Current Concepts in the Management of Acute Kidney Injury
ACVIM 2008
Cathy Langston, DVM, DACVIM (SAIM)
New York, NY, USA

New Concepts in Classification

In the veterinary literature, acute renal failure is generally defined as an abrupt decrease in renal function leading to retention of nitrogenous waste. Specifically, elevation of creatinine above the upper limit of the reference range, in the absence of clinical signs of chronicity, is the definition used by the few veterinary reports of ARF.1-3 While this definition has a high specificity for ARF, it lacks sensitivity. An increase of > 0.3 mg/dl or > 50% increase from baseline creatinine are definitions of ARF that detect more subtle renal injury. Because creatinine is poorly correlated with glomerular filtration rate at low levels of dysfunction, these changes in creatinine may represent dramatic decreases in renal function but still remain within the reference range for the laboratory. A new classification scheme proposed for humans has shown that even low levels of renal dysfunction that do not cause a classic "failure" state negatively impact prognosis, and the term acute kidney injury (AKI) is replacing acute renal failure.4 The classification scheme has 5 levels, abbreviated RIFLE, defined by glomerular filtration rate (GFR) or by urine output (UO). For people, the prognosis worsens at each step in the scheme. This scheme has not been evaluated in veterinary medicine.

 Risk: Increased sCr x 1.5 or GFR decrease > 25%; urine output < 0.5 ml/kg/h x 6 hr

 Injury: Increased sCr x 2 or GFR decrease > 50%; urine output < 0.5 ml/kg/h x 12 hr

 Failure: Increased sCr x 3 or > 4 mg/dl or acute rise > 0.5 mg/dl or GFR decrease > 75%; UO < 0.3 ml/kg/h x 24 hr or anuria x 12 hr

 Loss: Persistent ARF = complete loss of kidney function > 4 weeks

 End-Stage Kidney Disease: Present > 3 months

Pathophysiology of AKI

Four phases of ARF have been described. The initiation phase begins with the ischemic or nephrotoxic insult, and continues until there is a definable change in renal function, such as decreased urine output or an increased BUN or creatinine. The next stage is the extension phase, during which continued hypoxia and an inflammatory response propagate the damage to the kidney. The third phase is the maintenance phase, which generally lasts from 1 to 3 weeks, although there is great variability in the duration. Urine output during this phase may be increased or decreased. The fourth phase is the recovery phase. In oliguric patients, this phase is heralded by an increase in urine output that may or may not be accompanied by a decrease in urine sodium. During this period, extreme sodium losses leading to volume depletion can occur which may delay or interrupt renal recovery, if care is not taken to replace sodium and water.


Many toxins, infections, and insults can lead to AKI, and lists of causative agents can be found in most veterinary textbooks. Several emerging causes of AKI deserve comment. The incidence of ureterolithiasis in cats seems to be increasing dramatically over the past decade. These cats commonly present with an acute uremic crisis with evidence of pre-existing renal disease (i.e., one small irregular kidney and an acutely obstructed contralateral kidney). Removal of the ureteroliths after medical stabilization (generally surgically, occasionally via lithotripsy) can yield an excellent outcome, with a 2 year survival rate of 88% after surgery.5 Grapes and raisins in dogs and lily ingestion in cats can cause AKI. In early 2007, pet food contaminated with melamine and cyanuric acid caused both acute and chronic kidney dysfunction in dogs and cats. Over the past several years, the incidence of acquired Fanconi's syndrome has anecdotally increased dramatically. There is suspicion of food-borne contaminants as the cause of this syndrome, but no evidence is available as yet.

