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Chronic Kidney Disease, Part 3: Management

Dana Hutchinson, DVM, DACVN, Angell Animal Medical Center

S. Dru Forrester, DVM, MS, DACVIM (SAIM), Hill's Pet Nutrition

Angela Witzel Rollins, DVM, PhD, DACVN, University of Tennessee

Larry G. Adams, DVM, PhD, Purdue University

Todd L. Towell, DVM, MS, DACVIM, Global Veterinary Consulting

This content was published originally in the Small Animal Clinical Nutrition textbook. It has been updated and provided to readers of Clinician's Brief courtesy of the Mark Morris Institute.

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Chronic Kidney Disease, Part 3: Management

Continuation of previous parts of Chapter 37 of Small Animal Clinical Nutrition, 6th edition. Part 2 can be found here

Key Nutritional Factors

The goals of managing patients with CKD are to (Polzin et al, 2005):

  1. control clinical signs of uremia
  2. minimize disturbances associated with fluid, electrolyte and acid-base balance
  3. support adequate nutrition
  4. modify progression of CKD

Nutritional management plays a role in all of these goals and is indicated to address the etiopathogenic mechanisms that occur in CKD (Table 37-9). In addition, the use of an appropriately formulated commercial veterinary therapeutic renal food is the only treatment that has been shown in randomized, controlled clinical studies to prolong survival time and improve quality of life in dogs and cats with CKD (Polzin et al, 2009; Roudebush et al, 2009; Jacob et al, 2002, 2004; Ross et al, 2006). Therefore, nutritional intervention should be considered a critical component of managing patients with CKD.

Table 37-9.

Potential etiopathogenic mechanisms in chronic kidney disease and therapeutic approaches for each.

Factors Therapeutic Approaches
Chronic renal hypoxia

Maintain hydration (increased water intake)

Avoid excessive sodium intake

ACE inhibitors

Control anemia (erythropoietin)

Glomerular hypertension and hyperfiltration

Avoid excessive dietary protein and sodium

Increased dietary omega-3 fatty acids 

ACE inhibitors

Hyperphosphatemia and secondary renal hyperparathyroidism

Limit dietary phosphorus

Intestinal phosphate binders

Calcitriol (after normophosphatemia is achieved)

Hypokalemia Metabolic acidosis

Potassium supplementation

Avoid excessive dietary protein 

Alkalinizing foods (therapeutic renal foods)

Alkalinizing agents (bicarbonate, potassium citrate)

Proteinuria

Avoid excessive dietary protein

Increased dietary omega-3 fatty acids

ACE inhibitors 

Renal oxidative stress 

Avoid excessive dietary protein, phosphorus and sodium

Increased dietary antioxidants

Omega-3 fatty acid supplementation

Systemic hypertension

Avoid excessive dietary sodium

ACE inhibors

Calcium-channel antagonists (amlodipine)

Tubulointerstitial inflammation/fibrosis

Increased dietary omega-3 fatty acids

Avoid excessive dietary phosphorus and protein

When designing a therapeutic plan for dogs and cats with CKD, it is helpful to consider a food’s key nutritional factors. Recommended ranges of these key nutritional factors were determined by considering nutrient levels in foods evaluated in dogs and cats with naturally occurring CKD and experimentally induced kidney disease (Table 37-10).

Although numerous studies have been published about dogs and cats regarding the benefits of various combinations of these factors, little work has been done to isolate effects of individual nutrients (Adams et al, 1993; Barber et al, 1999; Bovee, 1991; Brown et al, 1991, 1998, 2000; Burkholder, 2000; Burkholder et al, 2004; Elliott et al, 2000; Finco et al, 1985, 1992, 1992a, 1998; Jacob et al, 2002; McCarthy et al, 2001; Polzin et al, 1982, 1983, 1983a, 1984, 1991, 1991a, 2000; Robertson et al, 1986; Ross et al, 1982, 2006; Valli et al, 1991).

Table 37-10.

Key nutritional factors for dogs and cats with chronic kidney disease.*†

Factors Dietary recommendations
Water

Parenteral fluid therapy if dehydration, blood volume contraction or renal hypoperfusion is clinically significant

Offer water free choice at all times

Recommend moist foods

Protein

14 to 20% in foods for dogs

28 to 35% in foods for cats

Phosphorous

0.2 to 0.5% in foods for dogs

0.3 to 0.6% in foods for cats

Sodium

≤0.3% in foods for dogs

≤0.4% in foods for cats

Chloride

1.5 x sodium levels in foods for dogs

1.5 x sodium levels in foods for cats

Potassium

0.4 to 0.8% in foods for dogs

0.7 to 1.2% in foods for cats

If patient becomes hyperkalemic, switch to a lower potassium food

Omega-3 fatty acids

0.4 to 2.5% in foods for dogs and cats

Omega-6:omega-3 fatty acid ratio of 1:1 to 7:1

Antioxidants
Vitamin E

≥400 IU vitamin E/kg of food for dogs

≥500 IU vitamin E/kg of food for cats

Vitamin C

≥100 mg vitamin C/kg of food for dogs

100 to 200 mg vitamin C/kg of food for cats

*All values expressed on a dry matter basis, unless otherwise indicated. †All patients should be treated on an individual basis; recommendations may require adjustment based on patient's concurrent disease and body and muscle condition.

Commercially available veterinary therapeutic foods for dogs and cats with CKD are usually designed with these key nutritional factors in mind. Compared with typical maintenance pet foods, appropriately formulated veterinary therapeutic foods for dogs and cats with CKD generally contain less protein, phosphorus and sodium and have increased fat, omega-3 fatty acids, B-vitamins and buffering capacity. Feline renal foods contain increased potassium to help prevent hypokalemia. In addition to key nutritional factors, it is important to consider available evidence supporting effectiveness of specific veterinary therapeutic renal foods and other treatments for CKD (Table 37-11). Finally, individual patient needs and responses and owner preferences must be considered to design an optimal therapeutic plan.

ACE = angiotensin-converting enzyme, IRIS = International Renal Interest Society

*Combined with feeding a veterinary therapeutic renal food. See Chapter 2 and Table 46-20 for more information about evidence grades I through IV.
ACE = angiotensin-converting enzyme, IRIS = International Renal Interest Society

*Combined with feeding a veterinary therapeutic renal food. See Chapter 2 and Table 46-20 for more information about evidence grades I through IV.

Table 37-11. Summary of evidence for treatment of chronic kidney disease. ACE = angiotensin-converting enzyme, IRIS = International Renal Interest Society *Combined with feeding a veterinary therapeutic renal food. See Chapter 2 and Table 46-20 for more information about evidence grades I through IV.

Table 37-11. Summary of evidence for treatment of chronic kidney disease. ACE = angiotensin-converting enzyme, IRIS = International Renal Interest Society *Combined with feeding a veterinary therapeutic renal food. See Chapter 2 and Table 46-20 for more information about evidence grades I through IV.

Water

Kidney disease causes a progressive decline in urine concentrating ability, and maximal urine osmolality approaches that of plasma (300 mOsm/kg) (i.e., isosthenuria). As CKD progresses; these changes may be observed in patients with stage 1 CKD. If total solute excretion remains normal, but the maximal achievable urine osmolality decreases, obligatory water loss occurs to eliminate the osmolar load. This obligatory water loss may lead to development of polyuria. Compensatory polydipsia occurs to maintain fluid balance. Dehydration, volume depletion, renal hypoperfusion and dietary salt (sodium) intake stimulate urine concentration. Concentrating urine solutes represents “osmotic work” for the kidneys and represents a burden for diseased kidneys. Reducing the amount of solutes to be concentrated by decreasing dietary protein and sodium intake or by providing more water for the excretion of the same amount of solutes independently reduces the amount of osmotic work. Patients with CKD should have unlimited access to fresh water for free-choice consumption. If readily consumed by the patient, moist foods are preferred because their consumption generally results in increased total water intake compared with dry food consumption.

Protein

There is general consensus that avoiding excessive dietary protein intake is indicated to control clinical signs of uremia in dogs and cats with CKD; uremic signs most often occur in stage 4 disease but may be observed earlier (Polzin et al, 2005; Elliott et al, 2006). Many of the extra-renal clinical and metabolic disturbances associated with uremia are direct results of the accumulated waste products derived from protein catabolism. Early studies in laboratory animals showed rapid improvement when dietary protein was reduced (Klahr et al, 1983; Brenner, 1983). However, urea by itself does not account for all, if any, of the clinical signs of uremia. Serum urea nitrogen generally is considered to simply be a marker for other more important uremic toxins. Excessive dietary protein is catabolized to urea and other nitrogenous compounds that normally are excreted by the kidneys. And, as mentioned above, endogenous proteins will be degraded if amino acid intake is insufficient to maintain nitrogen balance. The goal of managing patients with CKD is to achieve nitrogen balance and limit accumulation of nitrogenous waste products by proportionally decreasing protein intake as renal function declines.

The role of decreased dietary protein intake is less clear in patients with CKD that do not have clinical signs of uremia (Polzin et al, 2005). Limiting protein intake has been advocated to slow progression of CKD on the basis of studies in rats, which revealed that excessive dietary protein consumption was associated with glomerular capillary hypertension and hyperfiltration (Brenner et al, 1982). Decreased dietary protein intake prevents these hemodynamic changes and preserves normal glomerular structure in rats (Brenner et al, 1982). The role of decreased dietary protein in delaying progression of CKD in dogs and cats is less clear and has been the subject of numerous studies and a topic of considerable debate (Polzin et al, 2000; Finco et al, 1998a; Polzin et al, 2016; Scherk et al, 2016) (Box 37-1). The role of protein in management of cats with CKD is the subject of much controversy (Larsen, 2016). Box 37.2  summarizes two viewpoints on the role of diet in the management of CKD.

Box 37-1. Role of Dietary Protein in Progression of Chronic Kidney Disease

Box 37-2. Controversy on the role of dietary protein in the management of feline CKD

Despite the lack of clarity about the effects of dietary protein on progression of CKD in dogs and cats, potential benefits should be considered. Decreased dietary protein intake inhibits secretion of TGF-β, a cytokine that may be involved in progression of kidney disease (Fukui et al, 1993) (See Etiopathogenesis of Chronic Kidney Disease, Tubulointerstitial Changes). Decreased protein intake potentially reduces tubular hyperfunction by decreasing the renal acid load and decreasing renal ammoniagenesis. In general, protein metabolism is the major source of hydrogen ions. Consequently, avoiding excess dietary protein and decreasing endogenous protein catabolism for energy contribute markedly to the maintenance of acid-base balance (Relman et al, 1961). Primary dietary protein contributions to the renal acid load are from the sulfur-containing amino acids (methionine and cysteine). Animal proteins tend to be higher in sulfur-containing amino acids than plant protein sources. This is true whether the source of the animal protein is from food or catabolism of a patient’s body tissue. Catabolism of a patient’s protein stores can occur if insufficient energy (carbohydrates and fats) and/or protein are consumed. In the case of inadequate energy intake, the body’s amino acids stores (tissue protein) are used for gluconeogenesis to meet glucose needs. Avoiding dietary protein excess, without imposing dietary protein deficiency can help limit the acid load imposed on patients with CKD (Burkholder, 2000).

