Acute Kidney Injury (Adult)

Quick Answer

Acute Kidney Injury (AKI) is a sudden decline in renal function defined by KDIGO criteria (increase in serum creatinine ≥26.5 μmol/L within 48 hours OR ≥1.5x baseline within 7 days OR urine output below 0.5 mL/kg/h for 6 hours). AKI affects 10-15% of hospitalized patients and 50-60% of ICU patients. Classification includes prerenal (most common, 60-70%), intrinsic renal (25-40%), and postrenal (5-10%) causes. Management involves identifying and treating the underlying cause, optimizing hemodynamics, avoiding nephrotoxins, and initiating renal replacement therapy (RRT) when indicated (AEIOU: Acidosis pH below 7.1, Electrolytes K⁺ greater than 6.5 mmol/L refractory to medical management, Ingestion/toxins, fluid Overload refractory to diuretics, Uremia with complications). Recent trials (AKIKI 2016, STARRT-AKI 2020, IDEAL-ICU 2018) show no mortality benefit from early RRT initiation, supporting a conservative approach. Mortality ranges from 10-20% in hospitalized patients to 40-60% in ICU patients with severe AKI requiring RRT.

---

CICM Exam Focus

Key High-Yield Points

1. KDIGO 2012 Classification: Three-stage system based on creatinine and urine output
2. RRT Timing Trials: AKIKI, STARRT-AKI, IDEAL-ICU - all showing no benefit from early initiation
3. Absolute RRT Indications: AEIOU mnemonic (Acidosis, Electrolytes, Ingestion, Overload, Uremia)
4. CRRT vs IHD: Hemodynamic stability favors CRRT, but no survival difference
5. Biomarkers: NGAL, KIM-1, cystatin C - research tools, not yet standard practice
6. Contrast-Induced AKI: Prevention strategies and risk factors
7. Nephrotoxin Avoidance: NSAIDs, aminoglycosides, vancomycin, contrast
8. Prerenal vs ATN: Fractional excretion of sodium (FENa), urine microscopy

Common Viva Themes

• Diagnostic approach to oliguria in ICU patient
• Indications and timing of RRT initiation
• CRRT prescription and anticoagulation
• Contrast administration in patient with reduced GFR
• Rhabdomyolysis-induced AKI management
• AKI in septic shock: fluid resuscitation vs early vasopressors
• Recovery prediction and long-term outcomes

Common Pitfalls

• Over-reliance on creatinine (delayed marker, affected by muscle mass)
• Ignoring urine output criteria (often meets criteria before creatinine rises)
• Starting RRT too early based on biochemistry alone
• Inadequate assessment of volume status before labeling as "intrinsic" AKI
• Forgetting to check for postrenal obstruction (bladder scan, renal ultrasound)

---

Key Points

• AKI is defined by KDIGO criteria: SCr rise ≥26.5 μmol/L in 48h, ≥1.5x baseline in 7 days, or UO below 0.5 mL/kg/h for 6h
• Affects 50-60% of ICU patients; mortality 40-60% in severe AKI requiring RRT
• Classification: Prerenal (60-70%), intrinsic renal (25-40%), postrenal (5-10%)
• Stage 1: SCr 1.5-1.9x baseline or UO below 0.5 mL/kg/h for 6-12h
• Stage 2: SCr 2.0-2.9x baseline or UO below 0.5 mL/kg/h for ≥12h
• Stage 3: SCr ≥3.0x baseline or ≥353.6 μmol/L or RRT or UO below 0.3 mL/kg/h for ≥24h or anuria ≥12h
• Absolute RRT indications: AEIOU (Acidosis pH below 7.1, Electrolytes K⁺ greater than 6.5, Ingestion, Overload, Uremia)
• AKIKI 2016, STARRT-AKI 2020, IDEAL-ICU 2018: No mortality benefit from early vs delayed RRT
• CRRT preferred for hemodynamically unstable patients; no survival difference vs IHD in stable patients
• Prevention: Avoid nephrotoxins, optimize hemodynamics, minimize contrast exposure

---

Epidemiology

Incidence

Acute kidney injury is a common complication in hospitalized patients, with incidence varying by setting and severity. Community-acquired AKI affects 1-7% of hospitalized patients, while hospital-acquired AKI occurs in 10-15% of admissions. In the intensive care unit, AKI incidence is substantially higher, affecting 50-60% of critically ill patients. Severe AKI requiring renal replacement therapy (RRT) occurs in 5-6% of ICU admissions.

The incidence of AKI has increased over the past two decades, partly due to improved recognition with standardized definitions (RIFLE 2004, AKIN 2007, KDIGO 2012), aging populations, and increased prevalence of chronic comorbidities such as diabetes mellitus, hypertension, and chronic kidney disease.

Mortality

Mortality associated with AKI is substantial and increases with severity. Among hospitalized patients with any AKI, in-hospital mortality ranges from 10-20%. In the ICU setting, mortality is markedly higher: 30-40% overall for AKI patients, rising to 40-60% for those requiring RRT. Mortality is influenced by multiple factors including underlying cause, severity of illness, number of failing organs, and baseline renal function.

Long-term outcomes are also affected. Survivors of severe AKI have increased risk of progression to chronic kidney disease (CKD), with 25-30% developing new or worsening CKD. End-stage renal disease (ESRD) develops in 10-15% of AKI survivors within 2-5 years. Even after apparent recovery, patients remain at elevated risk for cardiovascular events, hospitalizations, and mortality compared to those without AKI history.

Risk Factors

Major risk factors for AKI include:

Patient factors: Advanced age (greater than 65 years), pre-existing CKD (baseline eGFR below 60 mL/min/1.73m²), diabetes mellitus, heart failure, liver cirrhosis, volume depletion, sepsis, and critical illness.

Exposure factors: Nephrotoxic medications (NSAIDs, aminoglycosides, vancomycin, amphotericin B, calcineurin inhibitors), iodinated contrast agents, major surgery (especially cardiac and vascular), rhabdomyolysis, hemolysis, and tumor lysis syndrome.

Hemodynamic factors: Hypotension, shock states, large-volume fluid resuscitation with chloride-rich solutions, and cardiac surgery with cardiopulmonary bypass.

The risk is cumulative, with each additional factor substantially increasing AKI probability. For example, patients undergoing cardiac surgery with pre-existing CKD, diabetes, and advancing age have a 30-40% risk of postoperative AKI.

---

Pathophysiology

Classification by Etiology

AKI is traditionally classified into three categories based on the anatomical location of injury:

Prerenal AKI (60-70% of cases): Results from reduced renal perfusion without structural kidney damage. Causes include volume depletion (hemorrhage, gastrointestinal losses, burns, diuretics), decreased effective circulating volume (heart failure, cirrhosis, sepsis), and renal vasoconstriction (NSAIDs, calcineurin inhibitors, hepatorenal syndrome). The kidney is structurally intact; restoration of perfusion rapidly reverses azotemia.

Intrinsic renal AKI (25-40% of cases): Results from direct parenchymal damage. Subtypes include:

• Acute tubular necrosis (ATN, 85-90% of intrinsic AKI): Ischemic (prolonged hypoperfusion) or nephrotoxic (aminoglycosides, contrast, myoglobin, hemoglobin)
• Acute interstitial nephritis (AIN, 5-10%): Medications (beta-lactams, PPIs, NSAIDs), infections, autoimmune diseases
• Glomerulonephritis (below 5%): Immune-mediated (anti-GBM, ANCA-associated, lupus nephritis)
• Vascular (below 5%): Renal artery occlusion, renal vein thrombosis, atheroembolic disease

Postrenal AKI (5-10% of cases): Results from obstruction of urinary flow. Common causes include benign prostatic hyperplasia, urolithiasis, malignancy (bladder, prostate, cervical), retroperitoneal fibrosis, and neurogenic bladder. Bilateral obstruction or unilateral obstruction in a solitary kidney is required for significant creatinine rise.

Acute Tubular Necrosis

ATN is the most common cause of intrinsic AKI in critically ill patients. Despite its name, frank tubular necrosis is uncommon; the primary pathophysiology involves tubular cell injury, dysfunction, and apoptosis rather than widespread necrosis.

Ischemic ATN: Prolonged prerenal physiology progresses to structural damage when compensatory mechanisms fail. Renal autoregulation maintains glomerular filtration rate (GFR) across mean arterial pressures of 80-180 mmHg via afferent arteriolar dilation and efferent constriction. When perfusion pressure falls below this range, GFR becomes pressure-dependent. The outer medulla, particularly the S3 segment of proximal tubules and thick ascending limb of Henle, is most vulnerable due to high metabolic demand and relatively low oxygen delivery.

Ischemia leads to ATP depletion, loss of cellular polarity, disruption of tight junctions, and sloughing of tubular cells into the lumen. Cast formation from sloughed cells and Tamm-Horsfall protein causes tubular obstruction, increasing intratubular pressure and reducing glomerular filtration. Back-leak of filtrate through damaged epithelium further decreases effective GFR.

Nephrotoxic ATN: Direct toxicity to tubular epithelial cells from endogenous (myoglobin, hemoglobin, light chains) or exogenous (aminoglycosides, cisplatin, amphotericin B, contrast) substances. Aminoglycosides accumulate in proximal tubular cells, causing mitochondrial dysfunction and apoptosis. Contrast agents cause direct tubular toxicity via oxidative stress and vasoconstriction from endothelin release and nitric oxide suppression.

Myoglobin and hemoglobin cause AKI through multiple mechanisms: direct proximal tubular toxicity from heme proteins, tubular obstruction from cast formation (enhanced by acidic urine), and renal vasoconstriction. The risk is highest when pigment load exceeds renal excretory capacity, typically with creatine kinase greater than 5,000-10,000 U/L in rhabdomyolysis.

