Chronic kidney disease (CKD) is the irreversible loss of the metabolic, endocrine and excretory capacities of the kidney. Although commonly considered an illness of older cats and dogs, CKD can occur in animals of all ages, and is considered to be the second most common cause of death in dogs and is the leading cause of death in older cats.

The etiology of CKD is multi-factorial however, replacement of functional nephrons by non-functional scar tissue is a unifying feature. The onset of renal insufficiency and renal failure tends to be gradual and insidious. The uremic syndrome manifests when the residual renal mass is generally less than 75% of the initial functional parenchyma and is insufficient to meet the metabolic and excretory needs of the body.

Historical findings include anorexia, lethargy, depression, weight loss, halitosis, nausea, vomiting, diarrhea, melena, polyuria, and polydipsia. Pale mucous membranes, dehydration, hypothermia, stomatitis, oral ulceration, dull dry hair coat and poor body condition may be noted on physical examination. Laboratory findings include azotemia, hyperphosphatemia, mild to severe metabolic acidosis, hypo or hyperkalemia, hypo or hypercalcemia, anemia, hyperlipidemia, hypertension, bleeding tendencies, and isosthenuria.

The pathogenesis of the uremic syndrome is complex and not fully understood. Protein catabolism and digestion produce many toxins including urea, creatinine, ammonia, guanidine and its derivatives, and "middle molecules". These toxins tend to accumulate when renal function is reduced and contribute many of the clinical consequences of uremic intoxication associated with CKD.

Dietary therapy has remained the cornerstone of management of CKD for decades. The goals of dietary modification are to:

1.  Meet the patient's nutrient and energy requirements

2.  Alleviate clinical signs and consequences of the uremic intoxication

3.  Minimize disturbances in fluid, electrolyte, vitamin, mineral and acid base balance

4.  Slow progression of the disease

It is important to realize that dietary therapy is only one aspect of conservative medical management of CKD. Recommendations regarding dietary therapy and other components of conservative medical management need to be individualized to patient needs based on clinical and laboratory findings. CKD is progressive and dynamic, hence serial clinical and laboratory assessment of the patient and modification of the therapy in response to changes in the patient's condition is integral to successful therapy.

Energy

Sufficient energy needs to be provided to prevent endogenous protein catabolism that results in malnutrition and exacerbation of azotemia. Although the energy requirements of dogs and cats with CKD are unknown, they are presumed to be similar to healthy dogs and cats. Dogs should be fed 132*body weight (kg)^0.73 per day and cats require 50-60 kcal/kg/day. Determination of caloric requirements may vary by as much as 25% and hence should be individualized to patients needs based on serial determinations of body weight and body condition score. Carbohydrate and fat proved the non-protein sources of energy in the diet. Diets designed for the management of CKD are usually formulated with a high fat content because fat provides approximately twice the energy per gram than carbohydrate. In addition, fat increases palatability (for dogs) and energy density of the diet that allows the patient to obtain its nutritional requirements from a relatively smaller volume of food.

Protein

Azotemia and uremia are due to the accumulation of protein metabolites derived from excessive dietary protein and degradation of endogenous protein. High protein intake exacerbates the azotemia and morbidity of CKD, while protein malnutrition is strongly correlated with morbidity and mortality. The rationale for formulating a diet that contains a reduced quantity of high quality protein and adequate non protein calories is based on the premise that controlled reduction of non essential protein results in decreased production of nitrogenous wastes with consequent amelioration or elimination of clinical signs even though renal function may remain essentially unchanged.

The minimal dietary protein requirements for dogs with CKD are not known, but are presumed to be similar to the minimal protein requirements of normal dogs. However, this degree of restriction is necessary only in animals with profound renal failure, and more liberal prescriptions can be fed to dogs with greater renal function. Every patient symptomatic for CKD should benefit from a protein restricted diet. Therapeutic recommendations for cats with CKD are poorly defined. It is more difficult to provide graded protein restriction because the dietary requirements for protein are considerable greater for cats than dogs. The cat is unable to down-regulate hepatic enzyme activity associated with protein catabolism even when dietary protein intake is low.

Protein restriction has been demonstrated to slow the rate of progression of renal disease in rats and people however, evidence of progression remains controversial in dogs and cats. Modified protein diets also moderate the magnitude of polyuria and polydipsia because less solute is delivered to the kidneys in the form of proteinaceous waste products. The magnitude of anemia may also be reduced, as nitrogenous waste products are incriminated in hemolysis, shortened red blood cell survival and blood loss by gastrointestinal ulcerations and impaired platelet function.

