Oliguria in Adults

Overview

Oliguria is defined as urine output less than 0.5 mL/kg/hr in adults, or less than 400 mL per 24 hours in an average 70 kg adult. [1] It represents a critical clinical sign that indicates impaired renal perfusion, intrinsic renal parenchymal injury, or urinary tract obstruction. Oliguria is a cardinal feature of acute kidney injury (AKI) and serves as both a diagnostic criterion and prognostic indicator in critically ill patients. [2]

The recognition and management of oliguria is fundamental to preventing progression to established AKI and subsequent chronic kidney disease. Early differentiation between prerenal, intrinsic renal, and postrenal causes is essential, as prerenal oliguria is potentially reversible with appropriate fluid resuscitation and hemodynamic optimization, whereas delays in diagnosis can lead to irreversible tubular injury. [3] In intensive care settings, oliguria occurs in approximately 15-25% of critically ill patients and is associated with increased mortality, prolonged hospital stay, and heightened risk of requiring renal replacement therapy. [4]

The systematic approach to oliguria requires understanding of renal physiology, careful clinical assessment, interpretation of urinary biochemistry, and knowledge of the KDIGO (Kidney Disease: Improving Global Outcomes) classification system for AKI staging. This topic is high-yield for MRCP, FRACP, and critical care examinations, particularly in scenarios involving shocked patients, postoperative oliguria, or complicated medical admissions.

Epidemiology

Oliguria is a common clinical presentation in both hospital and intensive care settings, with significant implications for patient outcomes.

Risk Factors for Development of Oliguria:

1. Patient Factors:

   • Advanced age (>65 years)
   • Pre-existing chronic kidney disease
   • Diabetes mellitus
   • Heart failure
   • Liver cirrhosis
   • Sepsis and multiorgan dysfunction

2. Iatrogenic Factors:

   • Major surgery (cardiac, vascular, abdominal)
   • Nephrotoxic medications (NSAIDs, aminoglycosides, ACE inhibitors, ARBs)
   • Radiocontrast exposure
   • Rhabdomyolysis-inducing drugs or conditions

3. Environmental and Clinical Context:

   • Hypovolemia and hemorrhage
   • Hemodynamic instability and shock states
   • Prolonged hypotension or cardiac arrest

The incidence of AKI has increased by approximately 10% per year over the last two decades, largely due to aging populations, increased prevalence of chronic diseases, and greater recognition through standardized definitions. [9]

Aetiology & Pathophysiology

Oliguria results from three broad pathophysiological categories: prerenal (functional), intrinsic renal (structural), and postrenal (obstructive). Understanding these mechanisms is critical for targeted management.

Prerenal Causes (60-70% of Cases)

Prerenal oliguria occurs when renal perfusion is inadequate to maintain glomerular filtration, despite structurally intact kidneys. The kidney responds appropriately by conserving sodium and water, producing concentrated urine with low sodium content. [10]

Mechanisms:

1. True Volume Depletion:

   • Hemorrhage (trauma, gastrointestinal bleeding, surgical)
   • Gastrointestinal losses (vomiting, diarrhea, nasogastric drainage)
   • Renal losses (diuretics, osmotic diuresis, diabetes insipidus)
   • Third-space sequestration (pancreatitis, bowel obstruction, burns)
   • Insensible losses (fever, tachypnea)

2. Relative Volume Depletion (Effective Arterial Blood Volume Reduction):

   • Heart failure with reduced ejection fraction
   • Cirrhosis with hepatorenal syndrome
   • Nephrotic syndrome with severe hypoalbuminemia
   • Septic shock with distributive physiology

3. Renal Artery Pathology:

   • Bilateral renal artery stenosis or thrombosis
   • Aortic dissection involving renal arteries
   • Atheroembolic disease

4. Afferent Arteriolar Vasoconstriction:

   • NSAIDs (inhibit prostaglandin-mediated vasodilation)
   • Calcineurin inhibitors (cyclosporine, tacrolimus)
   • Hypercalcemia
   • Hepatorenal syndrome

5. Efferent Arteriolar Vasodilation:

   • ACE inhibitors and ARBs (especially in bilateral RAS or volume depletion)

Exam Detail: Molecular Pathophysiology of Prerenal Oliguria:

When renal perfusion pressure falls below the autoregulatory threshold (typically mean arterial pressure less than 60-70 mmHg), glomerular filtration rate (GFR) decreases. This triggers a cascade of compensatory mechanisms:

1. Renin-Angiotensin-Aldosterone System (RAAS) Activation:

   • Juxtaglomerular cells detect reduced renal perfusion and release renin
   • Angiotensin II causes efferent arteriolar vasoconstriction, maintaining glomerular capillary pressure
   • Aldosterone increases distal tubular sodium reabsorption
   • Result: Fractional excretion of sodium (FENa) typically less than 1%

2. Antidiuretic Hormone (ADH) Release:

   • Stimulated by baroreceptors detecting reduced effective arterial blood volume
   • Increases water reabsorption in collecting ducts via aquaporin-2 channels
   • Result: Urine osmolality >500 mOsm/kg, urine:plasma osmolality >1.5

3. Sympathetic Nervous System Activation:

   • Enhances proximal tubular sodium reabsorption
   • Stimulates renin release
   • Causes renal vasoconstriction if severe

4. Tubular Response:

   • Increased proximal tubular sodium and water reabsorption (>98%)
   • Increased urea reabsorption (urea:creatinine ratio typically >20:1)
   • Preserved tubular function allows appropriate concentration

Critical Threshold Concept: If prerenal oliguria persists beyond 24-48 hours, ischemic tubular injury occurs, leading to acute tubular necrosis (ATN). This represents progression from functional to structural kidney injury and is characterized by loss of urinary concentrating ability and development of muddy brown casts on urinalysis. [11]

Intrinsic Renal Causes (25-40% of Cases)

Intrinsic renal oliguria results from direct injury to renal parenchyma affecting glomeruli, tubules, interstitium, or vasculature.