Prevention of AKI

Volume depletion is a significant risk factor for developing AKI.6,7 Nephrotoxic drugs or drug combinations were present in 70% of dogs developing AKI in the hospital.2 Other risk factors included age, chronic heart disease, preexisting renal disease, neoplasia, fever, and anesthesia.2

Prevention of "community-acquired" AKI involves a markedly different approach than preventing AKI from occurring in hospitalized patients. The majority of those efforts involve client education about potential toxins, vaccination for endemic diseases (esp. Leptospirosis), and potentially, screening for renal diseases that may contribute to an acute renal crisis (i.e., nephro-ureterolithiasis). Once a patient is in the hospital, careful attention to avoiding identified risk factors seems prudent, particularly in patients with risk factors that are not modifiable, such as age or preexisting renal disease. In patients receiving potentially damaging treatments for which there is no suitable alternative (i.e., aminoglycoside treatment for resistant infection), vigilance to avoid other risk factors may be beneficial. Particular attention should be paid to volume status, blood pressure, and perfusion.

Monitoring Patients with AKI or at Risk for AKI

Patients at risk for AKI include those with the risk factors listed above, and patients at risk for hemodynamic instability, which would likely include many patients in the intensive care unit. Physical examination provides a wealth of information about the patient. Diminished skin turgor may indicate dehydration (5% of body weight or greater), recent weight loss, or loss of elasticity due to aging. Dry mucous membranes or sunken eyes also suggest dehydration, whereas chemosis, serous nasal discharge, intermandibular or peripheral edema suggest volume overload. However, patients with a low colloid osmotic pressure (i.e., hypoalbuminemia) or alterations in vascular permeability may appear interstitially overhydrated based on skin turgor assessment, yet have intravascular volume depletion. Pulmonary edema from volume overload may manifest as increased breath sounds or crackles that are heard upon thoracic auscultation. The heart rate and rhythm may provide an indication of cardiovascular status. Pulse pressure does not directly reflect the mean arterial pressure, but may provide an estimate of circulatory status. Abdominal palpation can enable the clinician to detect renomegaly, presence of renal pain, and bladder size. Although a sick animal may lose up to 0.5-1% body weight per day due to anorexia, changes in body weight during hospitalization primarily reflect changes in body water.

Blood pressure monitoring is very important in ICU patients as both hypertension and hypotension are detrimental to renal function. Indirect methods, such as oscillometric methods or Doppler technology, are most commonly used. Although normal kidneys autoregulate blood flow between blood pressures from 80 to 160 mmHg, renal blood flow in failing kidneys is more linearly related to systemic blood pressure. A systolic blood pressure below 80 mmHg is insufficient for adequate renal perfusion and should be immediately addressed to avoid further renal damage.

Central venous pressure (CVP) monitoring provides information about the intravascular filling and is not technically difficult to perform. Normal values for CVP are 0-5 cm H2O. Cardiac output monitoring requires a pulmonary artery catheter and advanced equipment and is therefore rarely used in routine veterinary practice. A continuous electrocardiogram (ECG) can also provide important information pertinent to the development of AKI (i.e., arrhythmias leading to a significant decrease in cardiac output) or in established renal failure (i.e., conduction disturbances due to hyperkalemia). Echocardiography may occasionally be used to assess myocardial performance and volume status.

Trends in hematocrit and total solids may reflect changes in plasma volume, although other factors can impact the absolute values. Venous blood gas analysis is useful for determining acid-base status in patients with ARF. Electrolyte abnormalities are both a risk factor and an effect of AKI, and are frequently present in ICU patients. Therefore, regular electrolyte monitoring is advised. Blood urea nitrogen and creatinine concentrations are easily measured, but are insensitive markers of early renal dysfunction, since the GFR must be less than 75% of normal for these values to be elevated. As mentioned above, even minor increases in creatinine may signify acute kidney injury.

The importance of monitoring urine output and composition cannot be overemphasized. Urine volume can be precisely measured by placement of an indwelling urinary catheter. Collection of voided urine or determining the weight of wet litter or bedding (1 gm = 1 ml) is a less accurate method, but may provide useful information.

Treatment of AKI

Treatment is most successful during the induction and extension phases, and success diminishes once the maintenance or recovery phase have been reached. Therefore, prompt recognition and institution of specific therapy are important.