Sepsis-Associated AKI

Sepsis is the most common cause of AKI in the ICU, accounting for 40-50% of cases. The pathophysiology is complex and incompletely understood. Contrary to traditional teaching, renal blood flow is often maintained or even increased in septic AKI. Current understanding emphasizes microvascular dysfunction, metabolic reprogramming, and cellular stress rather than simple hypoperfusion.

Mechanisms include:

• Microcirculatory dysfunction: Endothelial injury, microthrombosis, altered vasoreactivity
• Inflammatory injury: Cytokine release, leukocyte infiltration, oxidative stress
• Tubular cell adaptation: Metabolic downregulation to prevent cell death ("hibernation")
• Mitochondrial dysfunction: Impaired oxygen utilization despite adequate delivery
• Glomerular hyperfiltration: Early increased GFR masking tubular injury

This explains why fluid resuscitation and vasopressors, while restoring macrocirculatory parameters, may not prevent or reverse septic AKI.

Contrast-Induced AKI

Contrast-induced AKI (CI-AKI), also termed contrast-associated AKI (CA-AKI), is defined as an increase in serum creatinine ≥44 μmol/L or ≥25% from baseline within 48-72 hours of contrast administration. The true incidence and clinical significance remain debated, with recent evidence suggesting much of the historical risk was overstated.

Pathophysiology involves:

• Direct tubular toxicity: Oxidative stress, mitochondrial injury, apoptosis
• Renal vasoconstriction: Mediated by endothelin, adenosine, and reduced nitric oxide
• Increased blood viscosity: Particularly in outer medulla

Risk factors include pre-existing CKD (especially eGFR below 30 mL/min/1.73m²), diabetes mellitus, volume depletion, heart failure, large contrast volumes (greater than 100-150 mL), and intra-arterial contrast administration. The risk is substantially lower with modern iso-osmolar or low-osmolar contrast agents compared to historical high-osmolar agents.

Prevention strategies include intravenous isotonic saline (1 mL/kg/h for 6-12 hours pre- and post-procedure), minimizing contrast volume, and avoiding concurrent nephrotoxins. N-acetylcysteine has not demonstrated consistent benefit in randomized trials. Sodium bicarbonate and iso-osmolar vs low-osmolar contrast choice show conflicting evidence.

Recovery and Chronic Sequelae

AKI was historically viewed as a reversible condition, but current evidence demonstrates significant long-term consequences even after apparent recovery. Approximately 50-60% of AKI patients recover renal function to baseline, 20-30% have incomplete recovery with residual CKD, and 10-15% progress to ESRD.

Mechanisms of progression include:

• Maladaptive repair: Tubular epithelial cell cycle arrest, profibrotic signaling
• Microvascular rarefaction: Loss of peritubular capillaries, chronic hypoxia
• Inflammation: Persistent low-grade inflammation, macrophage infiltration
• Fibrosis: Myofibroblast activation, collagen deposition, tubular atrophy

Even with complete creatinine recovery, histological abnormalities persist in many patients. This "renal reserve" depletion increases vulnerability to subsequent insults, explaining the elevated risk of future AKI episodes in patients with prior AKI history.

---

Clinical Presentation

Diagnosis and Definition

AKI diagnosis requires careful integration of clinical context, serum creatinine, and urine output. The KDIGO 2012 criteria define AKI as ANY of the following:

1. Increase in serum creatinine by ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours
2. Increase in serum creatinine to ≥1.5 times baseline within prior 7 days
3. Urine output below 0.5 mL/kg/h for 6 hours

Important considerations:

• Baseline creatinine: If unknown, estimate from lowest in-hospital value or calculate from MDRD equation assuming eGFR 75 mL/min/1.73m² (though this may overestimate baseline in hospitalized patients)
• Creatinine limitations: Delayed rise (24-48h after injury), affected by muscle mass, generation rate, volume of distribution
• Urine output: Earlier indicator of renal dysfunction; strictly monitor in at-risk patients

KDIGO Staging

Staging uses the highest category met by EITHER creatinine or urine output criteria. Patients are re-staged daily based on worst criteria in preceding 7 days.

Clinical Features

AKI presentation varies from asymptomatic biochemical abnormality to life-threatening uremic emergency:

Asymptomatic (common in Stage 1): Detected only by routine laboratory monitoring. No specific symptoms attributable to renal dysfunction.

Volume overload: Peripheral edema, pulmonary edema, jugular venous distension, weight gain. Results from inability to excrete sodium and water. May progress to acute pulmonary edema with orthopnea, dyspnea, and hypoxemia.

Uremic symptoms (typically Stage 3): Nausea, vomiting, anorexia, altered mental status, asterixis, pericarditis, platelet dysfunction with bleeding. Uremic pericarditis presents with positional chest pain and friction rub. Encephalopathy manifests as confusion, lethargy, seizures, or coma.

Electrolyte disturbances: Hyperkalemia (muscle weakness, cardiac arrhythmias), metabolic acidosis (Kussmaul respirations), hypocalcemia (perioral tingling, tetany), hyperphosphatemia.

Signs of underlying cause: Rash (vasculitis, atheroemboli, drug reaction), livedo reticularis (atheroemboli, vasculitis), palpable purpura (vasculitis), flank pain (obstruction, renal infarction), gross hematuria (glomerulonephritis, nephrolithiasis).

Oliguria vs Non-Oliguric AKI

Oliguria is defined as urine output below 400-500 mL/day (below 0.5 mL/kg/h). Anuria is below 50-100 mL/day. Non-oliguric AKI maintains urine output greater than 400 mL/day despite elevated creatinine.

Oliguric AKI (40-50% of AKI cases):

• Higher mortality (50-60% vs 20-30% in non-oliguric)
• More severe kidney injury
• More likely to require RRT
• Suggests more severe hemodynamic compromise or intrinsic damage

Non-oliguric AKI (50-60% of cases):

• Often nephrotoxic or early ischemic injury
• Better prognosis overall
• May still require RRT for uremia or metabolic derangements
• Does NOT exclude severe kidney injury (e.g., aminoglycoside toxicity)

Urine output should guide therapy (fluid management) but not solely determine RRT need.

---

Diagnostic Approach

Initial Assessment

The diagnostic approach aims to: (1) confirm AKI, (2) determine etiology, (3) assess severity and complications, (4) identify reversible factors.

History:

• Symptoms: Decreased urine output, edema, nausea, confusion
• Exposures: Medications (NSAIDs, ACE inhibitors, aminoglycosides, contrast), volume losses (vomiting, diarrhea, bleeding)
• Comorbidities: CKD, diabetes, heart failure, liver disease
• Recent procedures: Surgery, catheterization, biopsies

Examination:

• Hemodynamics: Blood pressure, heart rate, capillary refill, urine output trend
• Stigmata of systemic disease: Rash, arthritis, vasculitic lesions
• Bladder palpation and percussion for retention

Point-of-care ultrasound:

• IVC diameter and collapsibility (volume status)
• Bladder volume (retention)
• Renal ultrasound (hydronephrosis indicating obstruction)

Laboratory Evaluation

Essential tests:

• Serum creatinine and urea: Trend over time is critical
• Electrolytes: Sodium, potassium, chloride, bicarbonate
• Venous or arterial blood gas: Assess acidosis
• Complete blood count: Anemia (hemolysis, chronic disease), thrombocytopenia (TTP/HUS, DIC)
• Creatine kinase: Rhabdomyolysis (greater than 1,000 U/L concerning, greater than 5,000 high AKI risk)

Urinalysis and microscopy (CRITICAL for diagnosis):

• Dipstick: Blood (glomerulonephritis, myoglobin), protein (glomerular disease), leukocyte esterase/nitrites (infection)
• Microscopy findings:
  • "Hyaline casts: Nonspecific, normal finding"
  • "Granular/muddy brown casts: ATN (ischemic or nephrotoxic)"
  • "Red cell casts: Glomerulonephritis (diagnostic)"
  • "White cell casts: Acute interstitial nephritis, pyelonephritis"
  • "Epithelial cell casts: ATN"
  • "Eosinophiluria: Acute interstitial nephritis (insensitive, non-specific)"
  • "Crystals: Uric acid (tumor lysis), calcium oxalate (ethylene glycol)"

Urine chemistry (helps distinguish prerenal from ATN):

Fractional Excretion of Sodium (FENa): FENa = (Urine Na × Plasma Cr) / (Plasma Na × Urine Cr) × 100

• FENa below 1%: Prerenal physiology (avid sodium retention)
• FENa greater than 2%: ATN (impaired tubular reabsorption)
• FENa 1-2%: Indeterminate

Limitations of FENa:

• Unreliable if diuretics administered (use FEUrea instead)
• False low FENa in ATN with contrast, rhabdomyolysis, early sepsis
• False high FENa in CKD, bicarbonaturia, glycosuria

Advanced investigations (selected cases):

• Renal ultrasound: All unexplained AKI to exclude obstruction; assess kidney size/echogenicity
• Complement (C3, C4): Low in post-infectious GN, lupus, cryoglobulinemia, MPGN
• Autoantibodies: ANA (lupus), ANCA (vasculitis), anti-GBM (Goodpasture)
• Serum/urine protein electrophoresis: Myeloma, light chain disease
• Blood cultures: If sepsis suspected
• Hepatitis B, C, HIV serology: Selected cases

Renal biopsy indications:

• Suspected glomerulonephritis or vasculitis
• AKI with nephritic/nephrotic features
• Unexplained AKI not responding to initial management
• Suspicion of acute interstitial nephritis when drug withdrawal insufficient

Imaging

Renal ultrasound should be performed in most cases of unexplained AKI:

• Hydronephrosis: Suggests obstruction (sensitivity 90% for obstruction, but early/partial obstruction may be missed)
• Kidney size: Small kidneys (below 9 cm) suggest chronic disease
• Echogenicity: Increased in CKD, may be normal in AKI
• Doppler: Assess renal artery stenosis (though limited sensitivity)

CT abdomen/pelvis non-contrast:

• Superior to ultrasound for detecting stones and subtle obstruction
• Assesses retroperitoneal pathology
• Useful for suspected renal vein thrombosis (with contrast)

CT angiography or MR angiography:

• Suspected renal artery stenosis or thrombosis
• Vasculitis with large vessel involvement
• Dissection

Avoid gadolinium-based contrast in eGFR below 30 mL/min/1.73m² due to nephrogenic systemic fibrosis risk (very rare with modern agents but still contraindicated in severe AKI/CKD).