Another potential benefit of limiting dietary protein is its effects on proteinuria. Results of studies in rats with experimentally induced nephrotic syndrome suggest that the permselective properties of the filtration barrier are altered as a consequence of increasing dietary protein intake, permitting albumin to cross the capillary wall more readily (Kaysen et al, 1984; Hutchison et al, 1987, 1990). In healthy dogs and in dogs with kidney disease, increasing dietary protein intake increases renal blood flow and GFR, which may increase filtration of plasma proteins through the glomerular membrane, resulting in proteinuria (Polzin et al, 1983a, 1984; Devaux et al, 1996; Bovee, 1991; Brown et al, 1992; Bovee et al, 1981). Proteinuria may result in direct mesangial cell toxicity, glomerular fibrosis and eventual glomerulosclerosis (Figure 37-3). Excessive albuminuria and abnormally filtered transferrin may lead to increased oxidative stress, which appears to be an important mechanism of progressive renal injury (Figure 37-7) (See Renal Oxidative Stress). The end result of proteinuric-induced glomerulosclerosis and tubular damage is further loss of nephrons. This reduction of functional renal mass and subsequent increase in single-nephron GFR further increase proteinuria and progression of renal damage. The impact of varying dietary protein intake on glomerular hemodynamics and structure in dogs and cats with CKD is less certain; however, studies in dogs have shown that feeding a veterinary therapeutic renal food with decreased protein, before the onset of azotemia, has beneficial effects in dogs with proteinuria (Box 37-3) (Valli et al, 1991; Burkholder et al, 2004; Zatelli et al, 2016; Cortadellas et al, 2014).

Box 37-3. Nutritional Management of Patients with Proteinuria

Effects of decreased dietary protein intake have been studied in dogs with induced CKD (Polzin et al, 1983; Finco et al, 1992a). In a 40-week study, dogs were fed a commercial veterinary therapeutic food containing 8.2% DM protein, a commercial food with 17.2% DM protein or a control food with 44.4% DM protein (Polzin et al, 1983). Feeding the lower protein foods was associated with reduced mortality, serum urea nitrogen concentrations and clinical signs of uremia. Throughout the study, all dogs fed the highest protein food had reduced physical activity and poorer hair quality compared with those parameters in dogs fed the lower protein foods. There were other nutrient differences between foods, which may have contributed to the beneficial effects observed. In another study conducted for two years, reduced dietary protein (16% DM) was not associated with a significant effect on mortality compared with feeding a food containing 32% DM protein (Finco et al, 1992a). Some differences in treatment in addition to nutritional management could have affected study outcome, however (Box 37-1).

Two studies evaluated effects of dietary protein on progression of induced CKD for one year in cats (Adams et al, 1993; Finco et al, 1998). In one study, renal function did not progressively decrease, regardless of dietary protein amount and caloric intake (Adams et al, 1993). However, remnant kidneys of cats with induced CKD that were fed a food containing 52% DM protein had significantly more severe glomerular and tubulointerstitial damage than cats with CKD that were fed a food containing 28% DM protein (Adams et al, 1993). Phosphorus amounts were similar between study groups (0.54% DM in the high-protein group and 0.61% DM in the low-protein group); however, cats in the high-protein group consumed significantly more calories. Therefore, changes in renal morphology could have resulted from differences in protein and/or caloric intake. In the other study, no difference in renal function or glomerular lesions were found in cats consuming high-protein foods (52% DM) compared with lower protein foods (28% DM) (Finco et al, 1998). Phosphorus amounts were similar for all study groups (0.87 to 0.96% DM). There were mild and significant increases in cellular infiltrate and tubular lesions in cats that consumed more calories, but no differences were detected based on amount of dietary protein. The authors concluded that protein intake was not a risk factor for progression of renal lesions and that the practice of severe protein restriction was questionable. However, because renal function remained stable throughout both studies, it was not possible to assess the role of limiting dietary protein in decreasing progression of CKD.

Four clinical studies of cats or dogs with naturally occurring azotemic CKD (IRIS stages 2-4) compared effects of feeding a commercial veterinary therapeutic renal food with either a control or regular maintenance food that contained more protein (Harte et al, 1994; Elliott et al, 2000; Jacob et al, 2002; Ross et al, 2006). In a six-month study, mean serum creatinine and urea nitrogen concentrations progressively increased in 10 cats receiving more dietary protein (39.4% DM) and declined or remained stable in 25 cats that were fed a lower protein food (25.2% DM) (Harte et al, 1994). In a non-randomized, prospective study, cats receiving a lower protein food (22 to 24% protein) had significantly prolonged median survival time compared with cats that continued eating different maintenance cat foods with higher protein (48% DM) (Elliott et al, 2000). In a two-year study, cats eating a commercial veterinary therapeutic renal food with 28 to 29% DM protein had no uremic episodes or renal-related deaths whereas 26% of cats in the control group consuming a food with higher protein (46 to 48% DM protein) had a uremic crisis and 22% died as a result of CKD (Ross et al, 2006). Finally, dogs receiving a commercial veterinary therapeutic renal food with 14% DM protein had delayed time to onset of uremic crisis, slower decline in renal function and improved survival compared to parameters in dogs receiving a control food that contained 25% DM protein (Jacob et al, 2002). Based on these findings, it is clear that foods with less protein in these studies were associated with significantly improved quality and quantity of life in dogs and cats with naturally occurring CKD.

However, because the protein amount was not the only nutrient difference between the veterinary therapeutic renal foods and comparison foods, it is not possible to conclude that limiting dietary protein alone was the sole reason for beneficial effects. Box 37-4 provides detailed information about long-term studies that evaluated effects of veterinary therapeutic renal foods on survival time of dogs and cats with CKD.  

Box 37-4. Summary of Studies Evaluating Effects of Veterinary Therapeutic Renal Foods on Survival in Dogs and Cats with Naturally Occurring Chronic Kidney Disease

Early detection of declining GFR and therapeutic interventions, including dietary interventions, are critical to slow progressive loss of kidney function and extend lifespan. The recent availability of a reliable, commercially available biomarker (SDMA) provides the opportunity to investigate response to interventions earlier than previously possible. In recent years, a number of studies have investigated nutritional intervention in cats and dog with IRIS stage 1 CKD. Results from these studies suggest nutritional intervention can stabilize or slow disease progression in non-azotemic dogs and cats with IRIS Stage 1 CKD (Box 37.5).

Box 37-5. Summary of Studies Evaluating Effects of Nutritional Intervention on Biomarkers of Early Kidney Disease in Dogs and Cats.

In summary, limiting dietary protein intake is indicated to control clinical signs of uremia in dogs and cats with CKD. Recent studies that incorporate SDMA as an early and sensitive marker of changes in GFR support the use of renoprotective foods with controlled levels of protein for dogs and cats with CKD of all IRIS stages. Patients may be more likely to accept a change to a new food if it is offered before clinical signs of uremia occur and it may delay onset of uremic signs as CKD progresses (Polzin et al, 2005). On a practical note, it is difficult to achieve the degree of phosphorus restriction desired in veterinary therapeutic renal foods using typical ingredients without limiting the amount of dietary protein (Burkholder, 2000).

In regards to determining how much protein to recommend for dogs and cats with CKD, all patients should be monitored for signs of protein insufficiency and nutritional management adjusted to maintain ideal body condition (Box 37-6). 

Box 37-6. Dietary Protein Needs in Dogs and Cats with Chronic Kidney Disease and Maintenance of Lean Body Mass

For cats with CKD, the minimum dietary protein requirement identified in one study was 20% of calories (Kirk and Hickman, 2001); this translates to approximately 24% DM protein. Similar studies have not been reported for dogs. The minimum recommended allowances for DM dietary protein in foods for healthy adult dogs and cats are 10 and 20%, respectively (NRC, 2006). The minimum DM levels recommended by the Association of American Feed Control Officials are 18% for dog foods and 26% for cat foods (AAFCO, 2017). A report of the mean DM protein content of several popular U.S. grocery brand dog foods was 41.7% for moist foods and 25% for dry foods. For grocery brand cat foods, it was 51.5% for moist foods and 35.1% for dry foods (Allen et al, 2000). The recommended range for DM protein levels in foods intended for most patients with CKD has been 14 to 20% for dogs and 28 to 35% for cats. Foods with less protein may be needed to control signs of uremia in patients with more advanced CKD; in these patients, it’s important to monitor for signs of protein deficiency. In addition to the amount of protein, patients with CKD should receive protein of high biologic value. The concept of ideal protein is useful when considering biologic value (Baker and Czarnecki-Maulden, 1991). Lysine is the limiting amino acid in practical foods for dogs and cats (Baker and Czarnecki-Maulden, 1991). However, experience with typical ingredients used in commercial veterinary therapeutic foods suggests that tryptophan is more frequently limiting. Therefore, based on the concept of ideal protein, foods that meet the requirement for lysine and tryptophan can be assumed to meet the requirement for all indispensable amino acids.

Phosphorus

Decreased dietary phosphorus intake is indicated in dogs and cats with CKD to limit phosphorus retention, hyperphosphatemia, secondary renal hyperparathyroidism (Figures 37-8 and 37-9) and progression of kidney disease (Polzin et al, 2005; Rutherford et al, 1977; Barber at al, 1999). 

The effect of dietary phosphorus on serum parathyroid hormone (PTH) concentrations in dogs with experimentally induced kidney disease. Note that consumption of higher levels of phosphorus resulted in excessive PTH secretion. High phosphorus means dogs ingested 60 to 80 mg phosphorus/kg body weight/day, Low phosphorus means dogs ingested 15 to 40 mg phosphorus/kg body weight/day. (Adapted from Rutherford WE, Bordier P, Marie P, et al. Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog. Journal of Clinical Investigation 1977; 60: 332-341.)
The effect of dietary phosphorus on serum parathyroid hormone (PTH) concentrations in dogs with experimentally induced kidney disease. Note that consumption of higher levels of phosphorus resulted in excessive PTH secretion. High phosphorus means dogs ingested 60 to 80 mg phosphorus/kg body weight/day, Low phosphorus means dogs ingested 15 to 40 mg phosphorus/kg body weight/day. (Adapted from Rutherford WE, Bordier P, Marie P, et al. Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog. Journal of Clinical Investigation 1977; 60: 332-341.)

Figure 37-8. The effect of dietary phosphorus on serum parathyroid hormone (PTH) concentrations in dogs with experimentally induced kidney disease. Note that consumption of higher levels of phosphorus resulted in excessive PTH secretion. High phosphorus means dogs ingested 60 to 80 mg phosphorus/kg body weight/day, Low phosphorus means dogs ingested 15 to 40 mg phosphorus/kg body weight/day. (Adapted from Rutherford WE, Bordier P, Marie P, et al. Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog. Journal of Clinical Investigation 1977; 60: 332-341.)

Figure 37-8. The effect of dietary phosphorus on serum parathyroid hormone (PTH) concentrations in dogs with experimentally induced kidney disease. Note that consumption of higher levels of phosphorus resulted in excessive PTH secretion. High phosphorus means dogs ingested 60 to 80 mg phosphorus/kg body weight/day, Low phosphorus means dogs ingested 15 to 40 mg phosphorus/kg body weight/day. (Adapted from Rutherford WE, Bordier P, Marie P, et al. Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog. Journal of Clinical Investigation 1977; 60: 332-341.)

Plasma parathyroid hormone (PTH) concentrations in cats with chronic kidney disease that were fed either a veterinary therapeutic renal food with decreased phosphorus (blue line) (n=14) or a maintenance food with higher phosphorus (red line) (n=8). Results expressed as mean ± SEM. NS = not significant. P values represent statistical significance of each value compared with pre-treatment value (Day 0).

 

*No significant difference between groups at baseline (Day 0). (Adapted from Barber PJ, Rawlings JM, Markwell PJ, et al. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. Journal of Small Animal Practice 1999; 40: 62-70.)
 
Plasma parathyroid hormone (PTH) concentrations in cats with chronic kidney disease that were fed either a veterinary therapeutic renal food with decreased phosphorus (blue line) (n=14) or a maintenance food with higher phosphorus (red line) (n=8). Results expressed as mean ± SEM. NS = not significant. P values represent statistical significance of each value compared with pre-treatment value (Day 0).

 

*No significant difference between groups at baseline (Day 0). (Adapted from Barber PJ, Rawlings JM, Markwell PJ, et al. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. Journal of Small Animal Practice 1999; 40: 62-70.)
 

