Acute Kidney Injury Causes
Acute kidney injury results from three main categories: prerenal causes (>60% of cases) due to decreased renal perfusion, intrarenal causes from direct kidney parenchymal damage, and postrenal causes from urinary tract obstruction. 1, 2
Prerenal Causes (Most Common)
Prerenal AKI accounts for more than 60% of all cases and results from decreased renal perfusion without initial structural kidney damage. 1 This category includes:
Volume Depletion States
- Hypovolemia from fluid losses (hemorrhage, gastrointestinal losses, burns, excessive diuresis) 2, 3
- Fluid sequestration in third spaces such as pancreatitis or peritonitis 1
- Severe hypoalbuminemia from nephrotic syndrome causing decreased effective circulating volume 1
Hemodynamic Causes
- Decreased cardiac output from heart failure, cardiogenic shock, or arrhythmias 2, 3
- Systemic vasodilation from sepsis, anaphylaxis, or cirrhosis 2, 3
- Renal vasoconstriction from medications (NSAIDs, ACE inhibitors, ARBs) or hepatorenal syndrome 2, 3
Vascular Occlusion
Intrarenal (Intrinsic) Causes
Direct kidney parenchymal damage occurs through multiple mechanisms affecting different kidney structures. 4
Acute Tubular Necrosis (Most Common Intrinsic Cause)
- Ischemic injury from prolonged prerenal states or severe hypotension 3, 4
- Nephrotoxic medications: aminoglycosides (which are "potentially nephrotoxic"), contrast media, NSAIDs, chemotherapy agents 5, 3, 6
- Rhabdomyolysis with myoglobin-induced tubular injury 7
Glomerular Disease
- Glomerulonephritis from autoimmune conditions or infections 7
- Thrombotic microangiopathy including thrombotic vascular processes 7
Interstitial Disease
COVID-19 Specific Mechanisms
- Viral-mediated tubular cell injury with direct kidney infection 7
- Multi-organ failure associated with severe COVID-19 7
- Proximal tubular injury with Fanconi syndrome manifesting as hypokalaemia, hypophosphataemia, and salt wasting 7
Postrenal Causes
Urinary tract obstruction causes postrenal AKI and must be identified early as it is often reversible. 2, 3
- Ureteral obstruction from stones, blood clots, or external compression 2, 3
- Bladder outlet obstruction from prostatic hypertrophy, bladder stones, or neurogenic bladder 2, 3
- Urethral obstruction from strictures or external compression 2
High-Risk Patient Populations
Certain patient characteristics substantially increase AKI risk and require heightened vigilance. 3, 6
- Age >65 years represents an independent risk factor 1, 8, 3
- Pre-existing chronic kidney disease significantly increases susceptibility 1, 8, 3
- Diabetes mellitus increases AKI risk through multiple mechanisms 1, 8, 3
- Sepsis is a major precipitant in hospitalized patients 3, 6
- Cardiac surgery patients face elevated risk from hemodynamic instability 3
- Liver disease increases risk through altered hemodynamics and hepatorenal syndrome 1
Critical Medication-Related Causes
Multiple medication classes directly cause or exacerbate AKI and should be discontinued when AKI develops. 7, 6
- ACE inhibitors and ARBs impair autoregulation of glomerular filtration 7, 8, 6
- NSAIDs reduce renal perfusion through prostaglandin inhibition 7, 8, 6
- Diuretics can cause volume depletion and prerenal azotemia 7, 8, 6
- Aminoglycosides cause direct nephrotoxicity, particularly with inadequate hydration 5
- Contrast media causes AKI especially in patients with pre-existing kidney disease or diabetes 1
Diagnostic Approach to Determine Cause
The BUN/creatinine ratio helps differentiate prerenal from intrinsic causes: >20:1 suggests prerenal azotemia, while <15:1 suggests intrinsic kidney disease. 1, 2
- Fractional excretion of sodium (FENa) <1% indicates prerenal causes 3, 6
- FENa >2% suggests intrinsic kidney disease 3, 6
- Renal ultrasonography should be performed in most patients, particularly older men, to exclude obstruction 3, 6
- Urinalysis findings: muddy brown casts indicate ATN, red cell casts suggest glomerulonephritis, white cell casts indicate interstitial nephritis 3, 6