Phosphate binders

RE: Phosphate binders

David Mills — Thu, 14 Jan 2016 12:32:40 GMT

[quote user="Martin Atkinson"]One day there will be an EPIC trial on cats and it will show that I was right all along (possibly)![/quote]

You'll be six feet under by then, I suspect.

(And wrong)

RE: Phosphate binders

Martin Atkinson — Thu, 14 Jan 2016 11:12:06 GMT

[quote user="David Mills"]I certainly wouldn't use them pre-emptively. There is some evidence that using them (and frusemide) before heart failure can alter the RAAS response in a way that potentially accelerates heart failure. [/quote]My experience is the opposite although as said it is anecdotal but it is over many years. The problem with waiting for symptoms of cardiac failure in cats is that the first symptom is often death - its not the same as waiting until a dog gets a cough or a bit out of breath, so its a bit late. I therefore feel there is an obligation to act. The evidence that ACEi's can alter the RAAS response is spurious and IMO is outweighed by the potential benefits. In cats (with normal renal function) where I have measured their progress after induction with benazepril there has been a significant reduction in NT-proBNP, although I might change to pimobendan for new cases in future. I give my clients the benefit of my experience and tell them about the potential downsides and let them make the decision. One day there will be an EPIC trial on cats and it will show that I was right all along (possibly)!

RE: Phosphate binders

Robin Grimmer — Thu, 14 Jan 2016 08:39:46 GMT

Thanks Catriona, Unfortunately it's not available yet, but hopefully will be.

RE: Phosphate binders

Catriona MacIntyre — Wed, 13 Jan 2016 16:30:59 GMT

Hi Robin

It was a free webinar, run by ISFM/International Cat Care (used to be FABCats) and possibly one of the most useful small animal webinars I've watch in ages.

I don't have a link for the recording yet, but if you click to register on this link I think there's an email address to contact.

RE: Phosphate binders

Robin Grimmer — Wed, 13 Jan 2016 14:48:58 GMT

[quote user="Kate Richardson"]

I watched an excellent webinar on managing acute respiratory distress in cats last night

[/quote]

Was it a free one? And if so, do you have a link?

RE: Phosphate binders

Kate Richardson — Wed, 13 Jan 2016 12:22:23 GMT

I watched an excellent webinar on managing acute respiratory distress in cats last night and they got talking about ACE inhibitors in feline cardiac disease and the lecturer (Kieran Borgeat) said there is no evidence that ACE inhibitors have any benefits. Avoiding stress is the biggest factor so if multiple pilling is a problem (which is often the case in cats) then focus on frusemide and clopidrogrel. Pimobendan is specifically contraindicated on the data sheets for cats with cardiac disease; this is specifically related to outflow obstruction, however, he uses it in cats with and without outflow obstruction (with appropriate discussion with owner), particularly in cats where its do or die, and his experience is that it isn't problematic. However as specifically contraindicated on the data sheet, definitely needs a discussion with owner first, especially in first opinion practice.

Prior to this webinar I was in agreement that benazepril would be preferential in this cat, but after this I would rethink and I think I would consider changing to Semintra. Boehrimger obviously have an interest, but this is supported by many well known feline specialists.

RE: Phosphate binders

David Mills — Wed, 13 Jan 2016 11:27:41 GMT

[quote user="Anthony Dennison"] read a few papers on feline cardiomyopathy that mention their use in treatment[/quote]

There's nothing to recommend them from an evidence based perspective, not been shown to extend life or improve clinical signs more than frusemide alone. The only prospective trial was published as an abstract in (?)2002 and never written up.

Pimobendan on the other hand...

I certainly wouldn't use them pre-emptively. There is some evidence that using them (and frusemide) before heart failure can alter the RAAS response in a way that potentially accelerates heart failure.

RE: Phosphate binders

Anthony Dennison — Wed, 13 Jan 2016 09:18:55 GMT

[quote user="robloxley"]opening another can of worms - how strong is the evidence for ACE inhibitors in feline heart disease...[/quote]

currently on the cardiology unit of a certAVP module - read a few papers on feline cardiomyopathy that mention their use in treatment

RE: Phosphate binders

Martin Atkinson — Wed, 13 Jan 2016 09:07:28 GMT

[quote user="robloxley"]how strong is the evidence for ACE inhibitors in feline heart disease[/quote]In my anecdotal experience - very. The evidence for pimobendan is probably stronger however. I feel a David Mills response coming on and maybe a tangential move!

