Acute renal failure (ARF) is an acute suppression of renal function. The insult causing ARF equally and abruptly disrupts the function of all nephrons without time for compensatory mechanisms which are involved in chronic renal failure to "kick in".  ARF is contrasted with chronic renal failure (CRF) in which there is a gradual death of nephrons with the remaining nephrons functioning in a normal or supra normal capacity. ARF is potentially reversible whereas CRF is a progressive and irreversible condition.

Most (~80 to 90%) of ARF patients are oliguric. Oliguria is defined as urine production of less than 0.5 ml/lb/hr (1 ml/kg/hr). ARF patients which are polyuric (increased urine output) have sustained a lesser degree of renal injury compared to oliguric patients and therefore have a better prognosis. The damaged nephrons of ARF patients have reduced ability to form glomerular filtrate from blood, resulting in less filtration of urea nitrogen, creatinine, phosphorus and potassium leading to an increase of these substances in the blood.

It is important to differentiate ARF from prerenal azotemia. Both prerenal azotemia and ARF can be caused by hypovolemia and uncorrected prerenal azotemia can progress to ARF. The more severe and sustained the hypovolemia, the greater the probability that ARF will occur. The kidneys are able to "autoregulate" renal blood flow (RBF) and GFR to keep these parameters normal when mean arterial blood pressure is greater than 70 mm Hg. Mean blood pressures lower than 70 mm Hg are associated with reduction in renal blood flow and GFR. The prognosis for prerenal azotemia is good if the underlying disease causing prerenal azotemia is reversible. The prognosis for ARF is usually poor.

Urine specific gravity (USG) and urine sodium concentration are parameters which can be used to differentiate prerenal azotemia from ARF. The USG is concentrated and urine sodium is low in patients with prerenal azotemia. The USG is isosthenuric (1.007 - 1.017) and urine sodium is high in patients with ARF.

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Possible causes of ARF include:

• ischemic injury
• toxic or chemical insults
• infection
• glomerular diseases

ARF is most often caused by chemical insults (drugs or toxins) or by ischemic injury to the kidney.

Ischemic injury: The kidneys are very active organs. In order to function properly, the cells in the kidneys must be supplied with large amounts of oxygen and nutrients via the blood. If blood flow to the kidneys is diminished by hypovolemia, the kidney cells are "deprived" of oxygen and nutrients which results in cellular death. The death of epithelial cells lining the renal tubules is called "acute tubular necrosis" (ATN). The causes of hypovolemia include the same causes as those resulting in prerenal azotemia but the insults are more profound and sustained to result in ARF. An additional cause of reduced renal blood flow which will result in ARF is thrombosis of the renal arteries. Renal artery thrombosis may occur as part of a generalized hypercoagulable state (e.g. disseminated intravascular coagulation).

Toxic Injury

The kidneys are highly susceptible to injury from drugs and toxins. 20-25% of cardiac output each minute reaches the kidneys delivering large amounts of any drug in circulation to the kidneys. The glomerular blood vessels have a large endothelial surface for contact with drugs and drugs may be concentrated in tubular fluid by the normal reabsorption of water from the tubules. The kidneys contain enzymes that metabolize drugs and drug metabolites may be more toxic than parent compounds.

Chemical injury may occur as a consequence of either endogenous or exogenous toxins. The mechanisms of chemical-induced renal injury include direct toxicity, hypersensitivity reaction, immune mediated damage, precipitation of drug causing obstruction, or renal artery vasoconstriction with resultant renal ischemia.

Endogenous endotoxins include:

• Hypercalcemia is an uncommon cause of acute renal failure. Hypercalcemic patients often have polyuria, polydipsia and dilute urine but infrequently develop irreversible renal failure.
• hemoglobin from hemolysis,
• myoglobin from rhabdomyolysis (muscle breakdown).

Normal kidneys can excrete hemoglobin and myoglobin without damage but in the face of concurrent dehydration, nephrotoxicity and ARF may occur.

Pre-existing renal disease or dehydration may enhance the effects of toxins. Renal lesions may be reversible in days to weeks or may be irreversible.

