What are the causes of Acute Kidney Injury (AKI)?

Causes of Acute Kidney Injury

AKI is categorized into three main types: prerenal (>60% of cases), intrarenal (35%), and postrenal (<3%), with prerenal causes being by far the most common and often reversible if promptly addressed. 1, 2

Prerenal Causes (Most Common)

Prerenal AKI results from decreased renal perfusion without initial structural kidney damage and accounts for more than 60% of all AKI cases 2. These causes include:

Hypovolemia and Fluid Loss

• Hemorrhage, gastrointestinal losses, burns, or excessive diuresis cause absolute volume depletion 2
• Third-space fluid sequestration in pancreatitis or peritonitis reduces effective circulating volume 2, 3
• Severe hypoalbuminemia from nephrotic syndrome decreases effective circulating volume 2

Hemodynamic Compromise

• Decreased cardiac output from heart failure, cardiogenic shock, or arrhythmias 2
• Systemic vasodilation from sepsis, anaphylaxis, or cirrhosis 2
• Renal artery occlusion from thrombosis or embolism 1, 3

Medication-Induced Renal Vasoconstriction

• NSAIDs reduce renal perfusion through prostaglandin inhibition 2
• ACE inhibitors and ARBs impair autoregulation of glomerular filtration 2
• Diuretics cause volume depletion and prerenal azotemia 2

Intrarenal (Intrinsic) Causes

Intrarenal AKI involves direct damage to renal parenchyma and accounts for approximately 35% of cases 1. The American College of Radiology identifies these key causes 1:

Acute Tubular Necrosis (Most Common Intrinsic Cause)

• Ischemic ATN from prolonged prerenal states 1
• Nephrotoxic ATN from drugs (aminoglycosides, contrast media) and toxins 1, 4
• Rhabdomyolysis with myoglobin-induced tubular injury 2

Glomerular Disease

• Glomerulonephritis from autoimmune conditions or infections 1, 2
• Vasculitis affecting renal vessels 1

Interstitial Disease

• Acute interstitial nephritis from medications or infections 1
• Renal infection or infiltration 1

Vascular Causes

• Thrombotic microangiopathy including thrombotic vascular processes 2

Postrenal Causes (Least Common)

Postrenal AKI results from urinary tract obstruction and accounts for less than 3% of cases 1. The American College of Radiology notes 1:

• Ureteral obstruction from stones, blood clots, or external compression 2
• Bladder outlet obstruction from prostatic hypertrophy, bladder stones, or neurogenic bladder 2
• Urethral obstruction from strictures or external compression 2

Critical caveat: Postrenal obstruction is very uncommon in cirrhotic patients, so routine pelvic ultrasound is not needed unless specific risk factors are present 1.

High-Risk Patient Populations

Certain populations have significantly elevated AKI risk and require heightened vigilance 2:

• Age >65 years represents an independent risk factor 2
• Pre-existing chronic kidney disease significantly increases susceptibility 2
• Diabetes mellitus increases risk through multiple mechanisms 2
• Liver disease increases risk through altered hemodynamics and hepatorenal syndrome 1
• Critical illness with 30-60% of ICU patients developing AKI 1

Special Populations: Cirrhosis

In patients with cirrhosis and ACLF, the differential diagnosis requires special consideration 1:

• Prerenal azotemia (PRA) accounts for approximately 50% of AKI in cirrhosis 1
• Acute tubular necrosis accounts for 35% 1
• Hepatorenal syndrome-AKI (HRS-AKI) represents functional AKI from severe hemodynamic abnormalities 1
• Structural causes (glomerulonephritis, acute interstitial nephritis) are less common 1

The American Gastroenterological Association emphasizes that all diuretics should be withdrawn and a fluid challenge with albumin (1 g/kg up to 100 g/day) should be administered to differentiate prerenal from intrinsic causes 1.

Diagnostic Approach to Determine Etiology

Laboratory Differentiation

• BUN/creatinine ratio >20:1 suggests prerenal azotemia 2, 3
• BUN/creatinine ratio <15:1 suggests intrinsic kidney disease 2
• Fractional excretion of sodium (FENa) <1% suggests prerenal causes but has only 14% specificity in cirrhosis 1
• Fractional excretion of urea (FEUrea) <28.16% may better discriminate HRS from ATN (75% sensitivity, 83% specificity) 1

Urinalysis Findings

• Bland urine sediment suggests prerenal or postrenal causes 1
• Hematuria, proteinuria, or casts indicate structural renal disease 1
• Muddy brown casts suggest acute tubular necrosis 1

Imaging Considerations

• Renal ultrasound is indicated when postrenal obstruction is suspected (older males with prostatic hypertrophy) 1
• Small echogenic kidneys indicate chronic structural renal disease 1
• Hydronephrosis confirms postrenal obstruction 1

Critical Medication-Related Causes

The following medications are common culprits that must be identified and discontinued 2:

• Aminoglycosides cause direct nephrotoxicity with dose-dependent renal tubular damage 4
• Contrast media particularly in patients with pre-existing kidney disease or diabetes 2
• NSAIDs through prostaglandin inhibition 2
• ACE inhibitors/ARBs through impaired autoregulation 2

Important pitfall: Hospital-acquired AKI is 5-10 times more common than community-acquired AKI, emphasizing the need for vigilance regarding nephrotoxic exposures in hospitalized patients 1.