Figure 37-9. Plasma parathyroid hormone (PTH) concentrations in cats with chronic kidney disease that were fed either a veterinary therapeutic renal food with decreased phosphorus (blue line) (n=14) or a maintenance food with higher phosphorus (red line) (n=8). Results expressed as mean ± SEM. NS = not significant. P values represent statistical significance of each value compared with pre-treatment value (Day 0).   *No significant difference between groups at baseline (Day 0). (Adapted from Barber PJ, Rawlings JM, Markwell PJ, et al. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. Journal of Small Animal Practice 1999; 40: 62-70.)  

Figure 37-9. Plasma parathyroid hormone (PTH) concentrations in cats with chronic kidney disease that were fed either a veterinary therapeutic renal food with decreased phosphorus (blue line) (n=14) or a maintenance food with higher phosphorus (red line) (n=8). Results expressed as mean ± SEM. NS = not significant. P values represent statistical significance of each value compared with pre-treatment value (Day 0).   *No significant difference between groups at baseline (Day 0). (Adapted from Barber PJ, Rawlings JM, Markwell PJ, et al. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. Journal of Small Animal Practice 1999; 40: 62-70.)  

The mechanism for the protective effect of limiting phosphorus intake is unknown. Possible factors include reduced nephrocalcinosis, suppression of hyperparathyroidism, reduced cellular energy metabolism and altered renal hemodynamics. It is possible that these mechanisms may synergistically contribute to the beneficial effects of lowering phosphorus intake.

Several studies evaluated effects of limiting dietary phosphorus intake in cats and dogs with induced kidney disease. In cats, high dietary phosphorus intake (1.56% DM phosphorus) for 65 to 343 days was associated with renal mineralization, fibrosis and mononuclear cell infiltration whereas lower phosphorus intake (0.42% DM phosphorus) was not (Figure 37-10) (Ross et al, 1982). Progressive changes in GFR were not detected; however, in either the high- or low-phosphorus group. Effects of dietary phosphorus restriction were studied in dogs that were fed either a low-phosphorus (0.44% DM) food or a high-phosphorus (1.44% DM) food for 24 months (Brown et al, 1991). Both foods provided reduced amounts of protein (17% DM). Survival rate was significantly higher in the low-phosphorus group (75%) compared with the high-phosphorus group (33%) (Figure 37-11). Kidney function also deteriorated at a more rapid rate in the high-phosphorus group. Decrements of renal function were more closely related to nephrocalcinosis and tubulointerstitial lesions than to glomerular abnormalities (Brown et al, 1991). Specifically, in this study, progression and death were associated with interstitial fibrosis, tubular atrophy and dilatation and mineralization of cortical basement membranes, tubular epithelia and vascular and tubular lumina. The association of progression with tubulointerstitial lesions and nephrocalcinosis, however, does not necessarily establish a causal role for nephrocalcinosis. A similar study was conducted by investigators in the same laboratory to evaluate effects of dietary phosphorus restriction (0.48 vs. 1.46% DM) when a higher protein food (32% DM) was fed (Finco et al, 1992). In contrast to the previous study, improved survival was not observed in the group fed low-phosphorus food. An additional study compared the effects of feeding four foods of varying phosphorus and protein content (low phosphorus/low protein; high phosphorus/low protein; low phosphorus/high protein; high phosphorus/high protein) to four groups of dogs with CKD (remnant kidney model). In this study, survival was significantly increased by feeding either of the low-phosphorus foods (0.44 to 0.49% DM phosphorus) and was not affected by the amount of dietary protein (16.7 to 32% DM) (Finco et al, 1992a).

Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus).
Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)
 
Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus).
Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)
 

Figure 37-10. Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus). Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)  

Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus).
Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)
 
Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus).
Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)
 

Figure 37-10. Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus). Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)  

Figure 37-10. Photomicrographs of the renal cortex from cats with experimentally induced chronic kidney disease. (Left) Renal tissue from a cat fed a low-phosphorus food (0.42% DM phosphorus). Mineralized foci are not seen in this kidney (hematoxylin-eosin stain). (Right) Renal tissue from a cat fed a food with normal phosphorus levels (1.56% DM phosphorus). Mineralization (black foci), fibrosis and mononuclear cell infiltrates are extensive compared with that seen on a renal photomicrograph from a cat eating the lower phosphorus food (von Kossa’s stain). (Reprinted with permission from Ross LA, Finco DR, Crowell WA. Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. American Journal of Veterinary Research 1982; 43: 1023-1026.)  

Survival of dogs with experimentally induced chronic kidney disease fed low-protein foods with different levels of phosphorus. Note that survival was much improved in dogs consuming the low-phosphorus food. (Adapted from Brown SA, Crowell WA, Barsanti JA, et al. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. Journal of the American Society of Nephrology 1991;1:1169-1179.)
Survival of dogs with experimentally induced chronic kidney disease fed low-protein foods with different levels of phosphorus. Note that survival was much improved in dogs consuming the low-phosphorus food. (Adapted from Brown SA, Crowell WA, Barsanti JA, et al. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. Journal of the American Society of Nephrology 1991;1:1169-1179.)

Figure 37-11. Survival of dogs with experimentally induced chronic kidney disease fed low-protein foods with different levels of phosphorus. Note that survival was much improved in dogs consuming the low-phosphorus food. (Adapted from Brown SA, Crowell WA, Barsanti JA, et al. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. Journal of the American Society of Nephrology 1991;1:1169-1179.)

Figure 37-11. Survival of dogs with experimentally induced chronic kidney disease fed low-protein foods with different levels of phosphorus. Note that survival was much improved in dogs consuming the low-phosphorus food. (Adapted from Brown SA, Crowell WA, Barsanti JA, et al. Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass. Journal of the American Society of Nephrology 1991;1:1169-1179.)

Beneficial effects of limiting dietary phosphorus intake, by feeding a veterinary therapeutic renal food, have also been demonstrated in cats and dogs with naturally occurring CKD (Elliott et al, 2000; Barber et al, 1999; Jacob et al, 2002; Ross et al, 2006). In one study, feeding a dry or moist veterinary therapeutic renal food with low phosphorus (0.29 or 0.41% DM) was associated with significantly decreased plasma phosphorus and PTH concentrations compared with results from cats fed a typical maintenance food with higher phosphorus (1.9% DM) (Barber et al, 1999). In three additional studies, dogs and cats managed by feeding a veterinary therapeutic renal food with decreased phosphorus had significantly prolonged survival times compared with patients that were fed a higher phosphorus maintenance food (Box 37-3) (Elliott et al, 2000; Jacob et al, 2002; Ross et al, 2006).

The minimum recommended allowance for dietary phosphorus is 0.3% DM in foods for healthy adult dogs and 0.26% DM for healthy adult cats (NRC, 2006). The mean DM phosphorus contents of several grocery brand dog and cat foods were 1.39 and 1.54%, respectively (Allen et al, 2000). To achieve beneficial effects, the recommended phosphorus levels for foods used to manage CKD are 0.2 to 0.5% DM for dogs and 0.3 to 0.6% DM for cats.

Sodium and Chloride

As renal function deteriorates, fractional sodium excretion increases to maintain sodium balance and preserve extracellular fluid volume. The fractional excretion of sodium must change markedly to maintain sodium balance when dietary sodium intake changes (Klahr and Slatopolsky, 1973). Patients with decreased renal function can only vary sodium excretion over a limited range, which narrows progressively as GFR declines. Thus, patients with CKD may not tolerate excessively high or low dietary sodium levels. If excessive sodium is ingested, sodium retention with expansion of extracellular fluid volume can occur and produce or worsen preexisting hypertension, fluid overload and edema. If sodium intake is inadequate, negative sodium balance develops with resultant declines in extracellular fluid volume, plasma volume and GFR. Also, excessive dietary sodium intake may increase the absorptive workload on surviving nephrons, increasing oxygen consumption and contributing to hypoxia and increased production of damaging ROS. (See Antioxidants below.)

Limiting dietary sodium intake has been recommended for patients with CKD because of its potential to help manage concomitant hypertension; however, this has not been critically evaluated in dogs and cats with CKD. Systemic hypertension has been reported in 9 to 93% of dogs and 19 to 65% of cats with CKD (Elliott et al, 2001; Syme et al, 2002; Brown et al, 2007). The mechanism for hypertension in renal parenchymal disease is not well understood. It has been postulated that reduced intra-renal blood flow activates the renin-angiotensin- aldosterone system, which leads to chronic expansion of the extracellular fluid and elevations in blood pressure. Other possible mechanisms include secondary renal hyperparathyroidism and reduced levels of renal vasodilators such as prostaglandins. Kidney disease may cause hypertension, and the kidneys may suffer the consequences of uncontrolled hypertension. The mechanism by which hypertension damages the kidney is not completely understood (Klahr, 1989). Canine CKD patients with major reduction of functional renal mass have impaired renal autoregulation as evidenced by increased renal arterial pressure. Dysfunctional autoregulation may result in further renal damage during hypertensive episodes, which contribute to a progressive decline in kidney function (Brown et al, 1995). Dogs with surgically induced CKD with more pronounced hypertension had significantly lower GFR values, higher UPC ratios and increased renal lesions (Finco, 2004). Hypertension has been associated with increased risk of uremic crisis and death in dogs with naturally occurring CKD ( Jacob et al, 2003). In cats with CKD, however, hypertension has not been associated with decreased survival (Elliott et al, 2001; Syme et al, 2006; Jepson et al, 2007). Based on other studies, increased dietary sodium intake has not been associated with increased blood pressure in healthy cats, dogs, cats with induced kidney disease, or cats with naturally occurring CKD (Buranakarl et al, 2004; Greco et al, 1994; Luckschander et al, 2004; Kirk et al, 2006).

Currently, the role of sodium intake in progression of CKD is a topic of considerable interest in human medicine and has been mentioned in dogs and cats with CKD (Polzin, 2007; Chandler, 2008). Sodium may be directly nephrotoxic and restricting sodium intake may be beneficial in CKD, independent of its effect on blood pressure (Cianciaruso et al, 1998; Ritz et al, 2006; Jones-Burton et al, 2006; Sanders, 2004; Weir and Fink, 2005; Verhave et al, 2004). Potential mechanisms for the negative effects of salt in patients with CKD include: 1) increased TGF-β expression in renal endothelial cells, which may lead to renal fibrosis, 2) increased oxidative stress and 3) increased proteinuria. Angiotensin II or increased dietary salt intake may independently increase production of TGF-β (Sanders, 2004). Increased production of TGF-β, in turn, results in increased renal oxidative stress by production of ROS (Figure 37-7). In human patients with CKD, the anti-proteinuric effect of angiotensin-converting enzyme (ACE) inhibition was strongly dependent on dietary sodium restriction; increased sodium intake virtually abolished the anti-proteinuric effect of the ACE inhibitor lisinopril (Heeg et al, 1989). Administration of ACE inhibitors has been associated with decreased proteinuria in dogs and cats (Grauer et al, 2000; King et al, 2006; Mizutani et al, 2006). The role of dietary sodium on beneficial effects of ACE inhibition has not been evaluated in dogs and cats; however, most patients in these studies were also fed veterinary therapeutic renal foods, which likely contained decreased amounts of sodium. Additional clinical studies are needed to evaluate the role of salt in progression of CKD; however, until results of such studies are available, it has been recommended that modest dietary avoidance of salt be encouraged in human patients with CKD, especially if they have hypertension and/or proteinuria (Jones-Burton et al, 2006).

