Stem Cell Therapy for Feline Renal Failure?

Re: Stem Cell Therapy for Feline Renal Failure?

Hannah Wynne Richards — Sat, 08 Sep 2012 10:59:41 GMT

Malcolm I'm hoping (eventually ) to see the film I went to school with Nano-Carey Mulligan's mother-so have a bit of a personal interest-may find it rather harrowing though

Wynne

Re: Stem Cell Therapy for Feline Renal Failure?

Simon Neuhoff — Fri, 07 Sep 2012 20:57:17 GMT

[quote user="David Mills"]

[quote user="Martin Atkinson"]

The animals we neuter may not have a choice but if asked would you prefer to get rid of a bit of equipment you're not going to need but which by removing it could improve your life expectancy I wonder what they would answer?

[/quote]

This is a classic misappropriation, which while well-intentioned, is an inappropriate use of anthropomorphism. Animals are very, very unlikely to think in terms of life expectancy, largely from their largely contemperaneous view of the world where they cannot contextualise/rationalise current suffering in terms of future benefits - this underlies our overriding commitment to relieving suffering because for an animal it is likely to be more intense than for a human in the immediate sense. Therefore, in all likeliness an animal's primary interest lies overwhelmingly with avoidance of suffering, that is, a life worth living in the now; this is in sharp contrast to humans who will often suffer enormously in order to fulfil future desires and see the completion of long-laid plans. With this in mind, the case for donor and recipient cats is strengthened far more - the donor cat, living a life of severe autonomy restriction in a shelter, would, we can surmise far rather choose to live in a family home where he is far freer to do what he wants and his QoL is much better - and this would persist even if his life was shorter as a result of a nephrectomy if that lifespan was spent at a higher welfare than shelter where he may/not be adopted (although there is no evidence to say it is shorter). The benefits for the recipient cat are beyond doubt - the relief of the hangover-like state that afflicts CKD cats.

It is incredibly relevant to neutering. Again, the life expectancy argument is flawed. Neutering permanently changes an animal's telos, and is possibly the greatest breach of autonomy other than euthanasia. In doing so, it denies future behaviour around which many of the animal's systems are centered - reproduction (other being survival). There is therefore a denial of future possible good feelings; on some schemes this would be classed as suffering through denial. It also breaches one of the five freedoms. What's more, neutering is something an animal would never ever be likely to 'choose' because it doesn't change its immediate experience of the world for the better (in fact it involves suffering - vet visit, injections, spearation, recovery) - in this way it can easy be said that kidney transplant is more ehtically justifiable than neutering.

The argument regarding unwanted animals is essentially a distributive justice argument, and is far weaker than the individual's interests; in fact, it is a construct as a sticking plaster for irresponsible human control of their animals and in a just society would not be an argument at all; in that way, it is somewhat analogous to charity veterinary care.

[quote user="Martin Atkinson"]

As said the hypocrisy starts with pet ownership in the first place so where does it end? Also for the record I only have one functional kidney due to a congenital hydro-nephrotic kidney and hope to live a long and healthy life but given the choice I'd rather have the back-up of the second one.

[/quote]

Just because we restrict the autonomy of pets through ownership, this does not open the floodgates - we can still act reasonably in spite of ownership and ownership is not an excuse. This is what veterinary ethics is all about - what is justified, what is acceptable, what is reasonable. Ownership is an unalterable fact and that debate belongs in the completely hypothetical.

[/quote]

David I get that argument and can agree to a certain extent but in your argument the shelter/donor cat has to "choose" (anthropomorphising deliberately here) between two evils (ie shelter life or pts vs donating a kidney) that are both man made constructs. It may be the "better choice" but it is still a forced choice.

Re: Stem Cell Therapy for Feline Renal Failure?

Malcolm Ness — Fri, 07 Sep 2012 19:02:24 GMT

"Never let me go" , a novel by Kazuo Ishiguro is well worth a read if you want to anthropomorphise on this subject.

Re: Stem Cell Therapy for Feline Renal Failure?

Martin Atkinson — Fri, 07 Sep 2012 18:43:34 GMT

[quote user="Malcolm Ness"]

[quote user="Martin Atkinson"]from side effects due to immunosuppressive anti-rejection medication[/quote]

I don't understand that - the "donor" cats aren't given immunosuppressives.

[/quote] OK I got my wires crossed on this one.

Re: Stem Cell Therapy for Feline Renal Failure?

David Mills — Fri, 07 Sep 2012 18:28:50 GMT

[quote user="Martin Atkinson"]

[/quote]

[quote user="Martin Atkinson"]

[/quote]

Re: Stem Cell Therapy for Feline Renal Failure?