Drugs which are renally excreted need to have the dose or dose interval altered to prevent accumulation of toxic levels of the drug in patients with renal disease.

Exogenous toxins

Many drugs and chemicals have the potential to produce nephrotoxicity. Follows is a partial list of possible nephrotoxins. An individual animal can have an idiosyncratic reaction to any drug with a possible consequence of renal injury.

Analgesics

• NSAIDs (acetaminophen, ibuprofen, etc.)
• selective cyclooxygenase (COX) inhibitors

Antibiotics

• aminoglycosides (gentamicin, paromomycin, etc.)
• cephalosporins
• nafcillin
• polymyxin B
• sulfonamides
• tetracyclines

Antifungal

• amphotericin B

Chemotherapeutic agents

• adriamycin (doxorubicin) in cats
• cisplatin in dogs

Heavy metals

• lead
• mercury
• arsenicals
• thallium
• turpentine

Plants & Foods

• Lilly ingestion in cats   Acute renal failure caused by lily ingestion in six cats
• Raisin and grape toxicity in dogs

Misc.

• penicillamine (chelating agent/immune modulator)
• cyclosporin (immunosuppressive)
• radiographic contrast agents
• ethylene glycol
• Vitamin D toxicosis such as calcipotriol a synthetic analog of calcitriol present in the topical psoriasis medication, Dovonex.
• pesticides, herbicides and solvents

Nonsteroidal anti-inflammatory drugs   (NSAIDs) and selective cyclooxygenase (COX) inhibitors commonly used for management of joint pain and perioperative pain are potentially nephrotoxic. Vasodilatory renal prostaglandin's counterbalance the vasoconstrictor effects of other endogenous substances. The use of NSAIDs may precipitate ARF in predisposed patients by depressing production of vasodilator prostaglandin's, leading to reduced renal blood flow. Conditions in which renal function is dependent on prostaglandin synthesis include congestive heart failure, liver failure with ascites, volume/salt depletion,  general anesthesia, diuretic use, diabetes mellitus, and renal disease. Gastrointestinal toxicity is more often observed in dogs receiving NSAIDs than is renal failure but dogs are more susceptible to renal damage from NSAIDs and COX-2 inhibitors than are people due to differences in anatomy and distribution of COX-2 in kidney tissues. GI ulcers often precede development of ARF.

Although all NSAIDs are potentially toxic most toxicities involve ibuprofen and occur due to ingestion of excessive amounts or occur in animals with pre existent disease.

Aminoglycoside toxicity. Although increased awareness, monitoring of drug levels and use of safer antibiotics have significantly reduced the occurrence of aminoglycoside toxicity, several atypical cases have been reported either from topical absorption of gentamicin from large soft tissue wounds or systemic absorption of oral paromomycin which is used in treatment of trichomoniasis or cryptosporidiosis in cats.

References:

Nephrotoxicosis associated with topical administration of gentamicin in a cat.

Acute renal failure in four cats treated with paromomycin.

Infectious diseases that may lead to ARF include:

• Pyelonephritis
• Babesiosis
• Borreliosis
• Leptospirosis

Leptospirosis is an uncommon disease but seems to be re emerging with new serovars. Infection with L pomona and L bratislava are most likely to result in ARF.  Untreated bacterial pyelonephritis is more likely to compromise renal function over time resulting in CRF but can cause an abrupt disruption of function (ARF).

Glomerulonephropathy, which is usually immune mediated, can cause ARF but more often if glomerular disease results in azotemia, there is a gradual loss of renal function (CRF) rather than an abrupt decline in function (ARF).

All the etiologies of ARF are additive. For example, if a patient with bacterial pyelonephritis is treated with a nephrotoxic antibiotic and also becomes dehydrated, that patient is at greater risk for developing ARF than if only one of these conditions were present.  (infection = pyelonephritis + chemical insult = nephrotoxic antibiotic + ischemia = dehydration)

Very young and very old animals are at greater risk for development of ARF; the young because the kidneys are immature and the old because pre-existent renal disease is likely present.

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Pathophysiology

There is a large body of work which has been performed in an attempt to elucidate the mechanisms responsible for the reduction of GFR and urine flow in ARF patients. Four major mechanisms are believed to be involved in the initiation and maintenance of reduced GFR and reduced urine output.