The long-term effects of altering dietary sodium intake alone in cats and dogs with naturally occurring CKD have not been reported. Feeding veterinary therapeutic renal foods with decreased sodium (0.18 to 0.3% DM sodium in cats and 0.17% DM sodium in dogs) has been associated with increased survival time compared with feeding maintenance foods that contain more sodium (0.4 to 1.1% DM sodium in cats and 0.4% DM sodium in dogs) (Ross et al, 2006; Jacob et al, 2002; Elliott et al, 2000). Several reports describe short-term effects (seven days to six months) of feeding differing amounts of sodium on renal function in dogs and cats (Buranakarl et al, 2004; Greco et al, 1994; Luckschander et al, 2004; Kirk et al, 2006; Xu et al, 2009). In healthy adult cats (mean age = seven years), feeding foods containing 1.11% DM sodium was not associated with increased serum concentrations of urea nitrogen, creatinine or phosphorus, compared with feeding foods containing 0.55% DM sodium for six months (Xu et al, 2009). In this study, data from nine cats with serum creatinine values >1.5 mg/dl were evaluated; there were no significant differences between groups based on dietary sodium intake. Urine concentrating ability for these nine cats was not reported; however, mean urine specific gravity for all cats at the beginning of the study ranged from 1.049 to 1.053. A 2-year study in 20 healthy aged cats also failed to find significant differences in GFR, blood pressure and other routine clinical pathological variables in cats fed a high salt diet (3.1 g/Mcal NA, 5.5 g Mcal chloride) and those fed a control food (1.0 g/Mcal sodium, 2.2 g/Mcal chloride) (Reynolds et al, 2013).151 Interestingly USG was only different between the two groups at 3 months, indicating that the perceived benefit of increased sodium intake, dilution of urine specific gravity, is mild and transient. In a study in cats with induced kidney disease, three different amounts of sodium (0.34, 0.68 and 1.35% DM) were fed for seven days (Buranakarl et al, 2004). Feeding the lowest amount of sodium was associated with increased urinary potassium loss and reduced GFR (Buranakarl et al, 2004). The effects of high salt intake (1.19% DM sodium) for three months were evaluated in six cats with naturally occurring CKD (azotemia with urine specific gravity <1.035) (Kirk et al, 2006). The CKD cats fed the high-salt food had significant and progressive increases in blood urea nitrogen, serum creatinine and serum phosphorus compared with results from cats consuming food with 0.37% DM sodium (Kirk et al, 2006). Two of the cats were removed from the study after beginning the high-sodium food due to decreased food intake; this did not affect results of statistical analysis or study conclusions.

A number of studies examined the interaction of dietary sodium with other ions, including chloride. The full expression of sodium chloride-sensitive hypertension in people depends on the concomitant administration of both sodium and chloride (Kurtz et al, 1987; Boegehold and Kotchen, 1989; Luft et al, 1990). In experimental models using rodents with sodium chloride-sensitive hypertension and in clinical studies with small numbers of hypertensive people, blood pressure and volume were not increased by a high dietary sodium intake provided with anions other than chloride. Furthermore, high chloride intake without sodium has less effect on blood pressure than does sodium chloride intake (Kurtz et al, 1987; Boegehold and Kotchen, 1989; Kotchen et al, 1981). The failure of non-chloride sodium salts to produce hypertension or hypervolemia may be related to their failure to expand plasma volume because the renal tubular signal for renin release is responsive to renal tubular chloride (Boegehold and Kotchen, 1989; Luft et al, 1990; Kotchen et al, 1981, 1987). Chloride may also act as a direct renal vasoconstrictor (Boegehold and Kotchen, 1989). These findings suggest that both sodium and chloride are nutrients of concern in patients with hypertension and CKD.

Based on current information, dietary DM sodium intakes for patients with CKD are 0.3% or less for dogs and no more than 0.4% for cats. For comparison, the minimum recommended DM allowances for sodium in foods for healthy adult dogs and cats are 0.08 and 0.096%, respectively (NRC, 2006). The mean sodium levels in several moist grocery brand dog foods were 0.87% DM and 0.9% DM in moist cat foods, although some moist foods contain more sodium. In contrast, dry foods contained approximately half those amounts (Allen et al, 2000). The minimum recommended allowances for chloride for foods for healthy adult dogs and cats are 1.5 times the recommended sodium levels (NRC, 2006). That same factor is suggested for chloride content of foods for canine and feline CKD patients. Some patients may have obligatory urinary sodium losses and abruptly changing these patients to a low-sodium food may result in dangerous contraction of the extracellular fluid volume. Therefore, it is recommended that dogs and cats with CKD be gradually transitioned to foods with reduced amounts of sodium.  

Potassium

Cats with CKD appear to be particularly predisposed to disorders in potassium homeostasis (Figure 37-12 and Case 37-3). Decreased dietary potassium intake due to inappetence or vomiting and increased urinary losses due to polyuria can contribute to hypokalemia in CKD. Hypokalemia (potassium values <3.5 mEq/l) has been reported to occur in 19 to 20% of cats with CKD and was moderate to severe (potassium <3.1 mEq/l) in more than half of the cases in one study (DiBartola et al, 1987; Elliott and Barber, 1998). Conversely, hyperkalemia was observed in 9 to 13% of these cats. Hyperkalemia was observed in oliguric and polyuric kidney disease and was most common (22%) in cats with end-stage CKD.

Proposed relationship between dietary potassium intake, excessively acidifying foods and feline chronic kidney disease.
Proposed relationship between dietary potassium intake, excessively acidifying foods and feline chronic kidney disease.

Figure 37-12. Proposed relationship between dietary potassium intake, excessively acidifying foods and feline chronic kidney disease.

Figure 37-12. Proposed relationship between dietary potassium intake, excessively acidifying foods and feline chronic kidney disease.

Potassium depletion leads to functional and morphologic changes in the kidneys of dogs and cats. Functional changes include reduced GFR and urine concentrating ability. Chronic potassium depletion stimulates renal ammonia synthesis. In hypokalemic rats, increased renal ammoniagenesis contributed to chronic lymphoplasmacytic tubulointerstitial nephritis (Nath et al, 1985). Studies in cats demonstrated that potassium depletion may result from feeding acidifying foods that are high in protein and low in potassium. CKD was observed in three of nine adult cats fed a food high in protein (40% DM) and low in potassium (0.32% DM) content for two years. Lymphoplasmacytic interstitial nephritis and interstitial fibrosis were detected in these cats and in two other cats without laboratory abnormalities (DiBartola et al, 1993). The minimum recommended allowances for foods for healthy adult dogs and cats are 0.4% DM, and 0.52% DM, respectively (NRC, 2006). The potassium requirement for cats is proportional to the protein content of the food. Using purified foods, 0.3% potassium was required for growth in kittens fed a 33% protein food; however, 0.5% potassium was required with a 68% protein food (Hills et al, 1982). Acidifying foods and chronic metabolic acidosis may contribute to hypokalemia (Figure 37-12) (Dow et al, 1990).

The recommended range for potassium for foods for dogs with CKD is 0.4 to 0.8% DM and for cats 0.7 to 1.2% DM. For cats with hypokalemia, oral supplementation with potassium gluconate should be considered if diet alone does not maintain serum potassium concentration above 4.0 mEq/l (Polzin, 2007). Oral administration is safest and is the preferred route unless a critical emergency exists or if oral administration is impossible or contraindicated. Oral potassium gluconate appears to be tolerated well; the initial recommended dose is 2 to 6 mEq potassium gluconate/cat/day, depending on the size of the cat and severity of clinical signs. The potassium gluconate dose should be adjusted based on clinical response and serial analyses of serum potassium concentration. During initial treatment, serum potassium concentration should be checked every two to four days. Later, serum potassium should be checked every two to four weeks. Additional studies are needed to determine whether routine potassium supplementation is indicated in all cats with CKD, regardless of serum potassium concentration (Polzin et al, 2000).  

Omega-3 Fatty Acids

The specific dietary fatty acid content of a food can influence progression of CKD by affecting:

  1. renal hemodynamics
  2. platelet aggregation
  3. lipid peroxidation
  4. systemic blood pressure
  5. proliferation of glomerular mesangial cells
  6. plasma lipid concentration.

Appropriate levels of omega-3 (n-3) fatty acids (e.g., eicosapentaenoic acid [EPA] and docosahexaenoic acid) in foods compete with arachidonic acid in several ways to alter eicosanoid production. These alterations are considered to be renoprotective (Brown et al, 1998).

Specific ingredients (e.g., menhaden fish oil) contain increased levels of omega-3 fatty acids; therefore, animals fed menhaden fish oil have decreased levels of 2-series eicosanoids, which are normally derived from arachidonic acid, and increased levels of 3-series eicosanoids, derived from omega-3 fatty acids. The 3-series eicosanoids are less potent at inducing vasoconstriction and platelet aggregation than the 2-series eicosanoids. Saturated fatty acids found in animal fat do not serve as precursors for eicosanoid production.

In dogs with a remnant kidney model of CKD, dietary omega-3 fatty acid supplementation reduced proteinuria, prevented glomerular hypertension and decreased production of proinflammatory eicosanoids (Brown et al, 1998, 2000). Dietary fat composition altered the rate of CKD progression in dogs following 15/16 nephrectomy (Figure 37-13). A low-fat food (<1% DM fat) was supplemented with one of three different fat sources (menhaden fish oil, beef tallow or safflower oil) to achieve a total DM fat concentration in the food of 15%. Dogs were assigned to dietary treatment two months following nephrectomies and followed for 20 months. Compared with the other two groups, the group receiving the food supplemented with safflower oil had greater glomerular enlargement and mean glomerular capillary pressure. Dietary fatty acid composition appeared to alter hemodynamic responses to renal insufficiency. Final mean exogenous creatinine clearance was 1.3 ml/min./kg body weight for the menhaden fish oil group, 0.9 ml/min./kg body weight for the beef tallow group and 0.5 ml/min./kg body weight for the safflower oil group. Mean UPC ratios were 0.6 in the menhaden fish oil group, 1.5 in the beef tallow group and 2.1 in the safflower oil group. Survival was similar in groups receiving menhaden oil and beef tallow; however, four of seven dogs in the safflower oil group were euthanized. In other studies in dogs with a remnant kidney model of CKD, dietary supplementation with either omega-3 fatty acids or antioxidants was renoprotective and their effects were additive when used together (Brown, 2008).

Survival of dogs with experimentally induced chronic kidney disease fed foods with three different fat sources (fish oil, tallow, safflower oil). Note that survival was increased in those dogs consuming foods with either tallow or fish oil compared to safflower oil. Dietary fatty acid composition appears to affect hemodynamic adaptations to renal disease in dogs. (Adapted from Brown SA, Brown CA, Crowell WA, et al. Dietary lipid composition alters chronic course of canine renal disease (abstract). Journal of Veterinary Internal Medicine.&nbsp;1996;10:168.)
Survival of dogs with experimentally induced chronic kidney disease fed foods with three different fat sources (fish oil, tallow, safflower oil). Note that survival was increased in those dogs consuming foods with either tallow or fish oil compared to safflower oil. Dietary fatty acid composition appears to affect hemodynamic adaptations to renal disease in dogs. (Adapted from Brown SA, Brown CA, Crowell WA, et al. Dietary lipid composition alters chronic course of canine renal disease (abstract). Journal of Veterinary Internal Medicine.&nbsp;1996;10:168.)

Figure 37-13. Survival of dogs with experimentally induced chronic kidney disease fed foods with three different fat sources (fish oil, tallow, safflower oil). Note that survival was increased in those dogs consuming foods with either tallow or fish oil compared to safflower oil. Dietary fatty acid composition appears to affect hemodynamic adaptations to renal disease in dogs. (Adapted from Brown SA, Brown CA, Crowell WA, et al. Dietary lipid composition alters chronic course of canine renal disease (abstract). Journal of Veterinary Internal Medicine. 1996;10:168.)

Figure 37-13. Survival of dogs with experimentally induced chronic kidney disease fed foods with three different fat sources (fish oil, tallow, safflower oil). Note that survival was increased in those dogs consuming foods with either tallow or fish oil compared to safflower oil. Dietary fatty acid composition appears to affect hemodynamic adaptations to renal disease in dogs. (Adapted from Brown SA, Brown CA, Crowell WA, et al. Dietary lipid composition alters chronic course of canine renal disease (abstract). Journal of Veterinary Internal Medicine. 1996;10:168.)

