Acute Kidney Injury (AKI) refers to the sudden onset of renal parenchymal damage with or without recognizable loss of function.
Overview and Clinical Importance
Acute Kidney Injury (AKI) refers to the sudden onset of renal parenchymal damage with or without recognizable loss of function. AKI represents a spectrum ranging from mild, clinically inapparent nephron injury to severe, life-threatening failure of the kidneys to meet excretory, metabolic, and endocrine demands. The mortality rate remains high (45-60%) even with aggressive treatment, making early recognition and intervention critical for patient survival.
AKI differs fundamentally from chronic kidney disease (CKD) in its potential reversibility. While CKD represents irreversible structural damage, AKI may resolve completely with appropriate treatment if the underlying cause is addressed before permanent nephron loss occurs. However, surviving dogs may develop residual CKD, emphasizing the importance of long-term monitoring.
High-YieldOn the NAVLE, remember the key differentiating features between AKI and CKD: AKI presents with acute onset in a previously healthy animal, normal body condition, enlarged painful kidneys on palpation, and no history of PU/PD. CKD shows chronic weight loss, small irregular kidneys, and a history of progressive illness.
| Phase |
Characteristics and Clinical Significance |
| 1. Initiation |
Occurs during and immediately after insult. Pathologic damage is initiated but clinical signs may not be apparent. Biochemistry usually normal. Best time for intervention. |
| 2. Extension |
Continued ischemia, hypoxia, inflammation, and cellular injury. Leads to cellular apoptosis and necrosis. Laboratory abnormalities begin to appear. |
| 3. Maintenance |
Critical damage has occurred. Characterized by azotemia and uremia lasting days to weeks. Oliguria (less than 0.5 mL/kg/hr) or anuria may occur. Highest morbidity/mortality risk. |
| 4. Recovery |
Azotemia improves; renal tubules undergo repair. Marked polyuria may occur due to partial tubular function restoration and osmotic diuresis. Can take weeks to months. |
Pathophysiology of AKI
Four Phases of AKI
Understanding the phases of AKI is essential for appropriate timing of intervention and prognostication:
NAVLE TipRemember the phases as 'I-E-M-R' (Initiation, Extension, Maintenance, Recovery). The initiation and extension phases are the therapeutic window before irreversible damage occurs. By the maintenance phase, significant nephron loss has already occurred.
Cellular Mechanisms of Injury
The decrease in renal function is multifactorial:
- ATP Depletion: Ischemia causes rapid ATP degradation, leading to increased intracellular calcium, activation of proteases/phospholipases, and subsequent cellular damage
- Na+/K+-ATPase Dysfunction: Decreased activity alters intracellular concentration gradients, causing cell swelling and tubular obstruction
- Cytoskeletal Changes: Loss of brush border microvilli, redistribution of Na+/K+-ATPase to apical membrane, and tight junction disruption
- Inflammatory Response: Neutrophil activation, adhesion molecule expression, cytokine release, and capillary plugging all contribute to ongoing injury
| Category |
Common Causes |
Mechanism |
| Pre-renal |
Hypovolemia, dehydration; Decreased cardiac output; Systemic hypotension; Anesthesia without fluid support |
Decreased renal blood flow to structurally normal kidneys. Potentially reversible with fluid therapy. Can progress to intrinsic if prolonged. |
| Intrinsic Renal |
Nephrotoxins: Ethylene glycol, grapes/raisins, aminoglycosides, NSAIDs; Infectious: Leptospirosis, pyelonephritis |
Direct damage to nephrons. Most common AKI category (58% ischemic/inflammatory). May or may not be reversible. |
| Post-renal |
Urethral obstruction; Ureteral obstruction; Bladder rupture |
Obstruction to urine flow. Can lead to intrinsic AKI if prolonged. Usually reversible if obstruction relieved promptly. |
Etiology and Classification
AKI is classified by the anatomic location of the primary insult:
High-YieldHospital-acquired AKI is increasingly recognized in veterinary medicine (9% of cases) due to prolonged hospitalization, anesthesia without fluid support, and nephrotoxic drug administration. Always consider AKI risk in critically ill patients.