• reduced renal blood flow/renal artery vasoconstriction
• intratubular obstruction
• backleak
• decreased glomerular permeability

Renal artery vasoconstriction leads to a reduction of renal blood flow. Vasoconstriction can be catecholamine induced, caused by alteration of renal prostaglandin activity (reduced vasodilatory prostaglandins or increased vasoconstrictor prostaglandins), or the renal arteries may be occluded by thrombi.

Renal tubules can be obstructed from cell debris as tubular epithelial cells die from what ever insult is responsible for causing ARF. Drugs such as sulfonamides can precipitate in the lumen of the tubules causing obstruction. In experimental models of ARF, tubular obstruction appears to play a minor role in the genesis of ARF as the debris deposited in the tubular lumen can be "flushed" from the tubule with low pressures. Therefore tubular debris is probably a consequence of low fluid flow through the tubule rather than a cause of it.

The backleak theory is described as reabsorption of filtrate into blood after leakage through damaged tubular epithelium.

Decreased glomerular permeability caused by swelling of endothelial or epithelial cells which comprise the glomerulus may impair formation of glomerular filtrate.

All 4 of these mechanisms may contribute to the development of oliguria and accumulation of wastes in ARF patients.

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Clinical course

The clinical course of ARF proceeds through a sequence of overlapping phases:

• initiation phase
• oliguric phase
• polyuric phase
• phase of functional recovery

The initiation phase is defined as the time from renal insult to recognition of decreased GFR, decreased urine output and increased BUN and creatinine. This phase lasts 1-2 days. As an example, suppose a cat is under anesthesia for an exploratory surgery and becomes hypotensive during the procedure due to blood loss, the hypotensive effects of anesthesia and inadequate fluid administration. If hypotension is severe and not corrected, the kidneys are deprived of blood with resultant death of tubular epithelial cells. The BUN will not increase immediately and unless urine volume is being measured, it will not be immediately detected that urine production is decreasing. Within 1 to 2 days it will become apparent that the cat is in acute renal failure with decreased USG, reduced urine output and increased BUN.

The oliguric phase which is also called the maintenance phase, is the period of time during which oliguria persists. Some ARF patients are never oliguric. Whether an ARF patient is oliguric or polyuric probably reflects the severity of insult which caused the ARF. This has been demonstrated in rodents with chemical or ischemic induced ARF. The more severe the insult, the lower the urine output. As the majority (80 to 90%) of ARF dogs and cats become oliguric, it indicates that the situations which cause ARF in these species are severe and correlates with the poor prognosis for ARF patients.

In those patients which can repair the renal damage, the oliguric phase lasts 1-2 weeks. Many animals die or are euthanized during the oliguric phase because of the poor prognosis. The most life-threatening consequences of the oliguric phase include hyperkalemia and overzealous fluid therapy resulting in overhydration.

The polyuric phase = high output phase = diuretic phase is characterized by a progressive increase in urine volume in patients which were initially oliguric. The patients still have an increased BUN and creatinine and isosthenuric USG. The polyuric phase may indicate the beginning of renal repair and return of function or may be indicative of a less severe insult to the kidneys. Glomerular filtrate is entering tubules that are not fully functional and are acting as simple conduits for fluid without performing any work on the fluid. There are several causes for polyuria in these patients:

• impaired tubular sodium reabsorption causing loss of sodium in the urine
• excretion of solutes retained in the oliguric phase (small molecules like urea are osmotically active)
• impaired response of tubular cells to ADH (nephrogenic diabetes insipidus)
• medullary washout of solute (It requires tubular work to maintain a hypertonic gradient in the renal interstitium)
• iatrogenic over hydration during the oliguric phase

During the polyuric phase, renal loss of sodium and water can be substantial. If the patient can not drink enough to keep up with the renal loss of water, they will dehydrate resulting in a prerenal insult superimposed upon the already existent renal disease. Fluid therapy must be diligently managed to prevent dehydration. This phase lasts a few days to several weeks or longer.

