Acute Kidney Injury

Definition

The published KDIGO framework defines AKI by any of the following: serum creatinine increase ≥0.3 mg/dL within 48 hours, increase to ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/hour for at least 6 hours. A single criterion is sufficient (Stamatakis, 2026).

AKI Severity Staging

KDIGO stage	Serum creatinine criterion	Urine-output criterion
1	≥0.3 mg/dL increase or 1.5-1.9 × baseline	<0.5 mL/kg/h for 6-12 h
2	2.0-2.9 × baseline	<0.5 mL/kg/h for ≥12 h
3	≥3 × baseline, creatinine ≥4.0 mg/dL, or initiation of kidney replacement therapy	<0.3 mL/kg/h for ≥24 h or anuria for >12 h

Only one criterion is required to assign the higher stage. Urine output can identify severe AKI before creatinine fully reflects the loss of filtration, but nonoliguric AKI is common enough that preserved urine output does not exclude significant injury (Stamatakis, 2026).

Prerenal AKI

Prerenal AKI results from reduced kidney perfusion without primary parenchymal damage initially. Causes include intravascular volume loss, systemic vasodilation, reduced cardiac output, and altered renal hemodynamics. Intact tubules conserve sodium and water. Prolonged or severe hypoperfusion can progress to intrinsic tubular injury (Perlman & Heung, 2019; Stamatakis, 2026).

Intrinsic AKI

Intrinsic AKI results from injury within the kidney. Major sites include tubules, glomeruli, interstitium, and vasculature. Acute tubular injury (ATI), historically and still commonly called acute tubular necrosis (ATN), develops after ischemia or nephrotoxic exposure and may produce muddy brown granular casts. Acute interstitial nephritis commonly causes inflammatory urine findings such as pyuria, while glomerular injury can produce hematuria, proteinuria, and RBC casts (Perlman & Heung, 2019; Stamatakis, 2026).

Postrenal AKI

Postrenal AKI results from urinary outflow obstruction. Upstream hydrostatic pressure opposes filtration and, if prolonged, can reduce renal blood flow and trigger inflammation. Clinically significant AKI usually requires bilateral obstruction or obstruction of a solitary functioning kidney (Perlman & Heung, 2019; Stamatakis, 2026).

Prerenal, Intrinsic, and Postrenal Comparison

Feature	Prerenal	Intrinsic	Postrenal
Primary mechanism	Low perfusion	Renal tissue injury	Urinary obstruction
Tubules early	Intact, avidly conserve sodium/water	Often impaired	Variable
Sediment	Often bland	Depends on lesion; muddy brown casts in ATI, RBC casts in GN, WBCs in interstitial disease	Often bland; hematuria may occur
Imaging	Usually no obstruction	May be nonspecific	May show hydronephrosis/obstruction
Key principle	Restore perfusion before injury develops	Treat cause and prevent further injury	Relieve obstruction

Urinary and Laboratory Indices

Finding	Pattern that can support prerenal physiology	Important limitation
BUN:creatinine ratio	Often >20:1	Affected by protein intake, GI bleeding, catabolism, liver function, and other factors
FENa	Often <1%	Diuretics and several intrinsic renal disorders can make FENa misleading
Urine sodium/osmolality	Low urine sodium and concentrated urine when tubular conservation is intact	Less reliable after diuretics or when tubular function is abnormal
Urine sediment	Often bland	Sediment findings may be more informative for intrinsic mechanisms

These indices are physiologic clues, not standalone diagnostic tests. They are most useful when interpreted with the patient’s volume/perfusion state, medication exposure, urine sediment, and imaging rather than as rigid cutoffs (Stamatakis, 2026).

Diagnostic Approach

• Establish timing and trajectory of serum creatinine and urine output (Perlman & Heung, 2019; Stamatakis, 2026).
• Assess perfusion, volume status, cardiac function, sepsis, medication/nephrotoxin exposure, and recent procedures (Perlman & Heung, 2019; Stamatakis, 2026).
• Use urinalysis and sediment to look for tubular, glomerular, or interstitial clues (Perlman & Heung, 2019; Stamatakis, 2026).
• Exclude obstruction with bladder assessment and renal imaging when indicated (Perlman & Heung, 2019; Stamatakis, 2026).
• Interpret indices such as BUN/creatinine ratio or fractional sodium excretion cautiously because diuretics and other conditions can limit specificity (Perlman & Heung, 2019; Stamatakis, 2026).

Clinical Manifestations

AKI may present with oliguria, anuria, edema, dyspnea from volume overload, electrolyte or acid-base abnormalities, or manifestations of the underlying cause such as dehydration, sepsis, shock, drug exposure, or urinary obstruction. Some patients remain nonoliguric, so urine volume alone does not exclude AKI (Perlman & Heung, 2019; Stamatakis, 2026).

Findings That Refine the Mechanism

A bland sediment with a strong hypoperfusion history favors prerenal physiology; muddy brown granular casts support ATI; RBC casts and substantial proteinuria support glomerular injury; pyuria or WBC casts can support interstitial inflammation; hydronephrosis or bladder outlet findings support postrenal obstruction. Urinary indices can help but should not be interpreted as absolute discriminators (Stamatakis, 2026).

Differential Diagnosis

The differential includes prerenal hypoperfusion, ischemic or nephrotoxic ATI, acute interstitial nephritis, glomerulonephritis, vascular renal injury, and postrenal obstruction. Apparent acute creatinine elevation also requires comparison with prior values because previously unrecognized CKD can mimic AKI, and AKI may occur on top of CKD (Perlman & Heung, 2019; Stamatakis, 2026).

Treatment Principles

Management focuses on reversing the cause: restore effective perfusion when deficient, stop or adjust nephrotoxic exposures, treat sepsis or other systemic drivers, correct dangerous electrolyte/acid-base or volume abnormalities, and relieve obstruction. Intrinsic disease such as GN or AIN requires cause-specific evaluation and therapy rather than generic “renal failure” treatment (Stamatakis, 2026).

Red Flags

• Refractory hyperkalemia, severe metabolic acidosis, pulmonary edema, or other life-threatening complications of reduced kidney function (Perlman & Heung, 2019; Stamatakis, 2026).
• Anuria, bilateral obstruction, or obstruction of a solitary functioning kidney (Perlman & Heung, 2019; Stamatakis, 2026).
• Rapidly progressive glomerular findings or systemic vasculitic features (Perlman & Heung, 2019; Stamatakis, 2026).
• Progressive creatinine rise despite correction of apparent reversible causes (Perlman & Heung, 2019; Stamatakis, 2026).

High-Yield Distinctions

• Prerenal AKI is functional at first; prolonged ischemia can become intrinsic ATI.
• Muddy brown granular casts support ATI; RBC casts support glomerular injury.
• A unilateral stone usually does not cause severe AKI if the contralateral kidney functions normally.
• AKI can occur on top of CKD; chronic disease does not exclude an acute component.

Related YourDNP Resources

• Renal Pathophysiology Foundations
• Chronic Kidney Disease
• Glomerulonephritis
• Heart Failure

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References

Perlman, R. L., & Heung, M. (2019). Renal disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed., pp. 493–518). McGraw-Hill Education.

Stamatakis, M. K. (2026). Acute kidney injury. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.