1. Acute Tubular Necrosis (ATN) - Most Common Intrinsic Cause:

• Ischemic ATN: Prolonged or severe prerenal insult

  • Hypotension (mean BP less than 60 mmHg for >30 minutes)
  • Cardiac arrest
  • Major surgery with prolonged hypotension
  • Septic shock

• Nephrotoxic ATN:

  • "Medications: aminoglycosides, amphotericin B, cisplatin, vancomycin"
  • Contrast-induced nephropathy (especially with pre-existing CKD, diabetes, volume depletion)
  • "Endogenous toxins: myoglobin (rhabdomyolysis), hemoglobin (hemolysis), light chains (myeloma)"

2. Acute Glomerulonephritis:

• Rapidly progressive glomerulonephritis (RPGN)
• Post-infectious glomerulonephritis
• Lupus nephritis
• IgA nephropathy with crescents
• Anti-GBM disease (Goodpasture syndrome)
• ANCA-associated vasculitis

3. Acute Interstitial Nephritis (AIN):

• Drug-induced (beta-lactams, NSAIDs, PPIs, allopurinol, 5-ASA)
• Infection-related
• Autoimmune (SLE, Sjögren's, sarcoidosis)

4. Vascular Causes:

• Renal vein thrombosis
• Malignant hypertension
• Thrombotic microangiopathy (TTP, HUS, DIC)
• Scleroderma renal crisis
• Atheroembolic disease

Exam Detail: Pathophysiology of Acute Tubular Necrosis:

ATN represents the most common cause of intrinsic AKI and involves a complex pathophysiological sequence:

1. Initiation Phase (Hours to Days):

   • Tubular epithelial cell injury from ischemia or toxins
   • ATP depletion leads to loss of cell polarity and Na⁺-K⁺-ATPase function
   • Cytoskeletal disruption causes loss of brush border
   • Tight junction disruption allows backleak of filtrate

2. Extension Phase (Days)1):

   • Continued hypoxia despite restoration of blood flow (paradoxical phenomenon)
   • Inflammatory response with leucocyte infiltration
   • Endothelial dysfunction and microvascular congestion
   • Tubular obstruction from cellular debris and casts
   • Intratubular pressure increases, reducing GFR

3. Maintenance Phase (1-2 Weeks):

   • Established oliguria or anuria
   • Tubular cells undergo apoptosis and necrosis
   • Regeneration begins in surviving cells
   • GFR remains low despite adequate perfusion

4. Recovery Phase (Weeks to Months):

   • Tubular epithelial cell proliferation and differentiation
   • Restoration of tubular integrity
   • Gradual return of GFR
   • May transition through polyuric phase due to tubular dysfunction

Urinary Findings in ATN:

• Muddy brown granular casts (pathognomonic)
• Tubular epithelial cell casts
• FENa typically >2% (loss of tubular sodium reabsorption capacity)
• Urine osmolality less than 350 mOsm/kg (isosthenuria)
• Urine sodium >40 mEq/L

The transition from prerenal to ATN is not always clear-cut, and mixed patterns are common, particularly in critically ill patients with multifactorial AKI. [12]

Postrenal Causes (5-10% of Cases)

Postrenal oliguria results from obstruction at any level from renal pelvis to urethra. Bilateral obstruction (or unilateral in a solitary kidney) is required to produce oliguria/anuria.

Obstruction Locations:

1. Upper Tract (Bilateral or Solitary Kidney):

   • Calculi
   • Blood clots
   • Papillary necrosis
   • Retroperitoneal fibrosis
   • Malignancy (lymphoma, metastatic disease)
   • Iatrogenic (ureteric injury during surgery, ligation)

2. Bladder:

   • Neurogenic bladder
   • Bladder tumor
   • Blood clots

3. Bladder Outlet/Urethra:

   • Benign prostatic hyperplasia (most common in elderly men)
   • Prostate cancer
   • Urethral stricture
   • Blocked urinary catheter

Pathophysiology: Obstruction increases intratubular pressure, opposing glomerular filtration pressure. If unrelieved within 48-72 hours, irreversible tubular and interstitial damage occurs. [13] Early obstruction (less than 24 hours) may present with preserved renal function if unilateral; bilateral obstruction or solitary kidney involvement causes immediate oliguria/anuria.

