Breed and diet-based disease in dogs

Introduction

Many canine diseases can result from an incomplete or imbalanced diet. Whilst the nutritional needs of dogs are well known nowadays 1 various deficiency syndromes that can result from a failure to meet these needs are also recognized. We also know that some essential nutrients can be toxic if taken in excessive quantities, for example hypervitaminosis A and D, and also some mineral trace elements such as selenium, cobalt and iodine.

However, there are also other diseases in dogs that can result from an inappropriate diet. Consider, for example, how diet can affect the appearance of urinary tract disease – and urolithiasis in particular – and problems with the digestive system, including those involving the liver and pancreas. Food allergies and intolerances can also be included in this category, with signs that mainly involve the cutaneous and gastrointestinal systems. Excessive calorie intake leads to obesity, which can be regarded as a pathological condition which predisposes dogs to a multitude of problems. Furthermore, human medicine has shown that there is a relationship between people‘s eating habits and the risk of developing certain tumors, although this association has yet to be studied extensively in animals.

Although there are many diet-based diseases that affect dogs, this article will discuss only those that appear solely, or much more frequently, in certain breeds and which are evidently predisposed to disease due to reasons of heredity.

Urolithiasis 

The term “urolithiasis“ refers to the presence of stones in the urinary tract, and whilst the condition can affect any dog there is plenty of evidence that certain breeds are more predisposed to developing specific types of uroliths.

Ammonium urate calculi

A typical example of a canine pathology that reflects a breed predisposition is ammonium urate stones in Dalmatians. In most dogs uric acid is formed by purine catabolism and converted through the action of the enzyme uricase to allantoin, which is then eliminated in the urine ( Figure 1 ). In Dalmatians, although uricase is present, hepatic transformation of uric acid to allantoin is rather inefficient, due to a genetic autosomal recessive defect, and Dalmatians eliminate much greater amounts of uric acid than other breeds in the urine. The situation is complicated by the fact that re-absorption of uric acid at the level of the renal tubules in this breed is also less efficient. A combination of these factors results in the prevalence of urate stones (predominantly ammonium urate) being particularly high in Dalmatians, with the condition being much greater in males than in females ( Figure 2 ) 2.

Ammonium urate calculi are not exclusively seen in Dalmatians, however, and there are other breeds which show a greater prevalence of this problem than the average canine population, including English Bulldogs, Miniature Schnauzers, Shih-Tzus and Yorkshire Terriers.

Other risk factors for the development of ammonium urate stones – in addition to a genetic predisposition – include the presence of a portosystemic shunt or, more commonly, any serious liver disease which compromises the conversion of uric acid to allantoin and ammonia to urea. 

With respect to dietary therapy, dogs with a predisposition to developing this type of urolith should avoid diets rich in purines; these tend to be found in large quantities if a foodstuff contains high levels of ingredients such as meat and organs. Protein sources such as eggs and cheese are therefore preferred, or a commercial low-purine diet is widely available¹ . Diets that tend to acidify the urine should also be avoided, and if necessary the diet should be slightly alkalized by the addition of potassium citrate (80-150 mg/kg q24H) 3. As with any type of urinary calculus, it is important to stimulate water intake in order to obtain more dilute urine and reduce salt precipitation 4. Finally, uric acid formation may be reduced by using oral allopurinol (15 mg/kg q12H) which inhibits the activity of xanthine oxidase and therefore the conversion of hypoxanthine and xanthine to uric acid. Remember, however, that an animal treated with allopurinol will tend to form xanthine crystals in the bladder if fed a diet which contains high levels of purines.

¹ Royal Canin Urinary U/C low purine

Cystine calculi 

Cystine consists of two molecules of the sulfurous amino acid cysteine. When cystine is present in urine in high concentrations it tends to form crystals because of its poor solubility. Cystine urolithiasis in dogs is quite rare, with an incidence estimated to be only 1-3% of all cases of canine uroliths ( Figure 3 ) 5. However, forms of hereditary cystinuria have been observed in several breeds of dog, including Dachshunds, Basset Hounds, Irish Terriers and English Bulldogs, with a higher prevalence in males.