Fluid Therapy

The most important aspect of treatment of AKI is optimal fluid management. Some patients may present in hypovolemic shock, which is manifest as dull mentation, hypotension, poor perfusion of the periphery (cold extremities, pale/grey mucous membranes with slow capillary refill time), hypothermia, or tachycardia. Immediate correction of shock is necessary to prevent further and irreversible organ damage. The standard dose of crystalloids is 60-90 ml/kg for dogs and 45-60 ml/kg for cats, of which ¼ is given over 5 to 15 minutes. If hemodynamic parameters do not improve sufficiently with the first ¼ dose, a second dose should be given. Resuscitation efforts are continued until the patient is hemodynamically sound. If the patient remains hypotensive and there are concerns about volume overload, central venous pressure monitoring may be helpful. A 10-15 ml/kg bolus of crystalloid or 3-5 ml/kg of colloid will not change the CVP in hypovolemic patients, but will transiently increase the CVP by 2-4 cm H2O in the euvolemic patient, and cause a rise of over 4 cm H2O in the hypervolemic patient.

For patients presenting with dehydration, the dehydration deficit is calculated as body weight (in kgs) x estimated % dehydration = fluid deficit in L. Because dehydration of less than 5% cannot be detected clinically, a 5% dehydration deficit is presumed in patients that appear normally hydrated. If a fluid bolus was used for resuscitation, that volume is subtracted from the dehydration deficit. The rate of replacing the dehydration deficit depends on the clinical situation. In patients with AKI, who have presumptively become dehydrated over a short period of time, rapid replacement is prudent. This restores renal perfusion to normal levels and may help prevent further damage to the kidneys. In situations where urine output may be diminished, rapid replacement of dehydration deficits allows the clinician to quickly determine if oliguria is an appropriate response to volume depletion or is a pathologic change from renal failure. In that setting, replacing the deficit in 2-4 hours is recommended. If there is potential compromise of diastolic function of the heart, a rapid fluid bolus may precipitate congestive heart failure, and a more gradual rehydration rate (i.e., over 12-24 hours) may be prudent.

The concept of maintenance fluid rate is based on average fluid losses from insensible (respiration) and sensible (urine output) sources. The most commonly quoted value is 66 ml/kg/day. Ignoring normal individual variation, the presumption with this value is that urine output is normal and there are no other sources of fluid loss, which is rarely the case in patients with renal failure. However, it makes a reasonable starting point for calculating fluid administration volumes. If accurate measurement of urine output and on-going losses is available, fluid therapy can be adjusted precisely using the "ins-and-outs" method. If these parameters are not measured, an estimate of the loss should be included in the fluid administration rate. In practical terms, after an initial fluid resuscitation if needed for shock, the volume of fluid to administer is calculated by adding average maintenance fluids (66 ml/kg/day) plus replacement of dehydration (over selected time frame) plus ongoing losses (estimated volume of polyuria, vomiting).

Because uremic toxins are retained in renal failure, administration of a volume of fluid exceeding "maintenance" can improve excretion of some uremic toxins in animals with the ability to increase urine output in response to a fluid challenge. The volume is varied based on clinical situation and clinician preferences, but generally ranges from 2.5-6% of body weight per day, in addition to maintenance fluid administration rate. In practical terms, twice the maintenance fluid rate is equivalent to a maintenance rate plus a 6% "push" for diuresis (60 ml/kg/day = 6% of body weight).

If the urine output varies substantially from normal, either oliguria (< 0.5 ml/kg/hr) or polyuria (> 2 ml/kg/hr), a fluid plan based on these assumptions may be inadequate. Animals with renal failure may have urine output in a "normal" range (0.5-2.0 ml/kg/hr), but if their kidneys are unable to alter the urine volume to excrete a fluid load, the patient has "relative oliguria." The ins-and-outs method of fluid administration is appropriate in these situations. It should only be used after rehydration is complete and is not appropriate if a patient is still dehydrated.

There are three components of volume calculations in the "Ins-and-Outs" method, consisting of 1) insensible loss (fluid lost via respiration and normal stool) = 22 ml/kg/day; 2) urine volume replacement calculated by actual measurement; and 3) on-going losses (i.e., vomiting, diarrhea, body cavity drainage) which are generally estimated.