Clinical Presentation

Presenting Features

Primary Symptoms:

• Reduced or absent urine output (patient or nursing staff report)
• Uremic symptoms if prolonged: nausea, vomiting, confusion, pruritus
• Symptoms of underlying cause: dyspnea (heart failure), fever (sepsis), flank pain (obstruction)

Associated Symptoms by Cause:

Physical Examination Findings

Assessment of Volume Status:

1. Hypovolemia (Prerenal):

   • Orthostatic hypotension (SBP drop >20 mmHg or HR increase >20 bpm on standing)
   • Reduced skin turgor
   • Dry mucous membranes
   • Reduced jugular venous pressure (JVP less than 2 cm)
   • Prolonged capillary refill (>2 seconds)
   • Tachycardia
   • Cool peripheries

2. Euvolemia/Overload (Intrinsic Renal):

   • Edema (peripheral, periorbital, sacral)
   • Pulmonary edema (bibasal crackles)
   • Elevated JVP (>4 cm, may see hepatojugular reflux)
   • Gallop rhythm (S3)
   • Hypertension

3. Obstruction (Postrenal):

   • Palpable bladder (suprapubic mass, dull to percussion)
   • Enlarged prostate on digital rectal examination
   • Palpable kidneys (hydronephrosis, polycystic kidney disease)
   • Renal angle tenderness

Specific Signs by Etiology:

Clinical Pearl: The "Fluid Challenge" in Prerenal Oliguria:

A carefully monitored fluid challenge can differentiate prerenal from intrinsic oliguria:

Protocol:

1. Ensure patient is not overtly volume overloaded (no pulmonary edema, severe heart failure)
2. Administer 250-500 mL crystalloid (normal saline or Hartmann's) over 30-60 minutes
3. Monitor urine output, heart rate, blood pressure, JVP
4. Assess response

Interpretation:

• Positive response (prerenal): Urine output increases to >0.5 mL/kg/hr within 1-2 hours
• No response (intrinsic): Urine output remains low; risk of fluid overload if continued
• Partial response: May indicate mixed picture or early ATN

Caution: Avoid fluid challenges in:

• Acute pulmonary edema
• Severe heart failure (EF less than 30%)
• Suspected cardiorenal syndrome
• Central venous pressure >12 mmHg

Modern practice increasingly uses dynamic markers (pulse pressure variation, stroke volume variation on arterial lines, passive leg raise testing) to predict fluid responsiveness in ICU settings. [14]

Differential Diagnosis

The differential diagnosis of oliguria is systematically approached using the prerenal, intrinsic renal, and postrenal framework.

Key Differentials

Must-Not-Miss Diagnoses

1. Bilateral Ureteric Obstruction: Requires urgent decompression to prevent irreversible renal damage
2. Rapidly Progressive Glomerulonephritis: Window for treatment with immunosuppression is narrow
3. Rhabdomyolysis with Myoglobinuric AKI: Requires aggressive hydration and urinary alkalinization
4. Thrombotic Microangiopathy: May require plasmapheresis (TTP) or complement blockade (aHUS)
5. Renal Artery Occlusion: May benefit from revascularization if caught early

Investigations

A systematic approach to investigations allows differentiation of oliguria causes and guides management.

Immediate Bedside Investigations

1. Urine Dipstick:

   • Blood: suggests glomerulonephritis, vasculitis, stones
   • Protein: nephritic/nephrotic syndrome
   • Leucocytes/nitrites: infection (uncommon primary cause of oliguria)
   • Specific gravity: >1.020 suggests prerenal (concentrated urine)

2. Bladder Ultrasound/Catheterization:

   • Assess for retention (postrenal)
   • Measure post-void residual
   • If catheterized, ensure patency (flush if necessary)

3. Fluid Balance Chart Review:

   • Calculate cumulative fluid balance
   • Assess insensible losses
   • Review medication chart for nephrotoxins

First-Line Laboratory Investigations

Blood Tests:

1. Urea and Electrolytes:

   • Creatinine: baseline comparison essential; rate of rise indicates severity
   • Urea: urea:creatinine ratio >20:1 suggests prerenal
   • Potassium: hyperkalemia is life-threatening complication
   • Bicarbonate: metabolic acidosis in AKI
   • Sodium: may be dilutional hyponatremia

2. Complete Blood Count:

   • Anemia: may suggest chronic kidney disease, hemolysis, or bleeding
   • Thrombocytopenia: HUS/TTP, DIC, sepsis
   • Leucocytosis: infection, inflammation

3. Creatine Kinase:

   • Elevated (>1000 U/L, often >5000 U/L) in rhabdomyolysis

4. Liver Function Tests:

   • Assess for hepatorenal syndrome
   • Evaluate multiorgan dysfunction

Urinalysis and Microscopy:

Urinary Biochemistry and Indices:

Essential for differentiating prerenal from intrinsic renal causes.

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

FENa less than 1% indicates prerenal; >2% indicates intrinsic renal injury (ATN)

Important Caveat: FENa is unreliable if patient is on diuretics. In this case, use FEUrea:

**FEUrea = (Urine Urea × Plasma Cr) / (Plasma Urea × Urine Cr) × 100

FEUrea less than 35% suggests prerenal; >50% suggests intrinsic renal [15]

Exam Detail: Understanding Urinary Indices - Exam Favourite:

The physiological basis for urinary indices:

Prerenal State:

• Intact tubular function with enhanced reabsorption
• RAAS activation → aldosterone → distal Na reabsorption
• ADH release → water reabsorption → concentrated urine
• Result: Low urinary sodium, high osmolality, low FENa

ATN:

• Tubular injury impairs reabsorptive capacity
• Loss of concentration gradient in medulla
• Inability to reabsorb sodium → high urinary sodium
• Inability to concentrate urine → isosthenuria
• Result: High urinary sodium, low osmolality, high FENa

Limitations:

• Diuretics invalidate FENa (cause natriuresis despite prerenal state)
• Chronic kidney disease: baseline tubular dysfunction alters indices
• Mixed states: critically ill patients often have combined prerenal + ATN

Clinical Scenario (MRCP-style): "A 72-year-old with heart failure presents with oliguria. Urine sodium is 8 mEq/L but FENa is 0.4%. What does this suggest?"

