What is acute kidney injury?

What is Acute Kidney Injury?

Acute kidney injury (AKI) is a sudden decrease in kidney function occurring within 7 days or less, defined by an increase in serum creatinine ≥0.3 mg/dL (≥26.5 μmol/L) within 48 hours, OR an increase ≥50% from baseline within 7 days, OR urine output <0.5 mL/kg/h for 6 consecutive hours. 1, 2, 3

Clinical Definition and Diagnostic Criteria

The KDIGO (Kidney Disease: Improving Global Outcomes) criteria provide the standardized definition used globally for AKI diagnosis 2, 3. This definition is intentionally sensitive because even small increases in creatinine (≥0.3 mg/dL) are independently associated with a four-fold increase in hospital mortality, justifying this low diagnostic threshold 2, 3.

AKI represents an abrupt loss of excretory kidney function and is part of a broader continuum of kidney disease 4:

• AKI: Acute phase lasting ≤7 days 3
• Acute Kidney Disease (AKD): Subacute damage/dysfunction lasting 7-90 days after AKI initiating event 1, 5
• Chronic Kidney Disease (CKD): Kidney dysfunction persisting >90 days 1

Staging System

AKI severity is classified into three stages based on the most severe criterion achieved (either creatinine or urine output), with direct correlation between stage progression and increased mortality 2, 5:

• Stage 1: Creatinine 1.5-1.9 times baseline OR increase ≥0.3 mg/dL, OR urine output <0.5 mL/kg/h for 6-12 hours 2
• Stage 2: Creatinine 2.0-2.9 times baseline, OR urine output <0.5 mL/kg/h for ≥12 hours 2
• Stage 3: Creatinine ≥3.0 times baseline OR increase to ≥4.0 mg/dL (with acute increase >0.3 mg/dL or >50%), OR initiation of renal replacement therapy, OR urine output <0.3 mL/kg/h for ≥24 hours or anuria for ≥12 hours 2

Patients receiving acute renal replacement therapy are automatically classified as AKI stage 3 2.

Pathophysiology and Classification

AKI is conceptually classified into three etiologic categories, though most cases are multifactorial 6, 7:

• Prerenal: Impaired renal perfusion from hypovolemia, hypotension, or reduced cardiac output 6
• Intrinsic renal: Direct kidney parenchymal damage, most commonly acute tubular necrosis from ischemia or nephrotoxins 7
• Postrenal: Urinary tract obstruction 6

The pathophysiology involves diverse mechanisms including tubular cell injury from filtered toxins, tubular obstruction, allergic reactions, systemic hypotension, and intraglomerular hemodynamic effects 1.

Epidemiology and Risk Factors

In low-income and middle-income countries, infections and hypovolemic shock predominate as AKI causes, while in high-income countries, AKI mostly occurs in elderly hospitalized patients related to sepsis, drugs, or invasive procedures 4.

Key susceptibility factors include 1:

• Dehydration or volume depletion
• Advanced age
• Female gender
• Black race
• Pre-existing chronic kidney disease
• Chronic diseases of heart, lung, or liver
• Diabetes mellitus
• Cancer
• Anemia

Clinical Significance and Prognosis

AKI is associated with substantial short-term and long-term morbidity and mortality 4, 8:

• Increased length of hospital stay and healthcare costs 8
• In-hospital mortality that increases progressively with each AKI stage 5
• Long-term risks include cardiovascular events, progression to CKD, and increased long-term mortality 4, 8, 9

Even transient AKI (recovery within 3 days) is not benign, with hospital mortality rates of 15% 5.

Diagnostic Approach

Detection should occur in real-time based on initial changes in markers, without waiting for retrospective confirmation 2.

Initial evaluation must identify 2, 6:

• Use of nephrotoxic medications (NSAIDs, aminoglycosides, ACE inhibitors, ARBs, contrast agents) 1
• Recent exposure to iodinated contrast media 2
• Clinical context suggesting prerenal (volume depletion), intrinsic (sepsis, nephrotoxins), or postrenal (obstruction) causes 6

Initial laboratory workup includes 2, 6:

• Serum creatinine compared to known baseline 2
• Complete blood count 2, 6
• Urinalysis with microscopy 2, 6
• Fractional excretion of sodium (FENa) 2, 6

Renal ultrasonography should be performed in most patients, particularly in older men, to rule out obstruction 2, 6.

Critical Diagnostic Pitfalls

Relying solely on serum creatinine without considering urine output criteria may miss cases of AKI 3. Both criteria must be evaluated.

Failure to establish an accurate baseline creatinine leads to misclassification 3. Using known creatinine values is superior to imputation methods 1, 3.

In patients with cirrhosis and ascites, urine output criteria are unreliable because these patients are frequently oliguric with avid sodium retention yet may maintain relatively normal GFR 3.

Serum creatinine has inherent limitations, being affected by decreased creatinine formation from muscle wasting, increased tubular secretion, volume expansion dilution, and interference with creatinine assays by elevated bilirubin 3.

In patients with pre-existing CKD, percentage increases in creatinine are less evident and do not easily detect AKI superimposed on CKD 5.

Management Principles

Management involves control of the underlying cause, achievement and maintenance of euvolemia, optimization of nutrition, control of blood glucose, and appropriate pharmacotherapy 2.

Specific interventions include 2, 6, 9:

• Fluid resuscitation with isotonic crystalloid for volume depletion 6, 9
• Avoidance of nephrotoxic medications and contrast media 6, 9
• Correction of electrolyte imbalances 6
• Treatment of volume overload with diuretics when indicated 9
• Adjustment of prescribed drugs according to renal function 9

Nephrology referral is recommended for AKI stage 2 or 3, stage 1 with concomitant decompensated condition, unclear etiology, lack of improvement with treatment, or suspected glomerulonephritis 2.