While diet remains a cornerstone in the management of canine chronic renal failure, considerable controversy has developed surrounding how and when to recommend intervention with diet therapy. Most veterinarians approach the decision to recommend diet therapy in a fashion analogous to recommending drug therapy. Renal diets vary in several ways from typical maintenance dog foods (Table 1). However, clinical decisions concerning diet therapy rarely involve selecting specific levels of nutrients, but rather involve the decision to or not to advocate use of a renal diet. For the vast majority of canine patients, diet therapy means using a dry or canned diet designed specifically for dogs with renal failure. As such, the therapeutic decision is not based on what protein, phosphorus or salt restriction offer to a dog with chronic renal failure, but rather the benefits likely to accrue to patients from changing the diet from a typical maintenance diet to a therapeutic diet designed for renal failure patients. In making this decision, the impact of diet therapy on both quantity and quality of life should be considered, as well as the occurrence, if any, of adverse consequences of diet therapy. Such information can only be obtained by performing randomized, controlled clinical trials. Unfortunately, to date, most studies on the role of diet in canine chronic renal failure have been performed in young dogs with induced renal failure, a model that often fails to reflect the clinical course of spontaneous renal failure. Further, these studies have often used substitute endpoints that may be highly misleading in predicting the effects of treatment in clinic patients.

TABLE 1: Typical modifications characteristic of renal diets

Important clinical errors may result from using substitute endpoints and logical reasoning to justify treatments. One of the better known examples of the risk of using substitute endpoints comes from the cardiac arrhythmia suppression trial (Echt D, Liebson P, Mitchell L, et al., Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. New England Journal of Medicine 324: 781, 1991). In this study, three antiarrhythmic drugs were compared to placebo in their ability to reduce cardiac death following myocardial infarction in people. Since ventricular premature depolarizations (VPD) appear to be a risk factor for sudden and non-sudden cardiac death after myocardial infarction, it appeared logical to conclude that antiarrhythmic therapy would improve survival by suppressing these arrhythmias. A pilot study performed before the main clinical trial confirmed that the drugs to be used were effective in suppressing arrhythmias in the target population. Only patients that responded favorably to the drugs during the pilot study (i.e., had at least 80% suppression of VPD and 90% suppression of runs of ventricular tachycardia) were admitted to the study protocol. Despite the seemingly obvious benefit of suppressing arrhythmias in these patients, the trial had to be terminated prematurely because of an excess of deaths due to arrhythmia and due to shock after acute recurrent myocardial infarction in patients treated with all three antiarrhythmic agents. Not only were these antiarrhythmic agents ineffective, they were harmful to the patients. Had clinical guidelines been based solely on the finding that the drugs effectively suppressed the arrhythmia rather than results of a properly performed RCCT, a harmful (potentially fatal!) therapy could have been recommended.

The study described above is particularly applicable to companion animal medicine because the limited amount of research funding available often leads to the use of substitute endpoints due to economic considerations. It is typically less expensive to study substitute endpoints because they are easier to measure, their use may shorten study length, and they typically require fewer animals. Despite the economic realities of companion animal medicine, it is important to recognize the risks and limitations of therapeutic recommendations based on studies utilizing substitute endpoints and logical reasoning. Examples of inappropriate substitute endpoints in renal failure studies would be using reduced BUN values to justify dietary protein restriction or using reduced glomerular capillary pressures as an index of reduced progression of renal failure.

Surprisingly, one investigator in 1993 and 1994 suggested that diets formulated more like maintenance type diets may be optimum for renal failure patients (Kronfeld DS: Dietary management of chronic renal diseases in dogs: A critical appraisal. J Sm Anim Pract 1993; 34: 211-219 and Kronfeld DS: Health claims for pet foods: Particulars. J Am Vet Med Assoc 1994; 205: 174-177). We have performed a double-masked randomized, controlled clinical trial investigating the clinical effects of using a typical renal diet compared to a typical maintenance dog food in the conservative medical management of canine renal failure. Results of our study clearly indicate that the renal diet substantially reduced the risk for uremic crises and death compared to a maintenance dog food.