict blood vessels. The ACE inhibitor thus relaxes the blood vessels, which helps to reduce blood pressure and therefore reduces the work that the heart has to perform to pump blood through the body.

 

Benazepril (Fortekor, Benazecare, Lotensin)


One ACE inhibitor, benazepril, is also approved for the treatment of CKD in cats in Europe, Australasia and Canada. If you are in these countries, it is therefore highly likely that your vet will offer you this treatment at some stage. Indeed, in the UK, benazepril and prescription diets are often the only treatments offered (though if they were all that is available or suitable for CKD cats, this site would be a lot shorter than it is!).

 

Benazepril is sold under the trade names of Fortekor or Benazecare in Europe and Canada and under the trade name of Lotensin in the USA. 

 

Since in practice most people who are offered an ACE inhibitor will be offered benazepril, much of what is stated below focuses on this medication, particularly since almost all the research into the use of ACE inhibitors in cats relates to benazepril. 

 

Pet Place has some information about benazepril.

 

Enalapril (Enacard)


Another member of the ACE inhibitor family is enalapril (Enacard). This is excreted largely by the kidneys, so is not usually the best choice for a CKD cat. Benazepril is primarily excreted (85%) via the liver in cats, which puts less strain on the kidneys.

 

Mar Vista Vet has more information on enalapril.

 

Uses of ACE Inhibitors


 

Control of Intraglomerular Blood Pressure


As mentioned on the What Happens in CKD page, one of the kidneys' functions is to help to control blood pressure. There are two kinds of blood pressure in cats, within the cat's body generally (systemic blood pressure) and within the kidneys in particular (intraglomerular blood pressure).

 

It is not practicable to measure intraglomerular blood pressure in cats but it is usually higher than systemic blood pressure, and it may be elevated even if systemic blood pressure is not. If intraglomerular blood pressure is too high, it may cause loss of function and scarring in the kidneys.

 

ACE inhibitors work by preventing the conversion of a hormone called angiotensin I into another hormone called angiotensin II, the role of which is to constrict blood vessels. The ACE inhibitor relaxes the blood vessels, which helps to reduce both systemic and intraglomerular blood pressure (some blood pressure medications have no or only a limited effect on intraglomerular blood pressure).

 

This is a delicate balancing act because reducing blood pressure within the kidneys can lead to a reduction in the amount of blood flowing through the kidneys, which in turn may reduce the glomerular filtration rate, a measure of kidney function. This may have a negative effect on kidney function in some cats, which may be seen in the form of elevated BUN and creatinine levels. One study, Effects of benazepril hydrochloride in cats with experimentally induced or spontaneously occurring chronic renal failure (2007) Watanabe T & Mishina M Journal of Veterinary Medical Science 69(10) pp1015-1023, found that benazepril appeared to improve creatinine levels as well as proteinuria in cats with naturally occurring CKD, but other studies have found the opposite.

 

How much of a problem this can be is debatable. ACVIM Consensus Statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats (2007) Brown S, Atkins C, Bagley R, Carr A, Cowgill L, Davidson M, Egner B, Elliott J, Henik R, Labato M, Littman M, Polzin D, Ross L, Snyder P & Stepien R Journal of Veterinary Internal Medicine 21 pp542–558 states that in cats who do not also have heart disease "the administration of ACEI commonly produces only very modest increases in serum creatinine concentration (0.5 mg/dL; 50mmol/L) and this degree of change is usually tolerable."

 

In most cats this increase is temporary, which should be tolerable in cats in the early stages of CKD. However, Novartis states that Fortekor can be used at any stage of the disease, i.e. as soon as there is any evidence of decreased renal function right through to cats with very elevated urea (BUN) and creatinine levels. In principle it is possible that a rise in creatinine levels in a cat in IRIS Stage 4 might be enough to push a cat over the CKD precipice. 

 

Control of Systemic Blood Pressure


Some vets also like to use ACE inhibitors to control systemic blood pressure. They may wish to do this simply because they think it is the best treatment, but they may also want to do so because of something known as the renin-angiotensin-aldosterone system or RAAS.

 

If blood flow to the kidney is reduced, the kidneys are stimulated to produce hormones called renin and angiotensin. The adrenal gland is stimulated to produce another hormone called aldosterone. This is known as the renin-angiotensin-aldosterone system (RAAS). These hormones make the blood vessels in the body constrict, which in turn leads to hypertension.

