Managing acute renal failure (Proceedings)


Clinical signs associated with prerenal azotemia are often nonspecific and may be similar to those caused by ARF.

Treatment of prerenal azotemia

Clinical signs associated with prerenal azotemia are often nonspecific and may be similar to those caused by ARF. Although the initial fluid therapy may be the same for all azotemic patients, the subsequent treatment and prognosis vary greatly between prerenal azotemia and established ARF. Any condition that decreases renal blood flow may result in prerenal azotemia, including hypovolemia (e.g., dehydration, hypoadrenocorticism), hypotension (e.g., anesthesia, shock), and aortic or renal arterial thrombus formation. In most patients with prerenal azotemia the kidneys are structurally and functionally normal, and they respond to the decreased renal blood flow by producing hypersthenuric urine.

The differentiation between prerenal and renal azotemia may be more difficult if urine concentrating ability is impaired in patients with prerenal azotemia. Examples of this syndrome include addison's disease, pyometra, and paraneoplastic hypercalcemia, all of which can compromise urine concentrating ability and result in dehydration secondary to vomiting. A potentially easy and valuable way to differentiate prerenal azotemia from ARF is to assess response to fluid therapy. Azotemia caused by dehydration should resolve quickly with replacement of volume deficits and restoration of renal perfusion, whereas renal azotemia will not resolve with fluid therapy alone.

Fluid therapy for patients with suspected prerenal azotemia should be administered intravenously with the fluid volume calculated on the basis of percent dehydration, maintenance fluid requirements, and continuing fluid losses (Table 1). Many patients with suspected prerenal azotemia have gastrointestinal fluid losses associated with vomiting and diarrhea and therefore polyionic fluid solutions such as lactated Ringers solution or Normosol are good initial fluid choices. The magnitude of azotemia as well as any electrolyte abnormalities (e.g., hypokalemia, hyperkalemia, or hypercalcemia) should be confirmed from serum obtained prior to initiation of fluid therapy. Rechecking a biochemistry profile to assess the patient's response to fluids can be accomplished after 12-24 hours of therapy.

Table 1: Example of daily fluid requirements for a vomiting dog (20kg) with suspected prerenal azotemia.

Supportive treatment for established acute renal failure (Table 2)

Most dogs and cats with renal failure are dehydrated because of gastrointestinal fluid loss superimposed on their urine concentrating deficits. Replacement of these volume deficits will correct the "prerenal component" of the renal failure and help protect against any additional ischemic renal tubular damage. Once the patient is rehydrated establishing or augmenting a diuresis can facilitate excretion of solutes that are reabsorbed and secreted by renal tubular cells (e.g., urea nitrogen and potassium). Increasing tubular flow rates and volumes will hinder reabsorption and favor secretion of solutes.

Table 2. Treatment guidelines for dogs and cats with established acute renal failure

The goal of fluid therapy for established ARF is correction of renal hemodynamic disorders and alleviation of water and solute imbalances in order to "buy time" for nephron repair and compensation. A positive response to therapy is indicated by an increase in glomerular filtration (reduction in serum creatinine concentration) and increases in urine production (if the patient was oliguric). Induction of diuresis facilitates management of ARF by decreasing serum urea nitrogen and potassium concentrations and by lessening the tendency for overhydration to occur, however glomerular filtration and renal blood flow are frequently unchanged. The increased urine production observed with diuresis is usually a result of a relative decrease in the tubular resorption of filtrate (Table 3). Therefore, increased urine production alone does not indicate an improvement in glomerular filtration. It should also be noted that there are no prospective, controlled clinical trials in dogs or cats that demonstrate improved survival or enhanced or hastened recovery from ARF associated with the induction and/or maintenance of a diuresis.

Table 3: Hypothetical comparison of daily glomerular filtration, tubular reabsorption, and urine production in the normal and nonoliguric ARF state.

