Dietary management of chronic kidney disease

As in 1939, chronic kidney disease is still common in cats and dogs and is responsible for thousands of deaths every year. The kidneys normally filter blood, retain beneficial substances such as protein, and excrete waste products such as urea and creatinine into the urine. Typical clinical signs of chronic kidney disease are increased thirst and urination, weight loss and in later stages halitosis due to uraemia. End stage renal failure results in vomiting inappetance and a moribund state with no urine being produced followed by neurological signs, coma and death. By the time animals are struggling to concentrate their urine they only have 33 % of their functioning nephrons left; by the time they have high urea and creatinine in their blood the animals only have 25 % nephrons left. They are also retaining phosphate which stimulates parathyroid hormone secretion (a condition called hyperparathyroidism) which in turn activates osteoclasts in the bone to break down and release calcium and phosphate into the blood. Bones demineralise and at the same time soft tissues can become calcified, including glomeruli in the kidneys, so this hastens the loss of functioning nephrons. Dietary management aims to delay the rate of loss of surviving nephrons.

The formulation of canine and feline renal diets has changed only slightly over the years; they mainly involve the modifications listed in Table 1 and other features may include supplementation with n-3 fatty acids, B-complex vitamins and antioxidants.

Table 1.

Dietary management in chronic kidney disease (CKD)

A systematic review published in 2010⁽ Reference Roudebush, Polzin and Adams ^{2 )} reaffirmed that scientific evidence still supports dietary management as the most important intervention that can prolong survival time in canine chronic kidney disease (Table 2).

Table 2.

The scientific evidence to support strategies for managing chronic kidney disease (CKD)⁽ Reference Roudebush, Polzin and Adams ^{2 )}

In a prospective study in cats (n 50)⁽ Reference Elliott, Rawlings and Markwell ^{3 )} feeding a veterinary renal diet was associated with a reduction in plasma phosphate and urea concentrations and prevented the increase in plasma PTH concentrations seen in cats not receiving the diet; cats fed the veterinary diet survived for longer compared with those that were not (median survival times 633 v. 264 d).

Dissolution of uroliths (calculi)

According to Medscape^{( 4 )} ‘Medical therapy alone cannot rid the patient of struvite calculi and is typically adjunctive in nature’. However, in the cat and dog struvite uroliths can reliably be dissolved in situ in the urinary bladder averting the need for surgical removal. In dogs clinical signs of increased frequency of urination, straining and passing small amounts of blood typically appear suddenly and the dog is presented to a veterinary practice within 48 h. On radiographs there are usually large and small stones present (Fig. 1) and these can be dissolved within a 3-week period unless there is a urinary tract infection present that does not respond to antibiotic therapy (Figs 2–4). In cats a recent study has shown that dissolution can be achieved in 10–16 d⁽ Reference Lulich, Kruger and Macleay ^{5 )}. Clinical signs can resolve within a few days of starting dissolution and because of the risk of residual small stones dissolution still has to be done following surgical removal to reduce the possibility of a stone nidus encouraging further mineral precipitation and formation of a new stone. Consequently, experts at the University of Minnesota now consider surgical intervention in dogs with struvite uroliths to be professional negligence⁽ Reference Lulich ^{6 )}.

Fig. 1.

(Colour online) Struvite uroliths surgically removed from the urinary bladder of a dog.

Fig. 2.

(Colour online) Radiograph of the urinary bladder containing struvite uroliths in a dog.

Fig. 3.

(Colour online) Radiograph of the same dog as in Fig 1 1 week after starting dissolution using diet. The small stones have all gone and the large stones are smaller and less radiodense.

Fig. 4.

(Colour online) Radiograph of the same dog as in Figs 2 and 3 3 weeks after starting dissolution using diet.

Successful medical dissolution can also be achieved for urate and cystine uroliths in dogs.

Recognition that nutrient deficiencies can cause dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (DCM) was common in both cats and dogs (Fig. 5) and it was not until the 1980s that an underlying nutritional deficiency was discovered as a cause. It had been known since 1975 that deficiency of the β-amino acid taurine could cause central retinal degeneration and blindness in cats⁽ Reference Hayes, Carey and Schmidt ^{7 )} and whilst investigating the underlying mechanisms involved in this condition researchers at the University of Davis, California noted that several cats in their small research colony developed DCM. Staff cardiologist Paul Pion determined that the condition responded to taurine in these taurine-depleted cats and he went on to diagnose taurine deficiency and response to supplementation in feline outpatients diagnosed with idiopathic DCM⁽ Reference Pion, Kittleson and Rogers ^{8 )}.

Fig. 5.

Dilated cardiomyopathy in cats (and some breeds of dog) can be caused by taurine deficiency.

In Pion's study⁽ Reference Pion, Kittleson and Rogers ^{8 )} low plasma taurine concentrations associated with echocardiographic evidence of myocardial failure were observed in twenty-one cats fed commercial cat foods and in two of eleven cats fed a purified diet containing marginally low concentrations of taurine for 4 years. Oral supplementation of taurine resulted in increased plasma taurine concentrations and was associated with normalisation of left ventricular function in both groups of cats. In a follow-up study⁽ Reference Pion, Kittleson and Thomas ^{9 )}, 1-year survival rate was 58 % (twenty-one of thirty-six cats with a known outcome) in the taurine-treated group compared with a 1-year survival rate of 13 % (four of thirty-one cats with a known outcome) in a retrospectively evaluated population of thirty-three cats with DCM.