 

The RAAS can be activated by CKD, and may also be activated by the use of calcium channel blockers (such as amlodipine, the recommended treatment for hypertension in cats) to treat general hypertension. In contrast, since ACE inhibitors work by preventing the conversion of angiotensin I into angiotensin II, they not only do not activate the RAAS, they may reduce the risk of activation.

 

There is some debate as to how common activation of the RAAS is in CKD cats. In Feline hypertension: risks, diagnosis and management (2007) Atkins CE, Presentation to the World Small Animal Veterinary Association World Congress 2007, Dr Atkins states "several studies have indicated that the renin-angiotensin-aldosterone system (RAAS) is probably abnormally activated in many or, perhaps, most cats with systemic hypertension, particularly with concurrent renal disease." However, in Heart disease in the older cat (2006) Simpson K Presentation to the FAB Conference, Ms Simpson states that ACE inhibitors "appear fairly unreliable at decreasing blood pressure. A possible explanation for this may be that the hormonal axis which these drugs target (the reninangiotensin-aldosterone system (RAAS)) is not activated to the same degree in cats as in humans."

 

As Ms Simpson mentions, used alone, ACE inhibitors are not actually particularly effective at controlling systemic blood pressure. Effects of angiotensin-converting enzyme inhibition on plasma aldosterone concentration, plasma renin activity, and blood pressure in spontaneously hypertensive cats with chronic renal disease (2002) Steele JL, Henik RA & Stepien RL Veterinary Therapeutics: Research in Applied Veterinary Medicine. 3(2) pp157-66 found that "systolic blood pressure did not decrease below 170 mm Hg with ACE inhibitor monotherapy in 14 of 16 cats. These results suggest that continued activation of the RAAS is present in hypertensive cats despite treatment with an ACE inhibitor, and ACE inhibitors should not be used as first-line antihypertensive treatment in hypertensive cats."

 

Not only are ACE inhibitors not particularly effective at controlling blood pressure, they also cannot reverse the blindness sometimes caused by hypertension, whereas amlodipine may do so in some cases. Therefore, if your goal is to control systemic hypertension, particularly in a cat who has gone blind, you normally start by using amlodipine only. ACVIM Consensus Statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats (2007) Brown S, Atkins C, Bagley R, Carr A, Cowgill L, Davidson M, Egner B, Elliott J, Henik R, Labato M, Littman M, Polzin D, Ross L, Snyder P, and Stepien R Journal of Veterinary Internal Medicine 21 pp542–558 states that "In cats, although the renin-angiotensin-aldosterone axis may play a role in the genesis or maintenance of systemic hypertension, CCB [calcium channel blockers such as amlodipine] are often the first choice for antihypertensive therapy due to established efficacy." In Feline hypertension: risks, diagnosis and management (2007) Atkins CE Presentation to the World Small Animal Veterinary Association World Congress Dr Atkins states that "the literature and clinical experience would, nevertheless, lead one to appropriately conclude that amlodipine is the single best agent for the management of feline systemic hypertension." See the Hypertension page for more information on using amlodipine.

 

One possible compromise is to use amlodipine and benazepril together, particularly for cats whose blood pressure cannot be controlled with amlodipine alone. Although ACE inhibitors are not massively effective at controlling blood pressure alone, they may provide a necessary boost without reducing blood pressure too far, whilst simultaneously reducing the risks of RAAS activation. Plumb's Veterinary Drug Handbook states "There is concern that using amlodipine alone for treating hypertension in cats with renal disease may expose glomeruli to higher pressures secondary to efferent arteriolar constriction. This is caused by localized increases in RAAS axis activity thereby allowing progressive damage to glomeruli. It is postulated that using an ACE inhibitor with amlodipine may help prevent this occurrence." The ACVIM Consensus Statement cited above also says "Combination therapy may be especially useful in cats, in which there is some evidence for a beneficial effect of ACEI in CKD and for an established antihypertensive efficacy of CCB."

 

Control of Proteinuria


One area where benazepril appears to be effective is in reducing proteinuria (loss of protein in the urine, which may cause progression of CKD). It does this through its effects on GFR, which also minimises the risk of hypokalaemia (low potassium levels). In trials, cats with a urine protein:creatinine ratio greater than 1.0 who received benazepril showed improved appetite and weight gain, and had an average survival time of 402 days versus 126 days for those cats being treated with prescription diet only.

