Researchers who reviewed cases of 108 dogs in Australia that developed kidney disease after eating chicken jerky treats made in China concluded that the treats probably contained a toxic substance.

Through responses to a survey from clinicians, the researchers learned that about one out of three dogs recovered once they stopped eating the jerky — with no medical treatment required. In one instance, a dog that began medical treatment while still eating jerky did not recover until its veterinarians learned of the association between the treats and illness, according to Dr. Linda Fleeman, a member of the research team.

“We unfortunately did not have follow-up information for all 108 cases and so do not know for certain whether or not they all recovered after the treats were discontinued,” Fleeman said in an interview by email. “… However, anecdotal information is that almost all 108 cases recovered with discontinuation of treat feeding. I feel certain that we would have received feedback if the dogs had not recovered as expected.”

The findings appear in the September issue of the Australian Veterinary Journal, providing the largest case report to date of an international puzzle involving potentially and sporadically poisonous pet treats. The only other published case report, which appeared in the Journal of the American Animal Hospital Association in 2011, described jerky-associated illnesses in four dogs.

While the connection between jerky treats and renal illness in dogs is becoming better documented, what’s actually causing the illness is an abiding mystery. Dried chicken treats made in China — and other treats, to a lesser extent — have been implicated in sickening dogs in the United States and Australia since 2007, and in Canada since 2011. Investigators at the U.S. Food and Drug Administration (FDA) and elsewhere have been unable to pinpoint the problem.

“Based on the results of the testing performed to date, it remains unclear which specific ingredients or finished products may be responsible for causing illnesses in pets,” the FDA posted in an update earlier this year.

The agency has received thousands of reports of illnesses associated with jerky-treat consumption in the past six years. Most involve dogs and chicken-based snacks, but some relate to products other than chicken, and a few cats have been reported as ill.

However, because no one has identified a contaminant, many brands of jerky marketed by multiple companies remain on store shelves. (Some brands were recalled in January after they were found to contain unapproved antibiotics; the FDA and product manufacturers said the antibiotic residues did not explain the suspected toxicity problem.)

Veterinarians widely recommend refraining from feeding dogs jerky while the mystery continues.

Outbreak began shortly after jerky introduced

Cases of illness began occurring in Australia shortly after chicken jerky for dogs became available in that country, according to Fleeman, a private practitioner who was a senior lecturer in small animal medicine at the University of Sydney during the time. She said KraMar Pet Company Pty Ltd. had introduced chicken jerky products only two weeks before the first case was reported, and that KraMar had by far the greatest share of the country’s pet jerky market — 85 percent — during the disease outbreak.

Starting about September 2007 and continuing into 2009, Fleeman said, hundreds of dogs that had eaten the treats were reported ill. “It is my opinion that these 108 cases (described in the study) were the tip of the iceberg,” she said. “I personally heard of hundreds of cases, but only a minority of the vets who contacted me responded to the (study) survey.”

In late 2008, KraMar recalled its Supa Naturals Chicken Breast Strips. Although the company was responding to reports of illness, it emphasized that no scientific evidence had shown the treats to be the cause.

Of the 108 cases researchers reviewed, small dogs — those weighing less than 10 kg., or 22 pounds — predominated. The sick dogs shared a kidney condition known as acquired proximal renal tubulopathy, sometimes referred to as Fanconi-like syndrome.

Fanconi syndrome, which also occurs in humans, is a condition that’s typically inherited,  but sometimes may result from kidney damage. In dogs, the inherited disease is associated chiefly with Basenjis, a breed of hunting dog.

In patients with the disorder, the proximal renal tubules fail to resorb electrolytes and nutrients back to the body but instead, excrete them in urine. A hallmark of the condition is glucosuria, or glucose in the urine, in the absence of hyperglycemia, or high blood sugar.

Common clinical signs, according to the Australian research survey results and reports in the United States, are polyuria and polydipsia (excessive urination and thirst); lethargy; lack of appetite; vomiting; and weight loss.

Of 94 dogs for which the researchers in Australia received treatment information, 30 were treated successfully simply by withdrawing jerky. Those needing medical intervention received therapies including intravenous fluids and/or supplements of glucose, electrolytes and vitamins.

Several dogs needed to be tube-fed due to prolonged anorexia. Some returned to the hospital one or more times due to difficulty staying hydrated and maintaining proper electrolyte balance.

Six dogs died or were euthanized as a result of their illness.

The researchers were able to obtain recovery information for 35 survivors. While clinical signs in eight were resolved in fewer than two weeks, the rest took longer — anywhere from two weeks to six months.

The study describes one dog that required electrolyte supplementation more than four years later. Dr. Sue Foster, a study co-author who works as a small-animal medical consultant to Vetnostics, a diagnostic laboratory in Australia, said she’s followed that case and one other in which the dogs continue to be hypophosphatemic — having low blood phosphate — whenever the supplement is withdrawn.

“I think damage in the proximal renal tubules allows inappropriate excretion of phosphate in addition to glucose,” Foster explained by email. While the kidneys of most patients studied recovered once they stopped eating the treats, in these two cases, she said, “that function of the renal tubules did not appear to recover.”

