Life is Good – Rimadyl Toxicity Part 3

October 10, 2012

Today marks the one year anniversary of the day we nearly lost Billy to an accidental mega-overdose of Rimadyl. I was out of town when it happened, but thanks to Rich’s early detection and immediate response, and the skill and dedication of the doctors and staff at PetCare in Santa Rosa, he is alive and well today. And competing in agility (!), despite the gloom-and-doom kidney damage warnings we received when he was discharged. I summarized the 8 days of hell and the journey back in two previous posts: Rimadyl Toxicity – I wish I weren’t an expert, and The Journey from Hell to Healthy.

What am I feeding him now?

Our Internist has cleared him to return to adult food, but I have chosen to keep feeding him the Innova Senior food for two reasons: first, he had a mild weight problem when this whole thing started so I want to keep him from getting chunky; and second, that’s what my senior Border Collie eats so it’s just easier. I have, however, loosened up a little on the treat restrictions. I still keep the Phosphorus guidelines in mind so I avoid organ meat and bone meal, and with the exception of low-fat string cheese (because it’s so convenient), I opt for higher-fat versions of proteins when possible.

Update 10/28/13: My trust in Innova began to wane when they were bought by P&G, and following the recent salmonella scares and resultant recalls, I decided to switch. I repeated my Phosphorus research and landed on Wellness Super5 Chicken – 1.97 g/kcal of P. And our other dogs, a senior Border Collie and a tends-to-plump-up Rat-ihuahua, are now eating Wellness Senior.

Back to Agility

We began his conditioning and returned to training classes as soon as he got cleared by the Internist (about 6 weeks post illness) and he ran in competition 6 weeks later. He was fit and happy and showed no signs of any weakness or illness. Here’s a video from last weekend – happy, healthy, and fast! When he runs like this, it’s hard to remember that just a year ago we weren’t at all sure that he’d ever be able to compete again even if he survived.

What Will The Future Bring?

The damage is there and we may face chronic problems down the road. Since old dogs have kidney problems anyway, it will be hard to tell what is normal aging and what is accelerated by this injury. Nobody knows for sure. So we’ll continue to use good sense in feeding him, monitor his bloodwork every 6-12 months, ensure he always has access to fresh water, and enjoy every day that he’s alive.

Please, Protect Your Dogs

I’m using this milestone to remind my friends to take adequate steps (and after you read the original story, you might want to rethink what that means) to protect their dogs from ALL toxic threats. There is a frightening amount of stuff in our human world that is horribly toxic for dogs. Sadly, I know first-hand of  dogs who have died following ingestion of human medication and hops from a home-brewing supply. Most of us know about the “bad” food items like grapes/raisins, dark chocolate, onions, and macadamia nuts. But how many know that a common (and frequently unlabeled) artificial sweetener can kill them? Yep, Billy lived through that too – please read Xylitol Toxicity – Chewing gum IS bad for dogs. I can think of at least two friends whose dogs ingested toxic doses of Rimadyl AFTER Billy’s nightmare. So lock it up, put it up, or give it up – please don’t trust them to make good decisions.

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The Journey from Hell to Healthy – Rimadyl Toxicity Part 2

October 9, 2012

Last fall when I first posted on this topic (Rimadyl Toxicity – I wish I weren’t an expert), I had just brought Billy home from an 8-day hospitalization for a mega-toxic overdose of Rimadyl. We were sure we were going to lose him and went to hell and back during those 8 days. Somehow he survived, but the discharge instructions were very discouraging and included the following quotes from the doctor (my comments and thoughts in italics):

  • “The overdose has injured his liver and kidneys. He will need to be managed as a chronic renal failure patient for the rest of his life. His level of kidney disease is currently Stage 2 (out of 4).” This was accompanied by a verbal warning that he had to have sustained damage to at least 70% of his kidneys to show these findings.
  • “Resume normal activity.” Really? He’s not just a pet, he’s a 4-year-old Border Collie that just started his competitive agility career. Not sure we have the same interpretation of “normal”…
  • “Part of managing Billy’s chronic kidney disease will be feeding a low protein diet … [examples] … Hill’s k/d or Royal Canin LP… ” For this dog, low protein = not compatible with “normal” activity. And furthermore, both of those foods are grain-based (especially corn), which I concluded years ago was not the healthiest option for my dogs.