 

Evaluation of the clinical efficacy of benazepril in the treatment of chronic renal insufficiency in cats (2006) Mizutani H, Koyama H, Watanabe T, Kitagawa H, Nakano M, Kajiwara K & King JN Journal of Veterinary Internal Medicine 20(5) pp1074-9 tested benazepril on 61 cats with naturally occurring CKD in a randomised double-blind placebo-controlled study. The study found that UPC ratios were significantly (P < .05) lower with benazepril as compared with placebo at days 120 and 180. "Incidence rates of cats with IRIS classification stage 2 or stage 3 that remained in stage 2 or 3 without progressing to stage 4 were higher with benazepril (93 +/- 5%) as compared with placebo (73 +/- 13%)."

 

Tolerability and efficacy of benazepril in cats with chronic renal disease (2006) King JN, Gunn-Moore DA, Tasker S, Gleadhill A & Strehlau G Journal of Veterinary Internal Medicine 20(5) pp1054-1064 reports that "there was no difference in renal survival time between the two groups when all 192 cats were compared" but found that benazepril does appear to reduce proteinuria in cats.

 

Proteinuria in cats with chronic kidney disease (2008) is a video presentation by Dr CL Langston of the Animal Medical Center in NYC. Dr Langston starts benazapril if UPC is over 0.4.

 

Therapeutic implications of recent findings in feline renal insufficiency (2009) Scherk M Presentation to the International Congress of the Italian Association of Companion Animal Veterinarians states "Benazepril has undergone a large, multiinstitutional study to assess its effects on CRI in cats. Results of this and other smaller studies show that using benazepril or placebo didn’t make any significant difference in survival time for all CRI cats. For cats with urinary protein loss (urine protein:creatinine, UPC), benazepril treated cats had longer survival times and better appetite than placebo-treated urinary protein losing cats. Cats with an increased UPC (> 0.4) who are started on this medication, should be rechecked within 3-7 days and have their renal parameters, hydration, body weight, appetite and overall health monitored. Thereafter, re-evaluation should occur every 2-4 months in a stable patient. If there is no decrease in UPC, the medication should be discontinued."

 

ACE Inhibitor Cautions, Interactions and Side Effects


In some cats, creatinine levels may rise shortly after beginning benazepril. For this reason Novartis, the manufacturer of Fortekor, recommends that kidney bloodwork should be checked 5-10 days after starting Fortekor, though until 2013 I had yet to hear of a single vet who actually does this routinely. For most cats this increase will be temporary, but monitor your cat to be sure.

 

The use of ACE inhibitors may also lead to an increase in potassium levels in the blood, which can be a risk in a cat who already has high levels of potassiumDrugs discusses this. Novartis (manufacturer) - US website, with detailed information on how the drug works and cautions, including the risks of using Fortekor at the same time as potassium supplements or diuretics. 

 

There is some debate as to whether ACE inhibitors may exacerbate anaemia and/or induce some resistance to the use of human erythropoietin (Epogen, Procrit or Eprex) in humans. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin (1999) MacDougall IC Nephrology Dialysis Transplantion 14(8) pp1836-1841 reports on the evidence for and against this concern in humans.

 

Using ACE inhibitors at the same time as diuretics such as furosemide (Lasix), whilst sometimes necessary in cats with heart disease, can be dangerous.  Mar Vista Vet has more information about this.

 

Non-steroidal anti-inflammatories (NSAIDs), including meloxicam (Metacam), may increase the effects of benazepril and reduce blood pressure too far, so do not give both medications to your cat  without checking with your vet first. 

 

ACE inhibitors should be given two hours apart from phosphorus binders, because the binders may interfere with adsorbtion of the ACE inhibitors. Drugs has more information about this.

 

ACVIM Consensus Statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats (2007) Brown S, Atkins C, Bagley R, Carr A, Cowgill L, Davidson M, Egner B, Elliott J, Henik R, Labato M, Littman M, Polzin D, Ross L, Snyder P, and Stepien R Journal of Veterinary Internal Medicine 21 pp542–558 says "ACEI should not be used in dehydrated patients in which the GFR might drop precipitously. These patients should be carefully rehydrated and then re-evaluated before instituting antihypertensive therapy." Despite this, I often hear of British cats who have high kidney values being sent home with benazepril after a session on intravenous fluids, but with no access to sub-Qs. Please be careful if this applies to you, because your cat will probably become dehydrated without sub-Qs.

 

ACE inhibitors may cause lethargy, particularly when first begun. This may be a sign that blood pressure has fallen too low, which in turn may lead to an increase in creatinine levels as described above. Coughing may also be seen.

