TOXIN ALERT: GRAPES AND RAISINS

The following article is taken from a post in Chazhound Dog Forum. Click here to view the original post.

It has been a common practice to use grapes and raisins in various capacities with our pets—veterinarians have often suggested a grape or two as a low calorie snack for our weight conscious patients, and trainers have recommended using raisins as training treats for such events as obedience and agility. If a question had arisen just a few short years ago regarding potential grape or raisin toxicity, even the ASPCA’s Animal Poison Control Center (APCC) would have discounted any concern.

As a senior veterinary student at The Ohio State University College of Veterinary Medicine in the spring of 2001, I avidly read all veterinary journals delivered to my doorstep. A May 15, 2001 letter to the editor in the Journal of the American Veterinary Medical Association (JAVMA) caught my eye. Written by Sharon Gwaltney-Brant, DVM, PhD, et al. from the ASPCA’s APCC, it summarized a review of cases from their database. They noted 10 dogs with evidence of ingestion of large amounts of grapes or raisins and a correlation with acute renal failure (ARF). I recall being surprised at the information but resolved to not recommend grapes or raisins to my clients as treats for their pets.

Unfortunately in April, 2004, that mentally filed snippet of knowledge became essential information. Scotchie, a 5-year-old, 56 pound, male castrated Labrador mix had indulged in some mischievous activity while his owners were at work. Sometime between 7:30 AM and 4:30 PM, Scotch removed a cardboard canister of raisins (15 ounce container) and ingested the remaining contents (approximately 8 ounces). When his owner, Michelle, returned from work that evening, she cleaned up the pieces of the container but didn’t give the contents a second thought. Most pet owners wouldn’t. After all, as humans, we consume raisins with no ill effects, so why should pets be any different? Scotch began vomiting and having diarrhea about 1 AM with some body tremors. Still thinking the signs were due to dietary indiscretion and not wanting to wake anyone at that time of night, his owner kept him comfortable until she called our service at 7 AM. Our receptionist, Lois, had fortunately also seen something about raisin toxicity at some point and advised Michelle to bring Scotchie in at 8 AM. She then called me.

“Acute renal failure,” I thought. I commended Lois for her quick and accurate thinking and said we would run a general health profile, electrolytes and CBC on presentation. I also called our local specialty/emergency referral center and talked to one of the ER doctors, a former classmate, who was on duty. He had also heard about ARF and raisins but knew no more than I. He recommended contacting poison control. Our owner called the North Shore Animal Protection League Poison Hotline and received a case number and treatment recommendations for Scotch—IV fluids at 1 ½ times maintenance and follow-up renal values for 48-72 hours. On presentation, Scotch was bright and alert, weight was 58#, temperature 99.9 degrees F, panting, HR 130. Blood profile abnormalities indicated ALT 126 u/L (10-100), BUN 32.8 mg/dl (7.0-12.0), calcium 12.01 ng/dl (7.90-12.0), creatinine 5.20 ng/dl (0.50-1.80) and glucose 145.3 mg/dl (77.0-125.0). Electolytes and CBC were within normal limits. An IV catheter was placed in the left cephalic vein and Scotchie was started on lactated Ringer’s solution at 93 ml/hr. He remained alert with no vomiting and was taken out on 3 occasions to urinate. He failed to produce any urine in any of the three trips. At 5 PM his renal functions and electrolytes were repeated. Electrolytes were still normal but BUN had increased to 43.7 mg/dl and creatinine to 7.1 mg/dl. He had received nearly a liter of fluids at this point. I felt it was in his best interest to send him to the referral clinic for overnight monitoring and a urinary catheter. The owners agreed and headed out for the hour plus drive with fluids still running. I called the center and spoke with the ER doctor then on duty to alert her to my concerns for Scotchie. She had also heard of a correlation between ARF and raisins but had never seen a case. She concurred with my thoughts of placing a urinary catheter and monitoring urine output as well as continuing fluid therapy.

