Joseph W. Bartges, DVM, PhD, DACVIM (SA IM), DACVN
Chronic renal failure (CRF) is common in older animals and is characterized by irreversible renal structural lesions. Patients with CRF may survive for many months to years with a good quality of life. Clinical and laboratory effects of CRF result from loss of the kidneys to maintain homeostasis of filtration, secretion, reabsorption, and metabolism or biosynthesis. Conservative medical management of CRF consists of supportive and symptomatic treatment designed to correct deficits and excesses that occur with renal failure. The acronym NEPHRONS is used to reinforce treatment of CRF. It represents: N--nutritional status, E--electrolytes, P--pH of blood (acid-base balance), H--hydration, R-retention of wastes, O--other results insults (avoidance), N--neuroendocrine status (hyperparathyroidism, hypoproliferative anemia, and systemic arterial hypertension), and S--serial monitoring.
Adequate nutritional status should be maintained with CRF. Feeding a reduced protein, reduced phosphorus, reduced sodium, non-acidifying diet with adequate potassium content may minimize signs of uremia and possibly minimize progression of CRF.(1, 2) In addition, consumption of adequate calories is important to maintain overall health and general well being. Formulae used to estimate caloric requirements for dogs include: 2 [30(BWkg)] and 132 (BWkg0.75); for cats, the formulae include: 1.5 [30(BWkg) and 100 (BWkg0.75). These are initial estimates for the quantity to feed healthy dogs and cats and must be altered for animals with CRF. Omega-3 fatty acid consumption is associated with sustained GFR in dogs and may be of benefit in CRF.(3)
Anorexia is a common problem with CRF and should be addressed. Feeding a lower protein-containing diet decreases gastric acidity, and, therefore, may decrease uremic-ulcers. Hypergastrinemia occurs with CRF, and use of histamine-2-receptor blockers (such as ranitidine or cimetidine) decreases the gastric hyperacidity associated with hypergastrinemia. (4) Stimulation of appetite may be necessary and can be accomplished by warming food to near body temperature, providing positive reinforcement for eating, feeding small meals frequently, and administering appetite stimulants such as diazepam. If necessary feeding tubes may be used.(5)
When should dietary modification be instituted? Currently, I recommend a dietary change at the time of diagnosis of CRF regardless of severity of disease. Several lines of reasoning provide a rational basis for this recommendation. From a practical standpoint, the patient may have less resistance to diet change earlier in the course of disease simply because uremic gastroenteritis is less prominent and there is less pressure to change the diet rapidly. Hyperparathyroidism typically develops early in the course of CRF and can be effectively managed using dietary therapy at this stage of disease (see section on neuroendocrine changes with CRF).(6) It is unclear what impact, if any, intervention with phosphorous and/or protein restriction would have on limiting progression of CRF. However, there is no convincing evidence that early intervention would be harmful. In patients with progressive disease, it is logical that dietary protein restriction would forestall the time at which uremic signs develop. It may also provide a "buffer" against development of uremic signs should CRF be complicated by events that may promote mild additional prerenal azotemia (e.g., mild dehydration).
Hypokalemia is common with polyuric CRF, particularly in cats.(7) It may occur because of inadequate dietary intake combined with excessive renal losses, and may contribute to progression of CRF, metabolic acidosis, and anorexia. Many "renal failure" diets are replete in potassium; however, potassium supplementation using potassium citrate or potassium gluconate may be required.
pH OF BLOOD (ACID-BASE)
Metabolic acidosis is common because of a decreased ability to excrete organic acids and it may promote hypokalemia and progression of CRF.(8) Metabolic acidosis may be minimized by feeding a moderately protein restricted diet, by feeding a diet formulated to contain an alkalinizing agent or to not contain an acidifying agent, or by administering an alkalinizing agent in addition to the diet. Alkalinizing agents include sodium bicarbonate and potassium citrate. Potassium citrate may be preferred over sodium bicarbonate because its use may minimize hypokalemia as well as acidosis. Initial starting dosage for potassium citrate is 75 mg/kg PO q12hr; adjust as needed.