 

Fortekor has not been tested in cats weighing less than 2.5kg (5 lbs) so be careful if you have a small cat. 

 

Whether to Use ACE Inhibitors


The potential downsides of using ACE inhibitors (a decreased GFR and increased creatinine levels) are usually considered to be an acceptable price to pay for the benefits (reduced intraglomerular pressure) in humans. This trade off appears to also be accepted for cats in Europe, Australasia and Canada, where benazepril in particular is routinely prescribed for CKD cats. In the USA, ACE inhibitors are not used routinely, and are usually only prescribed if a cat has significant proteinuria, or if amlodipine alone is not sufficient to control hypertension.

 

Prolonging life and kidney function (2009) Chew DJ & DiBartola SP Proceedings of the Southern European Veterinary Conference & Congreso Nacional states "Angiotensin-converting enzyme (ACE) inhibitors (e.g. enalapril, benazepril) may have protective effects in patients with chronic renal disease due to their ability to block adverse effects of angiotensin II. ACE-inhibition reduces glomerular capillary hydraulic pressure by decreasing postglomerular arteriolar resistance. Proteinuria is decreased secondary to decreased glomerular hydraulic forces and development of glomerulosclerosis is limited when protein trafficking across the glomerulus is decreased. Remnant nephrons in animals with CRF have glomerular hypertension that can benefit from reductions in transglomerular forces. An additional potential benefit from ACE-inhibition is improved control of systemic blood pressure. This beneficial effect must be balanced against their potential to worsen azotemia since glomerular pressure provides the driving force for GFR in the “super-nephron”.

 

Chronic kidney disease in dogs and cats II: Principles of management (2010) Maddison J & Syme H Irish Veterinary Journal 63(2) pp106-9 states "There is evidence that use of ACE inhibitors (such as benazapril) will attenuate the progression of renal failure in humans and animals with significant proteinuria. However, the evidence that they are beneficial in patients with mild proteinuria (the majority of cats) has not yet been clearly established. There is a rationale for using ACE inhibitors in cats and dogs with renal failure as there may be some benefit provided the patient can be pilled easily and the owner can afford the treatment. However, dietary change (reduction in phosphate) carries significantly greater potential benefits in slowing the progression of non-proteinuric renal failure and ACE inhibitor therapy should not be regarded as a substitute for it. Treating cats and dogs that are severely azotaemic, or that have pre-renal azotaemia with ACE-inhibitors may actually speed their demise."

 

The effects of Rheum officinale on the progression of feline chronic kidney disease (2011) Hanzlicek AS Thesis submitted to Kansas State University College of Veterinary Medicine states "Based on easily measured clinical parameters, this study failed to detect a significant difference in cats administered a Chinese rhubarb supplement, benazepril, or both."

 

Some members of Tanya's CKD Support Group have found benazepril helpful whilst others felt it did not suit their cat and in some cases caused problems. Personally, I would be prepared to use benazepril if I had a cat with proteinuria. I would also be prepared to use it if my cat had hypertension uncontrolled by amlodipine alone. I don't think I would use it in a cat without these problems, particularly not in a cat with creatinine over 3.5 (USA) or 310 (international). This level is arbitrary, and simply reflects my own feelings of what might be a reasonable cut off point.

 

If your vet offers you benazepril, please discuss it fully with him/her and try to decide together whether you think it could benefit your cat with his/her particular symptoms, bloodwork and quality of life.  If you do decide to use it, please check Side Effects and Interactions above, particularly the part about dehydrated cats. Whatever your cat's numbers, you should have bloodwork run 5-10 days after beginning to use benazepril, and monitor blood pressure. Clinical epidemiology of kidney diseases in the cat (2008) Francey T & Schweighauser A Veterinary Focus 18(2) pp2-7 has some information about this.

 

If you are already using benazepril and you have any concerns, please also talk to your vet but do not stop it suddenly. As a heart medication, it should be gradually tapered down.

 

Angiotensin II Receptor Antagonists


Angiotensin II receptor antagonists work by blocking the receptor to which angiotensin II attaches, thus preventing ACE II from having an effect. See above for an explanation of all this. In human medicine they tend to be used when ACE inhibitors cannot be used for some reason.

 

Telmisartan (Semintra)


I first heard about telmisartan because an American vet school was investigating the use of telmisartan to control blood pressure.