The phase of functional recovery has neither a clearly defined beginning or end. In patients capable of repairing the renal injury, BUN, creatinine, and urine volume gradually return to normal. Concentrating ability is the slowest to return. Permanent defects in concentration, acidification, or permanent decreases in GFR may persist.

Some ARF patients progress to CRF.

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Diagnosis

The patient history, physical examination and laboratory data may all support a diagnosis of ARF.

The history may provide a clue as to the cause of ARF. For example the animal may have had recent anesthesia/surgery causing hypotension, may have been receiving a drug which has the possibility of being nephrotoxic or may be a free-roaming animal which has the potential for exposure to toxins such as antifreeze. Patients with chronic renal failure may have a history of polyuria and polydipsia and may abruptly decompensate, presenting in a crisis like an ARF patient. CRF patients can sustain acute insults (ARF super imposed upon CRF).

Physical examination often reveals a depressed, hypotensive, hypovolemic and sometimes hypothermic patient. Hypovolemia is due to fluid loss in vomitus and diarrhea and lack of intake and in some patients, hypovolemia is the cause of ARF.

Given the acute nature of their disease, the patient is often in good body condition compared to the chronic renal failure patient which may be in poor body condition.

Fever may be present if ARF is from an infectious cause such as acute pyelonephritis or leptospirosis. Tachypnea may be observed and is present to eliminate CO₂ to compensate for metabolic acidosis.

Bradycardia may exist due to hyperkalemia but hyperkalemic patients may have a normal heart rate. As the patients are usually hypovolemic and the cardiac response to hypovolemia is to increase the heart rate, the two opposing influences on heart rate may result in a normal heart rate.

The kidneys may palpate normal to large. Enlarged kidneys may be painful when palpated as pain receptors in the capsule of the kidney are stretched as the kidney enlarges.

The most common change in mentation is depression but seizures may occur in terminal uremia or due to toxins such as ethylene glycol.

Hematology

The CBC often discloses increased total protein and PCV due to hemoconcentration, unless blood loss caused hypovolemia and subsequent renal failure in which case total protein and PCV are decreased. Platelet number is normal but function is abnormal (thrombocytopathia). Thrombocytopathia is due to the retention of a waste product which makes the platelets less aggregable (less sticky). WBC is either normal or shows a stress response. Uremia interferes with the function of WBC which may predispose ARF patients to infection.

Chemistry

Biochemical analysis will show increased BUN and creatinine.

Sodium may be increased, decreased, or normal and depends upon the type of dehydration that is present and upon any previous fluid therapy. Dehydration in the ARF patient is primarily due to losses in vomiting and diarrhea and to lack of intake. Gastrointestinal losses of fluid contain electrolytes in addition to water in proportions comparable to blood resulting in isotonic dehydration. Therefore the proportion of electrolytes to water in the blood remains close to normal even though the actual amount of water and electrolytes is decreased compared to health. Sodium will be increased if the patient has greater than normal insensible losses (respiratory) as insensible losses contain primarily water and little electrolyte.

Elevated potassium (hyperkalemia) is often associated with oliguria. There may be cardiac disturbances when K > 6.0 mEq/L. Normal intracellular K is 160 mEq/L. The normal ICF to ECF ratio for K is 40:1. When ECF K increases, this ratio is reduced. This elevates the normal resting membrane potential (RMP) to a less negative state, creating partial depolarization of myocardial cells. The action potential produced is weaker and the spread of depolarization across the myocardium is slowed.

Inorganic phosphorus is increased. Calcium is usually normal early in ARF but may decrease within several days of onset. Calcium may deposit in damaged muscle with extensive rhabdomyolysis (muscle breakdown) (example "heat stroke" or crush injury) causing a rapid decline in serum calcium. This is followed by hypercalcemia during recovery as the calcium is mobilized from muscle. Calcium may be decreased in ethylene glycol poisoning due to the formation of calcium oxalate. Rapid correction of acidosis results in a decrease in ionized calcium and may precipitate hypocalcemic tetany. If hypercalcemia exists, the patient should be evaluated for the source of the increased calcium which could be the cause of ARF (primary or pseudohyperparathyroidism).

