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Acute Kidney Injury

Chapter 321 | Part 9: Disorders of the Kidney and Urinary Tract

KEY CLINICAL POINTS

  • AKI is defined by an increase in serum creatinine ≥ 0.3 mg/dL within 48 h or ≥ 1.5× baseline, or urine output <0.5 mL/kg/h for >6 h.
  • Etiology is classified into prerenal (volume depletion, drugs), intrinsic (ischemia, toxins), and postrenal (obstruction) causes.
  • KDIGO staging uses SCr and urine output to classify severity (Stage 1-3).
  • Management includes fluid resuscitation, discontinuation of nephrotoxins, and dialysis for severe cases.
  • Prognosis is poor in patients with preexisting CKD or severe complications like hyperkalemia.

1. DEFINITION & OVERVIEW

Acute kidney injury (AKI) is characterized by rapid decline in kidney function, leading to impaired excretion of nitrogenous waste and electrolyte imbalance. It is a clinical diagnosis, not structural, and can occur with or without parenchymal injury. KDIGO criteria define AKI as an increase in serum creatinine ≥ 0.3 mg/dL within 48 h or ≥ 1.5× baseline, or urine output <0.5 mL/kg/h for >6 h.

Table 321-1: Staging of Acute Kidney Injury Severity

STAGE SERUM CREATININE URINE OUTPUT
1 1.5–1.9× baseline OR ‡0.3 mg/dL increase <0.5 mL/kg/h for 6–12 h
2 2.0–2.9× baseline <0.5 mL/kg/h for ‡12 h
3 3.0× baseline OR ‡4.0 mg/dL OR initiation of RRT <0.3 mL/kg/h for ‡24 h OR anuria ‡12 h

1.1 Pathophysiology

AKI results from prerenal azotemia, intrinsic renal injury, or postrenal obstruction. Sodium balance, renin-angiotensin-aldosterone system (RAAS), and autoregulation of renal blood flow are critical in maintaining GFR. Disruption of these mechanisms leads to tubular injury, reduced filtration, and accumulation of waste products.

1.2 Clinical Spectrum

AKI ranges from asymptomatic to life-threatening. Early stages may present with subtle changes in urine output or electrolyte abnormalities. Severe cases can lead to uremic syndrome, cardiac arrhythmias, and multiorgan failure.

2. EPIDEMIOLOGY

AKI complicates 5–7% of hospital admissions and up to 30% of ICU admissions. Incidence in the US increased 4× since 1988, with ~500 per 100,000 annual cases. Morbidity is high, with >50% of ICU patients developing AKI. Long-term risks include CKD progression and cardiovascular disease.

2.1 Global Variations

In developing countries, AKI is more prevalent due to limited resources, infectious causes (malaria, leptospirosis), and trauma-related rhabdomyolysis. Mortality is higher in these settings due to delayed diagnosis and treatment.

3. ETIOLOGY & PATHOPHYSIOLOGY

AKI is classified into prerenal (volume depletion, drugs), intrinsic (ischemia, toxins), and postrenal (obstruction) causes. Pathophysiology involves disruption of renal autoregulation, sodium balance, and tubular function. Nephrotoxins like aminoglycosides, cisplatin, and contrast agents cause direct tubular injury.

Table 321-2: Major Causes, Clinical Features, and Diagnostic Studies for Prerenal and Intrinsic AKI

ETIOLOGY CLINICAL FEATURES LABORATORY FEATURES COMMENTS
Prerenal azotemia Volume depletion, NSAIDs, heart failure BUN/creatinine >20, FeNa <1% Response to fluid resuscitation is diagnostic
Sepsis-associated AKI Sepsis, hypotension Positive cultures, granular casts Common in ICU, poor prognosis
Ischemia-associated AKI Systemic hypotension, CKD Granular casts, FeNa >1% Often post-surgery or sepsis
Nephrotoxin-associated AKI Toxins (drugs, contrast) Granular casts, FeNa >1% Delayed rise in SCr, nonoliguric

3.1 Prerenal Azotemia

Caused by reduced renal perfusion (hypovolemia, heart failure, NSAIDs). Sodium reabsorption increases, leading to elevated SCr without tubular damage. Response to fluid resuscitation is diagnostic.

3.2 Intrinsic AKI

Includes ischemia (sepsis, surgery), toxins (drugs, contrast), and glomerular diseases (vasculitis, glomerulonephritis). Tubular necrosis, inflammation, and oxidative stress are key mechanisms.

3.3 Postrenal Obstruction

Caused by urinary tract obstruction (stones, tumors, catheter blockage). Leads to hydronephrosis and rapid rise in SCr. Prompt relief of obstruction is critical to prevent renal damage.