 

In December 2012 Boehringer Ingelheim were given approval in Europe for the use of telmisartan for the "reduction of proteinuria associated with chronic kidney disease (CKD) in cats” under the trade name of Semintra. See the Diagnosis chapter for more information about proteinuria and above for more information on the use of ACE inhibitors to treat proteinuria.

 

Boehringer Ingelheim announced the launch of Semintra in early September 2013, and within a week I was already hearing from people who had been offered it. I will report upon their experiences in due course.

The European Medicines Agency has some information about the approval of Semintra, and mentions that in one field trial of unspecified length involving 224 cats, Semintra was found to be as effective as benazepril in reducing proteinuria.

Drugs has some information about the use of this drug in humans, as does Patient UK.


Stem Cell Transplants                                                                                          Back to Page Index


What are Stem Cells?


There are two types of stem cell, embryonic, which are found in embroyos, and somatic or adult stem cells, which are found within the body, particularly in the bone marrow and within adipose tissue (fat). Adult stem cells are cells within the body which can help it to repair itself. There are ethical concerns regarding the use of embryonic stem cells, but the stem cell transplants discussed below use adult stem cells, often from the cat's own body.

 

Pet Place has an overview of stem cell therapy in cats.

Medical Video Tube has a video about stem cell therapy in a CKD cat.

MediVet has a helpful video about stem cell transplants.

 

Stem Cell Transplant Uses


Mesenchymal stem cells help to produce bone, cartilage and cells that help with the creation of fibrous connective tissue, so they can be helpful for arthritis. In the USA, stem cell transplants have been approved for some years to help dogs with arthritis.

 

As explained on the Research page, stem cell transplants have also been shown to improve kidney function, prevent scarring and improve protein loss into the urine (proteinuria) in rats. Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury (2010) Feng Z, Ting J, Alfonso Z, Strem BM, Fraser JK, Rutenberg J, Kuo HC & Pinkernell K Nephrology Dialysis Transplantation 25(12) pp3874-84 found that they seemed to help rats with artificially induced acute kidney injury, with 100% surviving rather than only 57% of the rats who were not given stem cell transplants. Therefore, some US vet schools have been studying the use of stem cells to help cats with CKD. 

 

Stem Cell Transplant Providers


There are four companies in the USA which offer stem cell treatments for vets to use on dogs with arthritis, Vet-Stem, MediVet, VivaStem and ReGena-Vet Laboratories. Vets are trained by these companies to take stem cells from the dog. Vet-Stem require the fat tissue to be sent to their own laboratory for processing, and they then return the cells to the vet for injection into the dog. MediVet sells kits to vets so they can provide same day treatment. VivaStem says that it uses stem cell fluid, so it is also a simple injection but it is not clear how they collect the stem cells. ReGena-Vet will treat local patients itself for inhouse trials, or can produce stem cells for remote use by other vets.

 

Stem cell transplants are not currently approved for CKD cats but one study into the use of stem cell therapy for CKD cats has taken place at Colorado State University (see below) and is continuing, and another study is in progress at the Animal Medical Center in NYC.

 

Vet-Stem is evaluating the use of its product for CKD in cats, and may agree to this treatment being given to a CKD cat if a vet requests it, on the basis of what it calls "compassionate use." The conditions for doing this can be found on page 42 of Feline chronic kidney disease: cell therapy perspectives (2012) Harman R Presentation to the Advanced Renal Therapies Symposium, NYC.

 

ReGena-Vet Laboratories is looking to enrol 12 cats in the San Francisco area into a clinical trial. The cats will be treated by their own vets, who therefore need to be prepared to liaise with ReGena-Vet Laboratories.

 

Apparently there are a couple of vets in Australia who offer this treatment, and they seem to charge a lot less. I am told the injections are given every week for three weeks, by which time one would expect to see a difference in the cat in terms of improved appetite and reduced vomiting. I only know of one person to date whose CKD cat has had this treatment, she didn't think it helped.

 

How Stem Cell Transplants are Performed


The vet makes a small incision in the abdomen, groin or behind the shoulder blade and extracts some fat. This normally requires anaesthesia but most cats will be able to come home the same day. The vet removes stem cells from the fat, then transplants them into the cat via an intravenous infusion (drip) (the process may be slightly different in vet schools, see below). The extraction takes several hours, but if your vet is trained to perform this procedure in-house, the transplant can normally be completed within a day. Otherwise your cat will normally have to return two days later to have the stem cells injected under sedation.

 

The stem cells then travel to areas of inflammation within the body where they help to repair damaged tissue.