Answer: This suggests cardiorenal syndrome type 1. Despite overall volume overload, reduced cardiac output causes renal hypoperfusion (prerenal physiology). The kidney appropriately reabsorbs sodium (low urine Na, low FENa), resulting in worsening fluid retention and congestion. Treatment requires diuretics and optimization of cardiac output, not fluid boluses. [16]

Second-Line/Specialist Investigations

Imaging:

1. Renal Ultrasound:

   • Indications: All cases of unexplained AKI
   • Findings:
     • Hydronephrosis: suggests obstruction (sensitivity 90% for obstruction)
     • Kidney size: small kidneys (less than 9 cm) suggest chronic kidney disease
     • Increased echogenicity: chronic disease or medical renal disease
     • Loss of corticomedullary differentiation: acute or chronic disease
   • Limitations: Early obstruction (less than 24 hours) may not show hydronephrosis; dehydration can reduce sensitivity

2. CT Abdomen/Pelvis (Non-Contrast):

   • Indications: Suspected obstruction with normal USS, suspected retroperitoneal pathology
   • Advantages: Identifies calculi (95% sensitivity), masses, retroperitoneal fibrosis

3. Doppler Ultrasound of Renal Vessels:

   • Indications: Suspected renal artery stenosis or thrombosis
   • Findings: Resistive index >0.80 suggests intrinsic renal disease; tardus-parvus waveform suggests RAS

Immunological Investigations (if Glomerulonephritis Suspected):

Renal Biopsy:

• Indications:

  • AKI of unclear cause after non-invasive evaluation
  • Suspected glomerulonephritis or vasculitis
  • Proteinuria or hematuria suggesting intrinsic renal disease
  • AKI not recovering after 3-4 weeks

• Contraindications:

  • Uncorrected bleeding diathesis (platelets less than 50, INR >1.4)
  • Uncontrolled hypertension
  • Single kidney (relative)
  • Small kidneys (less than 8 cm) suggesting chronic irreversible disease

KDIGO Classification of Acute Kidney Injury

The KDIGO criteria (2012) provide a standardized framework for defining and staging AKI, incorporating both creatinine changes and urine output. [17]

KDIGO Stages

Key Points:

• Either creatinine OR urine output criteria can define stage
• Baseline creatinine: value within previous 7 days, or lowest value within hospitalization, or estimated from eGFR of 75 mL/min/1.73m² if no baseline available
• Urine output staging requires continuous monitoring (typically ICU setting)

Exam Detail: Prognostic Significance of KDIGO Stages:

Multiple large cohort studies have validated the KDIGO classification's ability to predict outcomes:

1. Mortality Risk: [18]

   • Stage 1: OR 2.0-3.0 for in-hospital mortality
   • Stage 2: OR 4.0-6.0
   • Stage 3: OR 8.0-12.0

2. RRT Requirement:

   • Stage 1: 2-5%
   • Stage 2: 10-15%
   • Stage 3: 40-60%

3. Progression to CKD:

   • Stage 1: 5-10% at 1 year
   • Stage 2: 15-20%
   • Stage 3: 25-35%

Oliguria as Independent Predictor: Even with identical creatinine rises, oliguric AKI has worse prognosis than non-oliguric AKI:

• Oliguric AKI: 50-70% mortality in ICU settings
• Non-oliguric AKI: 20-30% mortality

This reflects greater severity of renal injury and often indicates inadequate renal perfusion or more extensive tubular damage. [19]

Viva Question: "Why might a patient with Stage 3 AKI by urine output criteria have normal creatinine?"

Answer: Creatinine is a late marker of renal function that requires time to accumulate (typically 24-48 hours for significant rise). Oliguria reflects real-time renal perfusion and function. In acute settings (e.g., immediate post-cardiac arrest), severe oliguria may be present before creatinine rises. Additionally, patients with low muscle mass (elderly, malnourished) may have minimal baseline creatinine rise despite significant GFR reduction.

Management

Management of oliguria follows a systematic approach: identify and treat the underlying cause, prevent complications, support renal recovery, and determine if renal replacement therapy is required.

Initial Assessment and Stabilization

1. Immediate Actions (First Hour):

• Ensure adequate monitoring: hourly urine output, vital signs, fluid balance
• Review drug chart: stop nephrotoxins (NSAIDs, gentamicin, ACEi/ARBs in appropriate context)
• Check catheter patency: flush if blocked, resite if necessary
• Obtain baseline investigations: U&E, FBC, CRP, urinalysis with microscopy, urinary indices
• Imaging: renal ultrasound to exclude obstruction

2. Assess for Life-Threatening Complications:

Check for and immediately treat:

• Hyperkalemia (K+ >6.5 mmol/L or ECG changes)
• Severe metabolic acidosis (pH less than 7.2, bicarbonate less than 12 mmol/L)
• Pulmonary edema (refractory to diuretics)
• Uremic complications (pericarditis, encephalopathy, bleeding)