Following the jerky recall by KraMar, Foster said she continued to diagnose new cases for a period of time, as stores sold the products at a discount instead of removing them from the shelves.

Diet, not just treats, is common thread

KraMar, which was acquired by Nestle Purina in 2010, has not returned the jerky to market, Fleeman said, but a small number of cases continue to occur, and several other pet comestibles have been implicated.

In 2009, Virbac Animal Health removed its VeggieDent chews from the Australian market after several cases of acquired proximal renal tubulopathy surfaced in dogs that had consumed VeggieDents, dental chews with no meat ingredients.

More recently, dried pig ears derived from pigs raised in Australia have been implicated, Fleeman said. As with the chicken jerky, clinical signs resolve once the dogs stop eating the treats.

Compounding the mystery, in a few cases, the sick dogs have no history of eating commercial treats of any kind, Fleeman said. However, “typically there is resolution following a diet change,” she said. “In (these) cases, it is reasonable to suspect that either the base diet might contain a toxin or the etiology of the problem is not associated with diet.”

She noted, “I am aware of several cases in Europe that were not associated with treats but responded to diet change.”

If the link is dietary, Fleeman said the focus on pet treats may prove misleading. “It might be preferable to change the focus from ‘pet treat’ to ‘food-associated acquired proximal renal tubulopathy,’ ” she mused.

“Unless a complete diet history is obtained each time a case is diagnosed,” she added, “there will be a risk of attributing blame or causation to a variety of individual treats and missing data that will help to establish true associations. It is also important to clearly demonstrate resolution of the problem following diet change.”

Dr. Kendal Harr, a veterinary clinical pathologist in the United States who has been following the jerky problem since 2007, said that identifying an unknown contaminant is like searching for a needle in the proverbial haystack.

“The problem isn’t that we haven’t found the toxin; the problem is that we haven’t guessed right about which specific compound we should use standards for in HPLC analysis,” she said, referring to high-performance liquid chromatography, a laboratory technique commonly used to identify toxicants.

“Therefore, when we do figure out what this is,” Harr continued, “it will be something that has not been previously identified as a contaminant.”

The Australian researchers’ conclusion that the chicken jerky is the likely source of acquired proximal renal tubulopathy “makes a lot of sense,” she said. The fact that small dogs seem more susceptible to getting sick from the treats is consistent with the idea that a toxicant is to blame, Harr observed. “You have a dose effect,” she said.

In the past, she said, multiple cases showing an association between eating something and getting sick would be accepted as demonstrating probable toxicity. That’s not so today. “We’re stuck in an age where we almost have too much science, because now we have to prove a (harmful) compound,” she said.

Dr. Stephen Page, director of Advanced Veterinary Therapeutics, an Australian veterinary clinical pharmacology and toxicology consultancy, made a similar point. “There are many other intoxications where the toxic agent is unknown — for example, lily poisoning in cats and raisin poisoning in dogs,” Page, a member of an Australian Veterinary Association task force that helped investigate the outbreak, said by email. “We know lilies and raisins are potentially lethal, but the causative agents are not known.”

He added: “It is unusual to ever have absolute certainty about cause and effect — there is a continuum of level of confidence about the link. And in many cases, intervention is clearly appropriate well before certainty is achieved.”

Pets underappreciated as sentinels?

In their paper, the Australian researchers observe that the disease outbreak “highlights the larger issue of widespread intoxication caused by the globalisation of food systems.”

They elaborate: “There are economic benefits of outsourcing raw materials, manufacturing and distribution processes, but this is accompanied by increased risk that contaminated raw material produced in a poorly regulated market may cross national boundaries and be used in manufacturing processes for numerous products. Toxicoses might involve complex interactions or require repeated exposures …”

The researchers note that the risk isn’t confined to pets. Rather, pets may just be more vulnerable because of the less-varied nature of their diets. They write: “Pets may act as sentinel populations for identification of ingredients toxic to humans, because individual foods tend to comprise a greater proportion of the diets of dogs and cats than is typical for human diets.”

Given the possibility that the pet-treat issue signals the potential for problems in the human food supply, Foster added by email: “I do not believe that sufficient attention has been paid to this issue. … At least in Australia, it has been just a dedicated group of veterinary volunteers trying to investigate and follow-up…”

In the researchers’ experience, the lack of urgency spans countries. Foster said that the research team originally submitted their study to the Journal of the American Veterinary Medical Association (JAVMA); the manuscript was judged to be of low priority and turned down before peer review.

The rejection letter stated that submissions are evaluated initially by editors on “whether they provide substantial new, important and clinically relevant information that will enhance readers’ ability to prevent, diagnose, control or resolve a challenging clinical problem.”

Harr, the American clinical pathologist, called the rejection disappointing. “I don’t understand the reasoning for that because it does seem to mimic exactly what we’ve seen in this country,” she said.

Sharon Granskog, a spokeswoman for the American Veterinary Medical Association, which publishes JAVMA, said the manuscript-review process is confidential, but the fact that the Australian study was turned down should not be interpreted to mean that the subject of Fanconi-like syndrome is a low priority for the organization.