Nutritional Management

7. Nutritional Management

Dietary therapy has remained the cornerstone of management of chronic renal failure 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, and (4) slow progression of the renal failure (Figure 11).

Figure 11. Dietary management of CRF: 4 main goals.

Energy

Sufficient energy needs to be provided to prevent endogenous protein catabolism which will result in malnutrition and exacerbation of azotemia. Although the energy requirements of dogs with chronic renal failure are unknown, they are presumed to be similar to healthy dogs. Dogs should be fed 132 kcal x body weight (kg)0.75 per day. Determination of caloric requirements may vary by as much as 25%. Hence energy intake should be individualized to the patient needs based on serial determinations of body weight and body condition score. Carbohydrate and fat provide the nonprotein sources of energy in the diet. Diets designed for the management of chronic renal failure are typically formulated with a high fat content because fat provides approximately twice the energy per gram of carbohydrate. Therefore fat increases the energy density of the diet which allows the patient to obtain its nutritional requirements from a smaller volume of food. A smaller volume of food minimizes gastric distention, which reduces the likelihood of nausea and vomiting.

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 chronic renal failure (Polzin et al., 1983), 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 is based on the premise that controlled reduction of non essential amino-acids results in decreased production of nitrogenous wastes with consequent amelioration or elimination of clinical signs, even though renal function remain essentially unchanged. Indeed, studies have shown that modifying dietary protein intake can reduce blood urea nitrogen and provide clinical benefits to dogs with chronic renal failure (Polzin et al., 1983; Finco et al., 1985; Polzin et al., 1988; Polzin & Osborne, 1988; Leibetseder & Neufeld, 1991; Jacob et al., 2002). Modified protein diets also moderate the magnitude of polyuria and polydipsia because less solute is delivered to the kidneys in the form of nitrogenous 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.

Protein restriction has been demonstrated to slow the rate of progression of renal disease in rats and people. It is less certain if protein restriction alters progression of renal failure in dogs (Finco et al., 1985; 1992a; 1992b; 1994; 1999; Robertson et al., 1986; Polzin et al., 1988). Most studies have been performed using the remnant kidney model, which does not necessarily reflect naturally occurring disease. In addition, some of the studies have been confounded by alterations in energy and/or phosphate intake in addition to protein restriction. Brown et al reported that protein restriction did not alleviate glomerular hypertension, hypertrophy, hyperfiltration or progression in dogs with induced renal failure (Brown & al., 1990; 1991a). Although protein moderation has been clearly demonstrated to improve the clinical status of the uremic patient, it is less clear what effect protein moderation has on progression of renal disease.

The goal of dietary protein restriction is to reduce the plasma urea as much as possible whilst avoiding protein malnutrition. Although urea is not a major uremic toxin it is regarded as an index for all nitrogenous wastes, hence therapies designed to reduce urea concentration are presumed to reduce other uremic toxins and usually correlate with clinical improvement (Leibetseder & Neufeld, 1991; Hansen et al., 1992; Jacob et al., 2002). Urea concentration may be influenced by dietary protein intake, dehydration, catabolism, gastrointestinal bleeding, sepsis, and drug administration (glucocorticoids, tetracyclines). Most pets have minimal clinical signs when the urea is less than 28 mmol/L or 1.7 g/L (BUN < 80 mg/dL) (Table 7).

The minimal dietary protein requirements for dogs with chronic renal failure are not known, but are presumed to be similar to the minimal protein requirements of normal dogs, i.e. 1.33 g/kg/day (2.62 g/kg BW0.75 or 20 g/1000 kcal ME according to NRC 2006, under press). 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 chronic renal failure should benefit from a protein restricted diet. Most renal dry diets contain between 12 and 18% proteins, i.e. 30 - 45 g/1000 kcal).

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.

Owner dietary compliance can be checked by calculating the BUN:Creatinine ratio (BUN and creatinine are expressed in mg/dl). On a normal diet it will be around 25 whereas on a restricted protein diet it will be around 10. A BUN:Creatinine ratio greater than 30 is usually associated with gastrointestinal bleeding, dehydration or sepsis.