| Test |
Expected Findings in AKI |
Clinical Significance |
| BUN/Creatinine |
Elevated; creatinine rises disproportionately higher in grape toxicity |
75% nephron loss before values elevate. SDMA may rise earlier (40% loss). |
| Potassium |
Hyperkalemia common (especially oliguric/anuric patients) |
Life-threatening: causes bradycardia, cardiac arrhythmias. Greater than 6.5 mEq/L = emergency |
| Acid-Base |
Metabolic acidosis (pH less than 7.2 or bicarbonate less than 12 mEq/L) |
Due to decreased acid excretion and bicarbonate reabsorption |
| CBC |
Usually no anemia (vs. non-regenerative anemia in CKD); may have neutrophilia |
Anemia develops in CKD due to decreased erythropoietin over time |
Clinical Presentation
Clinical Signs
Dogs with AKI typically present with acute onset of illness in a previously healthy animal:
- Lethargy (90%) - Often the first sign noticed by owners
- Anorexia (83%) - May be complete or partial
- Vomiting (68%) - Due to uremic gastritis and central stimulation
- Altered urine production - May be polyuric, oliguric (less than 0.5-1 mL/kg/hr), or anuric
- Dehydration - Common finding despite possible polyuria
- Oral ulceration and uremic halitosis - Appears 3-5 days into uremia
Physical Examination Findings
- Kidneys: Enlarged and painful on palpation (versus small, irregular in CKD)
- Body condition: Usually normal (versus cachexia in CKD)
- Cardiovascular: May have bradycardia with severe hyperkalemia
| Finding |
AKI |
CKD |
| Kidney Size |
Normal to enlarged |
Small, irregular |
| Corticomedullary Definition |
Usually preserved |
Lost or diminished |
| Perirenal Effusion |
May be present (indicator of AKI) |
Absent |
Diagnostic Approach
Laboratory Findings
Urinalysis Findings
- Urine specific gravity: Isosthenuric (1.008-1.012) - inappropriate concentration in face of azotemia
- Glucosuria: With normal blood glucose suggests proximal tubular damage
- Casts: Granular and epithelial casts indicate tubular injury
- Calcium oxalate monohydrate crystals: PATHOGNOMONIC for ethylene glycol toxicity
Diagnostic Imaging - Ultrasonography
High-YieldThe renal cortical thickness to aorta (RCT:Ao) ratio can help differentiate AKI from CKD. Normal = 0.67, AKI = 0.83 (enlarged), CKD = 0.50 (reduced).
| Grade |
Serum Creatinine |
Description |
Clinical Status |
| I |
Less than 1.6 mg/dL or increase 0.3 mg/dL within 48h |
Non-azotemic AKI |
Volume responsive |
| II |
1.7-2.5 mg/dL |
Mild azotemia |
Non-oliguric |
| III |
2.6-5.0 mg/dL |
Moderate azotemia |
Oliguric/anuric possible |
| IV |
5.1-10.0 mg/dL |
Severe azotemia |
Typically oliguric/anuric |
| V |
Greater than 10.0 mg/dL |
Life-threatening |
RRT indicated |
IRIS AKI Grading System
The International Renal Interest Society (IRIS) developed a 5-grade system based on serum creatinine and clinical parameters:
NAVLE TipEach IRIS grade is subgraded: (O) oliguric/anuric, (NO) non-oliguric, or (RRT) requiring renal replacement therapy. Anuria is associated with 2.5x increased odds of death (50% vs 28% case fatality rate).
| Stage |
Time |
Signs |
| 1 |
30 min - 12 hours |
CNS depression (resembles alcohol intoxication), ataxia, vomiting, PU/PD, hypothermia, seizures |
| 2 |
12-24 hours |
Cardiopulmonary: tachycardia, tachypnea, pulmonary edema |
| 3 |
24-72 hours |
Oliguric/anuric renal failure, severe metabolic acidosis, painful kidneys |
Major Causes of AKI: Diagnosis and Treatment
Ethylene Glycol Toxicosis
Ethylene glycol (EG) is a component of antifreeze with a sweet taste. Minimum lethal dose in dogs: 4.4-6.6 mL/kg. Mortality 59-70% if not treated within 8 hours.
Pathophysiology
EG is metabolized by hepatic alcohol dehydrogenase to glycoaldehyde, glycolic acid, glyoxylic acid, and oxalic acid. Oxalic acid binds calcium forming calcium oxalate crystals that precipitate in renal tubules.
Clinical Stages
Treatment
NAVLE TipRemember 'F-8': Fomepizole must be given within 8 hours in dogs. Prognosis excellent if treated within 5 hours, only 15% survive once azotemic. Activated charcoal is NOT effective for EG.