The dietary protein should be adjusted to minimize excesses in azotemia while simultaneously avoiding excessive restriction of dietary protein because of the risk of protein malnutrition. If evidence of protein malnutrition occurs (hypoalbuminemia, anemia, weight loss or loss of body tissue mass), dietary protein should be gradually increased until these abnormalities are corrected. High quality protein sources must be used in the formulation of restricted protein diets to minimize the risks of essential amino acid deficiency.

Vitamins, Minerals and Electrolytes

Phosphate retention and hyperphosphatemia occur early in the course of renal disease and plays a primary role in the genesis and progression of renal secondary hyperparathyroidism, renal osteodystrophy, relative or absolute deficiency of 1,25-dihydroxyvitamin D, and soft tissue calcification. By minimizing hyperphosphatemia, secondary hyperparathyroidism and its sequela can be prevented. In addition, dietary phosphorus restriction has been shown to slow the progression of renal failure in dogs, and cats. In one study of dogs with surgically induced reduced renal function, dogs fed a low phosphorous diet (0.44% DM) had a 75% survival versus a 33% survival in dogs fed a high in phosphorous diet (1.44% DM). Renal function also deteriorated more rapidly in the high-phosphorous group. Ross et al reported that cats with reduced renal mass fed a phosphorus-restricted diet (0.24% DMB) had little or no histological change compared to cats fed a normal phosphorus diet (1.56% DMB) who demonstrated mineralization, fibrosis, and mononuclear cell infiltration.

The goal of therapy is to normalize serum phosphate concentration. This may be achieved by limiting dietary phosphate intake. If normophosphatemia can not been accomplished within 2-4 weeks of implementing dietary phosphate restriction, intestinal phosphate binders should be added to the treatment plan. These agents should be administered with the diet. Normalization of serum phosphate concentrations by these methods is often associated with a reduction in the serum parathyroid hormone concentrations; parathyroid hormone concentrations may even return to the normal range.

Hypertension is common in dogs and cats with CRF, and has been implicated with progression of renal failure. Sodium restriction has historically been recommended to alleviate hypertension associated with failure to excrete sodium. However, a recent study in cats with surgically induced moderate renal disease, failed to show any adverse effect of feeding 2 g Na/1000 Kcal. Burankarl et al also suggested that NaCl restriction (0.5 g Na/1000 Kcal) could activate neurohumoral axes that contribute to the progression of renal disease and exacerbate renal potassium wasting. Therefore the ideal dietary sodium concentrations for dogs and cats with CKD are not yet clearly defined.

Potassium deficiency has been identified in cats with CKD. This is due to a combination of urinary potassium loss and decreased potassium intake. However, not all cats are hypokalemic. One study reported 13% of 116 cats with CKD were hyperkalemic, emphasizing the need to monitoring potassium status and adjust intake with oral potassium gluconate on an individual basis.

Acid Base Balance

The kidneys excrete metabolically derived non-volatile acid (sulfates, hydrogen ions) and hence are central to maintenance of acid base balance. As renal function is lost, the capacity to excrete hydrogen ions and reabsorb bicarbonate ions is lost and metabolic acidosis ensues. Metabolic acidosis results in increased renal ammoniagenesis which has been associated with activation of complement culminating in the progression of renal failure. In addition, metabolic acidosis increases catabolism and degradation of skeletal muscle protein, disrupts intracellular metabolism and promotes dissolution of bone mineral exacerbating azotemia, loss of lean body mass, and renal osteodystrophy. Dietary protein restriction results in the consumption of reduce quantities of protein-derived acid precursors however, supplementation with additional alkalinizing agents such as sodium bicarbonate, calcium carbonate or potassium citrate maybe required.

Long-chain Omega Fatty Acids

Long-chain omega 3 fatty acids compete with arachidonic acid and alter eicosanoid production. Preliminary studies have suggested that supplementation with ω-3 fatty acids reduces inflammation, lowers systemic arterial pressure, alters plasma lipid concentrations and preserves renal function. Omega 6 fatty acids (safflower oil) appear to be detrimental to renal disease. Some commercially available diets have an adjusted ω-6: ω-3 ratio of 5:1, however, the ideal ratio for diets has yet to be resolved. Rather than focusing on ratios, the absolute concentrations of specific omega-3 fatty acids would be more appropriate. Studies of the effect of variation in dietary fatty acid composition in cats with renal disease have not yet occurred.