Rajat — Fri, 07 Sep 2012 18:05:35 GMT

This is a very interesting ethical debate really enjoying reading it. I think in the US where a lot of 'shetler' cats get PTSd who are otherwise healthy it makes a lot of sense. The donor cats get to have a live and save a life too. I wonder as we went to the other extreme and went to a stiuation where 95% or more of shelter cats get adopted where the scales would tip.

For e.g. how about a shelter where cats were never put to sleep BUT the adoption rates weren't 100%. Cats would get fostered out or stay in a cattery long term if not adopted. Obviously gradually the population would increase but there would be people adopting some cats too - in this situation do we think it is ethical to nephrectomise one cat to save a different cats life - if the donor gets a home?

Is it worth losing a kidney to have a home and not live in a cattery? I am leaning towards yes - kind of like I would rather lose a kidney than potentially spend the rest of my life in prison!

Hannah - well copy and paste doesn't take long- I had some links saved and the sheep one I found on pubmed ;) I meant I would keep my bit brief cf the links LOL

Re: Stem Cell Therapy for Feline Renal Failure?

Malcolm Ness — Fri, 07 Sep 2012 17:52:24 GMT

[quote user="Martin Atkinson"] and may put that individual at greater risk of developing renal failure[/quote]

No need to theorise and speculate - the data is out there. The life expectancy of a kidney "donor" is indistinguishable from that of a normal cat.

[quote user="Martin Atkinson"]from side effects due to immunosuppressive anti-rejection medication[/quote]

I don't understand that - the "donor" cats aren't given immunosuppressives.

[quote user="Martin Atkinson"]As said the hypocrisy starts with pet ownership in the first place so where does it end[/quote]

We adopt the same position on neutering as you for the same reasons but many vets do routinely advise puppy castration and I think the comparison is valid, when looked at purely in terms of the patient's interests. There is no benefit to the patient and no measurable effect on the unwanted dog population (unless you are castrating the last dog in the area).

Re: Stem Cell Therapy for Feline Renal Failure?

Hannah Wynne Richards — Fri, 07 Sep 2012 17:11:27 GMT

I don't think there's any comparison Without neutering there would be far more suffering due to pets being unwanted

Wynne

Re: Stem Cell Therapy for Feline Renal Failure?

Martin Atkinson — Fri, 07 Sep 2012 16:13:32 GMT

[quote user="Malcolm Ness"]Most UK vets will happily separate a puppy from both of his testicles, without patient consent (informed or otherwise) and with little if any discernible benefit to that individual patient or any other dog.[/quote] I don't think this is quite a fair comparison, neutering or even cosmetic surgery is not going to relieve the animal of 50% of its basic equipment for survival and may put that individual at greater risk of developing renal failure and from side effects due to immunosuppressive anti-rejection medication. For the record I don't routinely castrate dogs but I do spay females and neuter male cats because we know that their chances of not developing associated diseases and survival into old age increases. The animals we neuter may not have a choice but if asked would you prefer to get rid of a bit of equipment you're not going to need but which by removing it could improve your life expectancy I wonder what they would answer? As said the hypocrisy starts with pet ownership in the first place so where does it end? Also for the record I only have one functional kidney due to a congenital hydro-nephrotic kidney and hope to live a long and healthy life but given the choice I'd rather have the back-up of the second one.

Re: Stem Cell Therapy for Feline Renal Failure?

Malcolm Ness — Fri, 07 Sep 2012 14:18:09 GMT

[quote user="James Laidlaw"]How long do you think the donor cats last in the new house? [/quote]

Why speculate when you could get data from the centres that have been doing the procedure for many years.

I first got pulled into this debate when I read a BVA paper that stated that renal transplantation was an experimental operation with an unknown outcome. At that time a brief pubmed search revealed more than 50 papers reporting clinical research directly related to feline renal transplantation including some substantial case series. Despite that information, much of the subsequent debate involved ill-informed individuals speculating and theorising about matters which had already been thoroughly investigated.

As has been pointed out, the crux of the matter is the "donor" cat. Many colleagues in the US and elsewhere are comfortable with the arrangements that see "donors" adopted into the recipient household as a requirement of the surgery. Others take a different view which, as David points out, is not as obviously superior as some might think. Most UK vets will happily separate a puppy from both of his testicles, without patient consent (informed or otherwise) and with little if any discernible benefit to that individual patient or any other dog.

Re: Stem Cell Therapy for Feline Renal Failure?