RE: Phosphate binders

Rob Loxley — Tue, 12 Jan 2016 22:27:21 GMT

[quote user="SER"]This cat also has heart disease so I think the benazapril is probably indicated over semintra[/quote]

opening another can of worms - how strong is the evidence for ACE inhibitors in feline heart disease...

RE: Phosphate binders

Sarah Keir — Tue, 12 Jan 2016 20:05:24 GMT

We still don't know if reducing proteinuria changes life expectancy or quality of life for these cats. It is currently a surrogate outcome.

RE: Phosphate binders

Sara Ramsey — Mon, 11 Jan 2016 20:43:49 GMT

I did look at this as we have Pronefra on the shelf but it contains calcium carbonate and I wanted to avoid calcium in this cat. This cat also has heart disease so I think the benazapril is probably indicated over semintra.

RE: Phosphate binders

Thomas Johnson — Mon, 11 Jan 2016 15:59:14 GMT

[quote user="Martin Atkinson"]

PS I still have a load of Renalzin on the shelf well in date as I stockpiled when I heard there was going to be a shortage. And no, I'm not giving it away but may if I still have it when it becomes short-dated so watch this space.

[/quote]

We've changed over to Pronefra, and most clients report that it is more palatable than Renalzin.

RE: Phosphate binders

Andrew Kent — Mon, 11 Jan 2016 09:45:23 GMT

[quote user="Mark Norcott"]

[quote user="SER"]I don't believe there is any point changing from Fortekor to semintra.[/quote]

I think Boehringer would have something to say about that - the company claims that Semintra has an advantage over Fortekor in that telmisartan as an angiotensin II receptor antagonist prevents 'ACE escape' which can occur with chronic use of ACE inhibitors (so angiotensin II levels increase).

JSAP Nov/Dec 2015 Comparison of Efficacy of Long-term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease

Conclusion: Both telmisartan and benazepril were well tolerated and safe. Telmisartan proved to be noninferior to benazepril and significantly decreased proteinuria relative to baseline at all assessment points whereas benazepril did not.

[/quote]

The problem is that (as is sadly the norm these days) it was a non-inferiority trial - so we cannot say based on this that telmisartan is any better than benazepril. Its possible it is but thats not demonstrated here, or at least it did not reach the level that would be consistent with superiority.

The major issue with these drugs is that, whilst they have been shown to improve proteinuria, they have not been shown to offer any survival advantage so using them is still rather speculative. Equally we don't really know if ACE escape is a major issue in our patients - but it is a good sales tool :-)

Andy

RE: Phosphate binders

Mark Norcott — Mon, 11 Jan 2016 09:16:03 GMT

[quote user="Martin Atkinson"]Well they would, wouldn't they?[/quote]

Well I did balance the post by providing the scientific paper which actually was from JVIM (Nov 2015) not JSAP!

I now use Semintra ahead of benazepril as a result of this.

Time will tell.

RE: Phosphate binders

Martin Atkinson — Sun, 10 Jan 2016 22:09:25 GMT

[quote user="Mark Norcott"]

[quote user="SER"]I don't believe there is any point changing from Fortekor to semintra.[/quote]

I think Boehringer would have something to say about that

[/quote]Well they would, wouldn't they? Last CPD meeting I went to on CKD the speaker stated that there was no advantage of Telmisartan over Benazepril and therefore he would not advise changing. Indeed as many CKD cats are also likely to have concurrent cardiac disease then benazepril seems to offer an advantage (that's my opinion not his). That said I have a number of cats that I've started treatment with Semintra since it was launched if they have no evidence of cardiac disease (one of my own cats has both so he's on benazepril. Maybe I can conduct a retrospective survey of relative benefits in a few years if I don't retire first.

RE: Phosphate binders

Mark Norcott — Sun, 10 Jan 2016 16:09:48 GMT

[quote user="SER"]I don't believe there is any point changing from Fortekor to semintra.[/quote]

JSAP Nov/Dec 2015 Comparison of Efficacy of Long-term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease

RE: Phosphate binders

Andrew Kent — Sun, 10 Jan 2016 10:22:48 GMT

I have done it in a small number of cases with pretty mixed results. The main problem with it is the additional expense of monitoring which most owners are not that keen on. Plus many cats do very well on more conventional management of CKD so without clear evidence of a survival benefit its difficult to recommend in most cases.