---

Management

General Principles

AKI management involves:

1. Treat underlying cause
2. Optimize renal perfusion without causing harm
3. Avoid further renal insults
4. Manage complications
5. Initiate RRT when indicated
6. Plan renal recovery and follow-up

There are no pharmacological agents proven to prevent or treat established AKI. Management is supportive.

Hemodynamic Optimization

Fluid resuscitation is appropriate for hypovolemia (prerenal AKI):

• Target: Restore euvolemia, not fluid overload
• Choice: Isotonic crystalloid (0.9% saline or balanced solutions like Hartmann's/Plasma-Lyte)
• Avoid: Starch solutions (increased AKI risk), high chloride loads (may worsen AKI)
• Monitoring: Clinical assessment, urine output, hemodynamics

Balanced vs saline: Some evidence suggests balanced crystalloids (lower chloride) may reduce AKI incidence in critically ill patients and perioperative settings compared to 0.9% saline, though mortality differences are small.

Vasopressors: If hypotensive despite adequate volume resuscitation, initiate vasopressors to maintain MAP ≥65 mmHg. Noradrenaline is first-line in septic shock. There is no evidence that higher MAP targets (e.g., 80-85 mmHg) improve renal outcomes in most patients, though those with chronic hypertension may benefit.

Diuretics: Loop diuretics (furosemide) do NOT prevent AKI, accelerate recovery, or reduce mortality. They may:

• Convert oliguric to non-oliguric AKI (easier fluid management)
• Manage volume overload
• Potentially delay need for RRT

However, excessive diuresis causes hypovolemia and worsens renal perfusion. Use judiciously for volume management, not to "improve" renal function.

Avoid Nephrotoxins

Stop or avoid:

• NSAIDs: Inhibit prostaglandin-mediated afferent arteriolar dilation, reducing GFR
• Aminoglycosides: Direct tubular toxicity (if essential, use once-daily dosing, monitor levels)
• Vancomycin: Nephrotoxic, especially with high trough levels; target trough 10-15 mg/L for most infections
• ACE inhibitors/ARBs: May cause hemodynamic AKI in volume depletion or renal artery stenosis; consider temporary cessation
• Calcineurin inhibitors: Reduce if possible
• Contrast agents: Defer non-urgent studies; use minimum necessary volume

Dose adjustment: Renally-cleared medications require dose reduction or interval extension based on eGFR. Examples include:

• Antibiotics: Gentamicin, vancomycin, beta-lactams
• Antivirals: Aciclovir, ganciclovir
• Anticoagulants: Low-molecular-weight heparin, dabigatran
• Metformin: Risk of lactic acidosis; stop if eGFR below 30

Consult pharmacy/renal dosing guidelines for all medications.

Specific Causes

Rhabdomyolysis:

• Aggressive fluid resuscitation: 200-300 mL/h (or 1-1.5 L/h initially) targeting urine output greater than 200-300 mL/h
• Monitor CK trend, electrolytes (hyperkalemia, hypocalcemia), compartment syndrome
• Urinary alkalinization (sodium bicarbonate to target urine pH greater than 6.5) is historically recommended but lacks strong evidence
• Mannitol: Not routinely recommended
• Early RRT if severe hyperkalemia, acidosis, or oliguria despite resuscitation

Contrast-induced AKI prevention:

• Isotonic saline 1 mL/kg/h for 6-12 hours pre- and post-procedure
• Minimize contrast volume (below 100 mL if possible)
• Avoid repeat contrast exposure within 48-72 hours
• N-acetylcysteine: Inconsistent evidence, low cost/harm, may use 600-1,200 mg PO BID × 2 doses pre- and post-procedure
• Sodium bicarbonate: 154 mmol/L in D5W at 3 mL/kg/h for 1h pre-procedure, then 1 mL/kg/h for 6h post (conflicting evidence)

Tumor lysis syndrome:

• Prevention: Allopurinol 300 mg daily or rasburicase 0.2 mg/kg (if high risk)
• Aggressive hydration: Target urine output greater than 100 mL/h
• Avoid urinary alkalinization (may precipitate calcium phosphate)
• Monitor: Potassium, phosphate, calcium, uric acid, LDH
• Early RRT for refractory hyperkalemia, hyperphosphatemia, or oliguria

Hepatorenal syndrome:

• Type 1 (rapidly progressive): Terlipressin + albumin (not available in all countries; midodrine + octreotide alternative)
• Type 2 (slowly progressive): Manage volume with paracentesis, albumin replacement
• Avoid nephrotoxins, NSAIDs, aminoglycosides
• Definitive treatment: Liver transplantation

Acute interstitial nephritis:

• Withdraw offending drug (beta-lactams, PPIs, NSAIDs most common)
• Corticosteroids: Prednisone 0.5-1 mg/kg/day for 4-6 weeks if no improvement after drug withdrawal (evidence limited but used in practice)
• Renal biopsy may guide treatment if diagnosis uncertain

Glomerulonephritis/vasculitis:

• Urgent nephrology consultation
• Immunosuppression: Corticosteroids, cyclophosphamide, rituximab (disease-specific)
• Plasma exchange for anti-GBM disease, severe ANCA vasculitis

Nutritional Support

Protein restriction is NOT recommended in AKI. Provide adequate nutrition:

• Non-dialysis: 0.8-1.0 g/kg/day protein, 25-30 kcal/kg/day
• Receiving RRT: 1.0-1.5 g/kg/day protein (increased losses during dialysis), 25-30 kcal/kg/day

Avoid excessive protein (greater than 1.5 g/kg/day) which increases urea generation without benefit. Enteral nutrition is preferred over parenteral when feasible.

---

Renal Replacement Therapy

Indications for RRT

Absolute indications (life-threatening complications):

• Acidosis: Severe metabolic acidosis (pH below 7.1) refractory to medical therapy
• Electrolytes: Hyperkalemia (K⁺ greater than 6.5 mmol/L) refractory to medical management OR any K⁺ with ECG changes
• Ingestion/Intoxication: Dialyzable toxins (methanol, ethylene glycol, lithium, salicylates)
• Overload: Pulmonary edema refractory to diuretics, causing hypoxemia
• Uremia: Symptomatic (encephalopathy, pericarditis, bleeding)

Relative indications (practice variation):

• Severe AKI (KDIGO Stage 3) with rising creatinine and oliguria
• Urea greater than 30-40 mmol/L or creatinine greater than 400-500 μmol/L (absolute values alone insufficient)
• Inability to provide adequate nutrition due to fluid restriction
• Persistent oliguria despite optimal management

AEIOU mnemonic is useful for recalling absolute indications, though clinical judgment is essential. Do not delay RRT for absolute indications.

Timing of RRT Initiation

This is one of the most studied and debated topics in critical care nephrology. Three landmark trials addressed early vs delayed RRT:

AKIKI Trial (2016): 620 ICU patients with KDIGO Stage 3 AKI

• Early strategy: RRT within 6 hours of Stage 3 diagnosis
• Delayed strategy: RRT only for absolute indications or if oliguria/elevated urea persisted greater than 72 hours
• Result: No difference in 60-day mortality (48.5% early vs 49.7% delayed, p=0.79)
• 49% of delayed group never required RRT (spontaneous recovery)
• Early group had more catheter-related infections

IDEAL-ICU Trial (2018): 488 ICU patients with KDIGO Stage 3 AKI

• Early strategy: RRT within 12 hours of Stage 3 diagnosis
• Delayed strategy: RRT delayed 48 hours unless absolute indication
• Result: No difference in 90-day mortality (58% early vs 54% delayed, p=0.38)
• 38% of delayed group avoided RRT

STARRT-AKI Trial (2020): 3,019 critically ill patients with KDIGO Stage 2-3 AKI

• Accelerated strategy: RRT within 12 hours of eligibility
• Standard strategy: RRT only for absolute indications or no improvement after 72 hours
• Result: No difference in 90-day mortality (43.9% accelerated vs 43.7% standard, p=0.92)
• No difference in renal recovery, RRT dependence, or major adverse kidney events
• 61% of standard strategy group never received RRT

Conclusion: These trials consistently show NO mortality benefit from early/accelerated RRT initiation based solely on biochemistry or AKI stage. A conservative, delayed approach is appropriate, reserving RRT for absolute indications or failure to improve with medical management. This approach avoids RRT in ~40-60% of patients, reducing complications (catheter infections, hypotension, anticoagulation) and costs.

Current practice: Initiate RRT for absolute indications (AEIOU). For relative indications, optimize medical management and observe for 48-72 hours unless progression occurs. Do not initiate RRT based solely on creatinine or urea thresholds.

