Acute Kidney Injury (AKI)

Acute Kidney Injury (AKI)

David Ray Velez, MD

Table of Contents

Definition and Classification
Causes
Risk Factors
Laboratory Evaluation
Treatment

Definition and Classification

RIFLE Classification – The Most Commonly Cited System

  • Acute Rise in Cr Over 7 Days
  • Risk of Renal Failure
    • Increase in Serum Cr ≥ 1.5x Baseline
    • Decrease in GFR ≥ 25% Baseline
    • UOP < 0.5 cc/kg/hr for 6 Hours
  • Injury of the Kidney
    • Increase in Serum Cr ≥ 2.0x Baseline
    • Decrease in GFR ≥ 50% Baseline
    • UOP < 0.5 cc/kg/hr for 12 Hours
  • Failure of the Kidney
    • Increase in Serum Cr ≥ 3.0x Baseline or Cr ≥ 0.5 mg/dL if Bassline Cr ≥ 4 mg/dL
    • Decrease in GFR ≥ 75% Baseline
    • UOP < 0.3 cc/kg/hr for 24 Hours or Anuria for 12 Hours
  • Loss of Kidney Function
    • Complete Loss of Function ≥ 4 Weeks
  • End-Stage Renal Disease
    • Complete Loss of Function ≥ 3 Months

Acute Kidney Injury Network (AKIN) Classification

  • Acute Rise in Cr Over 48 Hours
  • Stage I
    • Increase in Serum Cr ≥ 0.3 mg/dL
    • Increase in Serum Cr ≥ 1.5x Baseline
    • UOP < 0.5 cc/kg/hr for 6 Hours
  • Stage II
    • Increase in Serum Cr ≥ 2.0x Baseline
    • UOP < 0.5 cc/kg/hr for 12 Hours
  • Stage III
    • Increase in Serum Cr ≥ 3.0x Baseline or Cr ≥ 0.5 mg/dL if Bassline Cr ≥ 4 mg/dL
    • UOP < 0.3 cc/kg/hr for 24 Hours or Anuria for 12 Hours
    • Initiation of Renal-Replacement Therapy (RRT)

Kidney Disease Improving Global Outcomes (KDIGO) Classification

  • AKI Definition:
    • Increase in Serum Cr ≥ 0.3 mg/dL within 48 ourHours
    • Increase in Serum Cr ≥ 1.5x Baseline within 7 Days
    • UOP < 0.5 cc/kg/hr for 6 Hours
  • Stage I
    • Increase in Serum Cr ≥ 0.3 mg/dL
    • Increase in Serum Cr ≥ 1.5x Baseline
    • UOP < 0.5 cc/kg/hr for 6 Hours
  • Stage II
    • Increase in Serum Cr ≥ 2.0x Baseline
    • UOP < 0.5 cc/kg/hr for 12 Hours
  • Stage III
    • Increase in Serum Cr ≥ 3.0x Baseline or Cr ≥ 4 mg/dL
    • UOP < 0.3 cc/kg/hr for 24 Hours or Anuria for 12 Hours
    • Initiation of Renal-Replacement Therapy (RRT)

Comparison

Stage RIFLE AKIN KDIGO
1 Risk
  • Same as RIFLE Risk
  • Plus: Increase in Serum Cr ≥ 0.3 mg/dL
  • Minus: GFR Criteria
  • Same as AKIN Stage I
2 Injury
  • Same as RIFLE Injury
  • Minus: GFR Criteria
  • Same as AKIN Stage II
3 Failure
  • Same as RIFLE Failure
  • Plus: Initiation of RRT
  • Minus: GFR Criteria
  • Same as AKIN Stage III
  • Change: Cr ≥ 0.5 mg/dL if Bassline Cr ≥ 4 mg/dL to Simply Cr ≥ 4 mg/dL
  • All Have the Same UOP Criteria
  • Only RIFLE Uses GFR Criteria

Causes

Pre-Renal Causes

  • Low Blood Flow
  • Dehydration
  • Bleeding
  • Congestive Heart Failure
  • Sepsis

Intrinsic Causes

  • Acute Tubular Necrosis (ATN)
    • Ischemia
    • Prolonged Hypotension – Intraoperative Hypotension is the Most Common Cause of Post-Op AKI
    • Toxins
    • Contrast-Induced Nephropathy – *See Contrast-Induced Nephropathy
  • Acute Interstitial Nephritis (AIN)
    • Infection
    • Drugs
    • Inflammatory Disease
    • Neoplasia
  • Acute Glomerulonephritis
    • Infection
    • Vasculitis

Post-Renal Causes

  • Obstruction
  • Urinary Stones
  • Benign Prostatic Hypertrophy (BPH)
  • Neoplasia
  • Retroperitoneal Fibrosis
  • Urethral Stricture

