Introduction

Although dietary therapy has long been the central core of treatment of small animals with renal diseases, the level of evidence of most dietary interventions remains very low and based mostly on pathophysiological justifications and on extrapolation from other species. The incorporation of various concepts to facilitate the treatment of renal diseases has certainly the merit of facilitating the administration of medications to correct some of the multiple metabolic alterations associated with loss of renal function. The dietary therapy is however rarely designed individually with clear treatment goals and a monitoring plan for re-evaluation. The oversimplification of the concept of "renal diet for renal disease" should certainly be reviewed and take in consideration the various types of renal diseases and their degree of affection. It seems misleading to think that all types and degrees of renal diseases would require the same dietary approach and should be managed similarly. We will thus review the specific dietary considerations and the current recommendations for small animals with glomerular and tubulo-interstitial diseases.

Chronic Kidney Disease (CKD)

The essential role of the diet in CKD is exemplified by the fact that the first commercially available prescription diet has been elaborated to decrease the uremic manifestations of advanced renal failure. Decreased dietary protein content results in decreased generation of urea and of other metabolic waste products associated with the clinical manifestations of uremia. The exact nature of these uremic toxins and their mechanisms of toxicity remain elusive, but uremia seems to correlate with the serum urea concentration used as a surrogate marker for other uremic toxins. Although protein restriction is considered essential in advanced renal disease, the level of restriction and the stage of CKD at which it is indicated are still debated. Protein restriction is not the only characteristic of renal diets and their efficacy to combat uremia cannot be attributed solely to their lower protein content.

An important goal in early disease is not a decrease of the uremic manifestations (since these animals are not truly uremic) but the slowing down of the natural progression of CKD towards end-stage disease. Adaptive changes with glomerular hypertension, hyperfiltration, glomerular hypertrophy are beneficial on a short-term basis with compensation for the loss of renal function, but when activated chronically, they lead to glomerular sclerosis and chronic interstitial nephritis with accelerated loss of the residual function. Dietary manipulations have been shown to decrease this progression in dogs and in cats.^1,2 The administration of a renal diet to dogs and cats with CKD stages 2 and 3 markedly prolonged their renal and overall survival, it decreased the rate of decline of renal function, and it delayed the onset of uremic crises. These findings, although they don't answer the central question of the mechanism of protection, clearly show the value and the benefit of early dietary intervention in animals with CKD. In summary, we now know that dogs and cats with CKD stages 2 and 3 benefit from receiving a renal diet, but we do not know: 1) whether earlier intervention would be more beneficial; 2) whether all renal diets are equal in efficacy; and 3) what in the renal diet is truly beneficial. Most of these questions are likely to remain unanswered considering the difficulties of conducting appropriately powered clinical studies to address them. We have recently evaluated quantitatively the metabolism of urea in dogs with CKD using a combination of urinary and plasma clearances. Dogs with more advanced CKD displayed a marked increase in their extrarenal (GI) excretion of urea and a marked increase in their endogenous urea generation (catabolism).³ This approach could represent a minimally-invasive method to quantify protein and nitrogen metabolism in a clinical setting and a way to quantify more precisely the individual protein requirements of animals with CKD.

The design of home-made renal diets individually tailored to fit the taste of animals with CKD can be tempting but it is particularly difficult as long as we don't know the optimal composition of renal diets. They should certainly not be designed solely based on their protein content. Phosphorus restriction, alkalinizing properties, addition of antioxidants, and inclusion of anti-inflammatory n-3 fatty acids are likely to be just as critical for slowing disease progression. By individual coaching most dogs and cats can be switched to renal diets and it is important to realize that this change should be made slowly over weeks to months if necessary. In advanced CKD, dietary changes are certainly more difficult and affected animals are less likely to accept diets to which they have not been used. Feeding these animals necessitates either a compromise with more palatable (and less optimal) diets or the use of assisted feeding strategies including feeding tubes. The initial reluctance of most owners to accept feeding tubes that they view as artificial life support, is often overcome when truly exposed to them. Esophagostomy tubes or PEG tubes are commonly used for other indications and they can also markedly improve the quality of life of small animals with advanced CKD. Administration of water in sufficient amounts to help maintaining optimal hydration, ease and reliability of administration of medications, and administration of the qualitatively ideal food in sufficient quantity are the main benefits of feeding tubes. The use of this type of nutritional support is the only way to push the limits of the medical management of small animals with CKD without compromising their quality of life. The personal involvement of the owner and the time required for the feedings should however not be underestimated and be clearly explained to them.

Acute Kidney Injury (AKI)

Dogs and cats with acute kidney injury have very different nutritional requirements and goals. Provision of adequate nutrition has certainly been linked to better recovery rates in humans with AKI and it is likely to be similar in small animals. Here again, prospective studies are unlikely to be conducted with sufficient statistical power considering the lack of uniformity in the underlying etiology, the various degrees of function loss, and the paucity of clinical material. Recommendations are therefore mostly based on anecdotal observations and indirect lines of evidence.

