Larry D. Cowgill, DVM, PhD, DACVIM (Internal Medicine)
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis
Davis, CA, USA
Acute renal failure (ARF) is characterized by a rapid onset of renal insufficiency/failure, reduction in glomerular filtration rate and renal plasma flow, and the clinical and biochemical aftermath of the excretory failure. In some patients the syndrome is distinguished by oliguria or anuria, but today this classical feature of ARF is less predictable. The excretory failure is identified by rapid (hours to days) increases in BUN, serum creatinine and phosphate, and variable hyperkalemia and metabolic acidosis. Acute renal failure is a tenuously reversible state, which must be diagnosed quickly and aggressively treated. Failure to initiate therapy may result in irreversible parenchymal damage or death. Acute renal failure is frequently a complication of other surgical or medical diseases and must be recognized within the clinical features of these associated disorders.
The clinical presentation and outcome of ARF varies depending on the cause, severity, previous therapy, and associated diseases predisposing the renal injury. Consistent signs of severe ARF include the sudden onset and rapid development of listlessness, depression, anorexia, vomiting, and diarrhea. Oliguria and less frequently anuria were at one time considered signatures of ARF and discriminators for chronic renal failure. However, nonoliguric forms of ARF have become common due to earlier identification of ARF, routine use of intravenous fluids and diuretics in its initial management, and the frequent development of nephrotoxic forms of ARF which promote nonoliguric syndromes. Quantitation of urine output may not sufficiently differentiate acute renal failure from polyuric forms of chronic renal failure. A history of weight loss, polyuria, polydipsia, nocturia or isosthenuria, or laboratory evidence of preexisting renal insufficiency suggest an underlying chronic condition. Many animals with compensated and asymptomatic chronic renal insufficiency sustain subtle insults (e.g., fever, concomitant disease, vomiting, diarrhea, congestive heart failure, drug administration), which precipitate a seemingly acute uremic crisis (designated A acute-on-chronic@ renal failure).
Physical examination commonly demonstrates depression, dehydration (some animals who have received excessive volumes of parenteral fluid may be over hydrated), hypothermia, oral ulceration, "uremic breath", bile-stained fur, scleral injection, discoloration or necrosis of the tongue, tachycardia or bradycardia, tachypnea, abdominal pain, seizures, and palpably enlarged kidneys. Because of the abrupt onset of uremia, patients are usually well fleshed, have glossy well groomed hair coats, and pink mucous membranes in contrast to animals with chronic diseases and chronic renal failure. However, acute uremia is frequently superimposed on other diseases or chronic renal failure, and the physical manifestations of these primary conditions may dominate the clinical presentation and mask the features of ARF. Lameness, icterus, fever, discolored urine, back or flank pain, and dysuria are associated with some etiologies of ARF.
The etiology of ARF varies geographically as differences in infectious causes will differ regionally as will therapeutic practices that might predispose to acute renal injury. In a recent survey of dogs presenting with severe ARF requiring dialytic management over an 11 year interval, the causes for ARF were identified as toxic in 45%, infectious in 35%, hemodynamic/metabolic (shock, pancreatitis, hepatorenal, congestive heart failure, heat stroke, gastric torsion) in 7%, and inflammatory (glomerulonephritis, immune mediated) in 3% of cases. In 10% of cases the cause could not be determined. Within these categories, ethylene glycol toxicosis accounted for 34% of the total cases or 75% of the toxic etiologies. Leptospirosis represented 31% of all cause etiology and 88% of infectious causes.
The therapeutic approach must address each and every clinical disorder identified in the diagnostic evaluation.
Alterations in ECF Volume
Fluid therapy remains the foundation of medical therapy. Objectives are to resolve hemodynamic deficiencies, normalize fluid balance, and promote urine formation. Replacement fluids should mimic as closely as possible the type of fluid deficiency and effectively restore extracellular and intravascular volume. Deficits in extracellular fluid volume should be corrected with normal saline or balanced (isonatric) polyionic solutions delivered intravenously within the first few hours of therapy. The rate of fluid replacement must be tempered in animals with cardiovascular disease or historical heart failure to prevent circulatory congestion and incipient heart failure. Fluid deficits associated with profound hypovolemia and hypotension or severe blood loss must be replaced more rapidly and may require administration of colloid solutions or compatible whole blood. Fluid administration must be approached cautiously in animals who are oliguric or anuric. Hypervolemia is a common complication of overzealous fluid. All fluids must be STOPPED in hypervolemic animals to prevent hypertension, peripheral and pulmonary edema and congestive heart failure, and furosemide should be given to induce a diuresis.