These are indications for urgent renal replacement therapy. [20]

Cause-Specific Management

Prerenal Oliguria

Fluid Resuscitation:

Indications:

• Clinical or biochemical evidence of hypovolemia
• FENa less than 1% or FEUrea less than 35%
• No signs of volume overload

Approach:

1. Crystalloid Resuscitation:

   • First-line: Balanced crystalloids (Hartmann's/Ringer's lactate) or 0.9% saline
   • Bolus: 250-500 mL over 15-30 minutes
   • Reassess volume status and urine output after each bolus
   • Target: MAP >65 mmHg, urine output >0.5 mL/kg/hr

2. Colloids:

   • 4-5% albumin: consider in cirrhosis with spontaneous bacterial peritonitis, hepatorenal syndrome
   • Avoid starches (associated with increased AKI and mortality in sepsis) [21]

3. Blood Products:

   • If hemorrhage: target Hb >70 g/L (>80 g/L if active bleeding or cardiac disease)
   • Correct coagulopathy if bleeding

Vasopressors/Inotropes (if Hypotensive Despite Fluids):

Note: Low-dose "renal-dose" dopamine (2-5 mcg/kg/min) does NOT prevent or treat AKI and is not recommended. [22]

Clinical Pearl: The "Renal-Dose Dopamine" Myth:

For decades, low-dose dopamine was used to "protect" kidneys or enhance diuresis in oliguria. Multiple large RCTs have definitively shown:

• No reduction in AKI incidence
• No reduction in need for RRT
• No improvement in mortality
• Potential harms: arrhythmias, digital ischemia, immunosuppression

This practice has been abandoned in modern critical care. [22]

Instead, focus on:

• Adequate resuscitation and MAP >65 mmHg
• Minimizing nephrotoxin exposure
• Optimizing cardiac output

Special Scenarios:

1. Cardiorenal Syndrome:

   • Optimize cardiac output (consider echo-guided therapy)
   • Cautious diuresis: intravenous furosemide (start 40 mg, titrate up to 250 mg boluses or continuous infusion)
   • Consider inotropic support if low cardiac output
   • Avoid aggressive fluid resuscitation (worsens pulmonary edema)

2. Hepatorenal Syndrome (HRS):

   • HRS-AKI (formerly Type 1): Rapid, progressive AKI in cirrhosis
   • Treatment:
     • Volume expansion: 20% albumin 1 g/kg (max 100 g) on day 1, then 20-40 g/day
     • Vasoconstrictors: terlipressin (1-2 mg IV every 4-6 hours) or midodrine + octreotide
     • Treat precipitants: infection (SBP), bleeding
     • Consider transjugular intrahepatic portosystemic shunt (TIPS)
     • Definitive: liver transplantation [23]

Intrinsic Renal Oliguria (ATN)

Supportive Management:

ATN is largely supportive; no specific therapy reverses established tubular necrosis.

1. Fluid Management:

   • Euvolemia goal: Avoid both volume depletion (worsens ischemia) and overload (pulmonary edema)
   • Fluid restriction: Match input to output + insensible losses (typically 500 mL/day + previous day's urine output)
   • Daily weights

2. Diuretics:

   • Loop diuretics (furosemide): Do NOT improve renal outcomes but may facilitate fluid management
   • Indications: Volume overload, pulmonary edema
   • Dosing: IV furosemide 40-250 mg bolus or continuous infusion (10-40 mg/hr)
   • Convert oliguric to non-oliguric AKI: May simplify fluid/electrolyte management but doesn't change prognosis [24]

3. Nutritional Support:

   • Adequate calories: 25-30 kcal/kg/day
   • Protein: 1.2-1.5 g/kg/day (increased catabolism in AKI)
   • Avoid excessive protein restriction (worsens catabolism)

4. Monitor and Correct Electrolytes:

   • Hyperkalemia: Restrict dietary potassium, stop potassium-sparing diuretics, treat if >6.0 mmol/L
   • Hyperphosphatemia: Phosphate binders (sevelamer, calcium acetate)
   • Hypocalcemia: Usually asymptomatic; treat only if symptomatic or severe
   • Metabolic acidosis: Sodium bicarbonate if pH less than 7.2 (caution: may worsen volume overload)

5. Drug Dosing:

   • Adjust doses for reduced GFR
   • Avoid nephrotoxins
   • Check levels for renally excreted drugs (digoxin, vancomycin, gentamicin)

Specific Therapies for ATN Causes:

Glomerulonephritis and Vasculitis

Requires urgent nephrology referral and immunosuppression.

Rapidly Progressive Glomerulonephritis (RPGN):

1. Pulse Methylprednisolone: 500 mg-1 g IV daily for 3 days
2. Oral Prednisolone: 1 mg/kg daily (max 60 mg) after pulse therapy
3. Cyclophosphamide: 15 mg/kg IV every 2-3 weeks (or daily oral 2 mg/kg)
4. Rituximab: Alternative to cyclophosphamide (375 mg/m² weekly for 4 weeks)
5. Plasmapheresis: In severe ANCA vasculitis or anti-GBM disease [25]

Acute Interstitial Nephritis

1. Stop Offending Drug: Essential first step
2. Supportive Care: Spontaneous recovery expected in 60-70%
3. Corticosteroids: Controversial; consider if no improvement after 3-5 days of drug cessation
   • Prednisolone 1 mg/kg/day for 4 weeks, then taper
   • Earlier initiation may improve outcomes [26]

