Staging and the Conventional and Advanced Management of Acute Kidney Injury
World Small Animal Veterinary Association World Congress Proceedings, 2011
Larry D. Cowgill, DVM, PhD, DACVIM
School of Veterinary Medicine, University of California, Davis and UC Veterinary Medical Center, San Diego, CA, USA

Precise definitions for AKI have not been established in veterinary medicine. Recently, to emphasize the concept that AKI represents a continuum of renal injury, two staging schemes (RIFLE and AKIN) have been proposed for human patients to stratify the extent and duration of renal injury and to predict outcomes. There is considerable overlap between both system, and criteria for each staging category are based ostensibly on insensitive markers of renal injury including abrupt changes in GFR, serum creatinine, urine output, and duration of signs. Unfortunately, the criteria which define these staging schemes in humans rarely are applicable in animal patients with naturally occurring disease in which the abruptness of the disease and the magnitude of changes in GFR, azotemia, or urine production are rarely known or quantitated.

Progressive (and often subtle) azotemia is the hallmark of AKI, but is observed inconsistently in animals because the azotemia has not developed or is fully established at the time they are presented for evaluation or because serial observations are not performed. Despite its insensitivity and limitations as a biomarker of kidney injury, serum creatinine currently stands as the best, most time-tested, and most familiar marker of AKI. The IRIS staging system for chronic kidney disease (CKD) was developed to promote more uniform characterization and recognition of CKD in animals with the goal to better understand its pathophysiology and to facilitate its evaluation and rational management. It seems appropriate to classify and stratify the severity of AKI in dogs and cat similarly to facilitate its early recognition, biologic behavior, and responses to management. Unlike the IRIS staging for CKD, the staging of AKI implies the disease is neither stable nor at steady-state. The "stage" represents a moment in the course of the disease and is predicted to change as the condition worsens or improves or transitions to CKD. The following table outlines a proposed IRIS staging scheme for AKI in dogs and cats based on serum creatinine, urine formation, and requirement for renal replacement therapy. It is intended to facilitate classification, functional stratification, and therapeutic decision making.

Stage I defines animals with historical, clinical, laboratory (biomarker, glucosuria, cylindruria, inflammatory sediment, microalbuminuria, etc.), or imaging evidence of AKI who are non azotemic and/or whose clinical presentation is readily fluid volume responsive. Stage I also include animals with progressive (hourly or daily) increases in serum creatinine within the non azotemic range. A presumptive guideline to predict AKI is a 0.3 mg/dl (26 µmol/l) increase in serum creatinine within a 48 hour interval.

Stage II defines animals with documented acute kidney injury characterized by mild azotemia in addition to other historical, biochemical, or anatomic characteristics of AKI. This would include animals that have an increase from their baseline serum creatinine associated with pre-existing CKD.

Stages III, IV, and V define animals with documented AKI and progressively greater degrees of parenchymal damage and functional failure (uremia).

Each stage of AKI is substaged further on the basis of current urine production as oliguric or anuric or nonoliguric and the requirement for renal replacement therapy. Substaging is predicated on the importance of these parameters to the pathological or functional contributions to the kidney injury, influence on the clinical presentation and therapeutic options, need to correct life-threatening iatrogenic or clinical consequences of AKI (severe azotemia, hyperkalemia, acid-base disorders, overhydration, oliguria or anuria, elimination of nephrotoxins),and outcomes. The requirement for renal replacement therapy could occur at any of the proposed stages.

AKI stage*

Serum creatinine (mg/dl)

Clinical description

Stage I

< 1.6

a Non azotemic AKI or volume-responsive AKI
b Historical, clinical, laboratory, or imaging evidence of renal injury
c Progressive non azotemic increase in serum creatinine; ≥0.3 mg/dl within 48 hours

Stage II


Mild AKI: Historical, clinical, laboratory, or imaging evidence of AKI and mild static or progressive azotemia

Stage III


Moderate to severe AKI: Documented AKI and increasing severities of azotemia and functional renal failure

Stage IV

- 10.0

Stage V

> 10.0

*Each stage of AKI is further substaged on the basis of current urine production as oligoanuric (O) or non oliguric (NO) and on the requirement for renal replacement therapy (RRT); (see text)

Management of Established Acute Kidney Injury

Management strategies for existing AKI involve goal-directed supportive therapy specific to the life-threatening and morbid consequences of acute uremia. In circumstances where the etiology persists, every effort should be made to eliminate continued exposure. The goals of conventional therapy are to correct existing and ongoing hemodynamic deficiencies and alleviate abnormalities in body fluid volume and composition. Concurrent goals are to promote urine formation and correct biochemical abnormalities and manifestations of uremia until repair of the renal damage has occurred. Animals with IRIS AKI Stages I and II may regain adequate renal function within 2 to 5 days, forestalling life-threatening azotemia and electrolyte disorders and need only short-term support. Those with higher IRIS Stages of AKI may require weeks of supportive care before the onset of renal repair. Animals with severe kidney failure, IRIS AKI Stage IV or V, may die within 5 to 10 days despite appropriate conventional management unless supported with renal replacement therapy for an indefinite time. This disparity between the window of survival with conventional supportive therapy and the extended time required to repair severe acute renal injury underlies, in part, the poor prognosis and outcomes associated with severe stages of AKI.

