AKI(Acute Kidney Injury)

🚨 Acute Kidney Injury (AKI)

🔹 Definition

AKI is a rapid decline in kidney function (hours to days), resulting in the accumulation of nitrogenous waste, electrolyte imbalance, and dysregulation of volume and acid-base status.


🔬 KDIGO Criteria (Most widely used)

AKI is diagnosed if any of the following are present:

  • ↑ Serum creatinine (SCr) by ≥0.3 mg/dL within 48 hours
  • ↑ SCr ≥1.5× baseline within 7 days
  • Urine output (UO) <0.5 mL/kg/h for ≥6 hours

KDIGO Staging

Stage

Creatinine Criteria

Urine Output

1

1.5–1.9× baseline or ↑ ≥0.3 mg/dL

<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 SCr ≥4 mg/dL or RRT needed

<0.3 mL/kg/h ≥24 h or anuria ≥12 h



📊 Etiological Classification

Type

Mechanism

Common Causes

Pre-renal

↓ Renal perfusion

Hypovolemia, shock, heart failure, NSAIDs

Intrinsic

Renal parenchymal damage

ATN, glomerulonephritis, AIN

Post-renal

Obstruction of outflow

Stones, BPH, catheter kink, tumor



🔍 Pathophysiology in ICU

  • Ischemia, sepsis, toxins → tubular cell injury → ATP depletion → cell death
  • Tubular obstruction by debris (cast formation)
  • Endothelial injury, microvascular dysfunction
  • ↑ Inflammatory cytokines → systemic complications


🔬 Diagnostic Workup

Investigation

Use

Urine output & trends

Early marker

Serum creatinine, BUN

Diagnostic and staging

Urine sodium, FeNa

Distinguish pre-renal (<1%) from ATN (>2%)

Urinalysis, microscopy

Muddy brown casts → ATN; eosinophils → AIN

Renal USG

Rule out obstruction (post-renal)

Biomarkers (optional)

NGAL, KIM-1, IL-18 (early detection)



🧠 Key ICU Principles


✅ 1. Fluid Resuscitation

Goal: Restore perfusion in pre-renal/early AKI (esp. in sepsis)

Logic:

  • Hypovolemia → ↓ renal blood flow → ischemic injury
  • Resuscitation reverses pre-renal AKI and prevents ATN

Preferred fluid:

  • Balanced crystalloids (Ringer’s lactate, PlasmaLyte)
  • Avoid high chloride (NS) → renal vasoconstriction

Dosing:

  • Initial bolus: 500–1000 mL over 15–30 min
  • In sepsis: 30 mL/kg (Surviving Sepsis Campaign)

Caution: Avoid fluid overload (↑ mortality in AKI/ARDS)


✅ 2. Vasopressors

Why: To maintain renal perfusion pressure when fluids insufficient

First-line:

  • Norepinephrine: 0.05–0.5 mcg/kg/min (target MAP ≥65 mmHg)

Alternatives:

  • Vasopressin: 0.03 units/min if NE insufficient
  • Angiotensin II (in refractory vasodilatory shock; costly)

Logic: Hypotension → ↓ GFR → ischemic AKI. Maintaining MAP helps autoregulation.


✅ 3. Avoid Nephrotoxins

  • Drugs: Aminoglycosides, vancomycin, amphotericin B, contrast, NSAIDs
  • Adjust all drug doses based on eGFR/CrCl

Use renal-safe antibiotics:

  • Cefepime, meropenem, adjusted to renal function


✅ 4. Electrolyte & Acid-Base Management

Issue

Management

Hyperkalemia

Calcium gluconate 10 mL IV, Insulin + Dextrose, furosemide, dialysis

Metabolic acidosis

NaHCO₃ if pH <7.1 or bicarb <12

Volume overload

Loop diuretics (furosemide), RRT



✅ 5. Diuretics (for volume control only)

  • Furosemide: 20–80 mg IV bolus or continuous (e.g., 5–10 mg/h)
  • May help in oliguric AKI with fluid overload
  • Do not improve survival or prevent RRT need


✅ 6. Renal Replacement Therapy (RRT)

Indications: “AEIOU” mnemonic:

  • A: Metabolic Acidosis (pH <7.1 refractory)
  • E: Electrolyte imbalance (K⁺ >6.5 mmol/L or refractory)
  • I: Intoxications (e.g., lithium, methanol, salicylates)
  • O: Volume Overload (pulmonary edema, unresponsive to diuretics)
  • U: Uremia (e.g., pericarditis, encephalopathy)

Modes:

  • Intermittent HD: Hemodynamically stable patients
  • CRRT (CVVH, CVVHDF): Preferred in ICU/septic shock
    • Dose: 20–25 mL/kg/hr (effluent flow)
  • SLED: Hybrid between intermittent HD and CRRT

Timing:

  • Controversial – current trend: “wait for indications”
  • ELAIN trial favored early initiation
  • AKIKI trial showed no benefit with early RRT


✅ 7. Nutrition in AKI

  • Avoid overfeeding
  • Protein: 1.2–1.5 g/kg/day (↑ in RRT: 1.5–2 g/kg/day)
  • Monitor electrolytes (esp. K, Phos) closely


📋 Summary Table: ICU AKI Management

Intervention

Rationale

Doses / Notes

Fluids

Restore perfusion

Balanced crystalloids, 500–1000 mL bolus

Norepinephrine

Maintain MAP ≥65

0.05–0.5 mcg/kg/min

Diuretics

Volume control only

Furosemide 20–80 mg IV

RRT

AEIOU indications

CRRT preferred in ICU

Avoid nephrotoxins

Prevent further injury

Adjust all nephrotoxic meds

Electrolyte correction

Prevent arrhythmia/metabolic derangement

IV calcium, insulin, bicarbonate as needed



🧠 Special ICU Situations

Condition

AKI Link

Sepsis

Most common ICU AKI cause (SA-AKI); inflammatory + ischemic

Rhabdomyolysis

Myoglobin-induced ATN; aggressive hydration, alkalinize urine

Cardiorenal Syndrome

Low CO → ↓ GFR; treat heart failure, cautious diuresis

Hepatorenal Syndrome

Splanchnic vasodilation; treat with Terlipressin + albumin



🧪 Renal Biomarkers (Research/Early Detection)

Biomarker

Use

NGAL (Neutrophil gelatinase-associated lipocalin)

Early AKI detection

KIM-1, IL-18, Cystatin C

Ongoing research



🔍 AIN vs ATN: Differentiating Two Common Causes of Intrinsic AKI


🧠 Overview

Both ATN and AIN are causes of intrinsic acute kidney injury (AKI) but differ in pathophysiology, etiology, clinical presentation, urine findings, and management.


📊 Comparison Table: AIN vs ATN

Feature

Acute Interstitial Nephritis (AIN)

Acute Tubular Necrosis (ATN)

Site of Injury

Interstitial tissue ± tubules

Tubular epithelial cells

Common Causes

– Drugs (70–90%): NSAIDs, β-lactams, PPIs, rifampin, diuretics

– Infections: CMV, EBV, TB

– Autoimmune: SLE, Sjögren

– Ischemia: sepsis, hypotension, surgery

– Nephrotoxins: aminoglycosides, contrast, myoglobin, cisplatin

Onset

Subacute (days–weeks)

Acute (hours–days)

Classic Triad (seen <10%)

Fever, rash, eosinophilia

None

Urine Output

Often non-oliguric

Often oliguric (<400 mL/day)

Urine Findings

– WBCs, WBC casts

– Eosinophiluria (Hansel stain)

– Mild proteinuria

– Muddy brown granular casts (classic)

– Epithelial cell casts

– No eosinophils

FeNa (%)

Variable; often <1% (but not reliable)

Typically >2% (unless on diuretics)

Serum Findings

↑ Cr, ↑ eosinophils (50–80%)

↑ Cr, ↑ BUN

Kidney Biopsy

Interstitial edema, infiltrates (lymphocytes, eosinophils)

Tubular cell necrosis, loss of brush border

Treatment

Stop offending drug

± Steroids: Prednisone 1 mg/kg/day x 1–2 weeks, taper

Supportive care

Maintain perfusion

RRT if needed

Prognosis

Usually recovers if identified early

Recovery possible, but slower



💡 Key Differentiators in ICU

Clue

Suggests

Rash + fever + eosinophilia

AIN

Recent antibiotics / NSAIDs

AIN

Sepsis + hypotension

ATN

Nephrotoxic drug (e.g. gentamicin)

ATN

Muddy brown casts

ATN

Eosinophiluria

AIN (but not specific/sensitive)



📌 When to Biopsy?