On presentation to the referral center, Scotchie was ambulatory and alert, temperature was 100.3 degrees F, HR/pulse 124, respiration: panting, mucous membranes slightly injected, weight 56#. He had managed to chew his IV catheter out in the car so it was replaced. He had no abdominal pain but his bladder was not palpable. Heart sounds were normal and lungs were clear with normal respiratory effort.

Once the IV catheter was in place, he was started on 0.9% NaCl with 20 meq KCl at 140 ml/hr—2 times maintenance. He was given 15 mg famotidine IV and 600 mg keflin IV q 8 hr. (for the urinary catheter). A urinary catheter was placed and put on a closed collection system. An in house urinalysis was performed. Protein was 2+, pH 8 and specific gravity 1.012. All other values were normal. A urine culture/sensitivity (recommended by the Internal Medicine department) was sent out and was subsequently found to have no growth. Overnight Scotchie produced small amounts of urine (with lasix given) and began vomiting. At 1 AM he was bolused with 500 ml 0.9% NaCl and given 7.5 mg reglan IV. At 1:30 AM he vomited 3 more times. It was recommended then that he be transferred to Internal Medicine (IM) in the morning since the vomiting had become a problem. The owners agreed.


When I spoke to Scotchie’s IM doctor on the morning of the 15th, now two days after the exposure, he said the vomiting was still an issue and that urine production waxed and waned with lasix boluses. An abdominal ultrasound was planned as well as more bloodwork and continued aggressive fluid therapy and IV anti-emetics. That evening, I received a report of a normal ultrasound with minimal abdominal effusion and structurally normal kidneys. The blood chemistry profile, however, noted an ever-increasing BUN (76), creatinine (7.4), phosphorous (6.5) and potassium (6.3). On the CBC, hemoglobin was low at 12.8 gm/dl (14.0-18.0) as was plasma protein at 5.1 gm/dl (6.0-7.5) and lymphocytes at 0.66 x 1000 ul (1.20-5.20). Scotchie was bright and alert when his owners visited. At some point during hospitalization, Scotch’s fluids were switched to 0.45% NaCl with 2.5% dextrose, the rate in conjunction with urine output. He continued to receive IV keflin tid and blood pressures were monitored every 12 hours. His urine output was monitored every 2 hours.

On the morning of the 16th I learned that the vomiting had begun again. The plan was to continue with therapy as per the previous day and to recheck blood values. When I checked in that evening, I was told that Scotch was again bright and alert when his family visited. However, today his BUN rose to 106, creatinine to 8.5, phosphorous to 9.4 and potassium to 7.0. It had been decided to continue therapy through Saturday and then decide if any response to treatment had been achieved.

On Saturday morning I spoke to the technician assigned to Scotchie. She said the vomiting had subsided overnight but began again that morning. The plan was to repeat bloodwork and make a determination from there whether to continue treatment. She also said it was the first case of raisin toxicity they had ever seen at the center.

An electrolyte panel done at showed sodium at 141 mmol/L (145-157) and potassium at 6.1 mmol/L (3.7-5.3) with normal chloride. A CBC at 5 AM showed hemoglobin at 12.5 gm/dl (14.0-18.0), RDW at 10.9% (12.0-14.5) and lymphocytes at 0.36 x 1000 ul (1.20-5.20). The rest of the CBC was within normal limits. At 10 AM a profile was repeated. BUN was now 122, creatinine 10.0 and phosphorous 11.2. Throughout his hospitalization Scotchie’s urine production would vary between 150-200 ml per 2 hours to as little as 50 ml per 2 hours even with intermittent boluses of lasix to increase production. After 72 hours of aggressive fluid therapy, Scotchie’s level of azotemia continued to progress and his blood pressure rose to 230. Based on the poor response to therapy as well as the diuretics used to attempt to convert the oliguria and the overall poor prognosis, the owners made the heartwrenching decision to euthanize with private cremation. The next therapeutic step would have been an attempt at peritoneal dialysis. Cost estimates for this, even conservatively, could have run well over $10,000 with a very guarded to poor prognosis. I received the sad news from the attending DVM at 3 PM on Saturday afternoon.