Vitamins, Minerals and Electrolytes

Phosphorus

Phosphate retention and hyperphosphatemia occur early in the course of renal disease and play 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 sequellae can be prevented. In addition, dietary phosphorus restriction has been shown to slow the progression of renal failure in dogs (Brown et al., 1991b).

In one study of dogs with surgically induced reduced renal function, dogs fed a low phosphorus diet (0.44% DM) had a 75% survival versus a 33% survival in dogs fed a high phosphorus diet (1.44% DM) (Finco et al., 1991b). Renal function also deteriorated more rapidly in the high phosphorus group (Figure 12).

Figure 12. Influence of dietary phosphorus restriction on life expectancy of dogs with chronic renal failure (Finco et al., 1992a).

The mechanism of how phosphate restriction slows progression of renal disease is not fully understood. It may be related to decreased phosphate retention, decreased soft tissue mineralization or prevention of secondary hyperparathyroidism.

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.

Calcium

Dietary calcium is less important than phosphate in chronic renal failure and hypo, normo, or hypercalcemia may be observed. It has been recommended that the total calcium x phosphorus (expressed in mg/dL) product should not exceed 60. This may promote further soft tissue calcification and lead to progression of renal damage. For example, if the calcium concentration is 12 mg/dL and the phosphate concentration is 8 mg/dL, then the calcium x phosphate product is 12x8 = 96, which exceeds 60. Hence calcium supplementation needs to be individualized and adjusted according to response in terms of measured total blood calcium.

Sodium

Hypertension is common in dogs with CRF (Jacob et al., 2003). Furthermore, hypertension has been implicated as a factor that contributes to the progression of renal failure. Dogs with naturally occurring chronic renal disease and a systolic blood pressure greater than 180 mmHg were more likely to develop a uremic crisis and to die compared with dogs that have a normal systolic blood pressure (Jacob et al., 2003). Furthermore, the risk of developing a uremic crisis and of dying increased significantly as systolic blood pressure increased.

Sodium restriction has been recommended to alleviate hypertension associated with failure of the kidneys to excrete sodium. However, altering sodium intake from 0.5 to 3.25 g Na/1000 kcal did not influence development of hypertension or affect glomerular filtration rate in dogs with surgically induced renal reduction (Greco et al., 1994a; 1994b). Therefore the ideal dietary sodium concentrations for dogs with chronic renal failure are not yet clearly defined. Current recommendations are normal to mildly restricted sodium diets. The capacity to adjust sodium excretion rapidly in response to changes in intake becomes severely impaired as renal failure progresses. If sodium intake is rapidly reduced, dehydration and volume contraction may occur with the potential of precipitating a renal crisis. Hence, a gradual change from the pet's previous diet to the salt restricted diet is recommended.

When an ACE-inhibitor is prescribed in a dog receiving a low sodium diet, it is recommended to check the arterial pressure and the renal func-tion during the first few days of treatment.

Potassium

Potassium deficiency has been identified in some dogs with chronic renal failure. Potassium status should be monitored and intake adjusted accordingly with oral potassium gluconate on an individual basis.

Vitamins

Water-soluble vitamins are excreted in urine and deficiency may develop due to polyuria associated with chronic renal failure. These losses may be a contributing cause of anorexia and replacement of the losses may be beneficial in correcting or preventing anorexia. Commercially available renal failure diets contain additional amounts of water-soluble vitamins and further supplementation is not required.

Renal excretion of vitamin A is reduced in people with chronic renal failure. A recent study reported that dogs with naturally occurring renal disease had higher plasma concentrations of retinol compared to healthy dogs (Raila et al., 2003). Therefore, it appears prudent to avoid supplements containing vitamin A.

Acid Base Balance

The kidneys are central to the maintenance of acid base balance. As renal function declines, the capacity to excrete hydrogen ions and reabsorb bicarbonate ions is reduced and metabolic acidosis ensues. Metabolic acidosis increases renal ammoniagenesis which induces tubular inflammation and lesions due to complement activation, contributing to the progression of renal failure.

In addition, metabolic acidosis increases catabolism and degradation of skeletal muscle protein, disrupts intracellular metabolism, 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 may be required.