A catabolic condition is unlikely to be suited for adequate tissue repair and renal recovery. Dogs with AKI are however commonly observed to lose 10% of their dry body weight during the first week of therapy, indicating a very significant catabolism. Animals treated with conventional therapy are likely to require at least one week of intensive therapy and the appetite is rarely the first body function to recover. Aggressive nutritional support is therefore indicated from the first day of the disease using a combined enteral and parenteral approach in order to provide sufficient nutrition despite the marked gastrointestinal disturbances of these patients. Animals treated with renal replacement therapies are more likely to feel better and start eating within a few days. Additional nutrient losses notably in the form of filtered amino acids should however be compensated and nutritional support should therefore not be delayed in these animals as well. In all cases it may be useful to keep track of the administered calories similar to the fluid balance or to the administration of medications. This may increase the awareness of the treating staff to the importance of the nutrition and to the difficulties encountered in this constant struggle to reach an ideal nutritional goal.

The qualitative nutritional requirements are even more poorly characterized in dogs and cats with AKI. In light of the severe gastrointestinal manifestations associated to the acute uremia, a high quality, highly digestible, and fat-restricted diet may help to accelerate gastric emptying and decrease nausea. These diets are commonly less calorie dense, but they could be a reasonable start for the first days of therapy. Renal diets with high energy density and protein restriction may prove useful in a second phase to decrease uremia and to more adequately cover the caloric needs of animals with AKI. A progressive transition is encouraged due to the high fat content of most renal diets since this may delay gastric emptying or induce an acute pancreatitis. Energetically dense recovery diets can be used occasionally in animals with AKI but caution should be observed with their high fat and protein content. Dogs and cats treated with renal replacement therapy can usually tolerate high dietary protein contents since protein wastes are efficiently removed by dialysis. This may however result in an increased need for treatments and this approach should be considered carefully.

The design of a nutritional plan for an animal with AKI should be based on individual parameters including the degree of GI disturbances (and thus the possible tolerance for enteral route of nutrition); the degree of metabolic derangements (and thus their effects on appetite); the degree of renal impairment (and thus the degree of tolerance for proteins); the type of therapy provided (and thus the ability to remove generated wastes); and the degree of specific derangements of hydration, electrolyte, mineral, and acid-base balance (and thus the resulting specific qualitative nutritional requirements). Daily re-assessment of nutritional adequacy is mandatory since regular corrections and adaptations are the rule, based on the evolution of the disease and the animal's clinical status.

Glomerular Diseases / Protein-Losing Nephropathies

Urinary protein losses lead to protein malnutrition and weight loss as one of the classical manifestations of these diseases. Dietary intervention is therefore essential for the management of affected animals. Previous recommendations included increased dietary protein intake in order to compensate for the loss but this approach tends to increase the proteinuria and the resulting protein balance is even more negative in most dogs. Current recommendations include a seemingly paradoxical moderate (high-quality) protein restriction and the resulting decrease in proteinuria tends to improve the animal's nutritional status and to create a more positive protein balance. The decreased proteinuria has also a renoprotective effect by diminishing the secondary tubulo-interstitial damage and the progression to azotemia and end-stage renal disease. Since the individual protein requirement is difficult to evaluate for clinical patients, regular assessment of the animal's clinical and laboratory status, haircoat, and lean body mass is essential. The degree of protein restriction may need to be adapted in function of these data.

N-3 polyunsaturated fatty acids have many features beneficial for animals with glomerular diseases: they are anti-inflammatory (most glomerular diseases have an inflammatory component at the glomerular and/or the tubulointerstitial level); they decrease proteinuria (a central therapeutic goal); they are antihypertensive (systemic hypertension is a common manifestation of glomerular diseases); and they are beneficial for restoring normal renal hemodynamics (commonly perturbed in glomerular diseases). Since most renal diets have increased n-3/n-6 ratios, it is unclear what benefit additional administration can potentially bring. Despite this fact, most clinicians will tend to administer higher doses of n-3 PUFAs to small animals with glomerular diseases.

In conclusion, dietary interventions are central for the therapy of most renal diseases. A clear understanding of the metabolic derangements resulting from the disease and of the potential benefits of the dietary changes is essential for appropriate intervention. Similarly to most other forms of therapy, setting clear and realistic nutritional goals for the treatment and for its associated monitoring is necessary for an optimal nutritional support.

References

1.  Jacob F, et al. JAVMA 2002;220(8):1163.

2.  Ross S, et al. JAVMA 2006;229(6):949.

3.  Francey T, et al. (abs) JVIM 2008