 

Animal Medical Center explains more about how the stem cells are harvested.

 

Effectiveness and Cost


In 50-85% of cases, there will be an improvement. Some people see improvements quickly, but it can take a lot longer. In Feline chronic kidney disease: cell therapy perspectives (2012) Harman R Presentation to the Advanced Renal Therapies Symposium, NYC, Dr Harman states that 25 feline CKD cats had been treated by Vet-Stem as at February 2012, for an average period of 776 days, with the longest case to date being 1460 days. 84% of those treated thus far are still alive. For 14 of the cats, there is no outcome yet, but of the 11 with an outcome, one cat did not respond to the treatment, and another had only a mild response. 54% (seven people) felt their cat had a significant improvement in quality of life, and a further 15% (two people) felt there had been a mild improvement. 23% (three people) saw no change, and 8% (one person) felt their cat was worse.

 

The cost depends to a large extent on your vet. Most people who have the treatment performed on dogs with arthritis seem to pay around US$2000-4000. One member of Tanya's CKD Support Group was quoted US$3000 by her vet to treat her cat. She went ahead and her cat is recovering well, though he did not have it done because of CKD but because of severe immune-mediated anaemia.

 

Feline CKD Stem Cell Research


One study has already taken place, and there are several studies currently underway in the USA. ReGena-Vet Laboratories is looking to enrol 12 cats in the San Francisco area into a clinical trial. The cats will be treated by their own vets, who therefore need to be prepared to liaise with ReGena-Vet Laboratories. The following trials are also available:

 

Colorado State University


The Veterinary Teaching Hospital at Colorado State University has published the results of a preliminary study into stem cell transplants in cats with  stable chronic kidney disease (creatinine 2.0 to 5.0). Exclusion criteria included heart disease, kidney infection, stones in the ureter or other renal complications.

 

CSU found in earlier tests that it can be difficult to grow stem cells from older cats, which CKD cats often are, so they obtained and grew stem cells from the fat of young healthy cats (the cats were not harmed) and these cells were given to the CKD cat as an intravenous (IV) injection. The stem cell therapy was given once every two weeks for three treatments, and then monthly for three treatments if improvement was seen. At each visit, bloodwork was performed and an IV catheter placed to administer the stem cell treatment.

 

A member of Tanya's CKD Support Group enrolled the first cat in this study in February 2009, and she told me that the initial cost (for tests and visits) was in the region of US$600, although she was given a lot of free prescription food. Her cat had stem cells injected into one kidney initially, and she said he was a little quiet immediately afterwards, which she thinks might have been caused by the mild anaesthesia he was given, but he seemed OK otherwise. After one month, it appeared his kidney function had improved by approximately 15% according to a scintigraphy scan which checks glomerular filtration rate (not every cat will undergo this, he did so because he was the first participant). His creatinine fell from 6 to 5.2 and his BUN from 80 to 66. Sadly, her cat had kidney stones before he took part in the study, and he died in June 2009, probably because of the complications caused by the kidney stones. Cats with kidney stones are no longer eligible for the study.

 

Evaluation of intrarenal mesenchymal stem cell injection for treatment of chronic renal disease in cats: a pilot study (2011) Quimby JM, Gibbons DS & Dow SW Journal of Feline Medicine & Surgery 13(6) pp418-26 reports on the study. It concludes "Despite the possible benefits of intrarenal MSC injections for CKD cats, the number of sedations and interventions required to implement this approach would likely preclude widespread clinical application. We concluded that MSC could be transferred safely by ultrasound-guided intrarenal injection in cats, but that alternative sources and routes of MSC therapy should be investigated."

 

Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies (2013) Quimby JM, Webb TL, Habenicht LM & Dow SW Stem Cell Research & Therapy 4(2) reports on three studies (numbers 1, 2 and 3) conducted at Colorado State University in which the stem cells were administered intravenously. Cats in study 1 had no adverse side effects. Study 2 found that of the five cats in the study, side effects of vomiting (two cats) and increased respiration (four cats, one severe) were seen. This study used the same sort of cells but cells were taken directly from cryopreservation and higher doses were used than in the other two studies. Study 3 did not see any side effects, and the report states "Thus, we have concluded that the administration of a higher dose of aMSCs taken directly from cryopreservation, despite careful washing, was the source of the toxic reactions observed, and this form of administration is not recommended."

 

Unfortunately, although 40% of cats in studies 1 and 2 showed an improved GFR, the researchers felt that overall the improvement was modest. The paper concludes "Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters."