Sarah Mark — Fri, 07 Sep 2012 12:00:40 GMT

Good stuff!

Re: Stem Cell Therapy for Feline Renal Failure?

Hannah Wynne Richards — Fri, 07 Sep 2012 11:59:51 GMT

Just re-read last post-that's what makes this job so worthwhile

Wynne

Re: Stem Cell Therapy for Feline Renal Failure?

Hannah Wynne Richards — Fri, 07 Sep 2012 11:58:35 GMT

Gosh Rajat If that's what you think brief!!!!!!!!!!!!!!! Hope you and your patient are recovering from the marathon

Wynne

Re: Stem Cell Therapy for Feline Renal Failure?

Rajat — Fri, 07 Sep 2012 10:07:49 GMT

No worries Sarah, you're very welcome- managed to get 2.5 hrs sleep but dog is much better so it was worth it

Re: Stem Cell Therapy for Feline Renal Failure?

Sarah Mark — Fri, 07 Sep 2012 08:26:32 GMT

Many thanks Rajat - hope your night was not too bad!

Re: Stem Cell Therapy for Feline Renal Failure?

Rajat — Fri, 07 Sep 2012 00:42:33 GMT

Briefly - as I need to go back to work to finish my awful 24 hour shift that today has turned into -->

There has been an abstract/initial information published on intra arterial delivery of stem cells for renal disease, form what I remember encouraging results

I think these things in 10-20 years will become the norm - there is also research into stem cells for severe spinal injuries (at cambridge now for some time) also in Japan.

Personally - I am very excited about it. Progenitor cells can be harvested from fat as we all now know meaning it is relatively less invasive. Hoping for a study to come out for OA too! The stuff from tuta vet etc seems little more than anecdote at the moment.

I think to benefit form it the cat needs to travel to the AMC!

http://veterinarynews.dvm360.com/dvm/Medical+news/AMC-stem-cell-study-to-investigate-intra-arterial-/ArticleStandard/Article/detail/746142

Berent CKD Stem Cell Study

September 29, 2011 (published)

Allyson C. Berent, DVM, DACVIM

Animal Medical Center

Co-investigators:

Chick Weisse
Animal Medical Center
Cathy Langston
Animal Medical Center
Pam Schwartz
Animal Medical Center

Study Start Date: 07/15/2011
Study End Date: 07/15/2014

Study Title.
Chronic Kidney Disease (CKD) is the most common disease diagnosed in middle-aged to older cats (over 35% of aged cats or 16 million cats in the United States of America). The loss of kidney function is prolonged and progressive and there are currently no treatment options to aid in reversing or stopping the progression of this disease. The goal of this study is to investigate the use of stem cells that are derived from the cat's own fat cells (adipose mesenchymal stem cells [MSC]) to be delivered to the kidney and aid in kidney recovery, improvement in kidney function and ultimate prolonged patient survival. These stem cells have been found to repair damaged cells, prevent further cell damage, improve blood flow, and decrease inflammation and scar tissue formation in the tissue in which they are working. Because feline CKD is primarily a disease of inflammation and fibrosis (scar tissue), as well as the need for high blood flow, the use of stem cells in kidney recovery holds dramatic promise. The stem cells have many mechanisms of action but the release of chemicals (paracrine effects) from the surrounding tissues and cells will "turn on" sick cells and improve their ultimate function. Since CKD is so common in cats and renal cell death is the ultimate result, improving the health and environment of the cells that remain could improve the overall function of the kidneys and ultimately improve the survival times and quality of life in these patients. Stem cells can be delivered either intravenously or intra-arterially (into the artery of the kidney [renal artery]). If the cells are delivered into the vein of a leg then the first capillary bed to see the cells would be the lungs, and clearance of many of the cells would occur there, potentially diminishing the effect of these cells in the target organ (kidney). If the cells were directly delivered into the renal artery then the first capillary bed to uptake the stem cells would be the nephrons (or kidney cells), potentially resulting in more dramatic results.

The aim of this study is in 2 phases. First, is to prove the safety of intra-arterial delivery of stem cells in a small number feline patients over a 3 month period. If this procedure deems to be safe then the second phase of this study is to investigate the outcome of cats with naturally occurring CKD after the delivery of stem cells, comparing both selective renal arterial delivery versus peripheral venous delivery, and compare both of these groups to cats that do not get any stem cells. The investigators hypothesize that patients that receive stem cells will have an improved survival to those cats that do not, and the patients that receive the stem cells via selective renal arterial injection will have the best outcome overall. This study is fully funded for all 30 cats.

