Acute kidney injury (AKI) refers to the sudden onset of renal damage, with or without recognizable loss of function. It reflects a wide range of parenchymal damage, from mild, hardly detectable nephron injury to severe, life-threatening failure of the kidneys to meet the excretory, metabolic, and endocrine needs of the body.1
The major aims of the diagnosis will include the recognition of AKI, the grading of its severity, the search for its underlying etiology, and a detailed characterization of its clinical manifestations. This thorough workup is essential for the design of an adequate therapeutic plan and for the successful management of this severe organ failure with polysystemic manifestations.
Recognition of AKI
Most small animals with AKI are presented at a late stage with overt uremic manifestations reflecting the excretory failure and the loss of homeostatic control over essential body functions including blood pressure, fluid, electrolyte and acid-base balance. At this stage, the resulting accumulation of metabolic toxins (urea, creatinine, and phosphorus) and the fluid, electrolyte, and acid-base disorders dominate the clinical picture and rarely represent a major diagnostic challenge, although pre- and post-renal causes still need to be methodically excluded. The mandatory urinalysis indicates an inappropriate lack of urine concentration in light of azotemia, and diagnostic imaging procedures with ultrasonography and abdominal radiographs exclude urinary tract obstruction or rupture.
Especially in hospitalized animals or those with severe systemic diseases, the recognition may be more difficult and requires a high clinical suspicion in all patients at risk. Evidence of early stage of milder injury includes inappropriate urine dilution, renal glucosuria, and evidence of tubular damage in the urine sediment (cylindruria). Tubular injury may also be evidenced by measuring urinary enzymes (GGT, NAG) or using some of the more modern biomarkers (NGAL, KIM), although the latter still need additional clinical validation.2 Even though the excretory failure may not be obvious and remains unnoticed, changes in serum creatinine as small as 0.3 mg/dl are increasingly recognized as highly relevant, indicating a significant complication in the clinical course of another disease and worsening its prognosis. Such increases always warrant additional investigations into the fluid balance and the possibility of nephrotoxic injury from prescribed drugs.
An important step in the identification of AKI is its accurate differentiation from chronic kidney disease (CKD), even in animals with obvious acute clinical manifestations. Subclinical CKD may have progressed unnoticed for a time and manifest suddenly as an acute uremic episode. Details from the history, physical exam findings, and laboratory parameters are essential in this important diagnostic step. Renal ultrasonography further helps to recognize signs of CKD (e.g., irregular small kidneys with loss of corticomedullary distinction) or of AKI (e.g., perirenal effusion, enlarged kidney, elevated resistivity index). Kidneys without signs of either chronic or acute disease are most often indicative of AKI from a noninflammatory cause, but they may also be seen in chronic glomerular disease or amyloidosis.
Grading of AKI3
In order to standardize the definition of the disease severity and to avoid the use of the subjective concepts of renal insufficiency or failure, the IRIS group has recently recommended a grading system for AKI in dogs and cats. This 5-grade system of disease severity is based on the serum creatinine concentration, similarly to the CKD staging system. However, it is by definition not describing a steady-state condition, the renal function and the serum creatinine varying continuously in AKI. The AKI grade barely provides an estimate of the severity of the disease at a defined time point, with all the limitations associated to creatinine and the variability of the disease or its underlying etiology. It is also important to remember that the serum creatinine concentration is the delayed indicator of GFR that shows only 1–2 days later a worsening or an improvement of renal function. Therefore, the AKI grade should always be interpreted in light of the whole clinical picture, and no decision should be taken solely on the basis of this "objective number". Grade I AKI refers to non-azotemic AKI with a serum creatinine < 1.6 mg/dl (< 140 µmol/l); grade II, mild AKI with creatinine 1.7–2.5 mg/dl (141–220 µmol/l); grade III, moderate AKI with creatinine 2.6–5 mg/dl (221–439 µmol/l); grade IV, severe AKI with creatinine 5.1–10 mg/dl (440–880 µmol/l); and grade V, very severe AKI with creatinine > 10 mg/dl (> 880 µmol/l).
