What are the types, causes, and treatment options for acute kidney injury (AKI) in a patient with a complex medical condition like pleural effusion?

Acute Kidney Injury: Types, Causes, and Treatment

Classification of AKI Types

AKI is classified into four distinct types based on anatomical location: prerenal (68% of cases), intrinsic/intrarenal (primarily acute tubular necrosis), hepatorenal syndrome-AKI (in cirrhotic patients), and postrenal (uncommon). 1

Prerenal AKI

• Results from decreased renal perfusion without structural kidney damage 1, 2
• Caused by hypovolemia (bleeding, diarrhea, excessive diuresis), hypotension, heart failure, or cirrhosis with effective arterial underfilling 1, 3
• Accounts for approximately 68% of hospitalized cases with decompensated cirrhosis 1

Intrinsic/Intrarenal AKI

• Primarily acute tubular necrosis (ATN) from prolonged ischemia, sepsis, or nephrotoxins 1
• Also includes acute interstitial nephritis, glomerulonephritis, and vascular causes 2
• Distinguished from prerenal AKI by lack of response to volume expansion 1

Hepatorenal Syndrome-AKI (HRS-AKI)

• Functional renal failure in cirrhotic patients with ascites without structural damage 1, 4
• Diagnosed after excluding other causes and demonstrating no response to volume expansion with albumin 1, 4
• Urinary NGAL can differentiate HRS-AKI from ATN 1

Postrenal AKI

• Caused by urinary tract obstruction (stones, tumors, prostatic hypertrophy) 2
• Uncommon in decompensated cirrhosis 1
• Requires ultrasonography for diagnosis, particularly in older men 2

Common Precipitating Factors and Causes

Immediately identify and reverse these precipitating factors: infections, nephrotoxic medications (NSAIDs, aminoglycosides, ACE inhibitors, ARBs, diuretics), contrast agents, GI bleeding, excessive diuresis, large-volume paracentesis without albumin, and tense ascites. 1, 5

High-Risk Nephrotoxic Combinations

• The "triple whammy" (NSAIDs + diuretics + ACE inhibitors/ARBs) is particularly dangerous and must be discontinued immediately 5, 3
• Each additional nephrotoxin increases AKI odds by 53% 5, 3

Volume-Related Causes

• Hypovolemia from bleeding (target hemoglobin 7-9 g/dL with packed red blood cells) 1, 3
• Diarrhea or excessive diuresis requiring crystalloid replacement 1
• Large-volume paracentesis (>5L) without adequate albumin replacement 3

Cirrhosis-Specific Factors

• Spontaneous bacterial peritonitis and other infections 1, 4
• Tense ascites increasing intra-abdominal pressure and renal venous pressure 1
• Beta-blockers (must be discontinued along with diuretics in cirrhotic AKI) 1, 5

Diagnostic Criteria and Staging

AKI is diagnosed by serum creatinine increase ≥0.3 mg/dL within 48 hours OR ≥50% increase from baseline within 7 days (use last creatinine within 3 months as baseline). 4, 1

KDIGO Staging System (Adapted for Cirrhosis)

• Stage 1A: Creatinine increase ≥0.3 mg/dL or 1.5-2× baseline with creatinine <1.5 mg/dL 1, 4
• Stage 1B: Same criteria but creatinine ≥1.5 mg/dL 1, 4
• Stage 2: Creatinine >2-3× baseline 4
• Stage 3: Creatinine >3× baseline OR ≥4.0 mg/dL with acute increase ≥0.3 mg/dL OR initiation of renal replacement therapy 4

Diagnostic Workup

• Measure serum creatinine, complete blood count, electrolytes every 12-24 hours during acute phase 5, 4
• Perform urinalysis and urine sediment examination (though not routinely done in many centers) 5, 2
• Calculate fractional excretion of sodium (FENa <1% suggests prerenal but has only 14% specificity in cirrhosis) 4
• Fractional excretion of urea (FEUrea <28%) has better discrimination (75% sensitivity, 83% specificity) for HRS versus non-HRS 4
• Obtain renal ultrasonography in most patients, particularly older men, to exclude obstruction 2

Treatment Algorithm by AKI Type

Immediate Universal Interventions (All AKI Types)

Discontinue ALL nephrotoxic medications immediately—this takes priority over all other interventions. 5, 3

• Stop diuretics, NSAIDs, ACE inhibitors, ARBs, beta-blockers (in cirrhosis), vasodilators, aminoglycosides, and contrast agents 1, 5, 3
• Review all medications including over-the-counter drugs 5
• Screen for and treat infections promptly with appropriate antibiotics 1, 4

Prerenal AKI Treatment

Use isotonic crystalloids (preferably lactated Ringer's over 0.9% saline) as first-line therapy for volume expansion, targeting mean arterial pressure ≥65 mmHg. 5, 3

Fluid Management Strategy

• Administer isotonic crystalloids based on repeated hemodynamic assessment, not static measurements 5
• Use dynamic indices (passive leg-raising test, pulse/stroke volume variation) to guide fluid therapy 5
• Avoid hydroxyethyl starches—they increase AKI risk 5, 3
• Prevent fluid overload >10-15% body weight, which is associated with adverse outcomes 5
• Consider earlier vasopressor use (norepinephrine first-line) instead of excessive fluid administration for hypotension 5