 

Stem cell treatment is still available at Colorado State University for qualifying cats. See the Research Participation Opportunities page for more information.

 

Animal Medical Center, NYC


The Animal Medical Center is offering free stem cell treatment and three years long term management for qualifying cats. The cat needs to be in IRIS Stage 3 (i.e. creatinine level between 2.9 and 5.0) and must have a negative urine culture. The cat must have no history of stones or any other illness, although hypertension or proteinuria are acceptable.

 

This study is to investigate whether it makes a difference giving the stem cells via the intra-renal arterial route compared to the intravenous route. Some cats may receive a placebo.

 

The stem cells will be obtained from the cat's own fat, and will be transplanted into the cat's renal artery via the femoral artery. This procedure will be repeated 2.5 weeks later. Follow up care will be available free of charge for three years. Only approved treatments and supplements may be used during this period.

 

DVM News Magazine explains more about the trial.

 


Steroids                                                                                                                   Back to Page Index


 

Your vet may offer you steroids, either for a specific purpose, or as a general "pick me up".

 

There are two classes of steroids, corticosteroids and anabolic steroids, and both may help stimulate appetite. They may be given orally or via injection, but if you give them via injection (which is usually done only once a week or even once a month), you will often notice that the effects are wearing off by the time the next injection is due.

 

Mar Vista Vet discusses the potential problems of ongoing steroid use.

 

Corticosteroids


Commonly prescribed corticosteroids include prednisone and prednisolone (usually abbreviated as pred), which usually are used in pill form. Cats metabolise prednisolone better than prednisone (they have to convert prednisone into prednisolone in their bodies anyway before they can use it) so it is usually better to give prednisolone in the first place. Bioavailability and activity of prednisone and prednisolone in the feline patient (2004) Graham-Mize CA &  Rosser EJ Veterinary Dermatology 15(s1), pp 10 supports this view.

 

Corticosteroids commonly cause increased drinking and increased urination. They can have serious side effects with long-term use (including triggering diabetes, fluid retention, high blood pressure, and masking or increasing the risk of infections). They may also increase stomach acid and in the worst case may cause stomach ulcers and gastro-intestinal bleeding, not ideal for a CKD cat. According to Plumb's Veterinary Drug Handbook, corticosteroids may cancel out the effects of calcitriol. This is because calcitriol increases calcium absorption, whereas corticosteroids inhibit calcium absorption. NSAIDs (a type of painkiller) should not be used at the same time as corticosteroids.

 

If your cat develops congestive heart failure (CHF) within a week of starting corticosteroids, the steroids may be the cause. One study, Corticosteroid-associated congestive heart failure in 12 cats (2004) Smith SA, Tobias AH, Fine DM, Jacob KA, Ployngam T The International Journal of Applied Research in Veterinary Medicine 2(3) pp159-170 found that some cats developed a unique form of CHF within seven days of starting steroids. Five of the cats died, but once taken off the steroids the seven that survived did much better than the typical CHF patient.

 

In any event, it is recommended that corticosteroids should not be used in the renally impaired.

 

If for some reason you are using corticosteroids, these should never be suddenly discontinued: the dose must be tapered because using corticosteroids may suppress the adrenal glands' ability to produce cortisone naturally. Tapering the dose minimises the risk of adrenal insufficiency occurring as a result.

 

Veterinary Partner explains how corticosteroids work.

Newman Veterinary has helpful information about steroids.

Pet Education has detailed information on corticosteroids.

Mar Vista Vet explains more about prednisone and prednisolone.

VCA Animal Hospitals discusses the long term effects of using corticosteroids.

Glucocorticoids use in cats (2010) Lowe A Veterinary Medicine pp56-62 discusses the pros and cons of using corticosteroids.

 

Anabolic Steroids


Anabolic steroids can help build up muscle, and thus have their place in the treatment of CKD cats with muscle wasting; they may also be beneficial as an appetite stimulant and are sometimes used for mild anaemia.

 

Your vet may prescribe anabolic steroids in the form of either tablets or injections. Commonly used anabolic steroids in Europe are Nandoral (Ethylestrenol in tablet form) or Laurabolin (injectible Nandrolone). Stanozolol (Winstrol-V) was popular in the US but unfortunately, it is no longer routinely available, which apparently is related to some type of FDA regulation. It may still be obtainable from some compounding pharmacies. Pet Place has some information about Winstrol-V.