Identification of the Underlying Etiology
Aside from the level of care that can be provided, the cause of AKI and the type of injury are the most important prognostic factors for affected dogs and cats, and their identification is therefore essential for an accurate prognosis. Ischemic nephrosis typically carries a better prognosis, and if the animal can be maintained alive for 1–2 weeks, the chance of recovery is "reasonable". The prognosis of toxic nephroses is very variable and depends on the toxin and its dose. Whereas aminoglycoside and amphotericin toxicities carry a fair prognosis (as long as discontinued early enough), only 15% of dogs recover from ethylene glycol toxicity after several months of renal replacement therapy. Grape toxicity in the dog and lily toxicity in the cat have roughly 50% recovery rates, but often with residual renal damage and CKD. AKI from infectious causes are usually favorable, although the resulting severe damage can occasionally preclude any recovery, as observed in some cases of pyelonephritis. Canine leptospirosis usually has a good probability of renal recovery (80–90%), but its global prognosis depends predominantly on non-renal manifestations including liver and pulmonary involvement.4
Clinical Characterization of AKI
With a wide spectrum of clinical manifestations, AKI can potentially affect most organs and body systems. A major part of the diagnostic workup lies in the screening and the characterization of these manifestations in order to design a suitable therapeutic plan. Every animal with AKI should be evaluated regularly (e.g., once or twice a day) for fluid, electrolyte, and acid-base disorders, hyperphosphatemia, systemic hypertension, gastrointestinal manifestations, anemia, respiratory complications, nutritional status, and pain. Furthermore, the dosages of the prescribed medications and their potential interactions should be reviewed daily to avoid additional secondary iatrogenic complications.
The management of the animal with AKI can be divided into the treatment of the underlying cause and the symptomatic treatment aimed at alleviating or correcting the identified clinical problems. Appropriate fluid therapy is probably the cornerstone of the medical therapy of AKI, and it aims at restoring hydration and normovolemia. The temptation to exaggerate fluid therapy in order to force diuresis must absolutely be avoided, even and especially in oligo-anuric animals, since they cannot respond with increased urine production and they will invariably develop generalized edema and associated complications. The resulting iatrogenic worsening of organ functions contributes largely to the multi-organ manifestations of AKI. Once fluid balance has been restored, the best fluid therapy is the one that just maintains the animal's hydration and normovolemia as physiological as possible, even if that means without any additional fluid administration.
Diuretics, including furosemide and mannitol, can be used to increase urine output in a volume-replete animal. However, although this therapy may sometimes succeed to convert oligo-anuric animals to a non-oliguric state and thus facilitate their therapy, this is not associated with improved outcome.
One of the main limits of medical therapy for oliguric AKI is the development of hyperkalemia. Treatment of hyperkalemia with sodium bicarbonate, dextrose, or insulin-dextrose injections can correct hyperkalemia temporarily, but a real effect on outcome will depend on at least partial recovery of kidney function. Correction of metabolic acidosis with sodium bicarbonate, symptomatic treatment of gastrointestinal disturbances, and prudent treatment of systemic hypertension further contribute to improve the comfort of the affected animal.5 Altogether, however, medical therapy has serious limitations and is unable to accelerate renal recovery and, as clinicians, we are limited at waiting for a "spontaneous" recovery. Our ability to use the full recovery potential in affected animals is therefore dependent on our capability to maintain them alive for extended time periods. The use of renal replacement therapy as intermittent hemodialysis or continuous renal replacement therapy is thus our only possibility to improve outcome significantly past the initial stabilization. Since these therapies have become a widely used reality for small animals, they should be considered for all forms of severe AKI when the suspected etiology suggests a possible recovery.
1. Cowgill LD, Langston C. Acute kidney insufficiency. In: Bartges J, Polzin DJ, eds. Nephrology and Urology of Small Animals. Wiley & Sons; 2011.
2. Steinbach S, et al. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with acute kidney injury or chronic kidney disease. J Vet Intern Med. 2014;28(2):264–269.
3. IRIS. Grading of AKI. 2013. www.iris-kidney.com
4. Major A, et al. Increasing incidence of canine leptospirosis in Switzerland. Int J Environ Res Public Health. 2014;11:7242–7260.
5. Geigy CA, et al. Occurrence of systemic hypertension in dogs with acute kidney injury and treatment with amlodipine besylate. J Small Anim Pract. 2011;52(7):340–346.