Postrenal Oliguria

Urgent Decompression:

1. Lower Tract Obstruction:

   • Urethral catheterization (14-16 Fr Foley)
   • If unable to pass: suprapubic catheter insertion

2. Upper Tract Obstruction:

   • Percutaneous nephrostomy: Intervention radiology-guided
   • Ureteric stent: Urological procedure (cystoscopy + retrograde stenting)
   • Choice depends on local expertise and urgency

Post-Obstructive Diuresis:

• After relief of bilateral obstruction, expect massive diuresis (>200 mL/hr)
• Replace 50-75% of urine output with IV crystalloid
• Monitor electrolytes closely (hypokalemia, hypomagnesemia, hyponatremia)
• Diuresis usually resolves within 24-48 hours [27]

Renal Replacement Therapy (RRT)

RRT is indicated when conservative management fails to control complications of AKI.

Indications for RRT (AEIOU Mnemonic)

Absolute Indications:

• Acidosis: Severe metabolic acidosis (pH less than 7.1-7.2) refractory to bicarbonate
• Electrolytes: Hyperkalemia (K+ >6.5 mmol/L) refractory to medical therapy, especially with ECG changes
• Intoxication: Dialyzable toxins (methanol, ethylene glycol, lithium, salicylates)
• Overload: Pulmonary edema refractory to diuretics
• Uremia: Symptomatic uremia (encephalopathy, pericarditis, bleeding)

Relative Indications:

• Severe oliguria/anuria for >72 hours
• Urea >40 mmol/L or creatinine >500 μmol/L (thresholds vary)
• Anticipation that the above complications will develop (preemptive RRT)

Exam Detail: RRT Initiation Timing: Early vs Late Strategy

This has been a subject of considerable debate and several major RCTs:

Landmark Trials:

1. AKIKI Trial (2016): [28]

   • Early: RRT started within 6 hours of reaching KDIGO Stage 3
   • Late: RRT delayed until absolute indication developed
   • Result: No mortality difference; 49% of late group avoided RRT altogether
   • Conclusion: Delayed strategy safe; avoid unnecessary RRT

2. IDEAL-ICU Trial (2018): [29]

   • Early: RRT within 12 hours of KDIGO Stage 3
   • Late: RRT delayed 48 hours or until indication
   • Result: No mortality difference; fewer RRT-free days in early group
   • Conclusion: Supports delayed approach

3. STARRT-AKI Trial (2020): [30]

   • Largest trial (n=3019)
   • Accelerated: RRT within 12 hours of eligibility
   • Standard: RRT only if conventional indication
   • Result: No mortality difference at 90 days
   • Conclusion: Routine early RRT not beneficial

Current Consensus (KDIGO 2024 Update):

• No benefit to routine early/preemptive RRT
• Initiate RRT for absolute indications
• For isolated biochemical abnormalities without symptoms, watchful waiting is safe
• Exception: Consider earlier RRT in severe oliguria/anuria (>72 hours) or fluid overload compromising other organ systems

Viva Answer: "I would initiate RRT based on clinical indications rather than biochemical thresholds alone. Evidence from AKIKI and STARRT-AKI trials shows that delayed, indication-based RRT avoids unnecessary dialysis in up to 50% of patients without increasing mortality. However, I would not delay in the presence of life-threatening hyperkalemia, severe acidosis, or refractory pulmonary edema."

RRT Modalities

Anticoagulation for CRRT:

• Regional citrate anticoagulation: Preferred (less bleeding risk)
• Heparin: Alternative if citrate contraindicated
• No anticoagulation: If high bleeding risk, but circuit lifespan reduced

Prevention Strategies

High-Risk Patient Identification:

• Pre-existing CKD (eGFR less than 60 mL/min/1.73m²)
• Diabetes mellitus
• Age >65 years
• Heart failure, cirrhosis
• Scheduled for high-risk surgery (cardiac, vascular, major abdominal)
• Recent contrast exposure
• Concurrent nephrotoxic medications

Preventive Measures:

1. Avoid Nephrotoxins:

   • Stop NSAIDs perioperatively
   • Adjust aminoglycoside dosing, monitor levels
   • Hold ACEi/ARBs perioperatively in high-risk patients
   • Minimize contrast volume (less than 100 mL if possible)

2. Hydration:

   • IV isotonic saline or bicarbonate before contrast (1 mL/kg/hr for 12 hours pre and post)
   • Maintain euvolemia perioperatively

3. Hemodynamic Optimization:

   • Avoid prolonged hypotension (MAP >65 mmHg)
   • Goal-directed fluid therapy in high-risk surgery

4. Contrast-Induced AKI Prevention:

   • Minimum contrast volume
   • Iso-osmolar or low-osmolar contrast
   • IV fluids pre/post procedure
   • No proven benefit: N-acetylcysteine, sodium bicarbonate, theophylline (conflicting evidence)

5. Rhabdomyolysis Prevention:

   • Aggressive hydration if CK >5000 U/L
   • Target urine output 200-300 mL/hr
   • Urinary alkalinization if myoglobinuria present

Complications

Hyperkalemia Management Algorithm:

Mild (K+ 5.5-6.0 mmol/L):

• Dietary restriction
• Stop potassium-sparing drugs
• Treat acidosis
• Consider patiromer or sodium zirconium cyclosilicate (newer binders)