It emerged that although adequate taurine to meet known nutritional requirements was being added to canned cat foods, processing reduced bioavailability and so some (but not all) cats could not meet their daily requirement and became depleted. As a result more taurine is now added to complete cat foods and dietary deficiency as a cause of DCM is rarely seen. Discovery that taurine deficiency could cause DCM in cats prompted investigations into taurine status in dogs with DCM, and in some breeds a direct association has also been found, notably in Cocker Spaniels, Newfoundlands, Golden Retrievers and Beagles⁽ Reference Kittleson, Keene and Pion ^{10 )}.

Certain breeds of dog (including the Doberman, Boxer, American Cocker Spaniel and Great Dane) have also been shown to develop DCM caused by L-carnitine deficiency and some dogs with this condition respond to dietary supplementation with L-carnitine (50 mg/kg body weight three times daily)⁽ Reference Keene, Kittleson and Rush ^{11 ,} Reference Keene, Panciera and Atkins ^{12 )}.

Remission of signs of hyperthyroidism in cats with thyroid adenoma by dietary manipulation alone

Feline hyperthyroidism caused by a benign thyroid adenoma is the commonest endocrine disorder in cats with an estimated prevalence of 1/300 cats (Fig. 6). Clinical signs can be severe and distressing and include weight loss, increased appetite, tachycardia, hyperactivity, polydipsia, polyuria, vomiting and eventually heart failure.

Fig. 6.

(Colour online) Hyperthyroidism in cats is a common debilitating disease which can be controlled using a diet low in iodine content.

Until recently treatment options included surgical excision, radioactive iodine therapy, or lifetime medical treatment with carbimazole or methimazole. All of these interventions have potential complications; they do not work in all cases and may be inappropriate options for some cats.

The introduction of an iodine-restricted complete diet for cats with hyperthyroidism was seen as a major development for veterinarians. The diet does not directly affect the adenoma, but due to the inability of the tumour to produce thyroid hormone clinical signs resolve within 2–3 weeks. The diet has been shown to be effective in all cases, provided the cat does not eat other foods containing iodine. The recommended iodine content in food is 0·5–2 mg/kg. In hyperthyroid cats fed a diet containing 0·14 or 0·19 mg/kg (canned and dry respectively) total thyroxine can return to the reference interval, with 90 % of cats becoming euthyroid after 12 weeks of exclusive feeding⁽ Reference Melendez ^{13 )}.

There is a problem when the afflicted cat lives in a multi-cat household, because this diet is inappropriate for a cat that does not have hyperthyroidism and so under such situations controlled access is needed, which means preventing access, either by feeding in separate rooms or by using newer technology such as a microchip-controlled pet feeder.

Dietary management in osteoarthritis reducing non-steroidal anti-inflammatory drug dose

The strongest scientific evidence based on several randomised controlled trials supports the clinical benefits to patients of weight reduction or the use of special diets formulated for dogs and cats with osteoarthritis. These incorporate ingredients such as glucosamine, chondroitin, n-3 fatty acids or green-lipped mussel extract. In addition to improving mobility dietary manipulation can reduce the required dose for non-steroidal anti-inflammatory drugs. In one study 46 % of dogs with osteoarthritis fed a therapeutic diet (n 52) had dose reductions and a more rapid decrease in daily carprofen dosage than dogs in a control group fed a regular maintenance diet (n 57)⁽ Reference Fritsch, Allen and Dodd ^{14 )}.

Dietary management in canine lymphoma

There are many proposed mechanism by which dietary manipulation could alter the progression of neoplasia, but there are few clinical studies demonstrating efficacy. In a canine study⁽ Reference Ogilvie, Fettman and Mallinckrodt ^{15 )} thirty-two dogs with lymphoma were randomised to receive either a diet supplemented with menhaden fish oil and arginine or an identical control diet supplemented with soyabean oil. Dogs fed the special diet had significantly (P < 0·05) higher mean serum levels of the n-3 fatty acids DHA (C22 : 6) and EPA (C20 : 5) compared with controls. Higher serum levels of C22 : 6 and C20 : 5 were associated with lesser (P < 0·05) plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22 : 6 levels were also significantly (P < 0·05) associated with longer disease-free intervals and survival times for dogs with Stage III lymphoma fed the experimental diet (Figs 7–8). This study resulted in a diet formulated for use as an aid in the management of dogs with lymphoma.

Fig. 7.

Figure showing (a) the disease free interval and (b) survival times of dogs with lymphoma managed with (experimental) or without (control) dietary management.

Fig. 8.

Relationship between survival time and plasma docosahexaenoic acid (C22:6 fatty acid) concentration in dogs with lymphoma.

Summary

There have been some outstanding, important developments in the field of veterinary clinical nutrition in the past 30 years, and I have highlighted just a few in this overview. As we discover more about nutrigenetics and nutrigenomics, and as we expand our basic understanding of idiopathic diseases we are bound to identify more nutritionally related causes, and be able to develop novel dietary strategies to manage disease processes. Indeed, special diets are already being formulated using selected ingredients with the intention of altering gene expression to achieve clinical outcomes.