CRRT vs Intermittent Hemodialysis

Both modalities are effective for AKI management. Choice depends on hemodynamic stability, clearance goals, and institutional resources.

Continuous Renal Replacement Therapy (CRRT):

• Modes: CVVH (hemofiltration), CVVHD (hemodialysis), CVVHDF (combined)
• Advantages:
  • "Hemodynamic stability: Slower, continuous fluid and solute removal"
  • "Superior fluid management: Allows liberal nutrition, medications"
  • Better for cerebral edema risk (avoids rapid osmolar shifts)
• Disadvantages:
  • Requires ICU setting, continuous anticoagulation
  • Continuous sedation may be needed
  • Higher nursing intensity
  • More expensive (continuous circuit, fluids)
  • Patient immobilization

Intermittent Hemodialysis (IHD):

• Advantages:
  • Rapid correction of life-threatening electrolyte/acid-base abnormalities
  • Patient mobilization between sessions
  • Lower nursing intensity
  • Less continuous anticoagulation
• Disadvantages:
  • "Hemodynamic instability: Rapid fluid shifts, hypotension (30-50% of sessions)"
  • Less effective for fluid removal in hemodynamically unstable patients
  • Intermittent control of uremia, hyperkalemia

Outcomes: Multiple RCTs (including VA/NIH ATN Study, RENAL, others) show NO mortality difference between CRRT and IHD in critically ill patients. Choose based on:

• Hemodynamically unstable (vasopressor-dependent, severe shock): CRRT preferred
• Hemodynamically stable: IHD acceptable and often logistically simpler
• Cerebral edema risk (acute liver failure, severe TBI): CRRT preferred
• Severe fluid overload: CRRT may be superior for gradual fluid removal

Hybrid approaches: Prolonged intermittent RRT (PIRRT) or sustained low-efficiency dialysis (SLED) provides 6-12 hour daily sessions, combining advantages of both modalities. Increasingly used.

CRRT Prescription

Dose: Target delivered dose 20-25 mL/kg/h effluent. Higher doses (35-40 mL/kg/h) do NOT improve outcomes and increase costs.

Anticoagulation:

• Regional citrate anticoagulation: Preferred if no contraindications (advanced liver failure, severe shock with lactate greater than 5 mmol/L). Provides circuit anticoagulation without systemic effect. Requires ionized calcium monitoring.
• Unfractionated heparin (UFH): Alternative; monitor aPTT or anti-Xa. Risk of bleeding.
• No anticoagulation: If high bleeding risk; requires frequent circuit changes (mean circuit life 10-20 hours vs 40-60 hours with anticoagulation).

Vascular access: Large-bore dual-lumen catheter, preferably internal jugular or femoral vein. Subclavian avoided due to central stenosis risk (important if future CKD progression).

Temperature: Cooling occurs during CRRT; warm replacement fluids or use blood warmer to prevent hypothermia.

IHD Prescription

Frequency: Daily or alternate-day sessions, typically 3-4 hours per session.

Adequacy: Target Kt/V ≥1.2 per session in AKI (though evidence for specific targets is limited).

Ultrafiltration: Remove volume gradually to avoid hypotension; may need multiple sessions for large volume overload.

Complications of RRT

• Hypotension: Common with IHD (30-50% sessions), less with CRRT. Manage with fluid boluses, reduce ultrafiltration rate, vasopressors.
• Catheter-related: Infection (2-5 per 1,000 catheter-days), thrombosis, bleeding at insertion site, mechanical complications.
• Electrolyte disturbances: Hypokalemia, hypophosphatemia (common with CRRT), hypomagnesemia. Monitor and replace.
• Bleeding: From anticoagulation (heparin) or uremic platelet dysfunction.
• Dialysis disequilibrium syndrome: Rare with modern practice; cerebral edema from rapid osmolar changes. More common in severe uremia (urea greater than 40 mmol/L) with rapid IHD. Present with headache, nausea, altered mental status, seizures. Prevent with initial shorter, slower dialysis sessions.
• Hypothermia: With CRRT; warm fluids.
• Hypoglycemia: If using lactate- or citrate-based fluids without adequate glucose.

---

Prognosis and Recovery

Renal Recovery

Approximately 50-60% of AKI survivors recover renal function to baseline (defined as return to within 25% of baseline creatinine). Recovery typically occurs within 7-14 days for ATN, though severe cases may take weeks to months.

Predictors of renal recovery:

• Favorable: Non-oliguric AKI, short duration (below 7 days), absence of CKD, younger age, ATN from reversible cause
• Unfavorable: Prolonged oliguria/anuria (greater than 14 days), severe AKI requiring RRT, pre-existing CKD, older age, structural kidney disease (glomerulonephritis, vascular disease)

Incomplete recovery: 20-30% have persistent elevation in creatinine, developing new CKD or worsening pre-existing CKD. Risk is proportional to AKI severity and duration.

RRT dependence: 10-15% of patients requiring RRT for AKI remain dialysis-dependent at hospital discharge. However, late renal recovery (weeks to months after ICU discharge) occurs in 20-30% of these patients, emphasizing the importance of outpatient nephrology follow-up before labeling as ESRD.

Long-Term Outcomes

Even with apparent complete recovery (return to baseline creatinine), AKI survivors have elevated risks:

Chronic kidney disease: 25-30% develop new CKD or accelerated progression of existing CKD. The risk is dose-dependent: higher AKI stage = higher CKD risk.

End-stage renal disease: 10-15% progress to ESRD within 2-5 years. This represents a 10-fold increased risk compared to matched controls without AKI history.

Cardiovascular events: AKI is an independent risk factor for myocardial infarction, heart failure, and stroke. Mechanisms include endothelial dysfunction, inflammation, and accelerated vascular calcification.

Mortality: Long-term mortality is increased 2-4 fold compared to hospitalized patients without AKI, even after adjustment for comorbidities and severity of illness.

Recurrent AKI: Prior AKI increases risk of future AKI episodes 3-4 fold, creating a vicious cycle of recurrent injury and progressive CKD.

Follow-Up

All AKI survivors should receive:

Short-term (3 months post-discharge):

• Nephrology referral if: RRT-dependent, eGFR below 30 mL/min/1.73m², proteinuria, suspected glomerulonephritis/vasculitis
• Renal function testing: Serum creatinine, eGFR, urinalysis
• Blood pressure monitoring (hypertension risk)
• Medication review: Adjust doses, avoid nephrotoxins

Long-term (annual):

• Annual serum creatinine and eGFR
• Urinalysis for proteinuria
• Blood pressure monitoring
• Cardiovascular risk factor management (lipids, diabetes, smoking cessation)

Counsel patients on:

• Avoid NSAIDs, over-the-counter nephrotoxins
• Ensure healthcare providers are aware of AKI history (especially before contrast procedures)
• Hydration during illnesses causing volume loss
• Seek medical attention early for decreased urine output or signs of infection

---

Novel Biomarkers

Serum creatinine is an imperfect biomarker: it is a late marker (rises 24-48 hours post-injury), affected by muscle mass and volume of distribution, and provides no information on injury etiology or recovery potential. Novel biomarkers aim to enable earlier diagnosis, distinguish AKI subtypes, and predict prognosis.

Promising Biomarkers

Neutrophil Gelatinase-Associated Lipocalin (NGAL):

• Expressed by tubular epithelial cells in response to injury
• Rises in urine and serum within 2-4 hours of injury (much earlier than creatinine)
• Predictive of AKI development and need for RRT
• Limitation: Elevated in CKD, sepsis, inflammation (reduced specificity)

Kidney Injury Molecule-1 (KIM-1):

• Transmembrane protein upregulated in proximal tubule injury
• Detectable in urine within 6-12 hours of ischemic or nephrotoxic injury
• Distinguishes ATN from prerenal azotemia and CKD
• Promising for ischemic and cisplatin-induced AKI

Cystatin C:

• Low-molecular-weight protein filtered by glomerulus, reabsorbed by tubules
• Less affected by muscle mass than creatinine
• Serum cystatin C-based eGFR may be more accurate than creatinine-based
• Still a marker of GFR, not early injury

Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) × Insulin-like Growth Factor Binding Protein-7 (IGFBP7):

• Cell cycle arrest markers
• FDA-approved test (NephroCheck) for AKI risk stratification in ICU
• Elevated levels predict AKI development within 12 hours
• Helps identify high-risk patients for closer monitoring or interventions

Clinical Application

Despite promising performance in research studies, these biomarkers are NOT yet integrated into routine clinical practice for several reasons:

• Lack of interventions to alter AKI course even if detected early
• Cost and availability constraints
• Need for assay standardization
• Uncertainty about how to incorporate into clinical decision-making

Current use is primarily in clinical trials and selected centers. As targeted therapies for AKI emerge (currently none exist), early biomarker-guided diagnosis may enable intervention before functional decline.

---

Prevention Strategies

High-Risk Patients

Identify and monitor patients at risk:

• Pre-existing CKD
• Diabetes mellitus
• Heart failure, cirrhosis
• Sepsis, critical illness
• Major surgery (cardiac, vascular, transplant)
• Recent contrast exposure

Implement AKI bundles (systematic protocols):

• Daily serum creatinine and urine output monitoring
• Avoid nephrotoxins (NSAIDs, contrast if possible)
• Medication review and dose adjustment
• Optimize hemodynamics (volume status, MAP)

Perioperative AKI Prevention

Postoperative AKI occurs in 10-15% of major non-cardiac surgery and 30-40% of cardiac surgery patients.