The large volume of fluid and rapid administration rate necessary in ARF require that fluids be given intravenously. Jugular catheters are ideal as they facilitate frequent blood sampling, infusion of hypertonic solutions (e.g., mannitol), and allow access for central venous pressure (CVP) measurement. Deficit fluid requirements should be replaced over the first 4-6 hours of treatment, unless the patient has a cardiac disorder that requires a slower administration rate. A fluid bolus challenge of 20 ml/kg body weight given intravenously over 10 minutes can help assess the possibility of a subsequent volume overload. The CVP should not increase more than 2 cm of water if the patient's cardiovascular function is normal. The purpose of replacing volume deficits over the first 4 - 6 hours rather than over the normal 12-24 hours is to rapidly improve renal perfusion and decrease the likelihood of continued ischemic damage. Normal saline (0.9% solution) is the fluid of choice for rehydration unless the patient is hypernatremic; in which case a 0.45% saline and 2.5% dextrose solution should be used. The amount of fluid required to restore extracellular fluid deficits can be calculated by multiplying the estimated percent dehydration by the patient's body weight in kilograms (Table 1).

During this rapid rehydration phase, the patient should be closely observed for signs of overhydration. Frequent assessment of body weight, CVP, packed cell volume, and plasma total solids will help detect early overhydration. An increase in the CVP of > 5-7 cm of water over baseline values, suggests the likelihood of overhydration. Physical manifestations of overhydration include increased bronchovesicular sounds, tachycardia, restlessness, chemosis and serous nasal discharge. Auscultation of overt crackles and wheezes is usually a late sign indicating established pulmonary edema. Overhydration in dogs and cats with oligoanuric ARF is a common complication that frequently results in pulmonary edema. Overhydration in oligoanuric ARF patients is extremely difficult to correct.

Urine production should be measured and electrolyte and acid-base status assessed during the period of rehydration. Urine production (ml/kg/hour) should be measured so that maintenance fluid needs can be accurately administered. Approximately two-thirds of normal maintenance fluid needs are due to fluid loss in urine, therefore oliguric and nonoliguric patients can have large variations in their maintenance fluid needs (Table 4). Metabolism cages, urinary catheters, and manual collection of voided urine are methods used to collect and measure urine volume. In the case of indwelling urinary catheters, strict aseptic technique and closed collection systems must be used. Because of the possibility of urinary tract infection, intermittent urinary bladder catheterization is usually recommended over indwelling catheterization for timed urine volume collections. In cats, weighing the litter pan before and after voiding is a useful, although less accurate method for assessing urine production. Observation of urine voiding and urinary bladder palpation are the least reliable methods for determining the volume of urine produced.

Table 4: Hypothetical daily fluid requirements in oliguric and nonoliguric ARF patients compared with those of a normal patient.

Initially, most patients with ARF have normal serum sodium and chloride concentrations due to isonatremic fluid loss. Hypernatremia can develop however after several days of therapy with fluids containing large amounts of sodium (0.9% NaCl, lactated Ringer's solution, and Normosol) and/or in association with sodium bicarbonate treatment of metabolic acidosis. If hypernatremia occurs, the use 0.45% NaCl with 2.5% dextrose fluids will usually correct the problem.

Disorders of calcium balance can also occasionally be manifest in ARF patients. If moderate to severe hypercalcemia is observed, a primary hypercalcemic disorder (e.g., neoplasia or vitamin D3 intoxication) should be considered as the cause of the renal failure. Immediate treatment for hypercalcemia includes rehydration with 0.9% NaCl followed by diuresis induced with furosemide. Glucocorticoids will also help lower calcium concentrations by decreasing intestinal absorption and facilitating excretion, but their use may interfere with the diagnosis of the underlying disorder (e.g., lymphosarcoma). Conversely, significant hypocalcemia can be observed in dogs and cats with ARF associated with ethylene glycol intoxication.