Animals in CRF require more fluid intake because of polyuria. Thus, fluid balance in patients with CRF is maintained by compensatory polydipsia. If water consumption is insufficient to compensate for excessive water loss, dehydration and renal hypoperfusion may precipitate a uremic crisis and progression. Canned foods (containing approximately 70% moisture) or moistened dry food may be used to augment water consumption. Flavored liquids (e.g., clam juice or tuna juice) may be used to promote additional fluid consumption. Subcutaneously administered fluids may be necessary, particularly in cats.
RETENTION OF WASTES
With CRF, compounds normally eliminated by the kidneys are retained. The rationale for limiting protein intake with CRF is based on the premise that reduction of nonessential protein will result in decreased production of nitrogenous wastes, with consequent amelioration of clinical signs of uremia. Thus, animals may benefit from reduction of dietary protein intake once they are uremic. Whether dietary protein reduction slows or halts progression of CRF remains controversial.(9, 10) In clinical studies of spontaneously occurring CRF in cats(6, 11) and in dogs(1), dietary protein and phosphorous restriction prolonged survival and was associated with fewer adverse consequences when compared with no dietary protein or phosphorous restriction.
AVOIDING OTHER RENAL INSULTS
In order to prevent hastening of the progression of renal failure, administration of potentially nephrotoxic drugs should generally be avoided. Other diseases that may result in progression of renal failure, such as pyelonephritis and urolithiasis, should be appropriately treated. If anesthesia is performed on an animal with CRF, adequate fluid therapy should be administered to prevent dehydration and hypotension.
NEUROENDOCRINE Renal hyperparathyroidism (Calcium/phosphorus)
Retention of phosphate with consequent reduction of calcium with CRF results in parathyroid hormone (PTH) production and secretion. Renal secondary hyperparathyroidism is common with CRF. Increased circulating levels of PTH may be associated with uremia, extraosseous mineralization, systemic hypertension, and, possibly, progression. Thus, attempts to decrease serum concentration of PTH concentration may be beneficial. Hyperphosphatemia is treated by feeding a phosphorus restricted diet (12, 13) and, if necessary, administration of phosphate binders. Serum phosphorus concentrations should be monitored every 10 to 14 days, and the dose adjusted until the serum phosphorus concentration is normalized. Phosphate binders should be given with food. Side effects of phosphate binders include constipation and anorexia. A proposed treatment for renal secondary hyperparathyroidism is administration of vitamin D3, which decreases PTH production.
A normocytic, normochromic nonregenerative anemia may occur with CRF, and is believed, in part, to be due to decreased erythropoietin production by the failing kidneys. Poor nutritional status and blood loss through the gastrointestinal tract secondary to uremic gastroenteropathy may further exacerbate anemia. Anemia associated with CRF is treated by minimizing gastrointestinal hemorrhage, and administration of erythropoietin (recombinant human erythropoietin, rHuEPO). Another treatment for anemia is administration of androgens; however, they are not as effective as rHuEPO, and may be associated with hepatotoxicity.
Systemic hypertension is relatively common in CRF. Clinical signs associated with systemic hypertension include ocular changes (retinal hemorrhage, hyphema, blindness), cardiovascular changes (left ventricular hypertrophy, myoarteritis), neurologic disease (dementia, seizures, death), and possibly progression of renal failure. Anti-hypertensive medications have been recommended to treat systemic hypertension. Also, as mentioned previously, avoiding excessive intake of dietary sodium may decrease blood pressure, and may be necessary to achieve adequate response to antihypertensive medication.
Because CRF is progressive it is dynamic; therefore, periodic monitoring and adjustment of treatment is necessary to prolong a good quality of life.
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3. Brown SA, Brown CA, Crowell WA, Barsanti JA, Kang CW, Allen T, et al. Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs. J Lab Clin Med 2000;135(3):275-86.
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6. Elliott J, Barber PJ, Rawlings JM, Markwell PJ. Effect of phosphate and protein restriction on progression of chronic renal failure in cats. J Vet Intern Med 1998;12(3):221(abstract).
7. Dow SW, Fettman MJ, LeConteur RA, Hamar DW. Potassium depletion in cats: Renal and dietary influences. J Am Vet Med Assoc 1987;191(12):1569-1575.
8. DiBartola SP, Rutgers HC, Zack PM. Cinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984). J Am Vet Med Assoc 1987;190:1196-1202.
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12. Barber PJ, Rawlings JM, Markwell PJ, Elliott J. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. J Small Anim Pract 1999;40(2):62-70.
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