If a dog is prone to cystine urolithiasis a diet with a moderate protein content (to limit the intake of sulfurous amino acids) and which delivers an alkaline urine (if necessary by adding potassium citrate at the above dose) is recommended. Cystine has poor solubility in acidic urine but the solubility increases when the pH becomes alkaline, and cystine stones may be dissolved by dietary therapy alone through alkalinization of the urine. If dietary alteration is insufficient, drugs that further increase cystine solubility may be used, such as tiopronin (30-45 mg/kg q24H PO) or D-penicillamine (10-15 mg/kg q12H PO). When cystine stones are present it is also a good idea to increase water intake to dilute the urine. However, since a human study has shown that increasing dietary sodium intake corresponds to a higher elimination of cystine into the urine, it is advisable to avoid excessive use of table salt to induce thirst and increase the volume of urine. 5

Xanthine calculi

Xanthine also originates from the catabolism of purines and is the precursor of uric acid. Since xanthine is not very soluble, when present at high concentrations in the urine it can result in the formation of crystals and sometimes uroliths. As noted above, the presence of xanthine crystals and stones in the urine ( Figure 4 ) is generally a consequence of allopurinol therapy; this drug, as well as being used as a therapy for ammonium urate urolithiasis, is often used to treat leishmaniasis. However, there is also a hereditary form of xanthinuria, which is well known in humans and has also been reported in the Cavalier King Charles Spaniel (CKCS) 6. The problem seems to be rare; in the course of a recent study conducted on 35 CKCS dogs, none presented with xanthinuria 7. As with urates, if xanthine urolithiasis is detected a diet low in purines is recommended². 

² Royal Canin Urinary U/C low purine

Zinc-responsive skin disorders

There are many nutrients that an animal needs included in its diet to support a healthy skin; one of the most important is zinc. Any dog fed a zincdeficient diet will eventually develop a dermatosis, but there are two specific forms of zinc-responsive canine skin disorders. The first form typically affects puppies, especially large breeds, fed diets deficient in zinc or diets rich in substances capable of binding zinc and preventing its absorption, such as phytates, which are found in some raw plant materials. The second form is hereditary in nature and is usually seen in Northern breed dogs, such as the Alaskan Malamute and Siberian Husky, although Dobermans and Bull Terriers are also known to be affected ( Figure 5 ). Literature reports of this form of zinc-responsive dermatitis suggest that clinical signs – which can include crusting and erythema of the periorbital areas – may develop due to poor absorption of zinc in the intestine 8. This dermatosis should be treated by oral administration of a zinc salt, such as zinc methionine, zinc sulfate or zinc gluconate. The recommended dose is typically 2-3 mg/kg q24H of elemental zinc, but the clinician should be careful, as the labeling may be confusing. For example, a tablet labelled as “zinc sulfate 220 mg“ actually contains 50 mg of zinc, whereas a “zinc gluconate 50 mg“ tablet may contain 50 mg of actual zinc 8.

Copper-storage hepatopathy

Hereditary copper storage hepatopathy was typically associated with the Bedlington Terrier breed and has parallels with Wilson‘s disease in humans. In Bedlington Terriers the disease is transmitted by an autosomal recessive gene, which limits excretion of copper in the bile, causing copper to accumulate in the liver 9. The high levels of hepatic copper are toxic and promote the onset and progression of liver disease. Breeding programs have largely eliminated this problem from Bedlington Terriers, but hereditary copperstorage hepatopathies have also been observed in other breeds such as Skye Terriers, West Highland White Terriers, Dobermans, Dalmatians and Labrador Retrievers. It should also be remembered that if chronic copper-storage hepatopathy is found on biopsy, copper may have accumulated as a consequence of liver disease, rather than being the cause, as a liver disorder can reduce copper excretion into the biliary system 10.

In the presence of liver disease, if copper accumulation is detected (via analysis of a liver biopsy) it is essential that a diet with a copper concentration lower than the normal minimum requirements of the adult dog is offered. The diet should also contain high levels of zinc (at least 200 mg of zinc per kg of diet (DM)) 11, as this activates metallothionein, a protein that binds copper within the intestinal epithelial cells and inhibits its absorption. In cases where liver copper levels are particularly high, copper chelators (e.g., D-penicillamine at 10-15 mg/kg q12H PO) should be added to the diet to minimize intestinal absorption. Finally, the chosen diet must be suitable for managing chronic liver disease, and the clinician should assess potential diets for protein and fat content according to the clinical picture. The use of nutraceutical ingredients that act as antioxidants and promote regeneration of hepatic tissue should also be considered, for example extract of milk thistle (especially S-adenosyl-methionine (SAME, at 20 mg/kg q24H), ursodeoxycholic acid (15 mg/kg q24H) or silymarin; the therapeutic dose has not been determined for this latter drug, but the author recommends 4-8 mg/kg q24H) 12.