As I absorbed these paragraphs of doom and gloom, I was confronted with a happy hungry energetic young Border Collie who was thrilled to be home and more than willing to work (i.e. weave) for his breakfast. And who, after sleeping through the night zipped in a crate, showed no desperation to drink or pee when released. In other words, this dog didn’t display any classic “kidney dog” symptoms (lethargy, anorexia, polyuria, polydypsia).

Where was the disconnect between the diagnosis and the dog? Whereas some might blindly follow the discharge instructions and ignore the dog, and others might look only at the dog and ignore the history and evidence, anybody who knows ME knows what happened next – an intense flurry of activity involving hours and hours of web crawling, review of anecdotal evidence, personal conclusions and changes, and follow-up labs and appointments with specialists. I believe that I chose the informed and responsible route, and what follows is what I learned during the weeks and months following his crisis.

Web Crawling

If you have a dog with kidney issues, whether acute or chronic, let me save you a lot of trouble.  Here’s where you need to go:

DogAware.com. Read it all, click on all the links. In fact, I printed out most of the pages and have them organized in a binder.

K9KidneyDiet Yahoo group. Join it, follow the instructions to post your introduction, review the files and links, then decide what you want to get out of it.

RainGoddess. Phosphorus content of prescription and commercial dog foods. It’s a little dated, but it’s a starting point.

NutritionData. Nutritional content (including phosphorus) of human food. The FDA does not require phosphorus to be reported on labeling. This site overcomes that, though it’s a little tedious because you have to look up each individual item and make a note of what you find.

Anecdotal Evidence

I’m fortunate to be very connected with the dog agility community, which includes many regular folks who have faced extreme acute kidney crises, as well as veterinarians who have experience that they’re willing to share. Here is some of what I learned through that network:

Case study #1: 10-wk old Border Collie puppy with suspected mushroom ingestion in 2001. Extreme liver and kidney toxicity, not expected to live. 10 days in ICU. Discharged with ALT level of 414, creatinine 2.74, dietary restrictions TBD. 4 days later, ALT 134, creatinine 1.57, no dietary restrictions. Dog went on to have an extremely successful agility career culminating with an 8th place finish at Nationals in 2007. Retired from competition at the age of 10 due to unrelated neurological issues and is happy and healthy today at age 11-1/2.

Case study #2: Young adult PyrShep with a similarly extreme Rimadyl ingestion. Parallel treatment, equally grim findings and prognosis. Dog was treated with only moderate dietary restrictions, kidney values improved over a period of months, and the dog continued to compete until retired due to unrelated neurological issues.

Personal Conclusions

Phosphorus/Protein: Everything I read suggests that the issue for kidneys isn’t protein as much as it is Phosphorus (the elemental symbol is “P” – in the interest of space, that’s how I’ll refer to it). As one vet friend put it, “The P is the Key”. Since protein is a primary source of P, that explains the automatic “low-protein k/d diet” recommendation. But as it turns out, the equation is far more complex than that. Proteins vary widely in two important measures: Biological Value (BV), which is amount of absorbed protein that is actually used by the body (loosely, “efficiency”), and P content. Here is a summary of what I have gleaned so far:

  1. Animal protein has a higher BV than plant protein. And eggs and milk are even higher. But that’s not the whole story because of the role that P plays.
  2. Within a food category, medium-to-high fat versions have a lower P level than low-fat foods. This seems to be true for both meat and dairy.
  3. The exception to #2 is oily fishes (mackerel, sardines), which are relatively high in P. But the Omega-3 oils in salmon offset this to some extent because they are supportive to the kidneys.
  4. Whole eggs have one of the highest BV values. The yolks are much higher in P than the whites, but the balance is still pretty good for low-level kidney dogs.
  5. Green Tripe is one of the lowest P proteins, as long as it doesn’t have additives.
  6. Bones have off-the-charts high P levels. So bone meal is an ingredient I’ll be avoiding when I look at dog foods in the future.
  7. Processed white grains are lower in P than whole grains.

Water quality: I have lived in the country for 10 years and have never thought twice about giving my dogs untested well water out of the tap (which I won’t even drink). No more. My dogs now get purified water from the Glacier vending machines or the water store – it may not be perfect, but it has to be a hell of a lot better than what’s coming up from my well.

Kibble:

Before: Innova Adult (239 mgP/kcal)

Now: Innova Senior (186mgP/kcal).