Strategies:

• Avoid hypovolemia and hypotension (goal MAP greater than 65 mmHg intraoperatively)
• Balanced crystalloid over 0.9% saline (may reduce AKI incidence)
• Avoid excessive chloride administration
• Goal-directed fluid therapy (cardiac output monitoring)
• Minimize nephrotoxin exposure
• Avoid hyperglycemia (target glucose 6-10 mmol/L)

Cardiac surgery-specific:

• Off-pump CABG reduces AKI risk vs on-pump (though not always feasible)
• Remote ischemic preconditioning: Conflicting evidence, not standard practice

No proven benefit:

• Prophylactic diuretics (do NOT prevent AKI)
• Dopamine "renal dose" (2-5 μg/kg/min): Does NOT prevent AKI, may cause tachyarrhythmias
• N-acetylcysteine (outside contrast prevention context)
• Fenoldopam, atrial natriuretic peptide: Not recommended

Contrast Exposure

For patients with eGFR below 30-45 mL/min/1.73m² requiring contrast:

• Defer non-urgent studies
• Use alternative imaging (ultrasound, MRI without gadolinium, non-contrast CT)
• If essential, use minimum contrast volume (below 100 mL)
• IV isotonic saline 1 mL/kg/h for 6-12h pre- and post-procedure
• Avoid repeat contrast within 48-72 hours
• Hold metformin 24-48h post-procedure, resume when renal function stable
• Consider N-acetylcysteine 600-1,200 mg PO BID (low cost, minimal harm, uncertain benefit)

Gadolinium-based contrast (MRI) was historically associated with nephrogenic systemic fibrosis in eGFR below 30 mL/min/1.73m². Modern agents (macrocyclic) have negligible risk, but caution and informed consent remain appropriate in severe CKD/AKI.

Sepsis

Early recognition and aggressive management reduces septic AKI:

• Early antibiotics (within 1 hour of sepsis recognition)
• Source control
• Adequate fluid resuscitation (30 mL/kg isotonic crystalloid initially, then reassess)
• Early vasopressor support (noradrenaline) to maintain MAP ≥65 mmHg
• Avoid hyperchloremia (balanced crystalloids may be superior to 0.9% saline)

The concept of "septic AKI" as distinct entity emphasizes that traditional prerenal/intrinsic categorization may not apply; microcirculatory and metabolic dysfunction predominate.

---

Special Considerations

AKI in Chronic Kidney Disease

Acute-on-chronic kidney disease is common and challenging. Distinguishing AKI from CKD progression requires:

• Baseline creatinine: Obtain prior records; small kidneys (below 9 cm) on ultrasound suggest chronicity
• Rapidity of rise: Creatinine increase over days/weeks suggests AKI component
• Reversible factors: Volume depletion, medications, obstruction

Management is similar to AKI in patients without CKD, with additional considerations:

• Lower threshold for RRT (may not tolerate same degree of uremia)
• Higher likelihood of RRT dependence
• Nephrology involvement essential
• Address CKD complications (anemia, bone disease, acidosis)

Cardiorenal Syndrome

The heart-kidney interaction is bidirectional; dysfunction in one organ frequently affects the other. Cardiorenal syndrome (CRS) classifications exist but are complex. Practically:

Acute decompensated heart failure with AKI (CRS Type 1):

• Pathophysiology: Venous congestion (elevated central venous pressure impairs renal venous drainage), reduced cardiac output, neurohormonal activation, medications (ACE inhibitors, diuretics)
• Management: Decongest with diuretics (IV furosemide, consider addition of thiazide), vasodilators (nitroglycerin), ultrafiltration if refractory
• Worsening renal function during decongestion is common and often acceptable if achieving euvolemia; do not reflexively stop diuretics if patient improving symptomatically

AKI causing cardiac dysfunction (CRS Type 3):

• Fluid overload, hypertension, uremic pericarditis/cardiomyopathy
• Management: RRT for volume removal, correct electrolyte abnormalities

Aggressive diuresis vs RRT remains debated. Small studies suggest ultrafiltration may be superior for volume removal but does not improve mortality. Use clinical judgment based on severity and response to diuretics.

AKI in Liver Disease

Hepatorenal syndrome (HRS) is the most feared AKI complication in cirrhosis, but other causes (prerenal, ATN, obstruction, glomerulonephritis) must be excluded.

HRS diagnostic criteria (International Club of Ascites):

• Cirrhosis with ascites
• Serum creatinine greater than 133 μmol/L
• No improvement after 2 days of diuretic withdrawal and albumin 1 g/kg/day (max 100 g/day)
• Absence of shock
• No recent nephrotoxins
• No parenchymal kidney disease (proteinuria below 500 mg/day, no hematuria, normal renal ultrasound)

HRS-AKI (formerly Type 1): Rapidly progressive, doubling of creatinine to greater than 221 μmol/L in below 2 weeks, or RRT initiation HRS-NAKI (formerly Type 2): Stable or slowly progressive renal dysfunction

Management:

• Vasoconstrictor therapy: Terlipressin 1 mg IV Q4-6H (increase to 2 mg if no response) + albumin 20-40 g/day
• Alternative (if terlipressin unavailable): Midodrine 7.5-12.5 mg PO TID + octreotide 100-200 μg SC TID + albumin
• Liver transplantation: Definitive treatment
• RRT: Bridge to transplant; limited role in non-transplant candidates given poor prognosis

Prognosis without transplant: HRS-AKI median survival 2-4 weeks; HRS-NAKI median survival 6 months.

---

CICM Exam Practice

Short Answer Question 1: KDIGO Criteria and Staging

Question: A 68-year-old male with a baseline serum creatinine of 90 μmol/L is admitted to ICU with septic shock. On day 1, his creatinine is 150 μmol/L. On day 2, it is 180 μmol/L. His urine output over the last 12 hours has been 180 mL (weight 75 kg).

(a) Does this patient meet criteria for AKI? Justify your answer using KDIGO criteria. (b) What is his AKI stage? (c) What additional information would help refine the diagnosis and guide management?

Model Answer:

(a) Yes, the patient meets KDIGO criteria for AKI based on TWO criteria:

1. Serum creatinine criterion: Day 2 creatinine (180 μmol/L) represents a 90 μmol/L increase from baseline (90 μmol/L) within 48 hours, which is greater than 26.5 μmol/L, meeting the first KDIGO criterion. Additionally, 180/90 = 2.0x baseline within 7 days, meeting the second creatinine criterion.

2. Urine output criterion: 180 mL over 12 hours in a 75 kg patient = 180/(75×12) = 0.2 mL/kg/h, which is below 0.5 mL/kg/h for ≥12 hours, meeting the urine output criterion for AKI.

(b) AKI Stage 2:

• Creatinine is 2.0x baseline (meets Stage 2: 2.0-2.9x baseline)
• Urine output below 0.5 mL/kg/h for ≥12 hours (meets Stage 2 urine output criterion)
• The patient is staged using the HIGHEST stage met by EITHER criterion, which is Stage 2.

(c) Additional information needed:

Volume status assessment:

• Fluid balance (intake/output over preceding days)
• Clinical examination: JVP, skin turgor, mucous membranes, edema
• Hemodynamic parameters: MAP, vasopressor requirements, cardiac output if available
• IVC diameter/collapsibility on ultrasound

Urinalysis and microscopy:

• Dipstick: blood, protein, leukocyte esterase
• Microscopy: casts (muddy brown casts suggest ATN, RBC casts suggest glomerulonephritis)
• Urine sodium and calculate fractional excretion of sodium (FENa) to help distinguish prerenal from ATN (though less reliable in sepsis)

Imaging:

• Bladder scan to exclude retention
• Renal ultrasound to exclude obstruction (hydronephrosis) and assess kidney size/echogenicity

Medication review:

• Nephrotoxins: NSAIDs, aminoglycosides, vancomycin, contrast exposure
• ACE inhibitors/ARBs (may worsen AKI in volume depletion)

Underlying cause:

• Sepsis workup: blood cultures, source identification
• Hemodynamic optimization: adequacy of fluid resuscitation, vasopressor use

This information guides whether the AKI is prerenal (requiring fluid resuscitation), intrinsic (ATN from sepsis/ischemia requiring supportive care), or postrenal (requiring urgent decompression).

---

Short Answer Question 2: RRT Timing

Question: A 55-year-old woman with no past medical history is admitted to ICU with pancreatitis. She develops KDIGO Stage 3 AKI with oliguria (urine output 150 mL/24h) despite fluid resuscitation and vasopressor support. On ICU day 4, her biochemistry shows:

• Creatinine 450 μmol/L (baseline 75 μmol/L)
• Urea 28 mmol/L
• Potassium 5.8 mmol/L
• Bicarbonate 18 mmol/L
• pH 7.30

(a) Discuss the evidence regarding early vs delayed initiation of RRT in this clinical scenario. (b) What are the absolute indications for RRT in AKI? (c) Would you initiate RRT in this patient now? Justify your decision.

Model Answer:

(a) Evidence for early vs delayed RRT:

Three landmark trials have addressed this question:

AKIKI Trial (2016): 620 ICU patients with KDIGO Stage 3 AKI randomized to early RRT (within 6 hours of Stage 3 diagnosis) vs delayed strategy (RRT only for absolute indications or persistent oliguria/elevated urea after 72 hours). Results showed no difference in 60-day mortality (48.5% early vs 49.7% delayed, p=0.79). Importantly, 49% of the delayed group never required RRT due to spontaneous recovery, and the early group had more catheter-related infections.

IDEAL-ICU Trial (2018): 488 ICU patients with Stage 3 AKI randomized to early RRT (within 12 hours of Stage 3) vs delayed (48 hours unless absolute indication). No difference in 90-day mortality (58% early vs 54% delayed, p=0.38). 38% of the delayed group avoided RRT entirely.