The urinalysis may show signs of   tubular dysfunction which include isosthenuric specific gravity (1.007-1.017), proteinuria, glucosuria, increased urine sodium, or casts. Crystals may disclose the cause of ARF (e.g., calcium oxalate crystals of antifreeze poisoning).

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Radiology can be used to determine kidney size if size cannot be determined from palpation. Kidneys are normal to large in patients with ARF as compared to small kidneys in CRF. Ultrasound can also be used to assess renal size. Contrast studies of the kidneys (IVP) should not be performed simply to determine renal size. The quality of the contrast study is influenced by renal function as normal kidneys will concentrate the injected dye which delineates their structure. Inability to concentrate the dye results in a poor quality contrast study in patients with renal disease. Additionally, the contrast agent can be nephrotoxic.

Renal biopsy is not necessary to make a diagnosis of ARF but may yield prognostic information. The cause of ARF may be determined from renal biopsy, for example oxalate crystals are observed in the biopsy of patients with antifreeze poisoning. If a patient is not responding to therapy after 7 to 10 days, a biopsy may give clues as to the potential for reversibility based on the severity of renal damage and evidence for repair.

Renal biopsy can be performed "blindly", using ultrasound guidance, via a laparotomy or via laparoscopy. Risks associated with biopsy include bleeding as uremic patients have abnormal platelet function, and hypovolemia if the animal is sedated or anesthetized for biopsy. The risks versus benefits of biopsy must be weighed carefully.

A fine needle aspirate performed in an awake animal can sometimes yield information such as the presence of oxalate crystals, without the need to perform a biopsy.

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Conservative therapy of the ARF patient: Depending upon the degree of renal damage, the kidneys may repair themselves. The goal of treatment is to sustain life while the pathologic process in the kidneys heals itself. Management of the ARF patient is divided into 2 phases; immediate care when you first see the patient and maintenance encompassing both the oliguric and polyuric phases. Immediate care includes:

• identify if possible, and eliminate the inciting cause
• correct fluid deficits (dehydration) in an attempt to reestablish adequate renal perfusion

Initially the patient must be rehydrated and the amount of urine produced evaluated in response to fluid administration.
KEEP WRITTEN RECORDS OF ALL FLUID INPUT AND OUTPUT.

Isotonic saline or a polyionic solution such as LRS should be used for rehydration and the fluid deficit replaced over 2-6 hours at a rate of 10-20 ml/kg/hr or faster if the animal is hypovolemic. Avoid K+ containing fluids (such as LRS) if urine output is diminished, unknown or if K+ is increased.

A fluid pump is useful to deliver large volumes of fluid rapidly.

Failure to induce urine production of at least 1/2 ml/lb/hour (1 ml/kg/hr) indicates either that fluid replacement is inadequate or the presence of intrinsic renal failure. The patient must be closely monitored for signs of fluid overload. 

Monitoring may include:

• central venous pressure
• PCV/TP
• blood pressure
• auscultation
• pulse quality
• urine volume

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Diuretics may be administered if after fluid replacement urine production is inadequate. The value of diuretics in intrinsic renal failure is questionable but as a single dose of a diuretic carries minimal risk, diuretics are frequently tried in oliguric patients. Diuretics which may be used include:

• furosemide (lasix)
• mannitol
• hypertonic dextrose

Dextrose and mannitol are osmotic diuretics, drawing water from cells into extracellular spaces. Both can cause vascular overload if diuresis does not occur. Do not administer osmotic diuretics if the patient already shows signs of fluid overload. Do not repeat osmotic diuretics if diuresis fails to occur. If diuresis occurs, mannitol can be repeated every 4-6 hours for 24 hours. If urine output increases in response to hypertonic dextrose, it can be continued for 1-2 days. Divide the dextrose dose into several portions and alternate with 2-3 cycles of 3-5% body weight LRS or normal saline to maintain urine output. Furosemide (lasix) is the diuretic of choice if the patient is already showing signs of fluid overload.

Dopamine causes selective renal arterial vasodilatation when administered at 2-5 ug/kg/min. Dopamine has a duration of action of a few minutes so it is delivered as a constant drip in 5% dextrose. Dopamine potentiates the effects of furosemide. Dopamine should not be used in conjunction with metoclopramide as their actions antagonize one another. It has recently been demonstrated that cats do not have renal dopamine receptors.

