What are the steps to identify the cause of Acute Kidney Injury (AKI) in a patient with a history of kidney disease, diabetes, or heart failure?

Identifying the Cause of Acute Kidney Injury

Begin by categorizing AKI into prerenal (>60% of cases), intrarenal (~35%), or postrenal (<3%) through a systematic evaluation combining clinical assessment, laboratory analysis, and targeted imaging. 1

Initial Clinical Assessment

History - Focus on These Specific Elements

• Medication review for nephrotoxins: NSAIDs, ACE inhibitors, ARBs, diuretics, aminoglycosides, contrast agents, and combinations (the "triple whammy" of NSAIDs + diuretics + RAS inhibitors dramatically increases risk) 2, 3
• Volume status indicators: Recent fluid losses (hemorrhage, GI losses, burns, excessive diuresis), third-space sequestration (pancreatitis, peritonitis), or decreased cardiac output 1, 2
• Systemic illness markers: Sepsis, heart failure, cirrhosis, rhabdomyolysis, or autoimmune conditions 1, 2
• Obstructive symptoms: History of kidney stones, prostatic hypertrophy, neurogenic bladder, or pelvic malignancy 1, 2

Physical Examination - Assess These Parameters

• Volume status determination: Orthostatic vital signs, jugular venous pressure, skin turgor, mucous membranes, and presence of edema or ascites 1, 4
• Cardiac assessment: Signs of heart failure or cardiogenic shock 2
• Skin findings: Rashes suggesting vasculitis or systemic lupus erythematosus 1, 4

Laboratory Evaluation - Ordered Sequentially

First-Line Tests (Obtain Immediately)

• Serum creatinine and BUN: BUN/creatinine ratio >20:1 suggests prerenal azotemia; <15:1 suggests intrinsic kidney disease 2, 3
• Complete blood count: Assess for anemia (hemolysis, bleeding) or eosinophilia (interstitial nephritis) 1
• Serum electrolytes: Identify hyperkalemia, metabolic acidosis, or other imbalances requiring urgent intervention 1

Urine Studies (Critical for Differentiation)

• Urinalysis with microscopy:

  • Bland sediment suggests prerenal or postrenal causes 3
  • Red blood cells/red cell casts indicate glomerulonephritis 1, 3
  • White blood cells/white cell casts suggest interstitial nephritis or pyelonephritis 1
  • Muddy brown casts indicate acute tubular necrosis 1
  • Rapidly increasing albuminuria suggests alternative causes requiring nephrology referral 2

• Spot urine sodium (UNa):

  • <20 mEq/L: highly specific (>85%) for prerenal AKI 2, 5

  • 40 mEq/L: suggests intrinsic renal disease 5

• Fractional excretion of sodium (FENa):

  • <1%: suggests prerenal causes (but only 14% specificity in cirrhosis) 3, 4

  • 2%: suggests acute tubular necrosis 4

• Fractional excretion of urea (FEUrea):

  • <28.16%: better discriminates hepatorenal syndrome from ATN (75% sensitivity, 83% specificity) 3
  • Use when diuretics confound FENa interpretation 3

• Urine specific gravity (USG):

  • 1.020: highly specific (>85%) for prerenal AKI 2, 5

  • <1.010: suggests intrinsic disease 5

• Renal failure index (RFI = UNa/(UCr/PCr)):

  • <1: highly specific for prerenal AKI 2, 5

  • 2: suggests acute tubular necrosis 5

Important caveat: Loop diuretics, ACE inhibitors/ARBs, and pre-existing CKD do NOT significantly impact the reliability of UNa, USG, or RFI 5

Imaging Studies

Renal Ultrasound - Indicated When:

• Suspected obstruction: History of stones, prostatic disease, pelvic malignancy, or unexplained AKI 1, 6
• Findings to assess:
  • Hydronephrosis confirms postrenal obstruction 1, 3
  • Small echogenic kidneys suggest chronic kidney disease 1
  • Normal kidney size with increased echogenicity suggests acute intrinsic disease 1

Note: Routine pelvic ultrasound is NOT needed in cirrhotic patients unless specific risk factors are present, as postrenal obstruction is very uncommon 3

Contrast Studies - Special Considerations:

• Avoid iodinated contrast in AKI unless there is an overriding clinical question that cannot be answered otherwise 1
• Use ultrasound contrast media when microvascular imaging is needed, as these agents are not nephrotoxic 1

Advanced Testing - When Initial Workup is Inconclusive

Renal Biopsy Indications:

• Differentiation of nephritic versus nephrotic syndromes 1
• Suspected glomerulonephritis or vasculitis when diagnosis would change management 1
• Unexplained AKI with active urinary sediment 1

Novel Biomarkers (Emerging):

• NGAL (neutrophil gelatinase-associated lipocalin): Distinguishes ATN from hepatorenal syndrome in cirrhotic patients 6
• TIMP-2 and IGFBP7 combination: Predicts progression to severe AKI 6
• KIM-1 (kidney injury molecule-1): May diagnose AKI even without creatinine changes 6

Algorithmic Approach to Cause Identification

Step 1: Determine Volume Status

• Hypovolemic: Prerenal AKI likely → Check UNa <20, USG >1.020, BUN/Cr >20:1 2, 3
• Euvolemic or hypervolemic: Consider intrinsic or postrenal causes 3

Step 2: Review Urinalysis

• Bland sediment + prerenal indicators: Prerenal AKI or early ATN 3
• Muddy brown casts: Acute tubular necrosis 1
• RBC casts: Glomerulonephritis → Nephrology referral 1, 3
• WBC casts: Interstitial nephritis or infection 1

Step 3: Assess for Obstruction

• Risk factors present (stones, BPH, pelvic mass): Obtain renal ultrasound 1, 6
• Hydronephrosis confirmed: Postrenal AKI → Urology consultation 1

Step 4: Identify Nephrotoxin Exposure

• Recent contrast, NSAIDs, aminoglycosides, or "triple whammy": Drug-induced ATN likely 2, 3
• Discontinue offending agents immediately 2

Step 5: Consider Systemic Causes

• Sepsis, hypotension, cardiac failure: Prerenal or ATN 1, 2
• Rash, arthralgias, eosinophilia: Vasculitis or interstitial nephritis → Nephrology referral 1, 4

Critical Pitfalls to Avoid

• Do NOT discontinue ACE inhibitors/ARBs for creatinine increases <30% from baseline without volume depletion - this is expected autoregulation, not true AKI 2
• Do NOT rely solely on FENa in patients on diuretics - use FEUrea instead 3
• Do NOT assume oliguria always indicates hypovolemia - multiple etiologies exist including established ATN and fluid overload 1
• Do NOT delay nephrology referral for stage 2-3 AKI, glomerulonephritis, or unclear etiology 6, 7
• Do NOT overlook medication combinations - each additional nephrotoxin increases AKI odds by 53% 3

High-Risk Populations Requiring Enhanced Surveillance

• Age >65 years 2, 3
• Pre-existing chronic kidney disease 1, 2
• Diabetes mellitus 1, 2
• Heart failure or cirrhosis 2, 3
• Critical illness (30-60% of ICU patients develop AKI) 1, 3