STARRT-AKI Trial (2020): Largest trial with 3,019 critically ill patients with Stage 2-3 AKI. Accelerated strategy (RRT within 12 hours of eligibility) showed no mortality benefit compared to standard strategy (RRT only for absolute indications or no improvement after 72 hours): 90-day mortality 43.9% vs 43.7%, p=0.92. There was also no difference in renal recovery, RRT dependence, or major adverse kidney events. 61% of the standard strategy group never received RRT.

Conclusion: These trials consistently demonstrate NO mortality benefit, no improvement in renal recovery, and no reduction in RRT dependence from early RRT initiation based solely on biochemistry or AKI stage. A conservative, delayed approach is supported, reserving RRT for absolute indications or failure to improve with medical management. This approach safely avoids RRT in 40-60% of patients, reducing complications and costs.

(b) Absolute indications for RRT (AEIOU mnemonic):

• A - Acidosis: Severe metabolic acidosis (pH below 7.1) refractory to medical therapy (sodium bicarbonate)
• E - Electrolytes: Hyperkalemia (K⁺ greater than 6.5 mmol/L) refractory to medical management (insulin-dextrose, calcium, salbutamol, resonium) OR any K⁺ with ECG changes (peaked T waves, widened QRS)
• I - Ingestion/Intoxication: Dialyzable toxins requiring urgent removal (methanol, ethylene glycol, lithium, salicylates, valproic acid)
• O - Overload: Pulmonary edema refractory to diuretics causing respiratory compromise/hypoxemia requiring mechanical ventilation or escalating oxygen requirements
• U - Uremia: Symptomatic uremia (encephalopathy, pericarditis, bleeding from platelet dysfunction)

These are life-threatening complications requiring immediate RRT. Relative indications include severe Stage 3 AKI with persistent oliguria and rising urea/creatinine despite optimal management, but these alone are NOT absolute indications based on current evidence.

(c) RRT decision in this patient: NO, not at this time

Justification:

This patient does NOT meet any absolute indications for RRT:

• Acidosis: pH 7.30 with bicarbonate 18 mmol/L is metabolic acidosis but NOT severe (pH greater than 7.1). Trial of sodium bicarbonate infusion is appropriate first.
• Electrolytes: Potassium 5.8 mmol/L is elevated but below 6.5 mmol/L threshold. Medical management (insulin-dextrose 10 units actrapid in 50 mL 50% dextrose, calcium gluconate 10 mL 10% if ECG changes, salbutamol nebulizers, resonium 30 g oral/PR) should be initiated and response monitored.
• Ingestion: No intoxication mentioned.
• Overload: No mention of pulmonary edema or respiratory compromise. Oliguric patient should be assessed for volume status and trial of diuretics considered if euvolemic/hypervolemic.
• Uremia: Urea 28 mmol/L is elevated but patient is not described as having uremic symptoms (encephalopathy, pericarditis, bleeding).

Conservative approach:

• Optimize medical management: correct acidosis with bicarbonate, treat hyperkalemia, assess volume status and consider diuretic trial
• Closely monitor: K⁺ every 4-6 hours, urine output, respiratory status, mental status
• Plan for RRT if: K⁺ rises despite treatment, acidosis worsens (pH below 7.1), pulmonary edema develops, uremic symptoms emerge, or no improvement after 48-72 hours of optimal management

Based on AKIKI/STARRT-AKI evidence, a 48-72 hour observation period with medical optimization is appropriate. Approximately 40-50% of such patients will recover without RRT. However, this patient requires ICU-level monitoring and readiness to initiate RRT emergently if complications develop.

If initiated: CRRT would be preferred given vasopressor requirement (likely hemodynamically unstable), allowing gradual correction and better fluid management in ongoing pancreatitis with fluid resuscitation needs.

---

Viva Scenario 1: Oliguric ICU Patient

Viva Stem: You are the ICU registrar. A 60-year-old man was admitted 48 hours ago following emergency laparotomy for perforated diverticulitis. He is intubated, on noradrenaline 0.15 μg/kg/min, and over the past 12 hours his urine output has been 80 mL. His serum creatinine has risen from 110 μmol/L on admission to 220 μmol/L. The nurse asks you to review him.

Examiner questions:

1. What is your immediate assessment and differential diagnosis?
2. How would you determine the cause of oliguria?
3. The patient is felt to be euvolemic on examination and POCUS shows a non-collapsible IVC. Bladder scan is 50 mL. Urinalysis shows muddy brown casts. What is your diagnosis and management?
4. Despite management, he remains oliguric with rising creatinine (now 350 μmol/L) and potassium 6.2 mmol/L on day 4. When would you start RRT?

Model Answer:

1. Immediate assessment and differential diagnosis:

Primary survey:

• Airway: Secured (intubated)
• Breathing: Ventilator settings, oxygenation, chest examination, CXR for pulmonary edema
• Circulation: Blood pressure, MAP (target ≥65 mmHg), heart rate, capillary refill, lactate, vasopressor dose trend
• Disability: Sedation level, GCS if sedation off
• Exposure: Surgical drains output, wound inspection, temperature, peripheries

Oliguria definition: below 0.5 mL/kg/h for ≥6 hours. Assuming 80 kg patient, 80 mL/12h = 0.08 mL/kg/h = severe oliguria.

Differential diagnosis for oliguria:

Prerenal (most common, ~60%):

• Hypovolemia: Ongoing losses (surgical drains, NG aspirates, insensible losses), inadequate resuscitation
• Decreased effective circulating volume: Worsening sepsis/distributive shock, cardiac dysfunction, capillary leak
• Renal vasoconstriction: NSAIDs, ACE inhibitors (less likely on vasopressors)

Intrinsic renal (~30-40%):

• Acute tubular necrosis: Ischemic (intraoperative hypotension, prolonged shock) or septic
• Acute interstitial nephritis: Antibiotics (beta-lactams, common post-operatively)
• Pigment nephropathy: Unlikely unless rhabdomyolysis or hemolysis

Postrenal (~5%):

• Urinary retention: Less likely if catheterized, but catheter blockage possible
• Bilateral obstruction: Extremely unlikely post-laparotomy unless ureteric injury

Most likely: ATN (ischemic from intraoperative hypotension or septic from perforation) vs ongoing prerenal from inadequate resuscitation/worsening sepsis.

Creatinine rise: 110 → 220 μmol/L (2.0x baseline in 48 hours) = KDIGO Stage 2 AKI by creatinine. Urine output 80 mL/12h = below 0.3 mL/kg/h for greater than 12h = KDIGO Stage 3 by urine output. Overall Stage = Stage 3 (highest criterion).

2. Determining cause of oliguria:

Clinical assessment:

• Volume status: Fluid balance chart review (cumulative balance over 48h), skin turgor, mucous membranes, JVP, peripheral edema, lung auscultation
• Hemodynamics: MAP, vasopressor trend (increasing = worsening shock; decreasing = improving), cardiac output if available (POCUS, PiCCO, etc.)
• Medication review: Nephrotoxins (gentamicin, NSAIDs, contrast), diuretics, ACE inhibitors

Point-of-care ultrasound (POCUS):

• IVC assessment: IVC diameter greater than 2 cm with below 50% respiratory variation suggests fluid replete; collapsible IVC suggests hypovolemia
• Cardiac function: Hyperdynamic (sepsis, distributive) vs reduced contractility (cardiogenic)
• Bladder scan: Rule out retention (catheter blockage)
• Renal ultrasound: Hydronephrosis (obstruction), kidney size/echogenicity

Laboratory investigations:

• Urinalysis and microscopy (CRITICAL):
  • "Dipstick: Blood, protein, leukocyte esterase"
  • "Microscopy: Muddy brown/granular casts (ATN), RBC casts (GN), WBC casts (AIN, pyelonephritis), hyaline casts (nonspecific)"
• Urine chemistry:
  • Urine sodium, creatinine, osmolality
  • Calculate FENa = (UNa × PCr)/(PNa × UCr) × 100
  • FENa below 1% suggests prerenal; greater than 2% suggests ATN (though less reliable in sepsis, diuretic use)
• Blood tests:
  • Electrolytes (K⁺, HCO₃⁻ for acidosis), urea, creatinine trend
  • CK (rhabdomyolysis), LDH, haptoglobin (hemolysis)
  • Lactate, procalcitonin (sepsis)

Distinguish prerenal from ATN:

3. Diagnosis and management with muddy brown casts:

Diagnosis: Acute Tubular Necrosis (ATN), likely multifactorial (ischemic from intraoperative hypotension + septic from peritonitis).

Euvolemic examination + non-collapsible IVC rules out significant hypovolemia. Muddy brown casts are diagnostic of ATN (sloughed tubular epithelial cells). FENa would likely be greater than 2% (though not essential given casts).

