www.ivis.org Proceedings of the 34th World Small Animal Veterinary Congress WSAVA 2009 São Paulo, Brazil - 2009 Next WSAVA Congress : Reprinted in IVIS with the permission of the Congress Organizers
HOW I TREAT UREMIC CRISES IN DOGS AND CATS WITH CHRONIC KIDNEY DISEASE David J. Polzin, DVM, PhD, DACVIM University of Minnesota, St. Paul, MN, U.S.A. Uremia may occur in dogs and cats with chronic kdieny disease in association with prerenal, renal or postrenal causes for azotemia. The additional azotemia from any of these causes may cause sufficient additional azotemia to produce the clinical signs of uremia. When acute renal azotemia (acute kidney disease) occurs in patients with chronic kidney disease, the condition is known as acute-on-chronic. Acute kidney disease may result from many causes but most commonly results from ischemic and/or toxic renal insults. The term acute tubular necrosis (ATN) is used to describe the syndrome in which abrupt and sustained reductions in GFR result from ischemic or nephrotoxic injury. Reduced GFR is thought to result from a combination of vascular (renal vasoconstriction and reduced glomerular ultrafiltration coefficient) and tubular (renal tubular obstruction and back-leak of glomerular filtrate) effects, and cannot be immediately reversed by eliminating the initiating disturbance (e.g. renal ischemia due to hypovolemia). DIAGNOSTIC DATABASE FOR ACUTE UREMIC CRISIS Medical history Routine urinalysis Complete blood count Serum urea nitrogen Serum potassium Serum bicarbonate (or tco2) Serum phosphate Abdominal radiographs Arterial blood pressure Screen for toxins (±) Physical examination Urine culture Serum creatinine Serum sodium Serum chloride Serum calcium Freeze serum/urine samples Urinary ultrasound (±) Fundic examination Renal biopsy (±) Fluid therapy. Volume depletion is a consistent finding in patients with uremic crisis. Some patients appear to be normally hydrated but have historical findings consistent with fluid losses. It is practical to assume these patients are subclinically dehydrated; carefully administer fluids to them at the rate of 1 to 3 percent of body weight on the premise that mild over hydration is less likely to be harmful than unrecognized volume depletion. Even mild volume depletion may promote renal injury in patients predisposed to acute kidney disease. A substantial portion of volume depletion should be corrected over 2 to 6 hours unless the patient has known cardiac dysfunction, demonstrates intolerance to fluid administration, or becomes over hydrated (e.g. dyspnea, elevated neck veins, rales, S3 gallop rhythm, pulmonary edema). Administration of fluid at this rate will help to rapidly restore adequate renal perfusion. In addition, in patients with physiologic oliguria, urine volume will increase. Careful monitoring of the patient's response to fluid therapy is essential! If fluid overload occurs, the rate of fluid administration should be reduced or temporarily discontinued. Monitoring of central venous pressure may be necessary for patients with cardiac dysfunction or intolerance to fluid therapy. A favorable clinical response and normalization of blood pressure usually indicate successful restoration of normal hydration. The goal of subsequent fluid therapy is to maintain fluid balance and prevent hypovolemia. Because even subclinically volume depletion may promote additional azotemia and renal damage, it may be desirable to maintain mild over hydration over the subsequent 6 to 12 hours in nonoliguric patients that have normal cardiopulmonary function. However, overt over hydration must be avoided in patients with persistent pathologic oliguria. Patients may be predisposed to dehydration during maintenance and recovery phases of acute kidney disease because involuntary urine losses are often great. In order to prevent dehydration, the volume