Study Design:
Prospective, Placebo-controlled, Randomized

Sample Size:
30

Inclusion Criteria:

Feline patients diagnosed with CKD that have had no other experimental therapies.
Patients up to 18 years of age -Patients must be in IRIS Stage 3 CKD (either proteinuric or hypertensive is acceptable)
All patients must have a full workup as described above
All patients must have a negative urine culture. Patients can be enrolled once a positive culture becomes negative and there is a full 6 week course of antibiotics given
No patient can have a current or previous history of urinary tract stone disease
There can be no known comorbidities other than CKD (i.e. the presence of concurrent, unrelated disease [endocrine, hepatic/biliary, pancreatic, gastrointestinal, neurologic, neoplasia, dermatologic, orthopedic, cardiac, etc])
If a patient has a heart murmur an echocardiogram will need to be done to rule out feline cardiomyopathy (HCM, RCM, FOCM, DCM, etc).
All patients must have signed owner consent for participation in this study
All patients must follow the maintenance treatment protocol established by Drs. Berent and Langston without any other supplements

Exclusion Criteria:

Feline patients with concurrent anemia (PCV<30%)

Study Controls:
10 cats will receive IV saline (phase 2 only).

Study Endpoints:
The endpoints are 3 years or time of death in cats with IRIS stage 3 CKD

Samples:
Each patient will have the following tests prior to inclusion to be considered candidates for this study:

Complete history (by Dr. Berent or Dr. Langston)
Diet history
PE (including fundic exam)
Body weight measurement
Body conditioning scoring (1-9)
Hemogram
Serum chem panel
Serum total thyroxine assay
Felv/FIV
Urinalysis
Toxoplasma titers
Urine protein:creatinine ratio
Bacterial urine culture
Blood pressure test (Doppler)
Abdominal ultrasound
Abdominal Radiographs

Files for Download:
Protocol.

Costs/Reimbursments
All follow up care, stem cell treatment and examinations are paid for by the study if they are done at the AMC. Over $14,000 per patient is covered over a 3 year period if done at the Animal Medical Center.

Applications of stem cell therapy in kidney disease- conference proceedings -

https://docs.google.com/document/d/1l32z8PleVdb3RuUE0BOITiKkhDRgBrIOvMWGgPBghXA/edit -

Intra renal arterial injection of autologous mesenchymal stem cells in an ovine model in the postischemic kidney

Nephron Physiol. 2007;107(3):p65-76.

Luc Behr¹; Mehrak Hekmati; Gaëlle Fromont; Nicolas Borenstein; Laure-Hélène Noel; Martine Lelievre-Pegorier; Kathleen Laborde

¹INSERM, U872, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S872, Université Paris Descartes, UMR S872, Paris, France. luc.behr@imm.fr

Article Abstract

BACKGROUND AND AIMS: Acute renal failure (ARF) remains a major healthcare problem. Although modern medical therapy has improved its outcome, the syndrome still has high mortality and morbidity rates [Xue et al.: J Am Soc Nephrol 2006;17:1135-1142]. Recently, stem cell (SC) therapies have been proposed as an alternative for the treatment of ARF on the basis of the damaged cells' replacement or enhanced recovery or regeneration. The aims of this study were to investigate the engraftment of autologous mesenchymal stem cells (MSC) injected into the renal artery in an ovine model of ischemia reperfusion injury (IRI) and to assess the consequence of the delay between injury and cell transplantation on the engraftment. MATERIAL AND METHODS: MSC were transplanted in animals submitted to IRI or in healthy animals not submitted to IRI. Sheep with IRI were grafted at two different time points after injury. Unilateral renal IRI was performed by percutaneous transluminal placement of a balloon catheter in the renal artery. MSC were isolated from bone marrow, cultured, labeled and injected into the renal artery. RESULTS: All ewes showed renal engraftment by MSC, both in tubules and glomeruli. MSC expressed tubular epithelial cell markers and podocyte phenotype. There was a significant increase of engraftment of tubules by MSC when cells were injected early after injury indicating that the delay for cell transplantation after ischemic insult should be short. CONCLUSIONS: This is the first report of intra-arterial autologous transplantation of MSC in the kidney, resulting in a successful engraftment into tubular and glomerular structures. The results strongly suggest that the optimal time window for stem cell therapy is during the early phase of the ischemic injury.

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Re: Stem Cell Therapy for Feline Renal Failure?

Gillian Mostyn — Thu, 06 Sep 2012 22:37:42 GMT

[quote user="Martin Atkinson"]I'm not sure its right to prolong the life of geriatric humans with organ failure let alone animals.[/quote]

So what age do you consider to be a reasonable cut-off for receiving the same treatment a younger person would be entitled to?