That evening, I sent out a quick e-mail to about 25-30 people in my e-mail address book. Some are veterinarians, some breeders, but most just dog-loving pet owners. I asked that they please send the warning on to their friends. I included my name and clinic so anyone with questions could call to verify this was not another Internet hoax. Since then, we have been overwhelmed with calls from all over —veterinarians, breeders, groomers and pet owners—asking for confirmation of the story. I decided to write the case up with Michelle’s blessing and send the information back out to try to alert both animal care professionals and pet owners alike of the serious health risk.

When I called the North Shore Animal League’s to report Scotchie’s untimely passing, I learned more about grape/raisin toxicity. The spokesperson told me that the center has had reports of toxic episodes with as little as consumption of seven raisins. She also stated that initially it was thought imported grapes were the culprit (perhaps due to a specific pesticide being used). It has since been determined that domestically grown, untreated grapes were just as toxic.

Further literature investigation and communication by e-mail with Dr. Gwaltney-Brant revealed more published information. Dr. Charlotte Means, a veterinary toxicologist at the ASPCA’s APCC in, published “The Wrath of Grapes” in the ASPCA Animal Watch, Summer 2002, Volume 22, Number 2. There were 2 letters to the editor from veterinarians in the United Kingdom published in Veterinary Record on 3/8/03, p. 308; 152 (10) and 3/22/03, p. 376, 152 (12) recounting cases that were treated with aggressive fluid therapy, furosemide, dopamine and peritoneal dialysis. The animals were either euthanized or died from complications of renal failure.

In the Dr. Gwaltney-Brant article in JAVMA (Vol. 218, No. 10, May 15, 2001, p. 1555, Letter to the Editor) 10 cases reviewed from the ASPCA APCC computerized database noted 8 of the 10 were reported from 1999 through March, 2001. Various brands of commercial sun-dried raisins and grapes from various sources (the majority being red seedless) were involved. Vomiting began within the first few hours of ingestion in all dogs. Most passed partially digested raisins or grapes in the vomitus, feces or both. Some were reported to exhibit anorexia, diarrhea, lethargy or signs of abdominal pain. Some of the clinical signs continued from days to three weeks post ingestion.

Metabolically the animals exhibited hypercalcemia, hyperphosphatemia, increased BUN and/or increased serum creatinine 24 hours to several days after ingestion. Oliguria (decreased urine production) or anuria (no urine production) with or without isothenuria was reported in several dogs. Three dogs were euthanized and two died. Five recovered with aggressive fluid therapy which lasted up to 3 weeks in some cases. One dog receiving peritoneal dialysis recovered completely. At the time the letter was written, screening for various contaminants (e.g. mycotoxins or heavy metals) was negative, with further results pending.

One dog who underwent necropsy examination exhibited mild renal tubular damage and metastatic mineralization of numerous tissues, but the pathologist felt the severity of the lesions was insufficient to explain the severity of the dog’s clinical illness.

The important point of this discussion is simply that ingestion of grapes or raisins is a medical emergency. Recent ingestion should be handled as with other toxin exposure: emesis, lavage and activated charcoal. According to poison control, fluids should be administered for a minimum of 48 hours and serum chemistries monitored for 72 hours for the development of acute renal failure. It has been stated that if all bloodwork is normal after 3 days, it is unlikely the animal will develop renal failure. It has also been reported that dogs who become oliguric or anuric have the poorest prognosis for recovery. Further speculation regarding the inciting cause of the toxicity has ranged from an unknown nephrotoxin, an idiosyncratic reaction, contamination with mold toxin (ochratoxin), the presence of high levels of Vitamin D or other similar compound, pesticides or other environmental toxin or some unknown intrinsic toxin. As yet, no specific agent or cause has been confirmed.

Sources for further information include the ASPCA website and the Veterinary Information Network (VIN), a members only site.