Update 10/28/13: My trust in Innova began to wane when they were bought by P&G, and following the recent salmonella scares and resultant recalls, I decided to switch. I repeated my Phosphorus research and landed on Wellness Super5 Chicken – 197mgP/kcal.

Update 2/11/15: Wellness went through a rebranding about a year ago. I have confirmed with the company that the changes are in name and packaging only, the formulas didn’t change. The new name for Super5 Chicken is Complete Health Chicken and Oatmeal.

Training treats:

Before: Turkey hearts, green tripe K9 Delight (which has additives), string cheese

Now: green tripe K9 Krackle (no additives), Bravo Turkey Bites (all thigh meat), Natural Balance Duck & Potato Treat Roll, and limited string cheese for variety

Labs – What Do The Numbers Mean and Which Ones Matter?

Disclaimer: I am not an expert. This section is intended as a lay introduction to understanding lab values in acute liver and kidney toxicity. Reference values (aka Normal Limits or NL) vary by lab/machine and are here only for illustration.

Kidney

Urine Specific Gravity (USG): represents the degree to which the kidneys are able to concentrate urine. The USG has high variability even in healthy animals because it is influenced throughout the day by exercise and hydration. To ensure the most meaningful results, you need to always test consistently, which we were advised is first catch in the morning. NL=1.015 – 1.045.

Creatinine (CRE): creatinine phosphate is a natural breakdown product of protein which is normally filtered out of the blood by the kidneys. If the filtering capacity of the kidney is compromised, creatinine levels in the blood rise. NL = 0.4 – 1.8.

Blood Urea Nitrogen (BUN): Urea is a by-product from metabolism of proteins by the liver and is removed from the blood by the kidneys. The BUN test is a measure of the amount of nitrogen in the blood in the form of urea, and is thus a measurement of renal function. NL = 7 – 27.

Liver

Alanine Transaminase (ALT ): Elevated ALT levels often suggest liver health problems, but this value is highly variable and cannot be used alone – other values need to be considered to narrow down the significance. NL = 5 – 107.

Total Bilirubin (TBIL): Bilirubin is a breakdown product from red blood cells which is normally excreted by the liver (bile) and kidneys (urine). Elevated bilirubin levels indicate liver cell damage, which causes the bilirubin to “spill” into the blood. NL = 0.0 – 0.4

What about Billy?

We have done regular follow-up lab work since Billy’s hospitalization. The initial results were encouraging, but the results at 3 months post-insult were nothing short of miraculous: ALL of his numbers have recovered to WNL (Within Normal Limits), suggesting that his liver has recovered and his kidneys are compensating.

Advice from the Specialist

Six weeks after discharge and the questionable “resume normal activity” recommendation, we consulted with a Board-Certified Internist who is also an avid agility competitor. We knew that she would understand our concept of normal activity and offer a much clearer perspective on what that meant in terms of Billy’s prognosis and dietary recommendations.

After reviewing the numbers and examining Billy, she was much more encouraging. She had no concerns about competing him as long as we watched out for his hydration and conditioned him to get his fitness level back. She went on to say that she thought he could even return to a regular adult diet at some point. She reminded me that even if he does have 50% kidney damage (which is likely), mammals do quite well at that level, as evidenced by the humans who donate one of their kidneys for transplant. Kidney function is aggregated, so it doesn’t matter if the 50% comes from a well-functioning single kidney or from the remaining nephrons in two damaged kidneys.

I have always accepted the common wisdom that kidneys don’t repair themselves (in contrast to the liver), so I asked about the discrepancy between the recovering lab values and the likely extent of damage. She explained that acute kidney injury is different from chronic kidney disease, and when the former happens in young healthy animals, they can often compensate. The toxicity causes nephrons to die and slough off, leaving gaps. There is evidence that the neighboring healthy nephrons grow and expand into the gaps and become super-nephrons. There is even some evidence suggesting that stem cells may come into play and develop new nephrons.

We walked away from that consult with renewed optimism, a prescription for several months of medication for kidney support (Ursodiol and Vitamin E) and liver support (Denamarin), and no unusual dietary restrictions.

Where are we now?