Alterations in Systemic Hemodynamics and Body Fluid Volume

Deficiencies in body fluid volume are classic causes and consequences of AKI, and fluid therapy remains the foundation of medical management. Replacement fluids should mimic the composition of fluid losses and be formulated to restore depleted fluid compartments within the first 2 to 4 hours of presentation. Priority is given to restoration of intravascular and interstitial volume, normalization of arterial blood pressure and renal perfusion, and balancing ongoing fluid losses. Additional fluid may be administered cautiously if the initially estimated deficit was insufficient to restore hydration or promote normotension and urine formation. The onset or an increase in urine production of greater than 0.5 ml/kg/hr with fluid volume replacement predicts a significant volume-responsive (prerenal) contribution to the oliguria and azotemia. Failure to induce a significant diuresis after volume replacement indicates the parenchymal damage is severe and volume-unresponsive. Maintenance fluids must reflect both the volume of all ongoing outputs as well as their composition. Failure to replace the obligatory free water losses is a common therapeutic error.

All fluids must be administered cautiously to oliguric and anuric animals. Hypervolemia is a common complication of aggressive fluid administration in animals with IRIS AKI Stage III–V or inattentive monitoring of fluid balance. If initial administration of the estimated fluid deficit and additional mild volume expansion fail to induce an effective diuresis within the first 6 to 12 hours of therapy, it must be presumed the animal has volume-unresponsive AKI. Further fluid loading will not be beneficial and predisposes life-threatening overhydration.

Inadequate Urine Production

The conversion of anuric or oliguric stages of AKI to a non-oliguric state is been an important early goal for the medical management of AKI. Induction of an effective diuresis has potential to improve fluid and electrolyte imbalances, promote clearance of endogenous and exogenous toxins, and facilitate delivery of adjunctive therapies. Pharmacologic treatments to promote a diuresis continue to dominate the practice pattern for acute oliguric renal failure in animal patients. Their risks and contraindications are considered to be small, and they often are justified for management of other complications attending the AKI. Their use should never supplant judicious fluid and hemodynamic support, nor should they be provided as a rescue for excessive fluid administration.

Hypertonic mannitol (an osmotic diuretic) is used commonly for the prevention and management of oliguric forms of AKI in animals. In most clinical settings, mannitol is reported to have minimal therapeutic efficacy in the prevention or outcome of AKI. It also imposes potential adverse effects including fluid overload, hyperosmolality, increased renal oxygen consumption, volume depletion and hypernatremia. However, despite the absence of evidence-based justification, it has gained empirical recommendation when fluid therapy alone has failed to promote urine formation.

Loop diuretics (e.g., furosemide) are used nearly universally as a practice pattern in oliguric or anuric AKI without established evidence of their efficacy or benefit to improve outcomes. Nevertheless, furosemide has potential for adverse effects including: decrease effective blood volume and cardiac output, activation of the renin-angiotensin system, disruption of tubuloglomerular feedback, compromise renal perfusion and oxygen balance in the medulla, and promote additional injury. Current experience and evidence would challenge the rational use of furosemide or other loop diuretic to prevent or benefit the course of AKI or to improve outcomes for animals with oliguric forms of the disease.

Dopamine is a catecholamine with multiple dose-dependent actions in the kidney. Its major physiologic action is to alter renal vascular resistance, renal blood flow and distribution, and GFR and modulate sodium and water reabsorption along the nephron. The use of dopaminergic drugs has no clinical or experimental foundation and imposes potential risk. At a range of doses, dopamine can cause renal vasoconstriction, ventricular tachyarrhythmias, medullary hypoxia, and potential for myocardial, intestinal and renal ischemia. Fenoldopam can promote decreased systemic vascular resistance and hypotension. The narrow therapeutic margin and overlap in dosage effects, variable and uncertain elimination kinetics in AKI, and the variable sensitivity and binding affinities for catecholamines in uremic animals make their use risky.

The nutritional requirements of AKI are generally ignored but are fundamental to recovery and good outcomes. The goals of nutritional therapy are to meet the energy and nutrient requirements of the animal, correct protein-energy wasting, alleviate the azotemia, minimize disturbances in fluid, electrolyte, vitamin, mineral, and acid base balance, and aid renal regeneration and repair. Enteral tube feeding is the preferred route of nutritional support and is recommended in animals whose gastrointestinal health will tolerate feeding but fail to meet nutritional goals voluntarily. Esophageal feeding tubes are the most effective and safe enteral feeding device and generally are preferred over nasoesophageal or percutaneous gastrostomy tubes. Esophageal feeding tubes can be placed quickly under short general anesthesia and facilitate either short-term or indefinite feeding for dogs or cats with AKI.


Speaker Information
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Larry D. Cowgill, DVM, PhD, DACVIM
School of Veterinary Medicine
University of California-Davis
Davis, CA, USA

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