Oliguric ARF patients are at risk for hyperkalemia. Serum potassium concentrations greater than 6.5-7.0 mEq/L can cause cardiac conduction disturbances (bradycardia, atrial standstill, idioventricular rhythms, ventricular tachycardia, fibrillation and asystole) and electrocardiographic changes (peaked T waves, prolonged PR intervals, widened QRS complexes, or the loss of P waves). Mild to moderate hyperkalemia is largely resolved with administration of potassium-free fluids (dilution) and improved urine flow (increased excretion). More severe hyperkalemia (> 7-8 mEq/L) or hyperkalemia resulting in ECG abnormalities should be treated by agents that will decrease serum potassium concentrations or counteract the effects of hyperkalemia on cardiac conduction. Sodium bicarbonate (see dosage below) will help correct any metabolic acidosis and lower serum potassium concentration by exchanging intracellular hydrogen ions for potassium. Glucose and insulin can also be used to increase intracellular shifting of potassium. Regular insulin is administered at a dosage of 0.1 to 0.25 U/kg, IV followed by a glucose bolus of 1-2 g per unit of insulin given. Blood glucose monitoring should be maintained for several hours following administration of insulin since hypoglycemia may occur. Ten percent calcium gluconate (0.5-1.0 ml/kg IV over 10-15 minutes) will counteract the cardiotoxic effects of hyperkalemia without lowering the serum potassium and can be used in emergency situation. The effects of the above regimes are short-lived, and fluid and acid-base therapy to initiate and maintain a diuresis and maintain blood pH and bicarbonate within the normal range (see below) is important to maintain potassium excretion and normokalemia.

Mild to moderate metabolic acidosis also commonly resolves with fluid therapy, and specific treatment is usually not necessary unless the blood pH is less than 7.2 or total CO2 is less than 12 mEq/L. Bicarbonate requirements can be calculated utilizing the base deficit as determined from arterial blood gas, or an estimated base deficit [body weight (kg) x 0.3 x base deficit or (20 - T CO2) = mEq bicarbonate required]. Optimally, one-half the calculated bicarbonate dosage should be administered IV slowly over 15-30 minutes and then acid-base parameters reassessed. Overzealous bicarbonate administration may result in ionized calcium deficits, paradoxical CSF acidosis and/or cerebral edema.

If signs of overhydration are not present and oliguria persists after apparent rehydration, mild volume expansion (3 to 5% of the patient's body weight in fluid) may be initiated inasmuch as dehydration of this magnitude is difficult to detect clinically. If volume expansion is attempted, the possibility of inducing overhydration increases and close patient observation is necessary. Unfortunately, most patients that present with oliguria will remain oliguric after rehydration and volume expansion.

In the past, diuretic therapy has been frequently recommended in patients that are persistently oligoanuric despite appropriate fluid therapy. In comparison to those patients with diminished urine production, polyuric ARF patients are thought to have less severe tubular injury, improved excretion of solutes that are reabsorbed or secreted (e.g., urea nitrogen and potassium), and have less risk of developing overhydration and pulmonary edema. There is, however, no evidence that diuretic therapy will hasten the recovery from ARF or the mortality associated with ARF. In human beings with established ARF, there is increasing evidence that diuretic therapy may actually be associated with increased risk of death and non-recovery of renal function. If the choice is to use diuretics in dogs or cats with ARF, they should only be used after dehydration has been corrected and the patient has been volume expanded. Furosemide and mannitol are probably the diuretics of choice. Dopamine is not recommended because of its unpredictable effects on renal blood flow and glomerular filtration rate.

Furosemide blocks the reabsorption of chloride and sodium in the thick ascending limb of Henle resulting in natriuresis and an osmotic diuresis. Furosemide also has weak renovasodilatory properties that may help increase renal blood flow. The dose recommended for oligoanuric dogs and cats is 2-6 mg/kg IV q 8 hours, however in healthy dogs, constant rate infusion of furosemide with a 0.66 mg/kg IV loading dose followed by 0.66 mg/kg/hr resulted in more diuresis, natriuresis, calciuresis and less kaliuresis than did intermittent bolus infusion. Furosemide has been shown to exacerbate gentamicin toxicity and probably should be avoided in patients with ARF caused by aminoglycoside usage.