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Hyperkalemia is life threatening due to negative effects on myocardial cells. About 90% of body potassium is located within cells. As cells die in response to normal catabolic processes, intracellular potassium is released into extracellular fluid. Uremia is a state of accelerated catabolism resulting in a greater rate of cellular breakdown and release of intracellular potassium into blood. With impaired renal function potassium cannot be excreted and serum levels rise rapidly. The immediate management of hyperkalemia is based on antagonizing its cardiotoxic effects or by driving potassium back into cells in order to "buy" time until potassium elimination through urine or feces can be increased.

There are 3 intravenous treatments which can have immediate impact on the negative cardiac effects of potassium:

• sodium bicarbonate
• glucose (0.5 g/kg) with or without regular insulin
• calcium gluconate

Sodium bicarbonate combines with hydrogen ions in ECF. This creates a gradient for additional hydrogen ions to move out of cells, into ECF. As hydrogen ions move out of cells, potassium ions move into the cells.

As glucose moves into cells under the influence of insulin, potassium "tags" along into the cells. Glucose can be administered without insulin, depending upon endogenous insulin release from the pancreas or regular insulin can be administered with glucose. Regular insulin (crystalline) is very soluble and readily available. Do not administer insulin without administrating glucose or hypoglycemia will result.

Calcium counteracts the effects of hyperkalemia on the cardiac conduction system by re establishing the normal resting membrane potential of  -90 MV.  Calcium should be administered slowly over 5-10 minutes with electrocardiographic monitoring as calcium itself can be cardiotoxic. Calcium chloride can be used instead of calcium gluconate but  use ~1/10 the dose.

All 3 treatments have rapid effect but are of short duration lasting about 30-60 minutes. They can be repeated.

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Infections are common complications of ARF. Infection aggravates the catabolic state of the uremic patient resulting in a faster rate of protein breakdown and generation of nitrogen containing wastes and potassium.  Indwelling intravenous and urinary catheters used in the management of ARF patients are convenient avenues for infection. Strict attention to aseptic technique in catheter placement and management is essential. The benefits of catheters must be weighed against risks.

If an infection develops care must be taken in selecting antibiotics that are not nephrotoxic. If an antibiotic is eliminated from the body by the kidneys the dose may need to be altered to prevent accumulation of the antibiotic. The package insert for the drug is a good source of information regarding the need to alter the dose in patients with impaired renal function.

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Once the immediately life threatening consequences of ARF are addressed, it becomes a "waiting game" to maintain the animal until it can be determined whether renal function can be re established.

Maintenance includes:

• maintaining normal hydration
• maintaining normal potassium concentration
• acid- base balance
• providing nutrition
• controlling vomiting and hemorrhagic gastritis

Maintaining normal hydration: During the oliguric phase of ARF one of the most serious potential complications is iatrogenic fluid overload. After the initial correction of dehydration, fluid therapy consists of replacing ongoing losses including:

• insensible loss from skin and respiratory tract (approximately 10-12 ml/lb/day (hypotonic))
• urinary loss (estimated or measured - isotonic)
• losses from vomiting and diarrhea (estimated or measured - isotonic)

Careful records need to be kept of fluid intake, administration and losses.

The patient should be monitored frequently for signs of overhydration or dehydration by looking at:

• packed cell volume and total protein
• central venous pressure (CVP)
• blood pressure
• skin turgor
• body weight. An anorexic patient should lose 0.1 to 0.3 kg / 1000 calories required per day. Once this loss is considered any gain or loss of 1 kg body weight should be regarded as an excess or deficit of 1 liter of fluid.

Daily fluid administration should be divided rather than all at once to allow for easier correction of over or under assessment of fluid balance. As the patient enters the polyuric phase of ARF, exogenous fluid administration must be increased to prevent hypovolemia.

Sodium and potassium losses during the polyuric phase of ARF may be substantial and must be replaced. If it is necessary to administer potassium it should be done slowly, no faster than 0.5 mEq/kg/hr.