Surely treatment should always be based on current QOL and the likely benefits of treatment? Afterall, age is not a disease!

Re: Stem Cell Therapy for Feline Renal Failure?

James Laidlaw — Thu, 06 Sep 2012 21:55:43 GMT

Sorry. I'll take my null argument and spurious hypothesis and enjoy my 3 day weekend.

Re: Stem Cell Therapy for Feline Renal Failure?

David Mills — Thu, 06 Sep 2012 19:35:10 GMT

'The cat can't consent' is a null argument because down this path lies no operations, ever. Animals are not autonomous and cannot make choices about their care, or make the wrong ones (pulling out drips, escaping from kennels) - hence it falls on the VS-owner collaboration to perform surrogate decision making much like a paediatrician-parent setup. The crux is a cost/benefit analysis for all parties both of the procedure and after-effects, and its impact on the affected subjects' quality of life. For the donor cat, it gets a home in place of a kidney - nephrectomies appear to be very well tolerated generally so, as above, it amounts to little more than a spay - benefits strongly dominant. To call in a speculative argument about 'how long the donor cat lasts' is spurious, only serves to muddy the debate, and is a bad argument because its unvalidated and speculative. For the recipient cat their prognosis goes through the roof and the QoL is transformed. I am very, very unsure that it's that easy to make an ethical argument against this when we, by nature of being a vet, infringe animals' autonomy, severely, frequently - from holding for a blood sample to hospitalising to operating for our own convenience (neutering) to pretty much doing anything the animal cannot choose.

Re: Stem Cell Therapy for Feline Renal Failure?

Sarah Mark — Thu, 06 Sep 2012 19:08:35 GMT

Thanks for the link Mark, that's very interesting. This chap really is clutching at straws, his cat is actually quite well currently, but the prospect of her mortality is something he is struggling with. I have offered him a referral on more than one occasion. He does seem clued up about how much it is likely to cost and to be fair has never quibbled about money, I will have a frank chat with him and see if I can make some headway.

I appreciate everyone's input!

Re: Stem Cell Therapy for Feline Renal Failure?

James Laidlaw — Thu, 06 Sep 2012 17:43:38 GMT

How long do you think the donor cats last in the new house? Problem with any surgery is that animals can't give consent , but an owner can. Problem with kidney transplants in my mind is that they aren't owned cats donating, so no owner or guardian to consent. I don't think that's right personally, and wouldn't recommend it for that (amongst other) reason(s).

Re: Stem Cell Therapy for Feline Renal Failure?

Malcolm Ness — Thu, 06 Sep 2012 17:39:29 GMT

Chronic OA looks set to remain a surgical disease for some time to come. We are getting pretty good at putting in plastic hips, knees and elbows in dogs and people!

Re: Stem Cell Therapy for Feline Renal Failure?

Malcolm Ness — Thu, 06 Sep 2012 17:36:30 GMT

[quote user="Hannah Wynne Richards"]

Malcolm It's the harm done tothe donor cat that bothers me -as to harm done to owner's wallet-my attitude would be "it's their money-their legal right tospend it as they wish"-but not at the expense of another cat(the donor)

Wynne

[/quote]

I appreciate the ethical difficulty but in terms of "harm", looking at it objectively, the suffering of "donor" cat is similar to that of a cat being speyed. The up side (at least with all the programmes I have seen) is that the donor cat is adopted into the recipient household. I am not strongly for or against, but there has been, over the years, an awful lot of nonsense talked on this subject.

As an aside, I was asked to speak to several veterinary audiences along with Lord Soulsby when this issue was current a few years ago. One of the major problems perceived by many in the audiences was the need for life-long cyclosporin which was seen as a nasty, dangerous powerful drug that really shouldn't be used in veterinary patients. I wonder how many of those same objectors now use cyclosporin like sweeties in place of a derm diagnosis?

Re: Stem Cell Therapy for Feline Renal Failure?

Martin Atkinson — Thu, 06 Sep 2012 17:29:51 GMT

[quote user="Hannah Wynne Richards"]

Wynne

[/quote]This is true but don't we also have a moral obligation to protect desperate clients from exploitation by some who would willingly take their money knowing that in the end it is not in the better interests of the patient? I'm not sure its right to prolong the life of geriatric humans with organ failure let alone animals.A fool (and a desperate man) and his money is soon parted.

Re: Stem Cell Therapy for Feline Renal Failure?

Hannah Wynne Richards — Thu, 06 Sep 2012 16:24:27 GMT

Wynne