of parenteral fluids administered and oral fluids consumed should equal the sum of: 1) urine volume, 2) contemporary fluid losses (e.g. fluid lost via vomiting, diarrhea), and 3) insensible fluid losses (20 to 25 ml/kg/day). Because estimation of contemporary and insensible fluid losses may be inaccurate, serial determinations of body weight are commonly used to guide fluid therapy Correcting Hyperkalemia. In absence of serious cardiotoxicity, mild to moderate hyperkalemia usually does not require specific treatment. However, hyperkalemia associated with serious cardiac arrhythmias is a potentially life-threatening condition requiring immediate therapy. Transient correction of hyperkalemic cardiotoxicity can be achieved by intravenous administration of calcium gluconate (10% solution; approximately 0.5 to 1.0 ml/kg body weight). The solution should be administered slowly over 10 to 20 minutes with electrocardiographic monitoring. The effect of such therapy usually lasts only 15 to 20 minutes. Other treatments that may be used in cardiotoxic emergencies are intravenous administration of glucose (with or without insulin) or sodium bicarbonate to attempt to redistribute potassium intracellularly. Typically, glucose is administered at a dose of 0.5 to 1.0 gm/kg body weight. Duration of effect is limited to several hours. Sodium bicarbonate may be administered at a dose of 0.5 to 1.0 meq/kg body weight, or at a dose calculated from the base deficit of the patient. In one recent study of the effect of this treatment on lowering potassium in humans with hyperkalemia due to acute kidney disease, bicarbonate therapy appeared to be of limited benefit. Correcting Metabolic acidosis. Because metabolic acidosis typically has little immediate adverse effect unless blood ph is below 7.20 (blood bicarbonate or total CO2 concentrations less than 10 meq/l), alkalinization therapy should be considered for patients with blood ph values less than 7.20. Immediate correction of metabolic acidosis is usually unnecessary when blood ph values exceed 7.20. Mild to moderate metabolic acidosis often improves following fluid therapy alone. Metabolic acidosis is usually treated by administration of sodium bicarbonate. The goal of alkalinization therapy is not to normalize acid-base balance, but rather to increase blood ph values to about 7.20, a level likely to prevent adverse cardiac effects of acidosis. Converting Oliguria. If oliguria persists despite correction of fluid deficits, therapy designed to increase urine volume is indicated because clinical management of nonoliguric patients is easier and their prognosis appears to be better. Use of diuretics or vasodilators in nonoliguric patients is generally discouraged because they are rarely needed and therefore unnecessarily expose the patient to risk of fluid and electrolyte depletion, additional renal injury, or adverse drug reactions. A therapeutic trial with diuretics is indicated for most patients with oliguric kidney disease. Furosemide and mannitol are the diuretics most commonly used. Patients that fail to respond to one of these diuretics may respond to the other or a combination of both. Alternatively, diuretics may be used in combination with vasodilators such as dopamine. Furosemide has been the most commonly used diuretic in canine and feline patients with oliguric kidney disease because it is relatively safe, readily available, and familiar to most veterinarians. Initially it should be administered intravenously at a dose of 2 mg/kg body weight. If no substantial diuresis develops within one hour after administration, the dose may be doubled (4 mg/kg). If this dose also fails to induce diuresis, the dose may be further increased to 6 mg/kg body weight. If diuresis still does not ensue, very large doses of furosemide, an alternative diuretic (e.g. mannitol), or the combination of furosemide and dopamine may be considered. If furosemide successfully induces diuresis, it may be repeated at 8 hour intervals as needed to sustain diuresis and promote potassium excretion. However, the need for continued furosemide therapy must be considered in light of its potential adverse effects. It has been suggested that furosemide should not be used in patients with suspected gentamicin-induced acute kidney disease because it may promote aminoglycoside nephrotoxicity. Mannitol has at least three theoretical advantages over furosemide: 1) it may enhance renal function by minimizing renal tubular cell swelling via its osmotic properties, 2) mannitol exerts its diuretic