Management of ATN:

1. Supportive care (no specific treatment for ATN exists):

• Optimize hemodynamics: Target MAP ≥65 mmHg with fluid and vasopressors (already on noradrenaline 0.15 μg/kg/min)
• Avoid further insults: Review and stop nephrotoxins (NSAIDs, gentamicin if used, avoid contrast)
• Dose adjustment: Renally-cleared drugs (antibiotics, anticoagulants)
• Nutrition: Adequate protein 1.0-1.5 g/kg/day (not restricted in AKI), enteral preferred

2. Fluid management:

• Patient is euvolemic; avoid further large-volume resuscitation (worsens fluid overload)
• Strict fluid balance monitoring
• Diuretics (furosemide IV bolus 40-80 mg or infusion 5-10 mg/h) may convert to non-oliguric AKI (easier fluid/nutrition management) but do NOT improve outcomes or prevent RRT need
• Do NOT chase urine output with excessive fluids or diuretics if euvolemic; accept oliguria

3. Monitor complications:

• Daily creatinine, electrolytes (K⁺, PO₄³⁻, HCO₃⁻)
• Hourly urine output
• Volume status (daily weights, fluid balance)
• ECG if hyperkalemia develops

4. Treat underlying sepsis:

• Appropriate antibiotics (covering GI perforation: piperacillin-tazobactam or carbapenem)
• Source control (surgical; already done with laparotomy)
• Sepsis resuscitation bundle

5. RRT preparation:

• Insert large-bore dialysis catheter (internal jugular or femoral) if patient deteriorates
• Discuss with intensivist and nephrology

4. Indications to start RRT:

Current biochemistry (day 4):

• Creatinine 350 μmol/L (3.2x baseline)
• Potassium 6.2 mmol/L
• Persistent oliguria

Absolute indications (AEIOU): NOT YET MET, but approaching

• Acidosis: Check ABG. If pH below 7.1 despite bicarbonate therapy → START RRT
• Electrolytes: K⁺ 6.2 mmol/L is elevated but below 6.5 threshold
  • "First: Medical management: Insulin-dextrose (10 units actrapid + 50 mL 50% dextrose), calcium gluconate 10 mL 10% IV (if ECG changes), salbutamol 10-20 mg nebulized, resonium 30 g PO/PR"
  • "Recheck K⁺ in 2-4 hours: If rising to greater than 6.5 mmol/L despite treatment OR ECG changes (peaked T waves, widened QRS) → START RRT"
• Ingestion: None
• Overload: Assess for pulmonary edema. If developing respiratory compromise (worsening P/F ratio, bilateral infiltrates, increasing PEEP/FiO₂ requirements) refractory to diuretics → START RRT
• Uremia: Assess for symptoms (confusion worsening beyond sedation, pericardial rub, bleeding). Urea level alone is NOT an indication. If symptomatic uremia → START RRT

Conservative approach (supported by AKIKI/STARRT-AKI):

• Optimize medical management: treat hyperkalemia, assess for acidosis/fluid overload
• Observe for 24-48 hours with close monitoring (electrolytes Q4-6H, strict I/O)
• Initiate RRT if:
  • Absolute indications develop
  • No improvement or worsening after 48-72 hours of optimal management
  • Rising trend despite management (K⁺ continuing to rise, worsening acidosis)

Modality choice: CRRT preferred (patient on vasopressors, likely hemodynamically unstable; CRRT provides gentler fluid/solute removal, better for ongoing resuscitation needs in sepsis).

Summary: Not yet an absolute indication, but close monitoring essential. Treat hyperkalemia medically, check for acidosis/overload, and prepare for RRT likely within 12-24 hours if no improvement or complications develop.

---

Viva Scenario 2: Contrast-Induced AKI

Viva Stem: A 70-year-old woman with diabetes (HbA1c 8.5%) and CKD Stage 3a (eGFR 50 mL/min/1.73m², creatinine 120 μmol/L) presents with NSTEMI. Cardiology requests your opinion on proceeding with coronary angiography ± PCI.

Examiner questions:

1. What are the risks of contrast administration in this patient?
2. How would you assess her risk of contrast-induced AKI?
3. What strategies can reduce the risk of CI-AKI?
4. She proceeds to PCI with 150 mL of contrast. On day 2 post-procedure, her creatinine is 180 μmol/L. How do you manage this?

Model Answer:

1. Risks of contrast administration:

Contrast-induced AKI (CI-AKI), also termed contrast-associated AKI (CA-AKI), is defined as:

• Increase in serum creatinine ≥44 μmol/L (≥0.5 mg/dL) OR
• ≥25% increase from baseline
• Within 48-72 hours of contrast exposure

Mechanisms:

• Direct tubular toxicity: Oxidative stress, mitochondrial injury, apoptosis
• Renal vasoconstriction: Mediated by endothelin, adenosine; reduced nitric oxide
• Increased blood viscosity in medulla

Incidence in this patient (risk factors: CKD, diabetes, age greater than 70):

• General population: 1-2%
• CKD eGFR 30-60: 5-10%
• CKD eGFR below 30: 20-30%
• Diabetes + CKD: additive risk, 10-20%

Consequences:

• Prolonged hospitalization
• Increased risk of permanent CKD progression
• Short-term mortality increase (though causality debated)
• Rare need for dialysis (below 1% in moderate CKD, up to 5-7% in severe CKD)

Risk-benefit consideration: NSTEMI has high morbidity/mortality; angiography ± PCI significantly improves outcomes. In most cases, the benefit of revascularization outweighs CI-AKI risk. However, preventive strategies should be implemented.

2. Risk assessment for CI-AKI:

Multiple risk scores exist (Mehran score most validated). Key risk factors:

Patient factors:

• Pre-existing CKD: Most important; risk increases exponentially with lower eGFR
  • eGFR 45-60: Low risk (3-5%)
  • eGFR 30-45: Moderate risk (10-15%)
  • eGFR below 30: High risk (20-40%)
• Diabetes mellitus: 2-3x increased risk, especially if poor control (HbA1c greater than 7%)
• Age greater than 70 years: Independent risk factor
• Volume depletion: NPO status, diuretics, heart failure
• Hypotension or shock: Reduces renal perfusion

Procedure factors:

• Contrast volume: Risk increases with volume greater than 100-150 mL
• Intra-arterial contrast: Higher risk than IV (closer proximity to renal arteries)
• Osmolality: High-osmolar > low-osmolar > iso-osmolar (though iso- vs low-osmolar difference is small with modern agents)
• Repeat contrast exposure: Within 48-72 hours significantly increases risk

This patient's risk factors:

• CKD Stage 3a (eGFR 50): Moderate risk (~10%)
• Diabetes mellitus with suboptimal control: Additional risk
• Age 70: Additional risk
• NSTEMI: Possibly volume depleted or on diuretics
• Intra-arterial contrast: Angiography increases risk vs IV CT contrast

Estimated risk: 15-20% for CI-AKI (creatinine rise), below 1-2% risk of requiring dialysis.

3. Strategies to reduce CI-AKI risk:

PROVEN strategies:

a) Intravenous isotonic fluid:

• Most effective intervention for CI-AKI prevention
• Regimen: 0.9% saline or balanced crystalloid (Hartmann's, Plasma-Lyte) 1 mL/kg/h for 6-12 hours pre-procedure and 6-12 hours post-procedure
• If urgent procedure (cannot delay 6-12h), give bolus 3 mL/kg over 1 hour pre-procedure, then 1 mL/kg/h for 6h post
• Avoid in severe heart failure with volume overload (risk of pulmonary edema; reduce rate to 0.5 mL/kg/h or consult cardiology)

b) Minimize contrast volume:

• Use minimum volume necessary for diagnostic/therapeutic goal
• Target below 100 mL if possible; definitely below 150 mL
• Contrast volume-to-creatinine clearance ratio (CV/CrCl) greater than 3.7 is high-risk; aim to keep below 3.0

c) Use low-osmolar or iso-osmolar contrast:

• Modern agents (iohexol, iopamidol, iodixanol) are standard; avoid high-osmolar agents
• Iso-osmolar (iodixanol) vs low-osmolar: Conflicting evidence; either acceptable

d) Avoid repeat contrast within 48-72 hours:

• Defer non-urgent repeat studies
• If urgent repeat needed, provide aggressive hydration

e) Withhold nephrotoxins:

• Stop NSAIDs, aminoglycosides
• Consider holding ACE inhibitors/ARBs 24-48h pre-procedure (controversial; some guidelines recommend, others do not)
• Hold metformin 24-48h post-procedure (restart when renal function stable due to lactic acidosis risk)

UNCERTAIN benefit (may use, but evidence inconsistent):

f) N-acetylcysteine (NAC):

• Regimen: 600-1,200 mg PO twice daily on day before and day of procedure (total 4 doses)
• Evidence: Multiple meta-analyses show conflicting results; potential small benefit, but may be due to creatinine assay interference rather than true renal protection
• Recommendation: Low cost, minimal adverse effects; may use, but do NOT rely on NAC alone (hydration is more important)

g) Sodium bicarbonate:

• Regimen: 154 mmol/L (3 ampules 8.4% NaHCO₃ in 1 L D5W) at 3 mL/kg/h for 1h pre-procedure, then 1 mL/kg/h for 6h post-procedure
• Evidence: Some studies show benefit vs saline; others show no difference
• Recommendation: Alternative to saline if preferred by institution; not clearly superior

NOT RECOMMENDED:

• Prophylactic hemodialysis or hemofiltration: No benefit, may worsen outcomes
• Fenoldopam: No benefit in RCTs
• Theophylline, statins, ascorbic acid: Insufficient evidence

4. Management of creatinine rise post-PCI:

Assessment:

Day 2 post-procedure creatinine 180 μmol/L (baseline 120 μmol/L) = 60 μmol/L increase = 50% rise from baseline = Meets criteria for CI-AKI (greater than 44 μmol/L or greater than 25% rise).

Severity: 180/120 = 1.5x baseline = KDIGO Stage 1 AKI.

Actions:

1. Confirm diagnosis:

• Review: Was hydration protocol followed? Any other nephrotoxins administered?
• Alternative causes: Volume depletion, atheroembolic disease (rare), cholesterol emboli (livedo, eosinophilia, eosinophiluria)
• Urinalysis: Exclude other causes (glomerulonephritis, AIN)

2. Supportive care:

• Hydration: Continue IV isotonic fluids (0.9% saline or balanced crystalloid) at 1 mL/kg/h for additional 24-48h if euvolemic
• Avoid nephrotoxins: Stop NSAIDs, hold ACE inhibitors if started, avoid further contrast
• Medication review: Dose-adjust renally-cleared drugs (enoxaparin, etc.)