Leptospirosis
Leptospirosis is a zoonotic spirochete infection that has re-emerged as a common cause of AKI. Mortality 11-27%, but 80-90% renal recovery with treatment. 33-40% of survivors may have residual CKD.
Clinical Presentation
- Acute febrile illness with lethargy, anorexia, vomiting
- AKI with or without hepatic involvement (icterus, elevated liver enzymes)
- Muscle pain, stiffness, reluctance to move
- Thrombocytopenia (14-73%) - helps increase suspicion
Treatment
High-YieldLeptospirosis is ZOONOTIC. Implement contact precautions. Doxycycline is critical for clearing renal carriage - fluoroquinolones do NOT clear leptospires from kidneys.
Grape and Raisin Toxicosis
Grape and raisin toxicosis causes severe AKI. Tartaric acid is the likely toxic principle. Mortality approximately 50%. Marked individual variation in susceptibility.
Key Facts
- Toxic dose: Variable; as little as 1 grape/raisin per 4.5 kg body weight may pose risk
- All forms toxic: Seedless, seeded, red, green, organic, raisins, currants, sultanas
- NOT toxic: Grape juice, wine, grape seed oil (processing removes tartaric acid)
Distinctive Finding
Hypercalcemia with normal ionized calcium: Marked elevation of total serum calcium is characteristic and distinguishes it from other causes of AKI. May explain neurological signs (73% of cases).
Treatment
- Decontamination: Induce emesis if asymptomatic and within 2 hours (grapes remain in stomach up to 12 hours)
- Activated charcoal: 1-3 g/kg within 1-3 hours of ingestion
- IV fluid therapy: Minimum 48-72 hours
- No specific antidote: Supportive care only
Exam Focus: AKI + hypercalcemia + neurological signs + creatinine rising disproportionately higher than BUN = think grape/raisin toxicosis. NO specific antidote - treatment is entirely supportive.
| Treatment |
Dogs |
Notes |
| Fomepizole (4-MP) |
20 mg/kg IV initially, then 15 mg/kg at 12 and 24h, then 5 mg/kg at 36h |
TREATMENT OF CHOICE. Inhibits alcohol dehydrogenase. Must give within 8 hours. Commercial: Antizol-Vet |
| Ethanol (alternative) |
5.5 mL/kg of 20% solution IV q4h x 5, then q6h x 4 |
Competitive substrate. Causes CNS depression. Less preferred. |
General Treatment Principles
| Phase |
Antibiotic |
Dosage |
| Acute (vomiting) |
Ampicillin IV |
20-22 mg/kg IV q6-8h |
| Continuation |
Doxycycline PO |
5 mg/kg PO q12h x 14 days (clears renal carriage) |
Prognosis
Negative Prognostic Indicators: Anuria, higher IRIS AKI grade, multi-organ involvement, severe hyperkalemia, high anion gap, elevated Ca-P product.
| Goal |
Approach |
| Restore Fluid Balance |
IV crystalloids (LRS). Replace deficit over 2-4 hours. Goal urine output greater than 1-2 mL/kg/hr. |
| Correct Hyperkalemia |
If K+ greater than 6.5 mEq/L: Regular insulin 0.25-0.5 U/kg IV + dextrose 1-2 g per unit insulin. Calcium gluconate for cardioprotection. |
| Address Acidosis |
Treat if pH less than 7.2. Sodium bicarbonate: dose (mEq) = 0.3 x BW (kg) x base deficit. Give 1/4 dose, reassess. |
| Control Vomiting |
Maropitant (Cerenia) 1 mg/kg SC/IV q24h. Famotidine 0.5-1 mg/kg q12-24h or omeprazole 0.7 mg/kg q24h. |
| Manage Oliguria |
After rehydration: Furosemide 2-4 mg/kg IV bolus. Mannitol 0.5-1 g/kg IV if not anuric. Hemodialysis if unresponsive. |
| Etiology |
Survival Rate |
Notes |
| Overall AKI |
40-66% |
Variable based on cause and timing |
| Leptospirosis |
73-89% renal recovery |
Good prognosis with treatment |
| Ethylene Glycol |
15% (once azotemic) |
Excellent if treated within 5 hours |
| Grape/Raisin |
~50% |
Poor once anuric |