Mannitol, in a 10% or 20% solution, has been recommended as an osmotic diuretic at a dose of 0.5-1.0 g/kg, given IV as a slow bolus over 15-20 minutes. Urine output should increase within one hour if the treatment is effective. A second bolus may be attempted but the potential for volume overexpansion and complications such as pulmonary edema increases considerably if urine production does not increase. As an osmotic agent, mannitol may decrease tubular cell swelling, increase tubular flow, and help prevent tubular obstruction or collapse. Mannitol also has weak renal vasodilator properties that are probably mediated by prostaglandins or atrial natriuretic peptide in addition to weak free-radical-scavenging capabilities. In healthy cats, the renal affects of mannitol, when used as an adjunct to fluid therapy, are superior to those of the furosemide and dopamine combination. Mannitol, as compared with hypertonic glucose, is likely the better osmotic agent, since it is not metabolized or reabsorbed by the renal tubules. The use of any osmotic agent is contraindicated in an overhydrated patient because the resultant increase in intravascular volume may precipitate pulmonary edema.

Whether or not a diuresis can be established, fluid therapy should be tailored to match urine volume and other losses, including insensible losses (e.g. water loss due to respiration) and continuing losses (e.g. fluid loss due to vomiting or diarrhea). Insensible losses are estimated at 20 ml/kg/day. Urine output is quantitated for 6-8 hour intervals and that amount is replaced over an equivalent subsequent time period. The volume of fluid loss due to vomiting and/or diarrhea is estimated and that amount is added to the 24-hour fluid needs of the patient. If hypernatremia and hyperkalemia are not present and a diuresis has been established, polyionic maintenance fluids (e.g., lactated Ringer's solution, Normosol) should be utilized. In the recovery phase of ARF, urine volume and electrolyte losses can be great. Potassium supplementation may be necessary, especially if the patient is vomiting or anorexic.

Control of nausea and vomiting in dogs and cats with ARF is important in order to facilitate caloric intake. In addition, the inability to control vomiting is discouraging to owners and may result in a hastened decision for euthanasia. Please see the Management of Chronic Renal Failure Chapter for specific recommendations for the treatment of nausea and vomiting.

When fluid therapy is successful in inducing or maintaining a diuresis, the daily volume of fluid administered to the patient will eventually need to be decreased. Indications for tapering intravenous fluid volume include: 1) significant reductions in BUN and phosphorus concentrations, 2) control of vomiting and diarrhea, and 3) the patient feeling better and showing interest in eating and drinking. These indications rarely occur prior to 5-6 days of intense fluid therapy/diuresis and may require 10 or more days of treatment. Gradually reducing maintenance fluid requirements by 25% each day is usually recommended for fluid tapering. If the patient losses weight or increases in PCV, total protein, BUN and/or creatinine concentrations are observed, fluid therapy tapering should be discontinued and the previous maintenance volume reinstated for at least 48 hours.

Peritoneal dialysis should be considered in patients with severe, persistent uremia, acidosis, or hyperkalemia. Dialysis may also be used to treat overhydration and hasten elimination of dialyzable toxicants. Renal biopsy should be performed if the diagnosis is in doubt, if the patient does not respond to therapy within 3 to 5 days, or if peritoneal dialysis is considered. Long- term prognosis for dogs or cats with ARF is usually fair to good if the patient survives the period of renal tubular regeneration and compensation, however, several weeks may be required for renal function to improve. Animals with moderate/severe renal damage may require many weeks for renal repair and this prolonged time required for recovery results in poor prognosis. The severity of the initial azotemia/uremia, the response to fluid therapy, and assessment of renal histopathologic lesions are the most important prognostic indicators early in the course of ARF.

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