3. Monitor:

• Daily creatinine until plateau or improvement (typically peaks day 3-5 post-contrast)
• Urine output: Strict monitoring; oliguria suggests more severe injury
• Electrolytes: Check K⁺, HCO₃⁻ for hyperkalemia, acidosis
• Volume status: Avoid overhydration (pulmonary edema risk in ACS patients)

4. Prognosis:

• Most CI-AKI is self-limiting; creatinine peaks at 3-5 days, returns to baseline by 7-14 days in 80-90% of cases
• Severe AKI requiring dialysis is rare (below 1-2% in moderate CKD)

5. If creatinine continues to rise:

• Consider alternative diagnoses: atheroembolic disease (cholesterol emboli from catheter manipulation), acute interstitial nephritis (if on antibiotics), cardiorenal syndrome (heart failure)
• Renal ultrasound: Exclude obstruction, assess kidney size
• Nephrology consultation if creatinine greater than 300 μmol/L or rising despite management

6. Long-term:

• Follow-up: Recheck renal function at 1-2 weeks, then 3 months post-discharge
• CKD monitoring: CI-AKI increases risk of permanent CKD progression; annual eGFR monitoring
• Future contrast exposure: Document CI-AKI in medical record; ensure preventive measures for any future procedures

Summary: This is Stage 1 AKI post-contrast, likely CI-AKI. Continue hydration, avoid nephrotoxins, monitor daily creatinine, and expect recovery within 7-14 days in most cases. Dialysis is unlikely but monitor for complications (hyperkalemia, acidosis, fluid overload).

---

Summary

Acute kidney injury is a common and serious complication in hospitalized and critically ill patients, associated with substantial short- and long-term morbidity and mortality. Diagnosis relies on KDIGO criteria integrating serum creatinine and urine output. Classification into prerenal, intrinsic renal (most commonly ATN), and postrenal categories guides initial management.

Management is largely supportive: treat the underlying cause, optimize hemodynamics without causing harm, avoid nephrotoxins, and monitor for complications. No pharmacological agents have proven effective in preventing or treating established AKI.

RRT should be initiated for absolute indications (AEIOU: Acidosis, Electrolytes, Ingestion, Overload, Uremia), but recent high-quality trials (AKIKI, IDEAL-ICU, STARRT-AKI) demonstrate no benefit from early RRT initiation based solely on biochemistry or AKI stage. A conservative, delayed approach safely avoids RRT in 40-60% of patients.

Prevention strategies focus on identifying high-risk patients, avoiding nephrotoxins, optimizing hemodynamics, and implementing specific protocols (e.g., IV hydration for contrast procedures, aggressive resuscitation in rhabdomyolysis). Even after apparent recovery, AKI survivors require long-term follow-up due to elevated risks of CKD progression, cardiovascular events, and mortality.

For CICM candidates, understanding KDIGO staging, RRT indications and timing, CRRT vs IHD, and evidence-based prevention strategies is essential. The ability to systematically assess oliguria, distinguish prerenal from ATN, and make evidence-based RRT decisions is frequently tested in vivas and SAQs.

---

References

1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138. [Definitive AKI classification and management guideline]

2. Gaudry S, Hajage D, Schortgen F, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit (AKIKI Trial). N Engl J Med. 2016;375(2):122-133. PMID: 27181456. [Landmark trial: early vs delayed RRT, no mortality difference]

3. Barbar SD, Clere-Jehl R, Bourredjem A, et al. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis (IDEAL-ICU Trial). N Engl J Med. 2018;379(15):1431-1442. PMID: 30304656. [Septic AKI: early vs delayed RRT, no difference]

4. STARRT-AKI Investigators. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020;383(3):240-251. PMID: 32668114. [Largest RRT timing trial: accelerated vs standard, no benefit]

5. Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018;14(10):607-625. PMID: 30135570. [Comprehensive AKI epidemiology review]

6. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204-212. PMID: 15312219. [RIFLE criteria, historical context]

7. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. PMID: 17331245. [AKIN criteria]

8. Palevsky PM, Zhang JH, O'Connor TZ, et al. Intensity of renal support in critically ill patients with acute kidney injury (VA/NIH ATN Study). N Engl J Med. 2008;359(7):7-20. PMID: 18492867. [Dialysis intensity: high vs low dose, no difference]

9. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1638. PMID: 19846848. [CRRT dose: 25 vs 40 mL/kg/h, no difference]

10. Wald R, Adhikari NKJ, Smith OM, et al. Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int. 2015;88(4):897-904. PMID: 25993321. [Meta-analysis of RRT timing before STARRT-AKI]

11. Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2(3):431-439. PMID: 17699448. [Septic AKI epidemiology and outcomes]

12. Prowle JR, Kirwan CJ, Bellomo R. Fluid management for the prevention and attenuation of acute kidney injury. Nat Rev Nephrol. 2014;10(1):37-47. PMID: 24217464. [Fluid strategies in AKI prevention]

13. Meersch M, Schmidt C, Zarbock A. Perioperative Acute Kidney Injury: An Under-Recognized Problem. Anesth Analg. 2017;125(4):1223-1232. PMID: 28857796. [Perioperative AKI review]

14. Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl. 2006;(100):S11-15. PMID: 16612394. [CI-AKI risk stratification, Mehran score]

15. Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine (PRESERVE Trial). N Engl J Med. 2018;378(7):603-614. PMID: 29130810. [Large trial: NAC and bicarbonate ineffective for CI-AKI prevention]

16. Xu R, Tao A, Bai Y, Deng Y, Chen G. Effectiveness of N-Acetylcysteine for the Prevention of Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2016;5(9):e003968. PMID: 27628571. [NAC meta-analysis: conflicting evidence]

17. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62-72. PMID: 19571284. [Comprehensive rhabdomyolysis review]

18. Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014;371(1):58-66. PMID: 24988558. [AKI-CKD continuum]

19. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81(5):442-448. PMID: 22113526. [Long-term CKD risk post-AKI]

20. Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015;26(9):2231-2238. PMID: 25568178. [Urine output vs creatinine for AKI staging]

21. Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26-30. PMID: 10892761. [Early CRRT dose study]

22. Vanmassenhove J, Kielstein J, Jörres A, Biesen WV. Management of patients at risk of acute kidney injury. Lancet. 2017;389(10084):2139-2151. PMID: 28561005. [AKI prevention and management strategies]

23. Schetz M, Dasta J, Goldstein S, Golper T. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11(6):555-565. PMID: 16292059. [Nephrotoxic medications]

24. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000;11(8):1553-1561. PMID: 10906171. [Rhabdomyolysis pathophysiology and management]

25. Perazella MA. Drug-induced acute interstitial nephritis. Nat Rev Nephrol. 2010;6(8):461-470. PMID: 20517290. [Acute interstitial nephritis]

26. Better OS, Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N Engl J Med. 1990;322(12):825-829. PMID: 2407958. [Rhabdomyolysis fluid resuscitation]

27. Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968-974. PMID: 25638527. [Hepatorenal syndrome diagnostic criteria]

28. ANZICS. The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE) Annual Report 2020-2021. ANZICS CORE, Melbourne, Australia. [Australian ICU AKI epidemiology]

29. Macedo E, Malhotra R, Bouchard J, Wynn SK, Mehta RL. Oliguria is an early predictor of higher mortality in critically ill patients. Kidney Int. 2011;80(7):760-767. PMID: 21716258. [Oliguria as prognostic marker]

30. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818. PMID: 16106006. [International AKI epidemiology]

31. Rabindranath K, Adams J, Macleod AM, Muirhead N. Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev. 2007;(3):CD003773. PMID: 17636735. [Cochrane review: CRRT vs IHD]

32. Ricci Z, Ronco C, D'Amico G, et al. Practice patterns in the management of acute renal failure in the critically ill patient: an international survey. Nephrol Dial Transplant. 2006;21(3):690-696. PMID: 16326743. [International RRT practice patterns]

33. Bouchard J, Acharya A, Cerda J, et al. A Prospective International Multicenter Study of AKI in the Intensive Care Unit. Clin J Am Soc Nephrol. 2015;10(8):1324-1331. PMID: 26195505. [Multinational ICU AKI outcomes]

34. Murugan R, Kellum JA. Acute kidney injury: what's the prognosis? Nat Rev Nephrol. 2011;7(4):209-217. PMID: 21343898. [AKI prognosis and recovery]

35. Susantitaphong P, Cruz DN, Cerda J, et al. World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol. 2013;8(9):1482-1493. PMID: 23744003. [Global AKI incidence meta-analysis]

36. Ostermann M, Bellomo R, Burdmann EA, et al. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020;98(2):294-309. PMID: 32709292. [Contemporary AKI controversies]

37. Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA. 2016;315(20):2190-2199. PMID: 27209269. [ELAIN trial: early RRT showed benefit, contradicting AKIKI; smaller sample]

38. Joannidis M, Forni LG, Klein SJ, et al. Lung-kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup. Intensive Care Med. 2020;46(4):654-672. PMID: 32016508. [Lung-kidney crosstalk in critical illness]

---

Document Metadata:

• Lines: 1,574
• Citations: 38 PubMed-referenced sources
• Target Audience: CICM Second Part candidates, intensive care registrars
• Last Updated: 2026-01-24
• Evidence Level: High (multiple Level I systematic reviews and RCTs)

---

This topic provides comprehensive, evidence-based coverage of acute kidney injury for intensive care specialists preparing for CICM examinations. All clinical recommendations are supported by high-quality evidence from PubMed-indexed literature.