Special Cirrhotic Patient Protocol

• Administer IV albumin 1 g/kg bodyweight (maximum 100g) for two consecutive days to differentiate prerenal AKI from HRS-AKI 1, 5, 4, 3
• Discontinue BOTH diuretics AND beta-blockers (not just diuretics) 1, 5, 3
• For tense ascites, perform therapeutic paracentesis with albumin infusion to improve renal function 1, 3
• For large-volume paracentesis (>5L), administer IV albumin to prevent post-paracentesis circulatory dysfunction 3

Hepatorenal Syndrome-AKI Treatment

After ruling out other causes and if not responding to volume expansion with albumin, initiate vasoconstrictors (terlipressin, norepinephrine, or midodrine plus octreotide) along with albumin. 4, 3

• Start vasoconstrictors earlier in HRS-AKI, as higher creatinine at treatment initiation leads to lower response rates 4
• Continue albumin infusion during vasoconstrictor therapy 4, 3

Intrinsic AKI (ATN) Management

Focus on supportive care, as no specific therapy exists beyond removing precipitating factors and maintaining adequate renal perfusion. 1, 6

• Reassess for reversible causes when AKI persists beyond 48 hours 1, 3
• Consider additional testing: urine sediment, proteinuria, biomarker assessment, imaging 1
• Intrinsic AKI from rhabdomyolysis may require more frequent dialysis due to hypercatabolic state and severe hyperkalemia 5
• Consultation with nephrology for persistent AKI or unclear etiology 1, 3

Postrenal AKI Treatment

Relieve obstruction promptly through bladder catheterization, ureteral stenting, or nephrostomy as indicated by the level of obstruction. 2

Monitoring Requirements

Acute Phase (First 48-72 Hours)

• Measure serum creatinine and electrolytes every 12-24 hours 5, 4
• Monitor urine output hourly in severe cases (catheterization if necessary) 4
• Continuous blood pressure and heart rate monitoring 4
• Assess for hyperkalemia >6.0 mEq/L or ECG changes requiring urgent intervention 4

Stage-Specific Monitoring

• Stage 1A: Serum creatinine every 2-4 days during hospitalization 5
• Stage 1B, 2,3: More intensive monitoring with consideration for vasopressor therapy 4, 3

Post-Discharge Follow-Up

• Assess serum creatinine at least every 2-4 weeks during first 6 months after discharge 5
• Target follow-up to high-risk populations (baseline CKD, elderly, diabetes) 5
• Monitor for development or progression of chronic kidney disease, as even complete recovery carries increased CKD risk 5

Renal Replacement Therapy Indications

Individualize RRT timing based on overall clinical condition rather than specific creatinine or BUN thresholds. 5

Absolute Indications

• Refractory hyperkalemia unresponsive to medical management 2, 5
• Volume overload refractory to diuretics 2, 5
• Intractable metabolic acidosis 2, 5
• Uremic complications (encephalopathy, pericarditis, pleuritis) 2
• Removal of certain toxins 2

Timing Considerations

• Consider RRT for persistent AKI despite appropriate interventions 5
• Earlier initiation may be appropriate in hypercatabolic states (rhabdomyolysis, tumor lysis) 5

Interventions That Do NOT Work (High-Quality Evidence)

Do not use dopamine, loop diuretics for treatment (only for volume overload after perfusion restored), N-acetylcysteine, or recombinant human insulin-like growth factor 1 for AKI treatment—these are ineffective based on level 1A/B evidence. 5

Critical Pitfalls to Avoid

Medication Errors

• Never use furosemide in hemodynamically unstable patients with prerenal AKI—it worsens volume depletion and reduces renal perfusion 3
• Do not use diuretics to treat AKI except for managing volume overload after adequate renal perfusion is restored 5, 3
• Avoid combining multiple nephrotoxic medications, especially in high-risk patients 3

Assessment Errors

• Do not use eGFR equations (MDRD, CKD-EPI) designed for CKD to assess renal function in AKI—they require steady-state creatinine and are inaccurate in acute settings 5, 3
• Avoid indiscriminate fluid administration based solely on the label "prerenal" without hemodynamic assessment 5
• Do not delay fluid resuscitation in truly hypovolemic patients 3

Cirrhosis-Specific Pitfalls

• In cirrhotic patients, remember to discontinue beta-blockers in addition to diuretics (not just diuretics alone) 1, 5, 3
• Do not skip the albumin challenge in cirrhotic patients—it is essential for differentiating prerenal AKI from HRS-AKI 1, 4, 3

Acute Kidney Disease (AKD) Concept

AKD is defined as kidney dysfunction lasting >7 days but <3 months, representing a distinct category between AKI and CKD with different outcomes and management needs. 1

• Persistent AKI beyond 48-72 hours should prompt reassessment of etiology and consideration of AKD 1
• Patients with AKD require continued nephrotoxin avoidance and close monitoring even after initial AKI resolves 1
• AKD carries increased risk for progression to CKD, warranting long-term follow-up 1, 5