Fiber

Fermentable fiber is a recent addition to the nutritional management of CRF. It is hypothesized that the fermentable fiber provides a source of carbohydrate nutrition for gastrointestinal bacteria which consequently utilize blood urea as a source of nitrogen for growth, increasing fecal nitrogen excretion in the bacterial cell mass, decreasing urinary nitrogen excretion, and thereby reducing the need for protein restriction. However, the major concern with this concept is that unlike BUN, the classical uremic toxins (middle-molecules) are too large in molecular size to readily cross membrane barriers. As a consequence, it is highly unlikely that these toxins are reduced by bacterial utilization of ammonia. Furthermore, studies to document these changes have not yet been reported. As a consequence, widespread application of fermentable fiber as a nitrogen trap can not be recommended at this time. However, fermentable fibers may be beneficial for modulating gastrointestinal health in patients with CKD.

Feeding Strategy

Several companies produce diets designed for the management of CKD in cats and dogs. Each of these diets varies with respect to protein, carbohydrate, fat, fiber, mineral and fatty acid composition, providing the opportunity to select a diet that most appropriately suits the individual patient. Formulation of home-prepared diets is possible, although considerable care is required to ensure nutritional adequacy and consistency. If a client prefers a home-prepared food for their pet, a board certified veterinary nutritionist (Diplomate of the American College of Veterinary Nutrition) should be consulted to ensure the diet is complete and balanced.

Patients with CKD are often anorexic and have reduced appetites. In addition, an altered sense of taste and smell has been reported in people. These factors in combination contribute to the reduced caloric intake and refusal of the diet reported by many owners. Practical measures to improve intake include the use of highly odorous foods, warming the foods prior to feeding, and stimulating eating by positive reinforcement with petting and stroking behavior. Appetite stimulants such as the benzodiazepam derivatives or serotonin antagonists may be judiciously administered, however, in these cases, more aggressive therapy such as nasoesophageal or gastrostomy tube feeding is clinically indicated. Reduced palatability of the modified protein diets has often been cited as the cause of reduced dietary intake in dogs and cats with CKD. However, it not the palatability of the diets per se, but the effect of uremia on the sense of taste and smell, and the development of food aversion that contribute to inappetence. In this regard, it is not advisable to institute dietary changes when patients are hospitalized, as there is a high risk that the patient will develop food aversion. Rather, the renal support diet should be instituted in the home environment when the pet is stable. Dietary therapy is only effective in ameliorating the clinical signs of uremia if it is administered appropriately.

Clinical Studies of Naturally Occurring CKD

The effect of a modified protein, low phosphate diet on the outcome of 50 cats with stable, naturally occurring CRF has recently been reported. Twenty-nine of 50 cats received a modified protein, low phosphate diet, and the remaining 21 of 50 cats remained on their normal diets. The median survival time of the cats fed the modified protein, low phosphate diet was significantly greater then the cats fed the normal diet (633 days versus 264 days, p < 0.0036). Cats fed a renal diet had a median survival time that was 2.4 times longer than cats fed a maintenance diet. The results of this study suggest that feeding a renal diet to cats with CKD will double their life expectancy.

The effect of a modified protein, low phosphate diet on the outcome of dogs with stable, naturally occurring CRF has also recently been demonstrated. Dogs with mild to moderate CRF that were fed a renal diet had a 70% reduction in the relative risk of developing a uremic crisis, remained free of uremic signs almost 2.5 times longer and had a median survival that was three times longer than dogs with CRF that were fed a maintenance diet. Renal function declined more slowly in the dogs that were fed the renal diet. The primary cause of death in dogs fed the maintenance diet was renal-related.

Summary

CKD is the clinical syndrome resulting from irreversible loss of the metabolic, endocrine and excretory capacities of the kidney. CKD is the third leading cause of death in dogs, and second cause of death in cats. Nutrition has been the cornerstone of management for decades. The goals of dietary modification are to meet the patient's nutrient and energy requirements, alleviate clinical signs and consequences of uremia, minimize disturbances in fluid, electrolyte, vitamin, mineral, and acid base balance, and to slow progression of renal failure. Regular monitoring to ensure that dietary and medical management remains optimal for the needs of the patient is crucial for the well being and long term successful treatment of the CKD patient.

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