Treating the Uremic Patient

4. Treating the Uremic Patient [Late Stage III/ Stage IV CKD]

In this section use of renal care diets and dietary supplements or additives to treat the uremic syndrome (encountered in late stage III and stage IV CKD) is discussed. The average life expectancy of uremic cats is around 8 months (Figure 23), although cats presenting for the first time suffering from CKD and a uremic crisis often have a much shorter survival time in our experience. In this group of patients the dietary therapeutic goal is to improve the quality of life of the patient rather than trying to address factors which influence progression of CKD.

Figure 23. Average life expectancy of uremic cats (N = 28 uremic cats). From Elliott and Barber, 1998. 

This group of patients are particularly likely to be unstable and so close attention should be paid to:

1. Fluid balance – ensuring these patients receive the right quantity and quality of fluids to ensure they regain an adequate hydration status, particularly if their kidney function has suddenly deteriorated and they face a uremic crisis
2. Making any changes to their dietary management slowly and gradually with regular monitoring to ensure they are responding in an appropriate manner.

Management of Uremia

Once the nitrogenous waste products reach high levels they start to influence appetite and cause nausea and vomiting due to their irritant effects on mucous membranes. Once plasma urea concentrations exceed 30 mmol/L (84 mg/dL), dietary protein restriction is recommended to limit uremia and counteract these effects on the quality of life of the cat. It is important to ensure adequate calorie intake is maintained in these patients and close monitoring of body weight and body condition score is recommended. The urea to creatinine ratio can be used to factor out the effect of renal dysfunction on plasma urea and to determine the effect of response to dietary protein restriction on nitrogenous waste product formation. Reference ranges have been suggested according to the level of protein intake in dogs but have not been published for cats.

Very high ratios suggest owner noncompliance, dehydration, gastrointestinal bleeding or a hypermetabolic state (e.g. sepsis). Very low values indicate inadequate intake of diet and protein calorie malnutrition, such that body proteins are being used as a source of energy. If this state persists for any length of time, the animal will lose significant amounts of body mass and will exhibit signs of muscle wastage. Such a state can occur if the animal does not find the clinical diet palatable and so consumes inadequate quantities. In these cases, continuing to offer such a diet will be counter-productive and an alternative should be sought. Offering a variety of diets to find the individual animal’s preference may well be necessary.

The uremic syndrome is very often accompanied by oral, gastric and intestinal lesions leading to vomiting, diarrhea and anorexia. Incorporation of sodium silico-aluminate into the diet can be very useful to protect the digestive mucosa (Droy et al, 1985).

In the later stages of renal failure (late stage IV) (Figure 24), the animal’s voluntary appetite may be inadequate and protein-calorie malnutrition may be unavoidable unless the animal is fed via an enteral feeding device (see Chapter 14 about Critical Care). Some owners may find this mode of treatment unacceptable and opt for euthanasia at this point.

Figure 24. Post-mortem specimen of a kidney taken from a six year old Persian cat euthanazed with end stage kidney disease. The kidney shows the gross appearance of polycystic kidney disease.

In addition to reducing dietary protein to limit the formation of nitrogenous waste products, inclusion of dietary fiber / indigestible polymers that can bind nitrogenous waste and draw these substances into the gastro-intestinal tract is a complementary approach adopted by some renal care diets. Objective data demonstrating the efficacy of such products in lowering plasma urea concentrations and the clinical benefits which ensue following the introduction of such diets to stage IV CKD feline patients have not been published in the peer reviewed literature.

One practical problem encountered in the later stages of CKD in older cats is constipation. This probably results from a combination of factors:

• Dehydration leading to hard dry stools of low volume being formed
• Muscle weakness and reduced gastrointestinal motility, exacerbated by hypokalemia
• Unwillingness to defecate due to chronic pain on adopting the position to defecate (chronic arthritis; bone pain from renal osteodystrophy)
• Use of high doses of intestinal phosphate binders which can cause constipation as an adverse effect
• Use of calcium channel blockers as anti-hypertensive agents which may reduce intrinsic gastrointestinal motility.

Constipation can create a vicious cycle of reduced appetite and food intake leading to reduced stimulation of gastrointestinal motility and further problems with potassium balance. Dietary strategies which increase fecal bulk and ensure the production of soft but formed feces and maintain gastrointestinal motility will also be of benefit to the stage IV CKD patient.