Andy

RE: Phosphate binders

Sara Ramsey — Sat, 09 Jan 2016 21:58:58 GMT

My thanks too Andy.Calcium homeostasis is difficult. I have put my patient on alu-caps...going to try get the phosphate down and speak to owner about repeating the PTH assay and possibly an ultra- sound scan (we are getting a new one so looking for good cases to try and scan) to make sure we aren't missing another cause of hypercalcaemia.

RE: Phosphate binders

Bill Nolan — Sat, 09 Jan 2016 17:36:12 GMT

Thanks Andy! I had suspected that it was to do with the PTH suppression but couldn't get over the counter intuitive part; low dosing makes sense. Is this something you've (or anyone reading this for that matter) ever done in practice?

RE: Phosphate binders

Andrew Kent — Sat, 09 Jan 2016 15:09:19 GMT

Oh and you are right that its a bit counter intuitive because calcitriol would, typically, increase calcium as you describe, but the doses used in kidney disease are very low so the aim is to suppress PTH without increasing calcium!

RE: Phosphate binders

Andrew Kent — Sat, 09 Jan 2016 15:07:29 GMT

[quote user="Bill Nolan"]

[quote user="Andrew Kent"]

If this is genuinely renal (i.e. high PTH) then some people might use calcitriol therapy to try to control it but its an area of some controversy!

[/quote]

Hi Andy,

I was wondering if you could please explain further as to why you might use calcitriol? It was my understanding that activacted vitamin D contributes to hypercalcaemia by promoting resorption from bone, GI and kidney.

[/quote]

Hi Bill,

I was really hoping nobody would ask that :-p calcium homeostasis is a really horrible subject!

So the main reason to use calcitriol is because it has a negative feedback effect on PTH, and the theory is that some of the problems associated with chronic kidney disease are driven by PTH.

The mechanism of feedback is quite complex but calcitriol has a number of effects (I'm copying this from a guide I have its definitely not in my brain):

Calcitriol interferes in four ways with the ability of the parathyroid gland to elaborate toxic levels of PTH to the serum.

(1) It induces synthesis of the calcium receptor required to block secretion of PTH;

(2) it blocks synthesis of the PTH molecule within the gland by disallowing transcription of the PTH gene into a messenger RNA molecule;

(3) it prevents hyperplasia of the parathyroid gland during uremia; and

(4) it causes regression of the parathyroid gland which had previously been hyperplastic in response to the uremic state. Of these four mechanisms the second, decreased transcription of the PTH gene accounts for most of the lowering of serum PTH.

There has been some controversy over whether this actually helps and studies demonstrating this are lacking but there are some very strong advocates of it (mostly in the US). Initially it was felt that it should only be used in cats with normal ionised calcium, but actually this doesn't seem to be the case (they just have to be monitored more closely).

It is important to normalise phosphate first, otherwise the treatment won't be effective.

There are lots of things written about this approach, if you are a member of VIN (which if you are a student is free) then you can see lots more info about it from the americans.

I hope that explains it a little but happy to discuss further if you want!

Andy

RE: Phosphate binders

Bill Nolan — Sat, 09 Jan 2016 13:16:10 GMT

[quote user="Andrew Kent"]

If this is genuinely renal (i.e. high PTH) then some people might use calcitriol therapy to try to control it but its an area of some controversy!

[/quote]

Hi Andy,

RE: Phosphate binders

Martin Atkinson — Fri, 08 Jan 2016 14:22:34 GMT

[quote user="Andrew Kent"]Whilst total hypercalcaemia is common in CKD cats, most of them will have a normal ionised calcium.[/quote]Interesting, I find that most cats with raised ionised calcium are still idiopathic or I can't find the reason which may or may not be the same thing.

RE: Phosphate binders

Sara Ramsey — Fri, 08 Jan 2016 14:05:46 GMT

I will look when I am back in work! I was crossing my fingers that the high calcium was secondary to the kidneys given the CKD was diagnosed years before the hypercalcaemia, and also the chronicity- I think she was referred six months ago! But it is interesting what you said about ionised calcium in CKD. Haven't ever used calcitriol - even thinking about scrambles my brain with regard to calcium homeostasis