Hereditary gluten intolerances

The term “gluten” refers to the wheat proteins gliadins and glutenins. Wheat gliadins are very similar to the prolamins contained in other cereals, such as barley, rye and oats. In humans, gluten ingested in the diet is responsible for celiac disease, a chronic hereditary enteropathy that affects 1% of the world’s human population 13. Gluten enteropathy in Irish Setter dogs has been widely recognized 14, although selective breeding has now all but eliminated or greatly reduced this problem in many countries.

Gluten enteropathy is characterized histologically by a variable degree of atrophy of the intestinal villi, with the presence of cellular infiltrate in the lamina propria and the epithelium. The alteration of the intestinal architecture has various effects, including decreased enzyme activity of the ciliated border. Affected Irish Setters fed a gluten-containing diet typically show clinical signs of malabsorption, such as chronic diarrhea, weight loss and eventually emaciation, which can develop from around six months of age. Wheat gluten is certainly the trigger for the disease, but to date it is not clear whether barley, rye and (possibly) oats are also harmful for dogs with gluten enteropathy; all these cereals are generally detrimental in human celiac disease patients. The elimination of gluten from the diet leads to an improvement in clinical signs and resolution of the lesions in the intestinal epithelium, and for this reason it represents both the therapy and the only safe method to diagnose the pathology 13.

More recently, a possible role for gluten in the etiology of two other breed-related canine diseases has been proposed. Firstly, gluten seems to play a major role in the so-called “epileptoid cramping syndrome” seen in the Border Terrier. The condition is characterized by neurological signs, with episodes of paroxysmal dyskinesia, sometimes associated with gastrointestinal disorders 15. It has been postulated that this disease results from a hereditary gluten intolerance and at least one study has shown that feeding a gluten-free diet can cause resolution of clinical signs in affected animals 16. Secondly, the role of gluten has also been studied in protein-losing enteropathy (PLE) and protein-losing nephropathy (PLN) in Soft-Coated Wheaten Terriers 17. The authors of this study observed that the administration of gluten to affected dogs resulted in a reduction in blood globulins, but concluded that there were also other factors involved in the pathogenesis of the diseases, and that there did not appear to be a true gluten intolerance in this breed.

Amylase deficiency and starch digestion 

In the course of evolution, or (more accurately) in the process of domestication by humans, the canine species has acquired the capacity to digest starch 18. This contrasts with its progenitor, the wolf, which does not possess this ability. However, it is well recognized that this ability is not equally developed in all breeds; some dogs, especially the Northern breeds, have a lower capacity to digest starch, and affected dogs can develop intestinal disorders with signs such as malformed stools and diarrhea if fed high-starch diets. A recent report demonstrated that production of amylase, the pancreatic enzyme responsible for digesting starch, is less efficient in some Northern breed dogs, such as the Siberian Husky, Alaskan Malamute, Akita Inu and Shiba Inu ( Figure 6 ) 19. Note that this condition is distinct from the more commonly seen exocrine pancreatic insufficiency. It has been suggested that starch was not an important source of energy for the Northern breeds during their evolutionary selection. The same defect in starch digestion appears to exist in several other breeds, such as the Czechoslovakian Wolfdog ( Figure 7 ), but to date there are no scientific studies to prove this. Starch-intolerant dogs should be provided with a diet that is free from starch or contains it in quantities that the animal can tolerate.

Other pathologies

There are many other conditions in dogs with a hereditary basis and that are in some way related to nutrition. Space limits a discussion of such conditions but it is briefly worth noting two of them. Firstly, hypertriglyceridemia has been reported in the Miniature Schnauzer 20 and it has been suggested that dogs with severe hypertriglyceridemia might be at increased risk for the development of pancreatitis, seizures, or both, although the relationship between these disorders and the hypertriglyceridemia has not been proven 21. A diet low in lipids and enriched with fish oil (a source of omega-3 fatty acids that can reduce serum triglyceride levels) is advised for affected animals. Secondly, a defect in the intestinal absorption of vitamin B12 (cyanocobalamin) has been occasionally observed in some breeds, including the Giant Schnauzer, Border Collie, and Beagle22. Referred to as Imerslund-Gräsbeck syndrome (IGS), affected dogs may show a lack of appetite, failure to gain weight, lethargy and malaise that intensifies after eating. Clinically, anemia and excess proteinuria is observed. The treatment simply involves administration of cyanocobalamin on a long-term basis.

Knowledge of dog breeds and the diseases to which the various breeds are predisposed is of great help in daily practice and can enable the veterinarian to arrive at a correct diagnosis of these diseases more quickly. Many diseases with a breed disposition are diet-based and require action be taken with the animal‘s diet to better manage the problem.