Management of Metabolic Acidosis and Hypokalemia

The stage of CKD at which problems of metabolic acidosis become evident on laboratory testing tends to be late stage III and stage IV. The prevalence of metabolic acidosis was 15% at stage III (3/20) and 52.6% at stage IV (10/19) (Elliott et al, 2003a). This suggests that in the earlier stages of CKD, animals are able to excrete the acid ingested in the diet or that small imbalances between intake and excretion are being buffered in the body such that significant changes in plasma bicarbonate concentration are not detectable. The most likely place acid buffering would occur in these animals is in bone, resulting in the leeching of calcium from bone, thus contributing to renal osteodystrophy and increasing the risk of soft tissue mineralization (Leemann et al, 2003).

The contribution of metabolic acidosis to bone disease associated with CKD is well recognized in human medicine but has not been studied in cats. Indeed, in a longitudinal study of cats with CKD, the occurrence of metabolic acidosis was not detected on laboratory tests until cases had progressed from stage II to stage III/IV (Elliott et al, 2003b). Whether providing alkali supplementation prior to the detection of metabolic acidosis would be beneficial remains to be determined although no effect of three months of potassium gluconate supplementation on bone turnover (assessed by measurement biochemical markers of bone synthesis and degradation) was detectable (unpublished data). Clearly, at the later stages of CKD, metabolic acidosis contributes to the uremic syndrome and measures should be taken to treat this problem.

Treatment of metabolic acidosis involves alkali supplementation (Table 7). Response to treatment can be monitored by repeated measurements of plasma bicarbonate concentration with the aim to bring this back to the middle of the reference range if possible.

The choice of agent will be dictated by other factors, including palatability when added to the diet, presence of hypertension (when supplementation of sodium should be avoided), presence of hypokalemia (where potassium salts will be chosen) and the presence of hyperphosphatemia, where calcium salts may be considered because of their phosphate binding capabilities (provided hypercalcemia does not become a problem).

Metabolic acidosis tends to exacerbate the likelihood of hypokalemia occurring. Potassium tends to move out of the cells in response to metabolic acidosis and is lost in urine. In addition, reduced food intake and vomiting may accompany metabolic acidosis, both exacerbating loss of potassium ions. As described above, treatment with potassium gluconate or potassium citrate would be appropriate in such circumstances. The use of H2 blockers, such as famotidine (2.5 mg/cat once daily) can also improve the appetite in these cats by reducing gastric acidity. Hyperacidity occurs in CKD due to hypergastrinemia (Goldstein et al, 1998) secondary to reduced renal clearance of gastrin.

Management of Hyperphosphatemia

The degree of dietary phosphate restriction required to attain the post-treatment targets of plasma phosphate concentration will increase with the severity of kidney disease. At late stage III/IV it is unlikely this will be possible by feeding a renal care diet alone and intestinal phosphate binders may be needed to lower the plasma phosphate concentration below the target of 1.9 mmol/L (5.88 mg/dL) (Table 8). It is important to recognize that phosphate binders interact with the food and so should be mixed into the food to ensure maximal efficacy. This can create problems in that their addition to the food can reduce the palatability of the diet.

The following are generic recommendations for dosing phosphate binders:

• Starting dose 30 to 60 mg/kg should be used
• Powered and granular preparations are recommended in preference to liquids and gels which might affect palatability of the diet
• The binder must be mixed with the diet
• Plasma phosphate concentration should be reassessed every 4 weeks
• Increase the dose to effect (doubling increments to a maximum tolerable dose), reassess.
• For aluminum containing binders, drug-induced microcytosis, muscular weakness, and encephalopathy are possible
• Higher doses of binder will be required if consuming low amounts of clinical renal diets (or a diet which is relatively higher in phosphate) and as the stage of CKD increases
• Constipation is a potential complication of higher doses of any of the available intestinal phosphate binding agents
• Plasma calcium concentration should be monitored, particularly if using calcium containing phosphate binders to avoid problems of hypercalcemia.

