Your guide to managing acute renal failure

Q How do you manage acute renal failure?

A Dr. Linda A. Ross at the 2007 American College of Veterinary Internal Medicine Forum in Seattle gave an excellent lecture on management of acute renal failure. Here are some relevant points:

Acute renal failure (ARF) is defined as the rapid loss (over hours to several days) of nephron function, resulting in azotemia, fluid, electrolyte and acid-base abnormalities and uremia.

Many causes have been identified in dogs and cats, the most common of which are ischemia (secondary to pancreatitis, shock, sepsis, DIC), toxicities (ethylene glycol; calciferol-containing rodenticides or human topical dermatological preparations; drugs such as aminoglycoside antibiotics, cisplatin, NSAIDs, and amphotericin B; lily plants in cats; and raisins or grapes in dogs); infections (leptospirosis, pyelonephritis), and nephroliths or ureteroliths causing obstruction to urine outflow.

Pathological stages

Acute renal failure is divided into three stages. The first (initiation) occurs during and immediately after insult to the kidneys, when pathological damage to the kidney is occurring. The latter part of the initiation phase has recently been termed the extension phase. During this time, ischemia, hypoxia, inflammation and cellular injury continue, leading to cellular apoptosis and/or necrosis. The initiation phase usually lasts less than 48 hours, during which time clinical and laboratory abnormalities may not be apparent.

The second stage (maintenance) is characterized by azotemia and/or uremia, and may last for days to weeks. Oliguria (<1.0 ml urine/kg body weight per hour) or anuria (no urine production) may occur during the maintenance stage; urine production can be highly variable.

The third stage is recovery, during which time azotemia improves and renal tubules undergo repair. Marked polyuria may occur during this stage as a result of partial restoration of renal tubular function, and of osmotic diuresis of accumulated solutes. Renal function may return to normal, or the animal may be left with residual renal dysfunction. It is possible for animals to have acute renal failure with sufficient tubular damage to cause polydipsia and polyuria, but not enough to cause azotemia.

Therapy

Treatment of ARF consists of specific therapy for the cause, as well as supportive therapy based on the stage of acute renal failure and the animal's fluid, electrolyte and acid-base status. It is important to remember that the doses of drugs excreted primarily by the kidneys should be reduced or the dosage interval extended in proportion to the degree of azotemia.

If the cause of ARF is known, specific therapy should be instituted. All animals should receive antibiotics effective against common uropathogens until infection is ruled out, and dogs may require antibiotics effective against leptospires, such as penicillin, amoxicillin or doxycycline.

Intravenous (IV) fluid therapy is the cornerstone of treatment for ARF, with the appropriate fluid type and amount determined by frequent monitoring of the animal's hydration status, renal function, acid-base status and electrolytes. The increasing availability of in-house or bedside blood chemistry analyzers facilitates such monitoring. Placement of a catheter in the jugular vein allows monitoring of central venous pressure and intravascular volume status. However, the jugular veins should be preserved for placement of a hemodialysis catheter if that is a treatment option, and not be used for IV catheters or even venipunctures for blood samples.

The initial volume of fluid to be administered should be calculated based upon the animal's body weight and degree of hydration. Water deficits should be replaced within four to six hours in order to restore renal blood flow to normal as soon as possible. Maintenance fluid requirements must be met (44 to 66 ml/kg daily), as well as estimated fluid losses from vomiting or diarrhea. Urine production should be monitored during the first few hours of fluid therapy. Placement of an indwelling urinary catheter is the most accurate method for this determination. However, the benefits of an indwelling catheter must be weighed against the risks of ascending infection, and in cats, sedation or anesthesia to place the catheter.

An isotonic, polyionic fluid such as lactated Ringer's solution (LRS) or Plasma-Lyte A (Baxter) may be administered initially. If hyperkalemia is present or suspected, a potassium-free fluid such as 0.9 percent sodium chloride is indicated. After rehydration, the type of fluid should be adjusted based on the animal's fluid and electrolyte status. Maintenance fluids with less sodium, such as half-strength LRS or 0.45% sodium chloride in 2.5% dextrose, may be appropriate for long-term therapy.

Metabolic acidosis can occur in ARF, although alkalinizing therapy is not recommended unless the blood pH is less than 7.2 or the serum bicarbonate is less than 14 mEq/l after correcting fluid deficits.

Moderate to severe life-threatening hyperkalemia may occur if the animal is oliguric or anuric. Animals with severe hyperkalemia associated with cardiovascular abnormalities should receive specific therapy to reduce serum potassium levels. Hypokalemia may occur during the diuretic phase of ARF. Therapy consisting of IV or oral potassium chloride is indicated if the serum potassium concentration is below the normal range, although clinical signs are not usually apparent until it falls below 2.5 mEq/L.

Vomiting can be a significant problem in animals with ARF. Because uremia results in hypergastrinemia, drugs that inhibit gastric acid production are indicated. These include histamine receptor antagonists such as famotidine (0.5-1.0 mg/kg q24h, PO, IV) and proton pump inhibitors such as omeprazole (0.7 mg/kg q24h, PO), or lansoprazole (0.6-1.0 mg/kg q24h, IV). Centrally acting antiemetics may also be necessary. Metoclopramide, a dopamine antagonist, may be given as intermittent therapy at a dose of 0.2 to 0.5 mg/kg q8h IV or as a CRI at 1-2 mg/kg/day IV. Other centrally acting drugs include dolasetron (0.6 mg/kg q24h, PO or SQ, or diluted in compatible IV fluid and administered over 15 min IV) and ondansetron (0.1-0.2 mg/kg q8h, SQ or 0.5 mg/kg IV loading dose, then 0.5 mg/kg/hr CRI). Phenothiazine derivative antiemetics such as chlorpromazine (0.2-0.5 mg/kg q6-8h, SQ, IM or IV) can be tried if vomiting persists despite other therapy.