I’ve written up the one year status report in a separate post: Life Is Good – Rimadyl Toxicity Part 3

Important Disclaimer:

I want to reiterate that my discovery and decisions are specific to my dog, with his history and clinical findings. I don’t want anyone to walk away from this article thinking that what I did for Billy translates to another dog, especially a dog who truly does have chronic kidney disease. That said, the web resources are outstanding for those dogs, and I plan to follow up with a reference post on some of the data I gathered on Phosporus guidelines.


Rimadyl Toxicity – I wish I weren’t an expert…

October 19, 2011

… but I am.

Billy’s first exposure to Rimadyl was just over a year ago and was my fault – I left a bottle with about 10 of Jasmine’s chewable tablets on the counter after feeding time. Billy exploited the opportunity and as a result, he spent 3 days in the hospital for preventative diuresis. We were lucky and he walked away unscathed. After that, we made significant changes to the way we store the Rimadyl to avoid another accidental exposure.

We starting storing the dog food and medications on top of the fridge, with confidence that they were out of Billy’s reach. The meds we keep up there are in stainless steel water bottles with heavy screw tops. We thought that was safe – who wouldn’t? That strategy has worked fine for over a year, but it turns out that Billy’s determination far exceeds anything we could have imagined.

Day Zero: The Disaster Unfolds (Mon, 10/10/11)

At 6:00am on Monday morning, I flew to Salt Lake City for a 5-day conference, leaving Rich at home with the dogs. Sometime around noon, Billy managed to get access to the top of the fridge (there’s no counter or stool nearby, he must have just scaled the front somehow) and knocked nearly everything off onto the floor. He then took the stainless steel container of Rimadyl outside, unscrewed the top, and ate them all. I had recently refilled Jasmine’s prescription so there were around 150 tablets, an unimaginable overdose by any standards.

I chose to avoid the actual calculations until I was sure he was going to survive, but I have now determined that his exposure was ~425mg/kg. Therapeutic dosage is 4.4mg/kg, and the literature talks about renal concerns beginning at 40mg/kg. In other words, his overdose was massive – 100x therapeutic and 10x toxic.

Rich discovered the disaster around 1:30pm and had Billy at PetCare by 2pm. They began aggressive treatment immediately, which involves vomiting, activated charcoal, IV fluids for the kidneys, and meds to protect the liver and the GI tract. He somehow managed to survive the night and I flew home from Utah first thing Tuesday morning.

Days 1 to 5: To Hell and Back (Tues 10/11/11 – Sat, 10/15/11)

The vomiting subsided within a couple of days but he remained nauseous and had very little appetite. His kidneys had paid a price but appeared to have to have stabilized. Because of the massive amount he got, they opted to keep him on the fluids for an extra couple of days as a precaution. Our new concern at this point was the liver, which started to go south on Wednesday. His ALT (liver enzyme) rose dramatically from 62 on Tuesday (which is WNL) to 126 on Wed (way above NL), then 400 on Thurs. If the ALT had continued to rise at that rate into the 1000 range, we would expect acute (and potentially irreversible) liver failure to not be far behind. But it seemed to stabilize in the 400-450 range. His bilirubin (which causes jaundice) remained elevated, but was also unchanged between Wed and Thurs, which suggested it may have plateaued as well. He was definitely yellow, but his eyes seemed a little better on Thursday – I thought it might be my imagination, but the nurse said the same thing.

His clinical presentation has also improved. He began eating Thursday morning, and shows more and more real interest in food (rather than just humoring me by taking something out of my hand). By Friday morning he was seeking out the morsels that I tossed on the floor, that night he was catching them in mid-air, and on Saturday morning he actually offered simple behaviors, like sit and close. He will engage with a toy when I toss it and find the squeaker, but only once or twice. We go on short walks in the parking lot and he trots with his tail wagging, at least for a few steps at a time – he obviously fatigues very quickly and we’re keeping our visits short so he can rest.

Our schedule this week has been simple: visit at noon because that’s when they run the blood tests, stress all afternoon and evening, visit before bedtime, then try to sleep at night. The 24-hour wait between blood draws is excruciating, but we’re encouraged by the small clinical improvements we’re starting to see each time we visit. In fact, today for the first time, he tried to follow us out of the visiting room rather than going back to his cage with the nurse.