effects along the entire nephron and therefore may directly affect the proximal tubule, and 3) mannitol may expand the extracellular fluid volume. The major disadvantage of mannitol is the potential for vascular overload if oliguria persists. Therefore, mannitol should be avoided in over hydrated oliguric patients. Mannitol (20 or 25% solution) is administered intravenously over 5 to 10 minutes at a dose of 0.25 to 0.5 g/kg body weight. If substantial diuresis ensues, administration of mannitol can be repeated every 4 to 6 hours, or administered as a maintenance infusion (8 to 10% solution) during the initial 12 to 24 hours of treatment. Like diuretics, calcium channel blocking agents have been used primarily to attenuate the severity of acute tubular necrosis through administration before the renal injury. When administered after renal injury, some reports indicate renal protection, while others do not. Calcium channel blockers are therapeutically appealing because they may: 1) increase glomerular filtration rate (by increasing intraglomerular perfusion pressure and reversing the decline in ultrafiltration coefficient), 2) promote solute diuresis, and 3) have a cell cytoprotective effect by limiting cellular overload with calcium. Uremic signs. Clinical manifestations of uremia are ameliorated by a combination of dietary protein restriction and pharmacological control of uremic gastritis and vomiting. Adult dogs should receive approximately 8 to 12 percent of their calories as protein. Adult cats have a higher daily protein requirement than dogs, and therefore should receive approximately 20 percent of their diet calories as protein. Protein restriction minimizes production of nitrogenous waste products that may be responsible for many clinical signs of uremia. In addition, protein restriction may have a protective effect against additional ischemic or nephrotoxic renal injury. Cimetidine, zantac, or famotidine (H 2 blockers) are indicated to ameliorate uremic hemorrhagic gastritis because they blocks gastrin-stimulated gastric hyperacidity. Cimetidine (Tagamet ) is dosed at 5 mg/kg IM or slow IV, 1st dose; hereafter, 2.5 mg/kg q 12 h. Ranitidine (Zantac ) is given at 2.5 mg/kg q 12-24h. Famotidine (Pepsid ) is given at 0.5 to 1.0 mg/kg q 24h. Sucralfate (Carafate ) may also be indicated when gastric ulceration is suspected. Dosage is 0.5 to 1.0 gram per dog or 0.25 gram per cat given every 8 to 12 hours. Serotonin 5-HT 3 receptor antagonists (e.g. Ondansetron, Dolesatron ) are excellent antiemetics in uremia and have been shown to be about 4 times as effective as metoclopramide in humans with uremic vomiting. Options include: Anzemet (dolasetron dosage = 0.3 to 0.6 mg/kg oral or slow IV once daily) or Zofran (ondansetron dosage = 0.6 to 1 mg/kg oral or IV every 12 hours. Infections. Urinary and vascular catheters are likely sites for introduction of infection. Therefore, urinary catheters should be used only when necessary, and serial urine cultures should be performed to detect UTI as early as possible. Intravenous catheters should be placed using aseptic techniques and monitored frequently for signs of inflammation or infection. Success of treatment should be confirmed by performing urine or other appropriate cultures during as well as after treatment. Continuing Therapy, Prognosis, and When to consider Dialysis. The primary goals of continuing therapy are to maintain fluid, electrolyte, and acid-base balance, limit clinical signs of uremia, and prevent additional renal injury. Fluid balance should be monitored by measuring daily fluid intakes and outputs and body weights and adjusting fluid intake to maintain fluid balance. Serum electrolytes and acid-base balance should be assessed every few days or more often as necessitated. Electrolyte balance may be adjusted by altering electrolyte or base intakes. Microenteral nutrition is indicated during anorexia. However, parenteral or oral hyperalimentation may be considered to improve renal tubular epithelial regeneration and to maintain nutritional balance. Most patients will tolerate at least limited oral therapy after the initial period of acute therapy. Nasogastric tubes are preferable to force feeding. Parenteral therapy should probably be reserved for patients in which long-term support may be needed, but oral therapy is not tolerated.
Prognosis is determined in large part by response to therapy. Nonoliguria, eukalemia or minimal hyperkalemia, minimal acid-base disturbances, and reasonably well-controlled clinical signs of uremia are favorable prognostic findings that should prompt continued therapy. Severe hyperkalemia, severe metabolic acidosis, or intractable clinical signs of uremia suggest that the short-term prognosis is poor and peritoneal dialysis should be considered.