Indicated when:

  • Cause unclear
  • No improvement despite supportive care
  • Suspected AIN (for steroid decision)
  • Rapidly progressive renal failure


🧠 1. RIFLE Criteria (2004 – by ADQI group)

RIFLE is an acronym:

Stage

Meaning

R

Risk

I

Injury

F

Failure

L

Loss (persistent failure >4 weeks)

E

ESRD (failure >3 months)


🔢 RIFLE Staging (based on GFR or Creatinine + Urine Output)

Class

Creatinine/GFR Criteria

Urine Output Criteria

Risk

↑Cr ×1.5 or GFR ↓ >25%

<0.5 mL/kg/h for 6 h

Injury

↑Cr ×2 or GFR ↓ >50%

<0.5 mL/kg/h for 12 h

Failure

↑Cr ×3, Cr >4.0 mg/dL (acute rise ≥0.5) or GFR ↓ >75%

<0.3 mL/kg/h for 24 h or anuria for 12 h

Loss

Persistent renal failure >4 weeks

—

ESRD

End-stage kidney disease >3 months

—



🧠 2. AKIN Criteria (2007 – Acute Kidney Injury Network)

  • Modified and simplified RIFLE
  • Removed GFR criteria (hard to measure acutely)
  • Added absolute rise in creatinine ≥0.3 mg/dL
  • Must occur within 48 hours

🔢 AKIN Staging

Stage

Creatinine Criteria

Urine Output

Stage 1

↑ ≥0.3 mg/dL or 1.5–2× baseline

<0.5 mL/kg/h for ≥6 h

Stage 2

↑ 2–3× baseline

<0.5 mL/kg/h for ≥12 h

Stage 3

↑ >3× baseline or ≥4.0 mg/dL (with rise ≥0.5) or dialysis required

<0.3 mL/kg/h for ≥24 h or anuria ≥12 h



🚨 Phases of Acute Kidney Injury (AKI)


📌 Overview

AKI is characterized by rapid decline in renal function, with or without oliguria, leading to azotemia, fluid/electrolyte imbalance, and acid–base disorders.

AKI typically progresses through four sequential phases, though some may be absent or overlap.


🔄 1. Initiation Phase

  • Duration: Minutes to hours
  • Trigger: Insult causing decreased renal perfusion or direct tubular injury
  • Examples:
    • Hypotension, sepsis, nephrotoxins, rhabdomyolysis
  • Events:
    • ↓ GFR
    • ATP depletion in tubular cells
    • Endothelial dysfunction
    • Subclinical injury may be occurring before serum creatinine rises

📌 Potentially reversible if insult is corrected promptly


⛔ 2. Oliguric/Anuric Phase

  • Duration: Days to 1–2 weeks (sometimes longer)
  • Urine output: <400 mL/day (oliguria), or <100 mL/day (anuria)
  • Events:
    • Tubular epithelial cell necrosis and sloughing
    • Intratubular obstruction and backleak of filtrate
    • GFR remains low
  • Complications:
    • Volume overload
    • Hyperkalemia
    • Metabolic acidosis
    • Uremia → encephalopathy, pericarditis
    • Hyponatremia, hyperphosphatemia

🔬 Labs: Rising BUN, creatinine; hyperkalemia; low Na⁺ and HCO₃⁻


💧 3. Diuretic (Polyuric) Phase

  • Duration: Days to weeks
  • Urine output: Often >3–5 L/day
  • Mechanism:
    • Regeneration of tubular cells begins
    • Tubular dysfunction persists: can’t concentrate urine or reabsorb Na⁺/water
    • Osmotic diuresis due to accumulated urea and solutes
  • Consequences:
    • Polyuria, despite persistent azotemia
    • Electrolyte loss: K⁺, Na⁺, Mg²⁺ → hypokalemia, hypovolemia
    • Hypotension

⚠️ ICU patients may need aggressive electrolyte and volume replacement


🛠️ Why Polyuria Happens (Mechanism)

  1. Tubular epithelial cell regeneration: starts → tight junctions not fully functional
  2. Loss of concentrating ability: impaired medullary gradient, dysfunctional Na⁺/K⁺/Cl⁻ cotransporters
  3. Osmotic diuresis: from urea, retained solutes
  4. Impaired ADH responsiveness: temporarily
  5. Increased GFR but poor reabsorption → high-volume dilute urine


🟢 4. Recovery Phase

  • Duration: Weeks to months
  • Events:
    • Gradual restoration of normal tubular function
    • GFR returns toward baseline
    • Urine output normalizes
  • Complete recovery possible, but:
    • May have residual CKD, especially if older, multiple comorbidities
    • Some may develop progressive renal fibrosis → ESRD


🧠 ICU Clinical Implications

Phase

Clinical Action

Initiation

Prevent further insult: hemodynamic support, avoid nephrotoxins

Oliguric

Dialysis if needed (based on AEIOU), manage fluid/electrolytes

Polyuric

Monitor urine output hourly; replace losses; watch for arrhythmias (hypokalemia)

Recovery

Monitor creatinine trends; adjust medications as function returns