However, in normal and CKD dogs fed foods supplemented with safflower and menhaden fish oil, the oil supplement had no significant effect on the ratio of urinary eicosanoids (Crocker et al, 1996). The ratio of the urinary eicosanoids thromboxane B2 (a stable urinary metabolite of thromboxane A2) and prostaglandin E2 has been used as an index of renal vascular tone in normal and CKD dogs. Failure to demonstrate a change in the ratio may be related to the length of the washout period (three weeks) and uncertain stability of lipid supplements in this study.

A retrospective CKD study was conducted to evaluate survival times in 146 cats fed one of seven commercial veterinary therapeutic renal foods, compared with survival times in 175 cats fed regular maintenance foods (Plantinga et al, 2005). The median survival time for cats fed maintenance foods was seven months whereas the median survival time for cats fed veterinary therapeutic renal foods was 16 months. The group with the longest median survival time (23 months) was fed the food with the highest reported content of EPA. However, because of study design and differences between groups (e.g., age of cats, plasma creatinine concentrations) and foods (e.g., potassium, phosphorus) used, it is not possible to conclude that differences in survival times were due to increased amounts of EPA. In addition, EPA content was not determined for all foods used in the study.

Although the recommended amount of omega-3 fatty acids for foods for CKD patients has not been definitively determined, the amounts in the aforementioned studies in dogs (Brown et al, 1998, 2000; Brown, 2008) ranged from 0.41 to 4.37% DM. With a 5:1 omega-6:omega-3 fatty acid ratio, the lower end of the range (0.41%) was effective in reducing the magnitude of glomerular hypertension and renal generation of inflammatory eicosanoids (Brown, 2008). The omega-6:omega-3 ratio was not reported in the earlier studies (Brown et al, 1998, 2000). To date, studies like these have not been done in cats but it seems likely that similar levels would be effective. Based on results of canine studies described above, the recommended range for total omega-3 fatty acid content in foods for canine and feline CKD patients is 0.4 to 2.5% DM. Until there is definitive work, a somewhat broad range for the omega- 6:omega-3 fatty acid ratio is recommended (1:1 to 7:1). These recommendations are similar to omega-3 fatty acid content and omega-6:omega-3 ratios recommended for dogs and cats with cancer, osteoarthritis and inflammatory skin diseases.

Dietary omega-3 fatty acid supplementation in combination with antioxidants (See Antioxidants below.) can further reduce renal oxidant injury. In a study in dogs with the remnant model of CKD, dietary supplementation with omega-3 fatty acids and antioxidants (vitamin E, carotenoids and lutein), both were independently renoprotective; when combined, their effects were synergistic (Brown, 2008). In this model, addition of antioxidants reduced proteinuria, glomerulosclerosis and interstitial fibrosis independent of the ratio of dietary omega-6 to omega- 3 fatty acids (Brown, 2008).  

Antioxidants: Vitamins E and C

Oxidative damage is a component in the progression of renal injury in several types of kidney disease (Figure 37-7) (Diamond et al, 1986; Agarwal, 2003; Vasavada and Agarwal, 2005). Unquenched ROS may damage proteins, lipids, DNA and carbohydrates, resulting in structural and functional abnormalities and progressive renal injury. Renal oxidative stress occurs when production of ROS exceeds quenching capacity of antioxidant defense mechanisms (Brown, 2008). As previously discussed (See Etiopathogenesis), increased renal oxidative stress has been linked to proteinuria as a potential mediator of tubulointerstitial damage and to progression of CKD (Brown, 2008; Agarwal, 2003; Agarwal et al, 2004; Vasavada and Agarwal, 2005). Specifically, overloading tubular mechanisms for resorption of filtered albumin by proximal tubular cells can stimulate production of proinflammatory and profibrotic cytokines by activation of the redox-sensitive gene nuclear factor-β thereby contributing to tubulointerstitial damage (Agarwal, 2003; Rossert and Froissart, 2006).

Numerous antioxidant defense mechanisms are designed to minimize damage by ROS including several nutritional antioxidants: vitamins E and C and carotenoids to name a few (Brown, 2008). Supplementation of foods with these antioxidants has been evaluated in dogs and cats with naturally occurring CKD. In a canine study, 10 patients with CKD (IRIS stage 2 to 3) and 10 healthy dogs were evaluated to determine effects of supplementation of vitamins E (1,200 IU/kg DM) and C (150 mg/kg DM), and β-carotene (1.6 mg/kg DM) in a dry veterinary therapeutic renal food (Yu et al, 2006). Levels of vitamins E and C and β-carotene in the control food were not reported. The antioxidant supplementation reduced oxidative stress as measured by significantly reduced plasma malondialdehyde concentration. The antioxidant-supplemented renal food significantly reduced serum creatinine concentration and resulted in increased body weight and activity (8 of 10 dogs) in the CKD dogs compared with dogs receiving the unsupplemented commercial maintenance-type food (Yu et al, 2006).

Similarly, effects of antioxidants on renal oxidative stress were studied in 10 cats with CKD compared with healthy cats (Yu and Paetau-Robinson, 2006). Supplementation of vitamins E (742 mg/kg DM) and C (84 mg/kg DM) and β-carotene (2.1 mg/kg DM), compared with the control food containing 166 mg/kg DM vitamin E, less than 5 mg/kg DM vitamin C and 1.4 mg/kg DM β-carotene, resulted in reduced markers of oxidative injury. Antioxidant supplementation significantly reduced DNA damage in cats with CKD as evidenced by reduced serum 8-hydroxy-2’-deoxyguanosine (8-OHdG) and comet assay parameters (Yu and Paetau-Robinson, 2006). Based on these studies, supplementation with vitamins E and C and β-carotene as antioxidants may benefit dogs and cats with CKD.

Dietary supplementation with antioxidants in combination with increased omega-3 fatty acids (discussed above) reduces renal oxidant injury. Supplementation with vitamin E suppressed renal oxidative stress in rats with 5/6 nephrectomy (Tain et al, 2007). Also, as mentioned above in dogs with a remnant kidney model of CKD, dietary omega-3 fatty acid supplementation reduced proteinuria, prevented glomerular hypertension and decreased production of proinflammatory eicosanoids (Brown et al, 1998, 2000). In other studies in dogs with a remnant kidney model of CKD, dietary supplementation with omega-3 fatty acids and antioxidants (vitamin E, carotenoids and lutein) both independently were renoprotective and their effects were additive when used together (Brown, 2008). In this model, addition of antioxidants reduced proteinuria, glomerulosclerosis and interstitial fibrosis independent of the ratio of dietary omega-6 polyunsaturated fatty acids to omega-3 polyunsaturated fatty acids (Brown, 2008).

The DM requirement of vitamin E in foods for adult dogs is 30 IU/kg (NRC, 2006). An upper limit of 1,000 to 2,000 IU/kg food DM has been suggested for dogs (AAFCO, 2007). One antioxidant biomarker study in dogs indicated that for improved antioxidant performance, foods should contain at least 500 IU vitamin E/kg DM (Jewell et al, 2000). Besides helping to prevent chronic diseases associated with oxidative stress, increasing dietary intake of vitamin E, up to 2,010 mg/kg food DM in older dogs improved immune function (Hayes et al, 1969; Hall et al, 2003; Meydani et al, 1998). Based on the above studies, foods for canine CKD patients should contain at least 400 IU vitamin E/kg DM and higher levels are likely more beneficial. In one report, dietary supplementation of food for dogs with induced CKD, 5 IU/kg body weight was effective; this amount translates to approximately 450 IU/kg food DM (Brown, 2008).

The minimum recommended allowance of vitamin E in foods for healthy adult cats is 38 IU/kg DM (NRC, 2006). No safe upper limit has been established for cats. One antioxidant biomarker study suggested that cat foods should contain 600 IU/kg DM for improved antioxidant function (Jewell et al, 2000). A study in aged cats showed that increasing dietary intake of vitamin E to 272 and 552 IU/kg of food DM improved immune function (Hayes et al, 1969; Hall et al, 2003). Based on these data and studies in cats with CKD discussed above, foods for cats with CKD should contain at least 500 IU/kg DM and, as with dogs, higher levels are likely more beneficial. Foods high in polyunsaturated fatty acids (e.g., those containing fish oils), may require increased amounts of vitamin E (four or more times levels in typical foods) to prevent steatitis (NRC, 2006).

Healthy dogs can synthesize required amounts of vitamin C for normal maintenance conditions (Innes, 1931; Naismith, 1958; Chatterjee et al, 1975) and they can rapidly absorb supplemental vitamin C (Wang et al, 2001). However, in vitro studies indicate that dogs and cats have from one-quarter to one-tenth the ability to synthesize vitamin C as other mammals (Chatterjee et al, 1975). Foods for canine and feline CKD patients should contain at least 100 and 100 to 200 mg vitamin C/kg DM, respectively. This recommendation is based on the aforementioned vitamin E levels in foods for dogs and cats with CKD and data indicating that vitamin C regenerates vitamin E at about a 1:1 molar ratio (Barclay et al, 1985). This range is not a risk factor for urinary oxalate production in cats (Yu and Gross, 2005).  

Other Nutritional Factors

β-carotene

β-carotene is a carotenoid like lutein and lycopene. As mentioned above, the carotenoids have antioxidant properties. β-carotene can be absorbed by dogs and cats. β-carotene is also a precursor for vitamin A. Dogs, but not cats, are able to convert β-carotene to vitamin A. β-carotene can be pro-oxidant at high levels in people and laboratory animals (Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, 1994). β-carotene values in foods typically are difficult to obtain from manufacturers. For these reasons, at this time, β-carotene is not considered a key nutritional factor for foods for dogs or cats with CKD.

L-Carnitine

Carnitine is a conditionally essential nutrient required for the transfer of long-chain fatty acids into the mitochondria. As a nutrient essential for efficient metabolism of fat for energy carnitine plays a role in sparing lean body mass from being catabolized as a source of energy. This may in part explain why healthy dogs and cats fed a complete and balanced diet with 300 and 500 ppm carnitine, respectively, gained significant LBM (P<0.01) compared with healthy control dogs and cats, as assessed by dual-energy X-ray absorptiometry (Data on file, Hill’s Pet Nutrition).

Due to the role of carnitine in fat metabolism, maintaining optimal amounts to support efficient fat utilization has been deemed critical in patients suffering from loss of lean body mass. Interestingly, carnitine homeostasis in the body is controlled through the kidneys and in some patients with kidney disease levels may be reduced, potentially limiting use of fat for energy. Furthermore, carnitine also acts as an important antioxidant and therefore may play a role in minimizing oxidative stress associated with kidney disease. For all of the above reasons it is essential that patients with kidney disease maintain adequate carnitine stores.

Acidifiers and Buffers

Metabolic acidosis is a common finding in patients with CKD. Decreased venous blood pH and plasma bicarbonate or total CO2 concentrations are common, particularly in cats with uremic signs or end-stage disease (Lulich et al, 1992; Elliott and Barber, 1998; Elliott et al, 2003, 2003a). The kidneys play an important role in regenerating bicarbonate and excreting dietary acids, which may be derived from several sources. Sulfuric acid is formed when sulfur-containing amino acids (i.e., methionine and cysteine) are oxidized to sulfate. In general, animal-source proteins are higher in sulfur-containing amino acids than are plant-source proteins. Exogenous- and endogenous-source proteins are equally important. Insufficient energy intake results in protein catabolism and increased hydrogen ion production. Urinary urea production and total urinary hydrogen ion excretion are directly proportional. Organic acids are produced from partial oxidation of carbohydrates, fats, proteins and nucleic acids. Phosphoric acid can be ingested in the food or it can be produced endogenously. Phosphoric acid is used in some cat foods as a palatability enhancer, either separately or as a component of topically applied animal digests. Phosphoric acid can be derived from hydrolysis of phosphate esters in proteins and nucleic acids, if they are not neutralized by mineral cations (e.g., sodium, potassium and magnesium). The contribution of dietary phosphate to acid production depends on the type of protein ingested. Some proteins generate phosphoric acid, whereas others generate only neutral phosphate salts. Hydrochloric acid is generated when positively charged cationic amino acids (e.g., lysine and arginine) are broken down into neutral products.