An anuric patient should receive fluid administration to replace insensible loss only. If the patient is overhydrated, withhold the insensible loss. Overhydration in an anuric patient or inability to induce diuresis in an oliguric or anuric patient is an indication for dialysis.

Converting Oliguria to Nonoliguria

Although loop diuretics can increase urine flow, they do not increase GFR or improve outcome. A meta-analysis of diuretic uses suggests that people who respond with an increase in urine production have less severe renal failure with an intrinsically better outcome for recovery.8 In animals, loop diuretics may still play a role in management of oliguric AKI since dialysis is not universally available to address overhydration. In responsive patients, a continuous rate infusion (CRI) gives a more sustained diuresis with a lower cumulative dose compared to bolus infusion. Furosemide doses of 0.25 to 1 mg/kg/hr have been used.

Mannitol is an osmotic diuretic that has been used to induce diuresis, decrease cellular swelling, scavenge free radicals, and induce intra-renal prostaglandin production and vasodilation. No randomized studies have shown a better response with the use of mannitol and volume expansion than with volume expansion alone.9

Dopamine has been shown to make some oliguric human patients non-oliguric, but it does not increase GFR or improve outcome in people. Fenoldopam is a selective dopaminergic DA-1 receptor agonist, and as such, it selectively increases cortical and medullary blood flow, sodium excretion, and urine output while maintaining GFR in people. It does not have DA-2 or alpha or beta adrenergic activity, so it does not cause vasoconstriction, tachycardia, or arrhythmias as seen with dopamine.9 Although no studies have shown a benefit, studies with this drug in people are encouraging and larger clinical trials are needed.

Other Treatments

Atrial natriuretic peptide is not effective in treating AKI in human trials.9 Calcium channel blockers have been used in attempts to prevent or treat ARF.10 Growth factors enhance recovery after renal insult, and insulin-like growth factor, hepatocyte growth factor, and angiotensin type 1 receptor blockers are under investigation.

Dialysis is the treatment of choice for patients that fail to respond to medical management. The appropriate time to institute dialytic therapy has not clearly been established, although intractable hyperkalemia, life-threatening volume overload, or persistent uremic symptoms are uncontroversial. Early institution of dialysis may improve outcome compared to starting later in the course of the disease. Starting dialysis at a lower level of overhydration improves outcome in pediatric patients.11 The choice of extracorporeal renal replacement modality, whether intermittent (hemodialysis) or continuous (CRRT), has not been proven to affect outcome.12 Peritoneal dialysis is rarely used for ARF in critically ill people, but is more readily available for veterinary patients than extracorporeal renal replacement therapies.


The mortality rate of AKI is approximately 60% in dogs and 50% in cats.1-3 The etiology of AKI seems to impact mortality. Nephrotoxic causes have mortality rates of 60-80% in dogs and 50-60% in cats.1-3 Mortality rates of 15-30% in dogs and 0-40% in cats have been reported with infectious causes.1-3 In survivors, residual renal dysfunction is present in approximately half, but long-term survival is possible.1,3


1.  Vaden S, et al. JVIM 1997;11(2):58 ,

2.  Behrend E, et al. JAVMA 1996;208(4):537 ,

3.  Worwag S, et al. JAVMA 2008;232(5),

4.  Hoste, et al. Crit Care Med 2006;34(7):2016,

5.  Kyles A, et al. JAVMA 2005;226:937,

6.  Lane I, et al. Compendium 1994;16(1):15,

7.  Grauer G. Vet Forum 1999:46,

8.  Mehta R, et al. JAMA 2002;288(20):2547,

9.  Finn W. Acute Renal Failure, WB Saunders 2001, p 425,

10. Mathews K, et al. JVECC 2007;17(2):149,

11. Goldstein S, et al. Pediatrics 2001;107(6):1309,

12. Ronco C. Int J Artif Organs 2007;30(2):89

Speaker Information
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Catherine Langston, DVM, DACVIM (SAIM)
New York, NY

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