Risk Factors

Medical Comorbidities

  • Chronic Kidney Disease (CKD)
  • Hypertension
  • High Cholesterol
  • Congestive Heart Failure (CHF)
  • Diabetes
  • Cirrhosis
  • Peripheral Vascular Disease
  • Older Age
  • Genetics: TIMP2 and IGFBP7 Genes Can Accurately Predict the Risk for AKI in Septic and Postoperative Patients

Nephrotoxic Medications

  • Nonsteroidal Anti-Inflammatory Drugs (NSAID’s)
  • ACE Inhibitors
  • Diuretics
  • Aminoglycosides
  • Some Antibiotics
  • Contrast Dye

Acute Illness

  • Malnutrition
  • Dehydration
  • Infection/Sepsis
  • Anemia/Blood Transfusion
  • Mechanical Ventilation
  • Hemodynamic Instability or Vasopressors
  • Emergency or High-Risk Surgery
  • Trauma

Laboratory Evaluation

  Pre-Renal ATN
FENa < 1% 1-4%
FEUrea < 35% > 50%
BUN:Cr > 20 < 15
Urine Na < 20 > 40
Urine Osmolality > 500 < 350

Response to Fluid Repletion

  • Considered the Gold Standard in Distinguishing Pre-Renal Disease from ATN

Fractional Excretion of Sodium (FENa)

  • FENa = 100 x (Urine Na/Plasma Na) / (Urine Cr/Plasma Cr)
  • Generally Considered the Best Lab Test to Determine the Etiology of AKI
  • Limitations: Can Be Affected by Diuretics, Cirrhosis, Sepsis, and Heart Failure

Fractional Excretion or Urea (FEUrea)

  • FEUrea = 100 x (Urine Urea/Plasma Urea) / (Urine Cr/Plasma Cr)
  • Urea is Reabsorbed in the Proximal Nephron and Generally Not Affected by Diuretics
  • Limitations: Can Be Affected by Advanced Age and Sepsis
  • *Some Consider FEUrea to be Superior to FENa if on a Diuretic but the Measurement Can Still Be Affected, and it is Generally Not Any Better

Urinalysis

  • Pre-Renal AKI – Generally Have No Abnormal Casts or Sediment
    • Not Abnormal to See Hyaline Casts
  • Acute Tubular Necrosis (ATN) – Granular and Muddy Brown Casts
  • Acute Glomerulonephritis – Protein and Red Blood Cell (RBC) Casts
  • Acute Interstitial Nephritis (AIN) – Eosinophils and WBC Casts

Testing That is Generally Considered Not Reliable

  • BUN:Cr Ratio
  • Urine Osmolality
  • Urine Volume

Electrolyte Disturbances of Kidney Disease

  • Increased:
    • Potassium
    • Magnesium
    • Phosphorus
  • Decreased:
    • Vitamin D and Calcium
    • Erythropoietin and Hemoglobin

Treatment

General Management

  • Management is Primarily Supportive
  • Treat Any Underlying Causes
  • Avoid Nephrotoxic Medications
  • Fluid Resuscitation if Hypovolemic
  • Manage Any Electrolyte and Acid-Base Disturbances
    • Hyperkalemia is Generally the Most Immediate Threat in AKI
  • Assess for Uremia

Furosemide (Lasix)

  • May Be Given with the Onset of Oliguria
  • May Require High Doses or Continuous Infusion
    • Risk for Ototoxicity at High Doses (Not with Infusion)
  • No Significant Impact on the Need for RRT or Overall Survival
  • No Evidence to Support Routine Use

Renal Replacement Therapy (RRT)

  • Indications:
    • Acidosis: pH < 7.1
    • Electrolyte Disturbances:
      • Potassium > 6.5 mEq/L
      • Potassium > 5.5 mEq/L with Tissue Breakdown (Rhabdomyolysis) or Ongoing Potassium Absorption (GI Bleed)
      • Symptomatic Hyperkalemia (Cardiac Conduction Abnormality)
    • Intoxicants: Intoxicants or Poisoning
    • Overload: Fluid Overload with Pulmonary Edema
    • Uremia: Symptomatic Uremia (Encephalopathy, Coagulopathy, or Pericarditis)
    • MNEMONIC: “A-E-I-O-U”
  • Timing:
    • Previously Believed that Early Initiation of RRT May Improve Survival – Now Strongly Debated
    • Early vs Delayed Use Has No Effect on Mortality, ICU LOS, Hospital LOS, or Need for Dialysis at Discharge

Other Agents

  • Steroids – Consider for Rapidly-Deteriorating AKI Due to Glomerulonephritis
  • Medications with No Proven Benefit on Survival or Need for RRT:
    • Dopamine
    • Fenoldopam
    • Activated Protein C (Xigris)
    • Levosimedan

References

COVER: Lindstrom, et al. 3d Reconstruction of Nephrons Captured with a 63X Objective On a Nikon Confocal A1R Microscope. eLife. 2015. (License: CC BY-2.0)