Some commercial veterinary therapeutic renal foods are formulated with combinations of ingredients that will alkalinize the urine and blood, which minimizes dietary acid load (Burkholder et al, 2000). These foods are limited in protein ingredients, particularly those that are high in sulfur-containing amino acids. For patients with CKD, the serum total CO2 should be maintained within the reference range for healthy patients. Ideally, blood gas analysis should be done to more accurately confirm the presence of metabolic acidosis. As CKD progresses and acidosis becomes more severe, alkali therapy (e.g., sodium bicarbonate, potassium citrate) should be considered in addition to nutritional management. Although urinary pH may be used as an indirect assessment of acid/base status, monitoring venous blood gases is a more sensitive method to evaluate effectiveness of alkalinization therapy.  

Vitamin D

Calcitriol (1,25-dihydroxyvitamin D) plays an important role in the pathogenesis of secondary renal hyperparathyroidism. Patients with severe CKD have decreased circulating levels of 1,25-dihydroxyvitamin D because of decreased synthesis by the kidney. Hyperphosphatemia and the progressive loss of renal epithelial cells inhibit conversion of 25-hydroxyvitamin D to calcitriol by renal 1-α hydroxylase. At earlier stages of CKD, circulating levels of 1,25-dihydroxyvitamin D may be normal due to the compensatory effect of increased concentrations of PTH on renal 1- α-hydroxylase activity and tubular synthesis of 1,25-dihydroxyvitamin D.

Calcitriol is an important regulator of parathyroid chief-cell function. Calcitriol acts by decreasing PTH messenger RNA expression, increasing expression of vitamin D receptors and controlling the “set point” of chief cells, which determines responsiveness to negative feedback by ionized serum calcium concentrations. Decreased circulating calcitriol levels in CKD lead to chief-cell hyperplasia and increased secretion of PTH. Increased PTH levels have been suggested to play a role in the severity of clinical signs and progression of CKD (Nagode and Chew, 1992).

Avoiding excessive dietary phosphorus and using phosphate binders reduce the inhibitory effects of hyperphosphatemia on renal 1- α-hydroxylase activity, thereby increasing calcitriol production by tubular cells. Oral administration of low doses of calcitriol is associated with decreased serum PTH concentrations. Strong evidence supports the use of calcitriol therapy for slowing progression of CKD in dogs but not in cats (Polzin et al, 2005a; Polzin, 2007). The effect of varying vitamin D levels in foods has not been studied; therefore, it is not included as a key nutritional factor.

B Vitamins

Limited information exists concerning vitamin nutrition in dogs and cats with CKD; however, these patients are at risk for water soluble B-vitamin deficiency because of decreased appetite, vomiting, diarrhea and polyuria. Human patients with CKD apparently are especially prone to pyridoxine and folate deficiency (Gilmour et al, 1993). Thiamin and niacin deficiency may contribute to anorexia associated with renal failure. Empirical administration of vitamins seems appropriate in anorectic patients with CKD. However, care must be taken to avoid excessive amounts of fat-soluble vitamins. Patients eating adequate amounts of commercial veterinary therapeutic renal foods are unlikely to need B-vitamin supplementation.

Trace Minerals

Presumably, CKD alters metabolism of trace minerals. For example, nutrients such as copper and zinc that are highly bound to protein may be lost with severe proteinuria. Aluminum may accumulate in human patients with CKD who are treated with aluminum-containing phosphate binders. Aluminum toxicity can cause metabolic bone disease, encephalopathy and anemia. However, exact data are not available to support making a routine recommendation for dietary trace mineral modification for dogs and cats with CKD. There are no reports of trace mineral problems in dogs and cats with CKD that eat commercial veterinary therapeutic renal foods.

Soluble Fiber

It is well established that soluble fiber causes bacterial proliferation in the colon. Bacterial growth requires a source of nitrogen. Although dietary protein provides some nitrogen, blood urea is the largest and most available source of nitrogen for bacterial protein synthesis in the colon (Younes et al, 1995). Urea is the major end product of protein catabolism in mammals. When blood urea diffuses into the large bowel it is broken down by bacterial ureases and used for bacterial protein synthesis. These bacterial proteins are then excreted in the feces. The net effect is increased fecal urea excretion, reduced serum urea nitrogen concentration and reduced urinary urea excretion in rats and people (Younes et al, 1995, 1996; Bliss et al, 1996).   

Feeding Plan

Feeding Plan

There is strong evidence that, nutritional management with an appropriately formulated commercial veterinary therapeutic renal food should begin when serum creatinine exceeds 2 mg/dl in dogs and cats with CKD (stage 2 CKD and higher). More research is needed to determine the optimal nutrient levels for patients with stage I CKD, but based on studies available thus far implementing a diet plan with moderate levels of protein and phosphorus with high concentrations of omega-3 fatty acids seems prudent. Nutritional management is the cornerstone of treatment for dogs and cats with CKD; however, inappetence, vomiting and diarrhea may be prominent in patients with moderate to severe CKD and evidence of systemic illness (uremia). These patients should receive aggressive fluid and electrolyte therapy in an attempt to ameliorate azotemia, uremia, electrolyte abnormalities and acidosis before initiating a traditional feeding plan.

Assess and Select Food

Foods for dogs and cats with CKD should be evaluated for all the key nutritional factors previously discussed (Table 37-10). Tables 37-12 and 37-13 list commercial veterinary therapeutic foods designed for CKD patients (dogs and cats, respectively), including comparisons to recommended levels of key nutrition- al factors. These comparisons will help determine the best food to consider for initial feeding. Although commercial veterinary therapeutic renal foods share some features in common, they are not the same. It is important to consider the evidence supporting effectiveness of individual foods when making nutritional recommendations for patients with CKD (Table 37-11 and Box 37-4). In addition, it may be necessary to consider nutrients that may affect concomitant diseases (e.g., dogs with CKD and pancreatitis or cats with CKD and diabetes mellitus ) (Case 37-4).

Table 37-12. Key nutritional factors in selected commercial veterinary therapeutic foods for dogs with chronic kidney disease compared to recommended levels.*

Moist Foods

  Energy Density (kcal/can)** Protein (%) P (%) Na (%) K (%) Omega-3 fatty acids (%) Omega-6: Omega-3 Vit E (IU/kg) Vit C (mg/kg) Data
Recommended Levels   14-20 0.2-0.5 <0.3 0.4-0.8 0.4-2.5 1:1-7:1 3400 100-200 -
Hill's® Prescription Diet® k/d® Canine 437 kcal/13 oz. 15.0 0.30 0.20 0.82 2.4 NA 909 110 P
Hill's® Prescription Diet® k/d® Canine with Lamb 438 kcal/13 oz. 15.2 0.27 0.20 0.75 2.0 NA 661 78 P
Hill's® Prescription Diet® k/d® Canine Beef & Vegetable Stew 145 kcal/5.5 oz.; 330 kcal /12.5 oz. 16.0 0.27 0.16 0.98 1.4 NA 656 136 P
Hill's® Prescription Diet® k/d® Canine Chicken & Vegetable Stew 145 kcal/5.5 oz.; 330 kcal/12.5 oz. 16.0 0.29 0.16 0.98 1.4 NA 667 139 P
Hill's® Prescription Diet® k/d® + Mobility Canine Chicken & Vegetable Stew 351 kcal/12.5 oz. 16.0 0.32 0.16 0.95 4.4 NA 667 125 P
Hill's® Prescription Diet® g/d® Canine 388 kcal/13 oz. 18.6 0.42 0.21 0.71 0.7 NA 784 132 P
Hill's® Prescription Diet® u/d® Canine 499 kcal/13 oz. 13.4 0.33 0.30 0.54 0.5 NA 820 2 P
Purina®  Pro Plan® Veterinary Diets NF® Kidney Function 494 kcal/13.3 oz. 19.1 0.35 0.18 1.08 0.4 8.1:1 465 NA P
Royal Canin Veterinary Diet® Renal Support D Morsels in Gravy 352 kcal/13.5 oz. 21.7 0.42 0.63 0.94 0.9 6.8:1 1080 407 C
Royal Canin Veterinary Diet® Renal Support E  601 kcal/13.5 oz. 16.0 0.34 0.20 0.63 0.7 7.1:1 551 327 C
Royal Canin Veterinary Diet® Renal Support T 596 kcal/13.5 oz. 17.5 0.39 0.24 0.53 0.8 5.8:1 615 373 C
Rayne Clinical NutritionTM Restrict-CKDTM Canine 417 kcal/14.11 oz. 18.5 0.23 0.24 0.86 1.3 NA NA NA P

 

Dry Foods

  Energy Density (kcal/cup)** Protein (%) P (%) Na (%) K (%) Omega-3 fatty acids (%) Omega-6: Omega-3 Vit E (IU/kg) Vit C (mg/kg) Data
Recommended Levels   14-20 0.2-0.5 <0.3 0.4-0.8 0.4-2.5 1:1-7:1 3400 100-200 -
Hill's® Prescription Diet® k/d® Canine 402 15.5 0.33 0.19 0.84 1.0 NA 730 126 P
Hill's® Prescription Diet® k/d® Canine with Lamb 459 16.0 0.33 0.18 0.69 0.2 NA 730 126 P
Hill's® Prescription Diet® k/d® + Mobility Canine 496 15.3 0.29 0.19 0.68 3.8 NA 563 92 P
Hill's® Prescription Diet® g/d® Canine 361 18.3 0.43 0.20 0.71 0.8 NA 745 NA P
Hill's® Prescription Diet® u/d® Canine 398 10.9 0.22 0.23 0.55 0.8 NA 745 NA P
Purina®  Pro Plan® Veterinary Diets NF® Kidney Function 459 14.6 0.33 0.27 0.76 2.0 2.4:1 448 NA P
Royal Canin Veterinary Diet® Renal Support A  352 15.0 0.22 0.39 0.69 1.0 4.3:1 645 215 C
Royal Canin Veterinary Diet® Renal Support F  356 14.4 0.34 0.38 0.63 1.0 3.9:1 635 319 C
Royal Canin Veterinary Diet® Renal Support S 365 13.4 0.30 0.39 0.65 0.9 4.1:1 643 214 C
Royal Canin Veterinary Diet® Multifunction Renal Support + Hydrolyzed Protein 385 14.9 0.21 0.38 0.64 1.1 4:1 641 320 C
Blue Natural Veterinary Diet KS Kidney Support 427 16.9 0.38 0.22 0.92 2.3 1.5:1 652 33 P

 

P = phosphorus, Na = sodium, K = potassium, omega-6:omega-3 = omega-6 to omega-3 fatty acid ratio, Vit. E = vitamin E, Vit. C = vitamin C, na = information not available from manufacturer, g = grams.   *All values are reported on a dry matter basis unless otherwise indicated. Moist foods are best. All values were obtained from manufacturers’ published information.    **Energy density as fed (per can or cup) is useful for determining the amount to feed; cup = 8-oz. measuring cup; to convert kcal to kJ, multiply kcal by 4.184.                                    