As CKD progresses, achieving control of plasma phosphate concentration and maintaining voluntary consumption of adequate calories per day becomes increasingly difficult. If a gastrostomy tube is placed and food mixed with phosphate binders is administered via this route, control of plasma phosphate is more likely to be achieved. Quality of life is affected by marked hyperphosphatemia as metabolic bone disease becomes more pronounced and radiographically evident (Figure 25). Deposition of calcium and phosphate in the vasculature increases the risk of cardiovascular complications of CKD in human patients. Interestingly, the cause of death in cats was attributed to cardiovascular problems in about 20% of cases (Figure 26; data from cases presented in Elliott et al, 2000).
Figure 25. Radiograph of a cat with severe CKD and marked secondary renal hyperparathyroidism. Reproduced from Barber (1999).

Figure 26. Causes of death in 50 cats studied from diagnosis of stage II and III CKD.

Prevention of Anorexia and Loss of Body Mass

Sufficient energy needs to be provided to prevent endogenous protein catabolism which will result in malnutrition and exacerbation of azotemia. Cats require 50 - 60 kcal/kg/day. Energy intake should be individualized to the patient needs based on serial determinations of body weight and body condition score.

Carbohydrate and fat proved the non-protein sources of energy in the diet. Fat provides approximately twice the energy per gram than carbohydrate. Therefore fat increases the energy density of the diet, which allows the patient to obtain its nutritional requirements from a smaller volume of food. A smaller volume of food minimizes gastric distention, which reduces the likelihood of nausea and vomiting.

The efficiency of a renal diet depends upon it being fed exclusively and on a continuing basis. Thus, the diet must be palatable enough to avoid any risk of refusal. Correct energy content and high digestibility of the diet are important to maintain sufficient nutritional intake (Figure 27).

Figure 27. Body score and life expectancy in cats. From Doria-Rose & Scarlett, 2000.

At the later stages of CKD, appetite becomes a problem and consumption of sufficient calories to maintain body weight and condition is an issue. Adding flavorings (there are some commercially available products) to the formulated renal care diets can help improve the amount of food consumed. Sometimes warming the food and offering frequent small servings can assist in maintaining daily intake of calories. At the later stages of CKD when voluntary food intake is reduced, it may be necessary to provide additional vitamin supplements, particularly the water soluble vitamins (B and C) may be required since urinary losses of these nutrients may exceed intake. Evidence of vitamin deficiencies associated with CKD have not been documented although many renal care diets are formulated to provide increased amounts of water soluble vitamins when compared to standard maintenance diets.

Conclusion

Diet plays an important role in the management of the feline patient with CKD. It is important to tailor the diet to the needs of the individual patient and to understand the goals in the use of renal care diets at different stages of CKD. These are summarized below.

• At stages II and III formulated renal care diets have been shown to be of benefit improving survival and limiting uremic crises. The principles of therapy include:

• Limiting phosphate intake prevents whole body phosphate overload and progressive renal injury induced by nephrocalcinosis
• Reducing protein intake may have some utility to limit hyperfiltration and proteinuria in markedly proteinuric cases (UPC>1.0)
• The beneficial effects of supplementing n-3 PUFAs remain to be studied in the cat
• Supplementation of potassium is necessary in cats that are hypokalemic but appears to have no detectable benefit in normokalemic cats
• The benefit of reducing dietary sodium intake on control of blood pressure remains to be determined.

• At late stage III and stage IV diet can be used to improve the quality of life of cats entering the uremic phase of CKD. The important principles of therapy at this stage include:

• Limiting protein intake to reduce the build up of nitrogenous waste products, particularly when plasma urea concentration exceeds 30 mmol/L (84 mg/dL). The origin of the protein has to be taken into consideration: very highly digestible protein limits the protein by-products release in the blood
• The use of dietary components that remain in the gastrointestinal tract and trap urea and other nitrogenous waste products
• Supplementing alkali in the diet to treat metabolic acidosis which contributes to metabolic bone disease, inappetance and malaise
• Supplementing potassium as required to treat hypokalemia which contributes to inappetance, muscle weakness and general malaise
• Further reducing phosphate bioavailability in the diet by the use of intestinal phosphate binding agents to limit the extra-renal effects of hyperphosphatemia and hyperparathyroidism including metabolic bone disease and vascular calcification which affect quality of life.