During the oliguric phase, hyperkalemia must be prevented. Sodium polystyrene sulphonate (kayexylate) is an ion exchange resin which exchanges sodium for potassium in the intestinal tract resulting in removal of potassium from the body. The exchange resin is administered orally at 2 g/kg in 3 divided doses. It can also be given as a high enema if the animal is vomiting and cannot take oral medications. If the exchange resin is unsuccessful in controlling hyperkalemia, dialysis is necessary.

Acid Base status: Most ARF patients are acidotic. Bicarbonate is indicated to reestablish acid-base balance if blood pH < 7.2. The following formula can be used to determine the amount of bicarbonate to administer.

Body weight (kg) x 0.3 x base deficit = bicarbonate dose in mEq

A similar formula using (0.6 x base deficit) assumes that the bicarbonate will be immediately distributed through total body water which actually requires about 24 hours. Using a more conservative estimate to calculate bicarbonate dose (0.3 x base deficit) is often sufficient to improve the patient's acid base status to a point where the body's own buffer systems will re establish a closer to normal, acid -base status.

Example: (10 kg canine)

pH = 7.20
pO₂ = 88 mmHg
pCO₂ = 31 mmHg
HCO₃ = 11 mEq/L
Base excess (deficit) = ^-15

10 kg x 0.3 x -15 = 45 mEq of bicarbonate

To be even more conservative, administer 1/2 the calculated dose immediately and the other 1/2 over 12- 24 hours. The goal is to "add to" the body's own buffering systems, not to rapidly change acid-base status.  Rapid correction of acidosis can result in a decrease in ionized calcium by increasing the amount of calcium bound to proteins and may precipitate hypocalcemic tetany. Rapid correction of acidosis can also cause neurologic dysfunction through the development of paradoxical CSF acidosis.

If it is not possible to measure blood gas values, the degree of acidosis can be estimated based on the degree of uremia:

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Nutrition: To decrease the level of azotemia, the rate of protein catabolism should be decreased. Glucose has a sparing effect on protein catabolism in the fasting individual. If the patient can take food orally, diets should be comprised of high caloric density fats, carbohydrates and small amounts of high biologic value protein. The fluid content of the diet needs to be considered when calculating fluid intake. Anorexia and vomiting frequently preclude oral alimentation. Total parenteral nutrition (TPN) solutions may be administered IV.  TPN solutions contain an energy source, usually 30-50% glucose, and protein hydrolysate to provide essential amino acids. TPN solutions which contain hypertonic dextrose are irritating and must be administered in a large vein such as the jugular vein. Also see critical notes about PPN (partial parenteral nutrition).

Hemorrhagic gastritis

Gastrin levels in the blood are elevated in ARF due to reduced clearance. Gastrin directly stimulates H₂ receptors on parietal cells or stimulates mast cells to release histamine which stimulates parietal cell H₂ receptors with the result being HCL liberation by the parietal cell. Parietal cells also have acetylcholine receptors on their surface. Increased gastric acidity plus abnormal platelet function causes mucosal irritation and hemorrhage.

The administration of an H₂ blocker (cimetidine = tagamet, ranitidine = zantac, famotadine = pepsid) reduces the severity of hemorrhagic gastritis in uremic patients.

Anti emetics may also be used to control vomiting including metoclopramide, dolesatron, trimethobenzamide (Tigan), chlorpromazine or ondansetron. The kidneys excrete metoclopramide and the dose should be decreased 50% in patients with severe renal disease.

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Drug elimination: The kidneys provide the major route of elimination for many pharmacologic agents so avoid the use of any unnecessary drugs.  If drugs are used which are renally excreted, after the initial loading dose is administered either the drug dose or dose interval must be altered to prevent accumulation of the drug and subsequent intoxication. The drug package insert is a good source of information regarding the use of the drug in patients with impaired renal function. 

Prognosis: The prognosis for most ARF patients is poor. These patients are usually very ill, unstable and difficult to manage. ARF patients that are polyuric are much easier to manage and therefore have a better prognosis than the oliguric patient. The presence of oliguria indicates a more severe renal insult. If conservative measures are not successful in the treatment of an ARF patient dialysis should be considered.