Table 37-12. Key nutritional factors in selected commercial veterinary therapeutic foods for cats with chronic kidney disease compared to recommended levels.*

Moist Foods

  Energy Density (kcal/can)** Protein (%) P (%) Na (%) K (%) Omega-3 fatty acids (%) Omega-6: Omega-3 Vit E (IU/kg) Vit C (mg/kg) Data
Recommended Levels   28-35 0.3-0.6 <0.4 0.7-1.2 0.4-2.5 1:1-7:1 3500 100-200 -
Hill's® Prescription Diet® k/d® Feline with Chicken 177 kcal/5.5 oz. 30.0 0.49 0.24 1.11 1.0 NA 998 95 P
Hill's® Prescription Diet® k/d® Feline with Tuna 170 kcal/5.5 oz. 29.0 0.45 0.24 1.08 1.2 NA 912 NA P
Hill's® Prescription Diet® k/d® Feline Chicken & Vegetable Stew 70 kcal/2.9 oz. 30.0 0.49 0.23 1.05 1.1 NA 748 NA P
Hill's® Prescription Diet® k/d® Feline Vegetable & Tuna Stew 77 kcal/2.9 oz. 30.0 0.49 0.24 1.05 1.0 NA 1002 NA P
Hill's® Prescription Diet® k/d® Early Support Feline Chicken, Vegetable & Rice Stew 79 kcal/2.9 oz. 34.1 0.59 0.27 0.94 1.3 2.9:1 688 166 -
Hill's® Prescription Diet® k/d® + Mobility Feline Chicken & Vegetable Stew 68 kcal/2.9 oz. 29.6 0.48 0.24 1.05 1.7 NA 668 227 P
Purina® Pro Plan® Veterinary Diets NF Kidney Function® Early Care 162 kcal/5.5 oz. 38.7 0.43 0.39 1.49 0.7 6.1:1 1051 NA P
Purina® Pro Plan® Veterinary Diets NF Kidney Function® Advanced Care 165 kcal/5.5 oz. 27.8 0.39 0.34 1.52 0.7 7.2:1 1054 NA P
Royal Canin Veterinary Diet® Renal Support D 97 kcal/3 oz. 34.2 0.44 0.49 1.03 1.1 6.8:1 685 291 C
Royal Canin Veterinary Diet® Renal Support E  171 kcal/5.8 oz. 33.6 0.46 0.25 0.96 1.0 4.4:1 642 255 C
Royal Canin Veterinary Diet® Renal Support T 82 kcal/3 oz. 31.6 0.51 0.51 0.96 1.1 5.1:1 663 264 C
Blue Natural Veterinary Diet KM Kidney + Mobility Support 153 kcal/5.5 oz. 25.0 0.46 0.21 2.29 1.3 2.1:1 138 NA P

 

Dry Foods

  Energy Density (kcal/cup)** Protein (%) P (%) Na (%) K (%) Omega-3 fatty acids (%) Omega-6: Omega-3 Vit E (IU/kg) Vit C (mg/kg) Data
Recommended Levels   28-35 0.3-0.6 <0.4 0.7-1.2 0.4-2.5 1:1-7:1 3500 100-200 -
Hill's® Prescription Diet® k/d® Feline 541 30.1 0.51 0.25 0.75 0.9 NA 823 143 P
Hill's® Prescription Diet® k/d® Feline with Ocean Fish 444 29.9 0.52 0.25 0.75 1.1 NA 823 140 P
Hill's® Prescription Diet® k/d® Early Support Feline 536 34.0 0.56 0.25 0.75 1.6 2.9:1 1123 137 -
Hill's® Prescription Diet® k/d® + Mobility Feline 484 28.8 0.51 0.27 0.82 1.5 NA 621 127 P
Purina® Pro Plan® Veterinary Diets NF Kidney Function® Early Care 494 38.9 0.41 0.31 1.51 0.7 2.7:1 687 NA P
Purina® Pro Plan® Veterinary Diets NF Kidney Function® Advanced Care 536 30.4 0.38 0.31 1.56 0.7 2.5:1 627 NA P
Royal Canin Veterinary Diet® Renal Support A  345 24.1 0.45 0.37 0.95 0.8 4.1:1 523 210 C
Royal Canin Veterinary Diet® Renal Support F  373 27.1 0.46 0.41 0.95 0.9 4.5:1 626 209 C
Royal Canin Veterinary Diet® Renal Support S  398 25.8 0.44 0.44 0.93 0.9 4.4:1 631 316 C
Royal Canin Veterinary Diet® Multifunction Renal Support + Hydrolyzed Protein 400 26.3 0.48 0.40 0.95 1.0 4.9:1 631 210 C
Blue Natural Veterinary Diet KM Kidney + Mobility Support 458 29.6 0.52 0.27 0.91 2.4 1.5:1 645 34 P

P = phosphorus, Na = sodium, K = potassium, omega-6:omega-3 = omega-6 to omega-3 fatty acid ratio, Vit. E = vitamin E, Vit. C = vitamin C, na = information not available from manufacturer, g = grams. *All values are reported on a dry matter basis unless otherwise indicated. Moist foods are best. All values were obtained from manufacturers’ published information.  **Energy density as fed (per can or cup) is useful for determining the amount to feed; cup = 8-oz. measuring cup; to convert kcal to kJ, multiply kcal by 4.184.                                    

All possible sources of nutrients that patients with CKD will receive should be evaluated and discussed with pet owners. This includes both treats as well as foods used to give medications. Many owners give medications in meats, cheeses or peanut butter. All of these foods are inappropriate for pets with kidney disease due to the sodium, phosphorus and protein content. Through a diet history foods used to give medications should be identified and when necessary nutritionally appropriate alternatives should be given, including giving medications in a canned renal food which is not the pet’s primary diet, using small pieces of white bread molded around pills, trace amounts of unsalted butter (only enough to coat pills for easy administration), marshmallows, etc. In the case of treats it may be easy to simply recommend that owners not give any; however, the reality is that most owners give their pet treats. When asked how they showed affection to their pets, 71% of 1,212 dog owners and 44% of 820 cat owners said they give their pets treats and 42 and 25% of dog and cat owners, respectively, said they give their pets people food (Habits and Practices Study, 2002). The importance of providing treats to many pet owners’ relationships with their pets is also highlighted in a survey study of pet owners that indicated they would be willing to engage in veterinary guidance, adhere to diet modification, use a veterinary weight loss product, increase exercise, and attend an obesity clinic to get their pet to lose weight before they considered eliminating treats (Bland et al, 2010).

In a survey of dietary practices of owners of cats with CKD 56% reported giving commercial treats to their cats (Markovich et al, 2015). While the number of treats varied nearly half of the owners (48%) reported giving more than six treats per week. Therefore, when communicating feeding plan recommendations for dogs and cats with CKD, it’s important to discuss treats with pet owners. Treats formulated to maintain the appropriate nutrient profile of therapeutic renal foods are commercially available for dogs and cats. Alternatively it may be recommend that the owner keep kibbles of a dry veterinary therapeutic renal food in a separate container located in a different area from where the pet is normally fed and use these as treats. Small amounts of moist veterinary therapeutic renal food formed into balls could also be offered. If an owner insists on feeding other treats, the amount of treats and human foods fed should be less than 10% of the pet’s caloric intake. Many commercial pet treats and processed human foods contain excess sodium, chloride and phosphorus and should be avoided in CKD patients. However, some commercial treats contain moderate amounts of these nutrients. High-phosphorus human foods (e.g., milk, milk products, cheese, fish, beef, poultry, peanut butter, nuts and legumes) should be avoided. In addition to treats, it is important to discuss with owners what forms of food they prefer to feed and to offer them the same forms (dry and moist) of the veterinary therapeutic renal food. In a survey of more than 800 cat owners, 66% preferred to feed both moist and dry food to their cats (Habits and Practices Study, 2002). In this situation, if the owners purchased a dry veterinary therapeutic renal food from their veterinarian for a cat with CKD, it is highly likely they would buy a moist food elsewhere and use it with the dry food. Feeding a typical over-the-counter moist cat food that contains increased amounts of sodium, chloride and phosphorus could decrease or negate effectiveness of the veterinary therapeutic renal food.

Assess and Determine the Feeding Method

Changing the feeding method in the management of CKD may not be necessary, especially in patients with early or uncomplicated CKD. It is important, however, to verify that an appropriate feeding method is being used. Items to consider include access to water, amount fed, how food is offered, access to other foods and who feeds the pet. Patients with uremia and other signs of systemic disease may be partially or completely anorectic and require alternate feeding methods.

How the previous food was offered (e.g., free-choice feeding or multiple offerings per day of a prescribed amount) can be continued if the form of the food is unchanged and the pet is in optimal body and muscle condition.

The amount to feed is based on the patient’s energy requirement. The energy needs of patients with kidney disease are presumed to be similar to those of normal pets having the same level of activity. In general, energy intake tends to decrease as renal function declines because of progressive anorexia. In addition, numerous factors (e.g., gender, changes in environment and activity) influence the energy requirement for an individual patient. The starting point for estimating daily energy requirement (DER) for an individual patient is to calculate the resting energy requirement (RER) and multiply this number by a factor that varies based on the activity level of the pet. The formula for calculating RER in kcal/day is 70(BWkg)0.75. Table 5-2 also provides RER estimates for dogs and cats. The recommended  DER  range  for most adult dogs is 1.1 to 1.6 x RER. The DER range for most adult cats is 1.1 to 1.4 x RER. After the DER is estimated, it is divided by the energy density of the food on an as fed basis to determine the amount to feed. Feeding recommendations from the manufacturer of the selected food may also be used as a starting point. Feeding a caloric amount calculated based on the pet’s former food intake is the most accurate starting point if the pet is in optimal body and muscle condition. The initial food dose should be adjusted from these starting points to maintain optimal body weight and condition.

Gradual transition to a new food improves acceptance and also decreases the likelihood of problems in those patients that cannot rapidly adjust urinary sodium levels because of their renal dysfunction. Dogs with CKD usually tolerate a dietary change over seven to 10 days, whereas, cats may need three to four weeks or longer to make a successful transition. This requires patience and persistence by the pet owner and veterinary health care team. Some cats also transition well if offered the new and old foods side-by-side rather than mixing the two foods. However, the end result is worth it because feeding a commercial veterinary therapeutic renal food is the only treatment that has been shown to prolong survival time in dogs and cats with CKD. Unfortunately, the “cold turkey” approach to feeding (i.e., owners returns home with their pet and immediately switch to the new food), rather than transitioning to the new food gradually over several days to weeks is common. In this scenario, the outcome often results in failure to implement the nutritional recommendation. Changing the eating habits of most dogs and cats is relatively easy, but changing the feeding habits of some pet owners and veterinarians is often more difficult. Some veterinarians are still unaware that commercial veterinary therapeutic renal foods are as palatable, or more so, than regular maintenance foods.

Two recent yearlong studies have evaluated acceptance of a renal therapeutic food in pets with early kidney disease. Of 36 client-owned dogs with IRIS-Stage 1 CKD, all but one (97%) transitioned to the renal food and continued to eat it throughout the study. Owners reported that renal food was generally well liked (88%), dogs ate enthusiastically (76%), and dogs consumed most or all of the food offered (84%) (Hall et al, 2017). In a study of 128 client owned cats with IRIS stage 1-4 kidney disease 94 % of cats accepted the therapeutic renal food and continued eating it until the last assessment. Additionally owners reported that their cats liked the therapeutic renal food as much or more than their original food (Fritsch et al, 2015).

The feeding plan is more likely to be successful if the owner is told that the veterinary therapeutic renal foods are highly palatable (positive bias). Box 37-6 provides additional tips to aid in increasing acceptance of veterinary therapeutic renal foods by dogs and cats with CKD.

Box 37-6. Tips for Encouraging Acceptance of Veterinary Therapeutic Renal Foods in Patients with Chronic Kidney Disease.