Arterial hypertension may occur in animals with ARF, and can be due in part to fluid overload.

Treatment may include reducing the rate of IV fluids, administration of diuretics and dialysis to remove excess fluid if the animal is oliguric or anuric.

Pharmacologic treatment is limited because most antihypertensive drugs are available only in oral formulations, and the vomiting associated with ARF often precludes oral medication. If hypertension is severe, parenteral antihypertensives include nitroprusside (initial dose 1-2 mcg/kg/min CRI IV; titrate up q5min to achieve desired blood pressure) and hydralazine (0.5-3 mg/kg q12h IV or 0.1 mg/kg loading dose IV, then 1.5-5 mcg/kg/min CRI IV). Administration of both drugs requires close monitoring. Oral antihypertensives include amlodipine (0.1-0.25 mg/kg q12-24h, PO in dogs, 0.625-1.25 mg/cat q24h PO in cats) and angiotensin-converting enzyme (ACE) inhibitors such as enalapril (0.25-0.5 mg/kg q12-24h PO) and benazepril (0.25-0.5 mg/kg q24h, PO). ACE inhibitors have been associated with worsening of renal function in humans.

Nutritional support has been shown to be important for recovery from ARF. These animals are in a state of negative nutritional balance at a time when protein and energy are needed to support regeneration of damaged renal tissue. Enteral nutrition, utilizing an esophagostomy or gastrostomy tube, can be used if the animal is not vomiting; otherwise, parenteral nutrition is indicated.

Management of oliguria or anuria

Once the animal has been hydrated, urine flow should rapidly increase to 2-5 ml/kg per hour, depending upon the rate of IV fluid administration. If urine production is not sufficient, the animal's circulating blood volume should be assessed first. If the animal is normovolemic, the rate of fluid administration should be slowed to prevent overload. An indwelling urinary catheter should be placed if not already present. Calculation of "ins and outs" can then be used to provide appropriate quantities of IV fluids to match urine output. The maintenance fluid requirement (estimated at 20 ml/kg/day for insensible losses) is calculated for a short interval of time, typically four hours. The volume of urine during the previous interval is added to the maintenance amount, giving the volume of IV fluids to be administered over the subsequent four-hour period. This helps maintain hydration while minimizing the risk of fluid overload.

Specific therapy to increase urine flow is administered concurrently. Diuretics are administered first. Furosemide has traditionally been administered as escalating bolus doses. However, a loading dose of 0.66-1.0 mg/kg, followed by continuous rate infusion (CRI) at 0.66-1.0 mg/kg/hr, has been shown to be more effective in producing diuresis in normal dogs.

If furosemide fails to increase urine flow, osmotic diuresis with hypertonic mannitol solutions can be attempted. However, this is contraindicated in oliguric animals that are already volume overloaded because it will result in increased serum osmolality, circulating blood volume and blood pressure. Ten percent or 20 percent mannitol can be given as a bolus dose of 0.5-1.0-g/kg body weight over 15 to 20 minutes. If effective, urine flow will increase within one hour. Repeat bolus doses can then be administered every four to six hours, or it can be administered as a constant-rate infusion at a dose of 1-2 mg/kg/minute. Mannitol may have additional beneficial effects in addition to its action as a diuretic. It inhibits renin release because of its hyperosmolar effect on tubular luminal filtrate. In addition, it acts as a free radical scavenger, blunts damaging increases in intramitochondrial calcium and may result in a beneficial release of atrial natriuretic peptide.

Dopamine infusion traditionally has been recommended for oliguric or anuric animals. Dopamine stimulates two types of dopamine receptors (DA-1 and DA-2) as well as alpha- and beta-adrenergic receptors.

In dogs, it causes an increase in renal blood flow (RBF) and urine volume; glomerular filtration rate (GFR) either increases or is unchanged. In cats, increased urine production occurs in the absence of increases in RBF or GFR. This is most likely due to alpha-adrenergic stimulation that increases cardiac output and blood pressure, and induces natriuresis.

The use of dopamine has become somewhat controversial, because studies of its benefit in people with or at risk of ARF have failed to demonstrate improvement in clinical outcome despite transient improvement in urine output.

There is little or no documentation of the efficacy of dopamine in dogs and cats with ARF. It may have some benefit in dogs with oliguria or anuria, because increasing urine production is beneficial in managing fluid therapy. Its use in cats is less clear, because the higher doses necessary to promote urine production may result in adverse physiologic consequences that may negate its benefit.

For dogs, dopamine is diluted in an isotonic fluid and administered as an IV infusion at the rate of 0.5-3 mcg/kg per minute. High rates of infusion (greater than 10 mcg/kg per minute) may cause arrhythmias, increased blood pressure and vasoconstriction. Dopamine is inactivated in alkaline solutions. Electrocardiographic monitoring is recommended during dopamine infusion.

Furosemide administered concurrently with dopamine has been shown to be synergistic in maintaining GFR, RBF and urine flow in dogs with experimental ARF, and to reduce the severity of some forms of experimental ARF when administered prior to the renal insult. If oliguria persists despite these measures, dialysis would be the next therapeutic step.

Recently, a selective DA1 agonist (fenoldopam) has become available. Preliminary studies of its renoprotective effects in people have been promising. One experimental study in healthy cats found that an infusion of 0.5 mcg/kg per minute produced diuresis in a delayed manner. However, a study in experimental dogs undergoing nephrotomy showed no difference in GFR or urine volume between dogs receiving fenoldopam or saline. No clinical studies have been reported in dogs or cats with ARF, and its role in management of oliguric ARF is not yet known.

Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small-animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: jdhoskins@mindspring.com