Day 7: More Signs of Hope (Mon, 10/17/11)

Saturday night’s visit was quite uplifting. His attitude had improved even from the morning and we got a glimpse of the Border Collie we know and love – catching his toy in mid-air, snatching it off the ground and shaking it, even a little light tugging, and bringing it back for more. His appetite is obviously improving, as is his willingness to “work” for food. On Sunday, the nurse was pleased to report that he was eating rice and chicken out of a bowl (“like a dog”) instead of only out of her hand. And the fact that he was interested in that sort of bland-ish food was also an improvement because we had previously only been able to entice him with “junk food” (the Dr’s term) like hot dogs, string cheese, and green tripe treats.

This afternoon, we got good news from his first urinalysis – no urinary casts. These casts, if present, are positive indicators of kidney tubular damage. Absence doesn’t necessarily mean no damage, but it’s still very encouraging. He’s also not spilling protein into his urine. Plus his bilirubin level has dropped significantly and he’s noticeably less jaundiced today. Liver and kidney blood values still not what we’d like them to be, but he continues to eat and play and his stamina is improving. And my friend Sarah is quick to remind me (after her first-hand experience with Rav’s acute failure of both liver and kidneys as a puppy), “look at the dog, not the numbers”.

Following the good results from the urinalysis, they started tapering his fluids in anticipation of sending him home soon.

Day 8: Homecoming! (Tues, 10/18/11)

I’m beyond thrilled to report that 8 days after admission, Billy is home from the hospital! I picked him up on my way home from work and here we are.

Clinically, he’s getting better every day. Today when I visited him at lunchtime, he ran full-speed across the parking lot to chase a squirrel on top of the fence. He obviously has some reconditioning to do after 8 days of lying around in a cage (and more recently a 5’x5′ “room”), but I’m sure that will come back quickly once he’s released to run freely on the back hill. I’m keeping him confined for a day or two while we re-introduce him and Zack, and also I’m going to be a lot more compulsive about daily mushroom checks. It’s that time of year, and even a small insult that wouldn’t normally be a problem could be real trouble now.

Long-Term Prognosis

Chemically and medically, we definitely have some fallout. His liver numbers are far from perfect, but the Dr. is optimistic that those will recover over time – the liver is very resilient and can regenerate. However, his kidneys have almost certainly sustained some level of permanent damage and we’ll probably have to manage chronic kidney disease throughout his lifetime. Based on his current chemistry, he’s labeled as Stage 2 (out of 4).

Next steps include nutritional research and consultation, guidance from an internist (preferably one who understands what it is that we do), and careful monitoring of blood work and hydration.

How do we protect him in the future?

We may not be able to. Dietary indiscretion is no joke, and neither is his drive to exploit vulnerabilities. We can’t put him in a bubble, so all we can do is continue to make adjustments and hope for the best.

We started by buying a new storage cabinet, which now houses all of the food, medications, and garbage containers. It includes a shelf at about the right height that now serves as our food and medication prep center (instead of the kitchen counter).  The cabinet doors have hasp loops that will always be secured with a carabiner, and we have fabricated a nylon crossbar that inserts into the door handles for further security when we’re not here. And finally, the cabinet will be secured to the wall so he can’t pull it over.

I am sticking with the metal stainless steel water bottles, but I have purchased smaller 12-oz ones and will only store a limited number of meds (i.e. less toxic overdose potential) in the cabinet. The remainder will be stored safely somewhere else.

The other significant change is that Jasmine no longer gets tasty chewable Rimadyl tablets. I replenished her prescription with boring caplets. She won’t mind because she still likes Pill Pockets, which I buy by the case anyway, and which are also now secured in the new cabinet.

Soap Box: Don’t buy chewable Rimadyl

On the day Billy went to the hospital, there were three other dogs admitted for Rimadyl toxicity. One of them got it from its owner’s purse after having just been prescribed it therapeutically that day. Four dogs in one day in one hospital? Something is definitely wrong with this picture, and what’s wrong is packaging a toxic medication as a tasty treat.

Finally, I can breathe again

Last Monday night when I was alone in my hotel in Utah, I was certain I was going to lose my boy and I grieved. And my mood on Thursday night, after his liver went south, was equally dark or maybe even worse because I had let my guard down. But now he’s home, he’s hungry, he’s back to his happy playful joyful self, and he has no activity restrictions. I fully expect him to return to his agility training soon and hopefully he’ll lead a relatively normal life.

Life is good!

Please read the two updates – The Journey from Hell to Healthy, and Life is Good.