When switching to a veterinary therapeutic food, it may help to use a familiar form of food initially (e.g., moist or dry or a combination). However, some patients may switch their preferences after CKD develops and prefer different forms of foods. Moist veterinary therapeutic renal foods are often considered more palatable, particularly by cats, if warmed (not above body temperature). Alternatively, some dogs prefer foods cooled in the freezer for approximately 10 minutes which may reduce the aroma, beneficial in some nauseous dogs. Palatability of dry foods can often be increased by adding water or flavoring agents such as tuna juice, clam juice, unsalted chicken or beef broth, or sweeteners (dogs only) such as honey, agave nectar or maple syrup. Uneaten moistened foods should not be allowed to remain at room temperature for more than a two hours (Chapter 11). Some of the aforementioned supplements are high in sodium content (e.g., clam and tuna juice); however, and should not be used long-term due to excessive sodium intake above the amount in the veterinary therapeutic food. Environmental factors should also receive consideration when transitioning pets to a veterinary therapeutic renal food. Owner compliance and pet acceptance of the food must be adequate for nutritional management to be effective. Knowing who feeds the patient is important for compliance, and limiting the patient’s access to other foods improves acceptability (e.g., a dog having access to cat food or a cat living in a multi-cat household). Feeding location and presentation are important. Timid animals should be fed in a quiet place. Cats should be fed away from loud, persistent barking or other distracting noises. Food bowls should not be kept in close proximity to litter boxes and noisy areas. Food for cats should be offered in wide bowls or on a plate to avoid stimulation of tactile whiskers. Placing small quantities of palatable food in a patient’s mouth or on its paws (moist food) to stimulate licking or swallowing (i.e., hand feeding) may facilitate eating. Patients’ appetite can be influenced by the person feeding the patient (server). The likelihood of eating increases in direct proportion to the time the patient has spent with the server in a nonstressful situation (Delaney, 2006). For hospitalized pets, the ideal server is likely the pet owner followed by either a technician or kennel assistant who has not restrained or otherwise antagonized the patient.

Food aversion is possible if a nauseated pet is force-fed or if a painful or unpleasant experience is associated with feeding. Syringe and force feedings should be avoided. Pets may also develop food aversions associated with the feeding situation in the home (the bowl, room where food is offered, etc). It is often helpful to feed from a new plate or bowl and in a different room when dealing with pets suffering from chronic illness and a decreased appetite. Unpalatable medications (e.g., some phosphate binders) should not be mixed with veterinary therapeutic foods. Managing underlying abnormalities in fluid, electrolyte and acid-base balance will help minimize nausea and vomiting. Pharmacologic agents (e.g., ranitidine, famotidine, metoclopramide and sucralfate) can be used to limit uremic gastritis, nausea and vomiting. Appetite stimulants may increase food intake. Mirtazapine, a tetracyclic antidepressant, has been used in veterinary patients because of its anti-nausea, anti-emetic and appetite stimulating properties. A masked placebo-controlled crossover study in cats with CKD documented a statistically significant increase in appetite (P=0.02) and activity (p=0.02) and a significant decrease in vomiting (P=0.047) in cats receiving mirtazapine orally every other day for 3 weeks (Quimby et al, 2013). Weight gain occurred in 91% of cats during the mirtazapine administration phase while 82% of cats lost weight during the placebo phase. While there are no medications approved for the treatment of inappetence in cats, capromorelin has been approved by the FDA for stimulation of appetite in dogs. Capromorelin is a ghrelin receptor agonist. Like naturally occurring ghrelin it binds to specific cell receptors and affects signaling in the hypothalamus causing the feeling of hunger. In a controlled randomized study of 177 client owned dogs with reduced appetite of varying etiologies a significantly higher proportion of dogs in the treated group were judged by their owners to have increased appetite compared to the control group (68.6% vs. 44.6%; P=0.0078). While this may be an option for some inappetant dogs with CKD, the dosing instructions specify this drug should be used with caution in dogs with renal insufficiency. While not labeled for use in cats, one study has evaluated the safety of a daily oral dose of capromorelin in healthy cats.158 Abnormal clinical observations included emesis, hypersalivation, lethargy/depression, head shaking and lip smacking. There were no relevant differences in clinical pathology test results between treated and placebo groups. Efficacy studies have not been reported.

Veterinary therapeutic foods intended for long-term management of patients with CKD should not be offered during periods of hospitalization, nausea and vomiting to prevent possible food aversions. Consider using an appropriate, alternative food temporarily during hospitalization for dogs and cats with uremic signs.

Finally, a common approach that is used for “picky” eaters is to offer samples of several different foods and then recommend the food they will eat. This may be effective in some patients but there is a major disadvantage of using this approach in patients with CKD. The “cafeteria” approach should not be used in patients with diseases that commonly have a learned food aversion or that have limited commercial veterinary therapeutic food options (Delaney, 2006). Offering samples of all the commercially available veterinary therapeutic renal foods to a CKD patient that is not eating well or has uremic signs should be avoided to minimize the likelihood of a learned food aversion to all the foods the patient may need to be fed long-term (Delaney, 2006). In pets where a homemade diet is being considered it is critical that the client works with a board-certified veterinary nutritionist to ensure that all of the pet’s daily essential vitamin and mineral requirements are met and that the preparation meets the nutritional goals for the pet’s degree of kidney disease. In instances where a homemade diet is being considered in a hyporexic patient, it is recommended that the pet be fed appropriate commercial foods prior to instituting a homemade diet since many dogs will refuse commercial food once exposed to a home-prepared option. For this reason, it is frequently best to transition to the homemade diet once commercial options have been exhausted.  

REASSESSMENT

Frequency of reassessment depends on the stage of CKD and presence of concurrent conditions. Patients without azotemia but with elevated SDMA should be re-evaluated in 2-4 weeks. If SDMA remains increased additional assessments (e.g. complete urinalysis, urine culture, blood pressure measurement, UPC and imaging) are indicated. Long-term monitoring will depend on the results of the initial evaluation and interventions. Patients with azotemia should be rechecked every two to three months and uremic patients should be rechecked as often as every two to four weeks. Duration between evaluations may be longer in patients with stable disease. Parameters included in the reassessment are listed in Table 37-14. Serial evaluation of appropriate laboratory tests, including UPC ratios, is a good means of reassessment. Because of daily variation in UPC ratios, minor changes in UPC ratio may or may not be clinically important. It is important to monitor trends on multiple UPC ratios over time rather than rely on individual measurements. Increasing UPC ratios over time can indicate worsening glomerular disease, whereas serial declining UPC ratios are consistent with clinical improvement. Decreases in urine protein concentrations, however, may not always be associated with improved glomerular function. If accompanied by increases in serum creatinine concentrations, declining UPC ratios may reflect progressive glomerular sclerosis and obsolescence. As glomeruli become obsolescent, they no longer lose protein; however, these same glomeruli also lose their functional ability, potentially resulting in azotemia.

Table 37-14.

Reassessment of patients with chronic kidney disease.

Physical Examination
Abdominal palpation (size and contour of kidneys, presence of ascites)
Blood pressure measurement
Body condition/muscle mass
Body weight
Fundic examination (retinal hemorrhage, detached retina)
Hair and coat quality
Hydration status
Oral examination (uremic odor, ulcers, mucous membrane color)
Laboratory evaluation
Serum biochemistries (urea nitrogren, creatinine, albumin, phosphorus)
Serum electrolytes (calcium, potassium, chloride, sodium, magnesium)
Total serum cardon dioxide or venous blood gases (blood pH, bicarbonate, base excess) to evaluate acid-base status

Urinalysis

  • Mircoscopic sediment exam (pyuria or bacteriuria may indicate urinary tract infection
  • Urine specific gravity (crude index of tubulointerstitial function)
  • pH (very crude index of acid-base status)
Urine protein-creatinine ratio (assess proteinuria and response to treatment)
Diagnostic imaging
Abdominal radiographs (assess kidney shape and size, reference L vertebra on ventrodorsal view)
Excretory urogram (assess obstruction due to nephroliths)
Ultrasound (assess kidney and prostate gland, presence of hydronephrosis, hydroureter, uroliths

After nutritional management has been implemented for patients with CKD, it is very important to monitor for signs of malnutrition (e.g., accurate body weights over time, body condition score, muscle condition, hematocrit, serum albumin) so that food offerings can be adjusted as needed. Unfortunately, it is common to see gradual weight and muscle loss over time and increasing the amount of food offered does not help if the patient has anorexia. If the pet is not eating the recommended therapeutic renal food changing to a different commercial food or homemade food formulated by a board-certified veterinary nutritionist may be beneficial. Appetite may be cyclical in patients with advanced CKD, both in respect to overall appetite and food preferences. A dedicated owner is often required and a trial-and-error approach must be used with different foods, food forms (dry vs. moist) and feeding methods (Box 37-6). Pets with cyclical appetites may refuse a particular food or flavor one day but accept the same food when offered at a later time. In these cases, rotation between 2-3 different flavors of a food may help maintain interest in eating.

If caloric intake is insufficient to maintain body weight, clinical recommendations often include a stepwise approach designed to facilitate adequate food intake (Polzin et al, 2005; Polzin, 2007). The first step is to ensure that metabolic and other medical causes of decreased appetite have been corrected including dehydration, gastrointestinal hemorrhage, metabolic acidosis, hypokalemia, anemia, urinary tract infection, dental disease and drug-associated anorexia. Recombinant  human erythropoietin has been used successfully to improve clinical well-being of dogs and cats with CKD; improved appetite may precede improvement in hematocrit values in some CKD patients managed with erythropoietin (Cowgill et al, 1998). Significantly improved appetite also has been noted in cats with proteinuria (UPC ≥1), when managed with the ACE inhibitor benazeprilj (King et al, 2006). When metabolic and other medical causes of anorexia have been excluded or corrected, therapy for uremic gastroenteritis should be initiated with an H2-antagonist such as ranitidine or famotidine. If inappetence still persists, appetite stimulants such as cyproheptadine, mirtazapine or capromorelin can be attempted; however, results are unpredictable, intermittent and tend to be short-lived (Delaney, 2006). Regardless of the effects of the above treatments on appetite, it is important to confirm that any apparent response to such therapy sufficiently enhances food intake to meet nutritional goals.

If food intake remains inadequate to meet caloric needs for more than three to five days with no trend toward improving, assisted feeding is indicated (Delaney, 2006). Long-term use of percutaneous gastrostomy or esophagostomy tubes has been very successful for delivering food, extra water and medications to patients with CKD (Elliott et al, 2000a; Elliott, 2009) (Chapter 25). Anecdotal reports suggest that tube feeding can reverse the progressive weight loss associated with CKD and patients can have extended periods of improved quality of life (Polzin et al, 2005; Polzin, 2007).  

SUMMARY

CKD is commonly diagnosed in dogs and cats and increases in frequency with age. A variety of compensatory and adaptive responses are likely involved in the pathogenesis and progression of naturally occurring CKD. The goals of managing patients with CKD are to improve quality and quantity of life. Nutritional management plays a key role in both of these goals. Although there are many available treatments, a veterinary therapeutic renal food is the only one that has been shown to prolong survival time and improve quality of life for dogs and cats with CKD. Therefore, nutritional intervention is a critical component of managing patients with CKD. When designing a therapeutic regimen for dogs and cats with CKD, it is helpful to consider key nutritional factors (water, protein, phosphorus, omega-3 fatty acids, antioxidants, sodium, chloride and potassium). In addition to key nutritional factors, it is important to consider available evidence supporting effectiveness of specific veterinary therapeutic renal foods as well as other treatments for CKD. Individual patient needs and responses and owner preferences must also be considered to design an optimal therapeutic regimen. Transitioning to a therapeutic renal food often requires a team approach and effective communication involving the owner and health care team. There are many strategies that can be used to increase therapeutic success and thus improve the lifespan and quality of life for dogs and cats with CKD.

ACKNOWLEDGMENT

The authors and editors thank Dr. David J. Polzin and Timothy A. Adams for their contribution to this chapter in previous editions.

References

CHAPTER AUTHORS

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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