4. CLINICAL FEATURES

AKI presents with oliguria, anuria, or changes in urine output. Other signs include edema, hypertension, and electrolyte abnormalities. Symptoms may be subtle in early stages but progress to uremic syndrome with severe complications.

4.1 Urinary Findings

Urine may show red blood cells (hematuria), white blood cells (pyuria), casts (granular, RTE), or crystals (oxalate, uric acid). Pigmented casts suggest rhabdomyolysis or hemolysis.

4.2 Systemic Manifestations

Hyperkalemia, metabolic acidosis, and uremic toxins cause fatigue, confusion, and cardiac arrhythmias. Severe cases may present with pericarditis, pulmonary edema, or encephalopathy.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnoses include prerenal azotemia, chronic kidney disease (CKD), and postrenal obstruction. Conditions like sepsis, heart failure, and drug toxicity must be considered. Urine sediment and imaging help distinguish etiologies.

5.1 Prerenal vs. Intrinsic AKI

Prerenal azotemia shows low FeNa (<1%), while intrinsic AKI has FeNa >1%. Urine output and response to fluids differentiate prerenal from intrinsic causes.

6. INVESTIGATIONS & DIAGNOSIS

Diagnosis relies on SCr, urine output, and urine analysis. Imaging (ultrasound, CT) identifies postrenal obstruction. Biomarkers like NGAL and KIM-1 improve early detection. KDIGO criteria guide staging and management.

6.1 Laboratory Tests

Serum creatinine, BUN, electrolytes, and urine electrolytes (Na, K, urea) are critical. Urine sediment analysis reveals casts, RBCs, or crystals. FeNa helps differentiate prerenal vs. intrinsic AKI.

6.2 Imaging

Renal ultrasound or CT identifies obstruction. Doppler ultrasound assesses renal perfusion. Contrast-enhanced CT may detect parenchymal disease or stones.

7. MANAGEMENT & TREATMENT

Management includes fluid resuscitation, discontinuation of nephrotoxins, and dialysis for severe cases. Supportive care addresses electrolyte imbalances and complications. Renal replacement therapy (RRT) is indicated for hyperkalemia, uremia, or volume overload.

Table 321-3: Management of Acute Kidney Injury

GENERAL ISSUES SPECIFIC ISSUES
Optimize hemodynamics, discontinue nephrotoxins Nephrotoxin-specific (e.g., fluids for rhabdomyolysis)
Maintain MAP >65 mmHg Volume overload (salt/water restriction, diuretics)
Ensure adequate nutrition (20–30 kcal/kg/day) Hyponatremia (restrict free water, hypertonic saline)
Initiate RRT when indicated Hyperkalemia (loop diuretics, potassium binders)

7.1 Fluid and Electrolyte Management

Fluid resuscitation with isotonic saline or lactated Ringer’s. Diuretics (furosemide) for oliguria. Monitor for hyperkalemia, acidosis, and volume overload.

7.2 Dialysis Indications

Indicated for severe hyperkalemia, uremic symptoms, fluid overload, or when medical management fails. Continuous renal replacement therapy (CRRT) is preferred in hemodynamically unstable patients.

8. PROGNOSIS & COMPLICATIONS

AKI is associated with high mortality, especially in patients with preexisting CKD or sepsis. Complications include CKD progression, cardiovascular disease, and uremic syndrome. Long-term outcomes depend on severity and underlying causes.

8.1 Long-Term Risks

AKI increases risk of CKD, cardiovascular events, and mortality. Survivors may develop chronic kidney disease or require long-term dialysis.

8.2 Uremic Complications

Uremic toxins cause neurological symptoms (confusion, seizures), cardiovascular instability, and bleeding. Dialysis is critical to remove toxins and correct electrolyte imbalances.

9. SPECIAL CONSIDERATIONS

Pregnancy (preeclampsia), elderly (decreased renal reserve), and pediatric patients (drug toxicity) require tailored management. AKI in CKD patients is more severe and less responsive to treatment.

9.1 Pregnancy

Preeclampsia is a leading cause of AKI in pregnancy. Monitoring for hypertension, proteinuria, and fetal well-being is critical. Dialysis may be required for severe cases.

9.2 Pediatrics

Children are at higher risk for AKI due to drug toxicity (contrast, aminoglycosides) and infections. Early recognition and fluid resuscitation are vital.

10. KEY POINTS & CLINICAL PEARLS

AKI is a clinical diagnosis with KDIGO criteria. Prerenal azotemia responds to fluids, while intrinsic AKI requires addressing underlying causes. Dialysis is indicated for severe complications. Early recognition and management improve outcomes. Biomarkers like NGAL and KIM-1 aid in early detection.