Omega 3 & 6 Fatty Acids

Long chain ω-3 fatty acids (EPA-DHA) compete with arachidonic acid and alter eicosanoid, thromboxane and leukotriene production (Bauer et al., 1999). Remnant kidney studies in dogs have reported that long chain ω-3 fatty acid supplementation (menhaden fish oil) reduces inflammation, lowers systemic arterial pressure, alters plasma lipid concentrations and preserves renal function (Figure 13) (Brown et al., 1996; 1998a; 1998b; 2000). The efficacy of shorter chain ω-3 fatty acids such as those found in linseed oil, are not yet known.

Figure 13. Influence of feeding different dietary fatty acids over 20 months on glomerular filtration rate in 3 groups of dogs suffering from CRF (Brown et al., 1996). Compared to a diet consisting of mostly omega 6 fatty acids, a diet with a high fish oil content appears to improve GFR in the long term whilst minimizing the development of glomerulosclerosis.

Omega 6 fatty acids (safflower oil) appear to be detrimental in dogs with naturally occurring renal disease by acutely increasing glomerular filtration rate (Bauer et al., 1997).

Some commercially available diets have an adjusted ω-6: ω-3 ratio however, rather than focusing on ratios, the absolute concentrations of specific omega-3 fatty acids would be more appropriate. Such studies have not yet been reported.

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 for gastrointestinal bacteria which consequently utilize blood urea as a source of nitrogen for growth. The increase in bacterial cell mass increases fecal nitrogen excretion and has been suggested to decrease the blood urea nitrogen concentration and reduce 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 cannot be recommended at this time.

However, even moderate renal disease alters duodenojejunal motility and decreases colonic transit time in dogs (Lefebvre et al., 2001). Therefore, dietary fiber may be beneficial for improving gastrointestinal health and motility.

Antioxidants

Endogenous oxidative damage to proteins, lipids and DNA is thought to play an important role in the progression of renal disease in humans (Locatelli et al., 2003; Cochrane et al., 2003).

Nutrients such as vitamin E, vitamin C, taurine, carotenoids and flavanols are effective antioxidants that trap free radical species. Humans with chronic renal disease have been shown to have lower concentrations of vitamin E and vitamin C, and high concentrations of markers of lipid peroxidation (Jackson et al., 1995). These studies suggest that humans with chronic renal disease have oxidative stress. Studies in rats have suggested that supplementation with vitamin E may modulate tubulointerstitial injury and glomerulosclerosis, suggesting that vitamin E may slow progression of renal damage (Hahn et al., 1998; 1999). One study in children with focal segmental glomerulosclerosis reported that vitamin E supplementation decreased proteinuria (Tahzib et al., 1999). There have not been any studies evaluating oxidative stress or antioxidant status in dogs with renal disease.

Flavanols, a subclass of flavonoids, are polyphenolic antioxidants which are found in a variety of plants (Figure 14). Epigallocatechin gallate is recognized as one of the most active flavanols in protection against oxidation (Figure 15). Within plants, flavanols are powerful antioxidants that protect the integrity of the cell membrane and genetic material. Flavanols also chelate metal ions such as iron and copper, which may contribute to their antioxidant activity by preventing redox-active transition metals from catalyzing free radical formation. In addition, flavonols also appear to modulate antioxidant enzyme systems.

Figure 14. Catechin molecule. The base structure of flavanols consists of two aromatic rings connected with three carbons to form a six-member heterocyclic ring.

Figure 15. Flavanols within the family of polyphenols. Plants that have high flavanol concentrations include cocoa, grapes, and green tea.

Flavanols have been reported to be beneficial in renal disease. Flavanols stimulate the production of nitric oxide which relaxes the vascular system. Daily administration of flavanols to rats was associated with a significant reduction in both systolic and diastolic blood pressure (Jouad et al., 2001).

Flavanols appear to decrease glomerular capillary pressure in rats with chronic renal failure by:

1. Stimulating the production of nitric oxide
2. Relaxing the smooth muscle fibers
3. Inhibiting angiotensin converting enzyme.