Worried about your cat's liver and kidney values?

You should be. Here's why:

It is a well-established fact that cats suffering from FIP often experience liver and kidney problems. I am not going to address them in details, or how to resolve them, if at all possible. If you are interested, our website fipcaregroup.com has detailed pages on the topics, or you can join our FIP Advisory and Care group on Facebook.
You may have read in some FIP groups that promote black-market GS-441524 that all you need is a few B12 injections and Denamarin pills, and it will all be okay. You may even have come across statements that out of range liver or kidney values are of no clinical significance.

WELL, NOT SO FAST.

The FIP Advisory and Care group has long advocated using well-known, safe supplements such as B12, Denamarin (silymarin), slippery elm bark, probiotics, etc. – so these are nothing new. But do they work for cats treated with nucleosides or nucleotides derivatives? These are a whole new ballgame, and the damage they can do may be well beyond the reach of natural supplements.

Understanding nucleotides and nucleosides.

Let’s have a general understanding of nucleosides and nucleotides in not-too-scientific terms. There’s no question they can prove useful against viral replication, but they are far from innocuous.

Nucleosides are the precursors of nucleotides, which constitute the building blocks of nucleic acids, RNA and DNA. Living organisms, including mammals such as humans and cats, depend on replication of DNA and transcription of RNA, whereas coronavirus and its pathogenic mutants that cause FIP have RNA as their information storage. They need to replicate RNA to reproduce.

In the synthesis of DNA or RNA, specific sequences of coding nucleotides are chemically linked together to form DNA or RNA polymers by enzymes called polymerases. Non-natural nucleoside derivatives such as GS-441524 can be uptaken by cells and converted into nucleotide analogs that “trick” coronavirus’ own polymerases into using them as building blocks for synthesizing RNA. When that happens, the integrity of coronavirus RNA could be compromised, and its synthesis halted. As a result, no additional viruses are produced.

Unfortunately, the non-natural nucleosides and nucleotides don’t stop there. At high concentration or prolonged use, these non-natural nucleosides or nucleotides are uptaken by the host (human, cat or otherwise) and trick the host’s own healthy polymerases into using those and replacing good ones. This will induce detrimental effects to the homeostasis of the host – in this case, the cat. Contaminants carried over from the preparation and reconstitution of GS-441524 could also compromise the well-being of the host. The consequence is toxicity.

For example, a cat treated at a 4mg/kg dose of GS-441524 for 12 weeks is subject to a certain level of toxicity. A cat administered twice the dosage (8mg/kg, sometimes higher) for 12, 18, 22 weeks or longer, is exposed to much higher levels. Many cats currently treated with black market GS HAVE elevated liver and kidney values. Their owners should be CONCERNED. That is the direct consequence of using unregulated substances and insufficiently tested therapies. You don’t know what’s going to happen, and when you find out, it’s maybe too late. There is more to FIP than just the virus itself. What is the point of controlling the infection, if the treatment causes irreparable damage to body functions?

And it does not stop there. Remember the part about RNA replication? After several rounds of replication –with coronaviruses, they happen very fast – the evolutionary mechanism will find a way to recognize AND bypass the aberrant nucleotide incorporation into its RNA genome. The consequence is drug resistance. The antiviral is rendered powerless. Once that happens, the process is irreversible, and the fight is lost.

Beyond the sales pitch...

Does it mean that all cats treated with black-market GS-441524 will end up with damaged kidneys and liver, or develop drug resistance? We don’t know the answer to that question. Some may; others may not. The point here is that people are under the impression that they are using a safe method to cure their cats. They base their assumption of safety and efficacy on this February 13, 2019 study “Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis

They ignore a few essentials:
– One clinical field trial on 31 carefully selected cats does not reflect the reality of FIP. Especially not with a marked preference for wet FIP and the exclusion of neuro or ocular FIP. Nor does it indicate what to expect when using an uncontrolled substance instead of the Gilead-supplied GS-441524.
– As for the study’s claim that “no significant changes were observed over the entire treatment periods” with regards to liver or kidney values, I am puzzled. The supplemental tables 1, 2, and 3 in the study do not exactly show smooth, flat curves, which would be consistent with “not significant.” On the contrary, you see a lot of ups and downs over 20 weeks of monitoring, and that is from compounded numbers (from all cats).
liver and kidney values tables
It would be interesting to see the same tables but for each cat. They may well paint a different picture and show that some cats do better than others. It is possible that the cats who relapsed, were euthanized, or treated longer than 12 weeks had significantly higher values. But that information is not available to the public, so we don’t know one way or the other.
– There is no available scientific data on prolonged use, higher dosage (some cats are injected at twice or more than the suggested dose), or to eliminate coronavirus from non-FIP cats.

The bottom line is that you have to do your due diligence. Whatever you decide to do  cannot be based on what others tell you because of their personal agenda. Sellers depend on convincing cat guardians that they offer a safe, miracle cure. And because their product is not legal, there is no accountability, should the result be different than promised. Like, for example, cats suddenly showing elevated creatinine, BUN, ALP, AST, etc. Those are not normal. You should NOT accept that they are.