Inadequate Urine Production
Oliguria and anuria are life threatening features of ARF. If fluid therapy alone fails to promote an adequate diuresis (>1-2 ml/kg/min), diuretic and specific renal vasodilator therapy is usually warranted even though their efficacy remains controversial. A bolus injections of hypertonic (20-25%) mannitol (an osmotic diuretic) is administered first to fluid repeat patients; with the onset of a significant diuresis, a constant rate infusion is administered for the subsequent 12-36 hours to sustain the effect. If the initial dose of mannitol fails to initiate a diuresis, furosemide, alone or in combination with dopamine, is added to the therapeutic regimen. The effects of furosemide may be enhanced in dogs if combined with low-dose dopamine infusion. These drugs may enhance urine formation without significant improvement in GFR, renal blood flow, the clinical course or outcome. The use of diuretics and vasodilator therapy is no substitute for proper fluid and electrolyte therapy, and clinical supervision and may induce dehydration. In cats, low-dose dopamine is an ineffective diuretic agent, and its use at higher doses is conceptually inappropriate in oliguric cats.
Hyperkalemia is a common complication of acute uremia whose management is determined by its severity. Severe hyperkalemia (> 8 mmol/L) associated with serious ECG disturbances is life-threatening and treated with 10% calcium gluconate as required to correct the ECG abnormalities. The effects are rapid in onset but short-lived and have no effect to lower the serum potassium. Calcium infusion should be regarded as a "stop-gap" until longer-lasting controls are initiated. Moderate hyperkalemia (6.0-8.0 mmol/L) usually resolves with fluid diuresis or administration of furosemide to promote a kaluresis. If serum potassium is not controlled with diuretics, the animal should be taken off potassium containing fluids and sodium bicarbonate given to correct existing bicarbonate deficits. The administration of bicarbonate, however, is contraindicated in animals with metabolic alkalosis. If sodium bicarbonate administration is inappropriate or ineffective, an infusion of hypertonic glucose may be given alone as an intravenous bolus or in combination with regular insulin. The benefits of bicarbonate and/or glucose/insulin are effective rapidly but must be repeated as clinical circumstances require until the potassium load is alleviated.
Acid-base abnormalities develop commonly from the underlying disease processes and imposed therapy. Most animals develop metabolic acidosis in proportion to the severity of the uremia. However, metabolic alkalosis (protracted vomiting) or mixed acid-base disturbances (metabolic acidosis/respiratory acidosis, metabolic acidosis/respiratory alkalosis) may develop due to pulmonary complications associated with concurrent diseases, pulmonary edema, uremic pneumonitis, hyperventilation, or pulmonary thromboemboli. Mild metabolic acidosis may resolve with fluid administration and the onset of diuresis. More severe acidosis (serum bicarbonate <16 mmol/l) should be managed with intravenous sodium bicarbonate administered to correct the base deficit. Most uremic animals have an ongoing requirement for sodium bicarbonate to offset production of metabolic acids. The respiratory component of acid-base disorders must be corrected by management of the pulmonary disease and ventilation.
Retained uremia toxins contribute to signs of anorexia, nausea, vomiting, CNS depression/seizures, stomatitis, oral ulceration, gastroenteritis, diarrhea, bleeding tendencies, and hypothermia. It may not be possible to eliminate these uremia toxins in the initial stages of treatment and symptomatic therapies especially for vomiting must be instituted. Peritoneal dialysis or hemodialysis are the only specific approaches which can alleviate the consequences of the uremic intoxications.
Once the vomiting is controlled blended foods or liquefied renal diets can be administered through nasal esophageal tubes, esophageal feeding tubes, or percutaneous gastrostomy tubes if the animal refuses to eat. If the animal is vomiting, caloric and nitrogen requirements must be provided with parenteral nutritional formulations.
OUTCOME AND PROGNOSIS
The prognosis for recovery from ARF depends importantly on the etiology and the nature and extent of the underlying renal injury, the presence of co-morbid diseases, the extent and severity of multiple organ involvement, and the availability of diagnostic and therapeutic services. The typical all-cause mortality for dogs with ARF is on the order of 60% from death or euthanasia. Dogs surviving ARF have been shown to maintain relatively stable renal function or to subsequently develop chronic renal failure. The outcome of the divergent observations may reflect the underlying causes of the ARF or the therapeutic approaches employed to support survival. Survival from infectious or hemodynamic/metabolic etiologies is considerably more favorable than survival from toxic causes. For dogs with severe ARF treated with hemodialysis survival was nearly 80% for dogs with infectious causes, 40% for dogs with noninfectious and nontoxic etiologies yet less than 20%for dogs with toxin induced ARF despite comparable degrees of renal failure at presentation. Survival statistics for cats with ARF is poorly documented. In a preliminary analysis, we documented that44% of the cats with ethylene glycol intoxication and severe azotemia to warrant hemodialysis survived despite being oliguric or anuric at presentation. As some of these cats received renal transplants, the intrinsic survival may more closely resemble that for dogs. Nearly 100% of cats with acute pyelonephritis survive if supported with hemodialysis. In both the dog and cat, the magnitude of the azotemia at presentation did not predict survivability if the animals could be maintained with dialysis to permit repair of the renal injury.
Acute renal failure is a serious and frequently fatal disease in both dogs and cats. Recovery is best for animals with infectious etiologies and worst for animals with nephrotoxic causes or multiple organ failure. Early recognition, aggressive and appropriate fluid therapy, and supportive therapy with dialysis offer the greatest opportunity for a favorable outcome.