 

Thomas took anabolic steroids whilst he had CKD. He received a monthly shot at the vet's. We were able to reduce Thomas's steroid dose, but he still seemed to do better overall when he was taking his steroids. 

 

If you do use steroids, opt for anabolic ones and your vet should monitor liver values, because these sometimes increase with steroid use, in which case the steroids should be discontinued.

 

Pet Education has information about anabolic steroids.

 


Kidney Transplants                                                                                              Back to Page Index


A Treatment, Not a Cure


Some people are surprised to find kidney transplants listed as a treatment, but that is exactly what they are - a form of treatment, not a cure.

 

One centre has stated that the average survival time for a cat receiving a kidney at its facility is only 18 months; whilst The Animal Medical Center in New York has stated that 25% of cats who undergo transplants there do not even survive the initial operation of receiving the kidney, and only 60% survive one year. Even at one of the most longstanding centres, The University of California at Davis, 20-25% of cats died in the year following the transplant. Another vet school with extensive experience, University of Pennsylvania School of Veterinary Medicine, states that approximately 60-70% of recipients are still alive after one year.

 

Problems arise for a number of reasons. Firstly, this is major surgery, and by definition it is being performed on seriously sick cats. Secondly, immuno-suppressive drugs (usually cyclosporine), which stop the body rejecting the new kidney as a foreign body, are required. These must be given religiously at set times (usually every twelve hours), but even so, they may not work for every cat, and then the new kidney is rejected by the cat's body and ceases to work. Since these drugs suppress the immune system, transplant recipients are also vulnerable to infections, which may damage the new kidney.

 

Unfortunately these anti-rejection medications also increase the chances of the cat developing cancer, with a 14% incidence rate reported in cats at one facility who survived more than one year after the transplant. 10% of cats also develop diabetes.

 

Because of the foregoing, as The University of California at Davis has stated, "Due to all the inherent risks with transplantation, it is not considered a prophylactic procedure, and those cats that are doing well with medical management are not considered candidates for transplantation."

 

Transplants are also extremely expensive: the Animal Medical Centre in NYC estimated the cost at US$8000 for the initial surgery and hospitalisation, follow-up care at US$4000 in the first year, and medications and check-ups at US$3000 for each further year. University of Pennsylvania School of Veterinary Medicine gives the cost of the initial transplant as US$12000 - 16000, but gives much lower figures than AMC for ongoing maintenance costs.

 

Ethical Considerations


The transplanted kidney is taken from a healthy cat, who usually then goes to live with the family of the recipient. The major UK charities, Cats Protection, the RSPCA and the International Cat Care, are opposed to kidney transplants because of the ethical issue of removing a kidney from a healthy donor cat with no benefit to that cat, a concern which I share. It is often argued that using a shelter cat "saves a life"; but in the UK, very few cats are euthanised compared to the millions in the USA; and in any event, all the US transplants I have heard about in recent years used a cat purpose-bred by the transplant facility though apparently this is not always the case at the University of Pennsylvania School of Veterinary Medicine. I also wonder what would happen should the donor cat develop CKD him/herself later in life; presumably such a cat, with only one functioning kidney, would develop end stage renal failure more quickly than a cat with two kidneys.

 

Both Cats Protection and the RSPCA have stated that they will not supply cats as donors, and Cats Protection have gone so far as to state that they would "support rigorous punishment measures for any individual who acquires a cat, through whatever means, to use as a donor for feline kidney transplantation".

 

Availability


Kidney transplants are available at a limited number of facilities in the USA and at one location in Australia. The Animal Medical Center in New York and The University of California at Davis are not currently performing kidney transplants.

 

Transplants have not yet been performed in the UK, but on 27 February 2003, the Royal College of Veterinary Surgeons (RCVS) issued guidelines for the procedure. According to the RCVS, the guidelines were published in order to ensure the highest welfare standards for both the recipient and the donor. The RCVS envisages that approved transplant centres will have to meet very strict criteria, so it is expected that it will be quite some time, perhaps even years, before it is possible to perform the procedure in the UK. They are not currently (December 2012) available in the UK.

 

I do find it ironic that the RCVS is prepared to permit kidney transplants when it makes so little effort to promote other, far cheaper and less invasive treatments such as sub-cutaneous fluids.

 

Royal College of Veterinary Surgeons - press release concerning the guidelines.

International Cat Care - article opposing transplants.

Hobbes' story - one cat's experience of a kidney transplant.

 

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This page last updated: 06 December 2013

Links on this page last checked: 25 April 2012