Moderate (K+ 6.0-6.5 mmol/L) or ECG Changes:

• Calcium gluconate: 10 mL of 10% IV over 2-3 minutes (cardiac protection, onset less than 1 minute, duration 30-60 minutes)
• Insulin-dextrose: 10 units actrapid in 50 mL 50% dextrose IV (shifts K+ intracellularly, onset 15-30 minutes, duration 4-6 hours)
• Salbutamol: 10-20 mg nebulized (adjunct, shifts K+ intracellularly)
• Sodium bicarbonate: 50-100 mEq IV if acidotic
• Resonium (calcium/sodium polystyrene): 15 g PO/PR TDS (removes K+ from body, onset 2-24 hours)

Severe (K+ >6.5 mmol/L) or Refractory:

• All above measures
• Urgent RRT

Clinical Pearl: ECG Changes in Hyperkalemia (High-Yield for Exams):

Sequential changes with increasing K+:

1. K+ 5.5-6.5 mmol/L: Peaked T waves (tall, narrow, symmetrical)
2. K+ 6.5-7.5 mmol/L: Prolonged PR interval, flattened P waves
3. K+ 7.5-8.0 mmol/L: Widened QRS complex
4. K+ >8.0 mmol/L: Sine wave pattern (pre-arrest), ventricular fibrillation, asystole

Critical Point: ECG changes may not correlate precisely with serum K+ level. Treat based on ECG changes, not just laboratory values. Calcium gluconate does NOT lower K+ but stabilizes cardiac membrane, buying time for definitive treatment.

Prognosis

Prognosis in oliguria/AKI depends on severity, etiology, patient comorbidities, and complications.

Short-Term Outcomes

Mortality:

• Community-acquired AKI: 10-20%
• Hospital-acquired AKI: 30-50%
• ICU-acquired AKI requiring RRT: 50-70% [31]

Renal Recovery:

• Complete recovery (return to baseline creatinine): 50-70%
• Partial recovery (improved but not baseline): 15-25%
• RRT dependence at hospital discharge: 5-15%
• Long-term dialysis (>90 days): 2-5%

Factors Associated with Poor Prognosis:

• Advanced age (>70 years)
• Pre-existing CKD (stage 3-5)
• Severe oliguria (urine output less than 200 mL/24 hours)
• KDIGO Stage 3 AKI
• Sepsis or multiorgan dysfunction
• Need for RRT
• Prolonged AKI duration (>7 days)
• Nephrotoxic ATN vs ischemic ATN (worse outcomes in ischemic)

Long-Term Outcomes

Progression to Chronic Kidney Disease: Even after apparent renal recovery, AKI survivors have increased risk of:

• CKD development: 15-30% at 1 year [7]
• Progression to ESRD requiring long-term RRT: 2-5% at 5 years
• Cardiovascular events (myocardial infarction, stroke): 2-3 fold increased risk
• Recurrent AKI episodes: 20-30% within 1 year

Mechanisms of AKI-to-CKD Transition:

• Incomplete tubular regeneration
• Maladaptive repair with fibrosis
• Chronic inflammation
• Microvascular rarefaction
• Ongoing endothelial dysfunction [32]

Follow-Up Recommendations:

All AKI survivors should have:

• Renal function check at discharge and 3 months post-AKI
• Nephrology referral if:
  • eGFR remains less than 45 mL/min/1.73m² at 3 months
  • Persistent proteinuria
  • Recurrent AKI
  • Unclear etiology requiring investigation
• Cardiovascular risk factor modification
• Annual monitoring if complete recovery

Prevention & Screening

High-Risk Surgical Patients

Preoperative Assessment:

• Baseline creatinine within 7 days of surgery
• Calculate eGFR
• Identify nephrotoxin exposure
• Optimize volume status

Intraoperative Strategies:

• Goal-directed fluid therapy (GDT) using dynamic parameters
• Avoid prolonged hypotension (MAP >65 mmHg)
• Minimize nephrotoxic drugs
• Consider continuous renal output monitoring in high-risk cases

Postoperative Monitoring:

• Daily creatinine for 48-72 hours in high-risk patients
• Strict fluid balance
• Early detection and intervention for oliguria

Contrast-Induced AKI Prevention

Risk Stratification (Mehran Score):

High-risk patients (score ≥11):

• CKD (eGFR less than 60)
• Diabetes
• Heart failure
• Age >75 years
• Anemia
• Hypotension
• Use of intra-aortic balloon pump
• High contrast volume (>100 mL)

Preventive Measures:

• Minimum essential contrast volume
• Iso- or low-osmolar contrast agents
• Discontinue nephrotoxins 24 hours before
• IV isotonic saline 1 mL/kg/hr for 12 hours before and after
• Consider staged procedures if >100 mL contrast needed

Sepsis-Associated AKI Prevention

• Early recognition and treatment of sepsis
• Rapid fluid resuscitation (crystalloids)
• Early antibiotics (less than 1 hour)
• Source control
• Avoid nephrotoxic antibiotics if alternatives available
• De-escalate antibiotics based on cultures

Key Guidelines

KDIGO Clinical Practice Guideline for AKI (2012, Updated 2024)

Key Recommendations:

1. Definition and Staging: Use standardized KDIGO criteria for diagnosis and staging [17]
2. Risk Assessment: Identify high-risk patients and implement preventive bundles
3. Discontinue Nephrotoxins: Stop or avoid nephrotoxic agents when possible
4. Fluid Management: Use isotonic crystalloids for resuscitation; avoid starches
5. Functional Hemodynamic Monitoring: Use dynamic parameters to guide fluid therapy in unstable patients
6. Avoid Diuretics for Prevention: Loop diuretics do not prevent AKI
7. No Low-Dose Dopamine: Renal-dose dopamine not recommended
8. RRT Initiation: Indication-based rather than early/preemptive initiation
9. Nutritional Support: Provide 20-30 kcal/kg/day with adequate protein (1.2-1.5 g/kg/day)
10. Follow-Up: Assess renal function at 3 months post-AKI; refer to nephrology if abnormal

NICE Guideline: Acute Kidney Injury (NG148, 2019)

Key Recommendations:

1. Detection: Use AKI detection algorithms in hospitals to identify cases early
2. Alerts: Implement e-alerts for rising creatinine
3. Investigation: Measure urinary sodium and osmolality in unexplained AKI
4. Imaging: Perform renal ultrasound within 24 hours if cause unclear
5. Specialist Referral: Refer to nephrology if KDIGO Stage 3, unclear cause, or not improving

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Exam-Focused Sections

Common Exam Questions

Written Exam (SBA) Questions:

1. "A 68-year-old man with heart failure is admitted with oliguria. FENa is 0.3%. What is the most likely diagnosis?"

   • Answer: Cardiorenal syndrome (prerenal physiology despite volume overload)

2. "Which finding on urinalysis is most specific for acute tubular necrosis?"

   • Answer: Muddy brown granular casts

3. "What is the primary indication for urgent dialysis in a patient with oliguria and creatinine 450 μmol/L?"

   • Answer: Refractory hyperkalemia with ECG changes (not creatinine level alone)

4. "A patient develops oliguria 24 hours post-cardiac surgery. Urine sodium is 60 mEq/L, urine osmolality 280 mOsm/kg. What is the diagnosis?"

   • Answer: Acute tubular necrosis

5. "What is the appropriate first-line fluid for resuscitation in prerenal oliguria?"

   • Answer: Isotonic crystalloid (Hartmann's or 0.9% saline)

Viva Points

Viva Point: Opening Statement: "Oliguria is defined as urine output less than 0.5 mL/kg/hr or 400 mL per 24 hours in adults. It is a cardinal feature of acute kidney injury and can be caused by prerenal, intrinsic renal, or postrenal mechanisms. Systematic assessment using clinical examination, urinary indices, and imaging allows differentiation of causes and guides management."

Key Facts to Mention:

• KDIGO Stage 1 AKI: less than 0.5 mL/kg/hr for 6-12 hours
• FENa less than 1% suggests prerenal; >2% suggests ATN (unless on diuretics, then use FEUrea)
• Absolute indications for RRT: AEIOU (Acidosis, Electrolytes, Intoxication, Overload, Uremia)
• Evidence from AKIKI and STARRT-AKI trials supports indication-based rather than early preemptive RRT
• 15-30% of AKI survivors develop CKD, requiring long-term nephrology follow-up [7]

Classification System to Quote: "I would use the KDIGO 2012 classification to stage AKI based on creatinine rise and urine output. Stage 3 is defined as creatinine 3 times baseline, absolute creatinine >354 μmol/L, RRT initiation, or urine output less than 0.3 mL/kg/hr for 24 hours or anuria for 12 hours."

Evidence to Cite:

• Balanced crystalloids vs 0.9% saline: SMART trial showed lower mortality with balanced solutions in critically ill patients [33]
• AKIKI trial (2016): Delayed RRT strategy safe; 49% avoided RRT without increased mortality [28]
• Renal-dose dopamine: Multiple RCTs show no benefit; not recommended (KDIGO 2012) [22]

Common Mistakes

❌ Mistakes that fail candidates:

1. Using FENa in patients on diuretics: Diuretics cause natriuresis and invalidate FENa. Use FEUrea instead.

2. Aggressive fluid resuscitation in cardiorenal syndrome: This worsens pulmonary edema. Requires diuretics + cardiac optimization, not fluids.

3. Attributing oliguria solely to creatinine level: Oliguria is an independent AKI criterion. Severe oliguria can occur with normal creatinine (early AKI, low muscle mass).

4. Recommending low-dose dopamine: This is outdated practice with no evidence of benefit and potential harm. Shows lack of current knowledge.

5. Missing postrenal causes: Always check for bladder retention (palpate, catheterize) and perform renal USS to exclude obstruction.

6. Initiating early/preemptive RRT without indication: Recent trials (AKIKI, STARRT-AKI) show this doesn't improve outcomes and subjects patients to unnecessary RRT risks.

7. Forgetting post-obstructive diuresis: After relieving bilateral obstruction, massive diuresis can occur. Requires IV fluid replacement (50-75% of losses) to prevent hypovolemia.

8. Not stopping nephrotoxins: NSAIDs, aminoglycosides, ACEi/ARBs (in appropriate contexts) should be stopped immediately in AKI.

9. Inadequate hyperkalemia treatment: Calcium gluconate is first-line for cardiac protection, but must be followed by treatments that shift/remove potassium (insulin-dextrose, salbutamol, RRT if refractory).

10. Forgetting long-term follow-up: AKI survivors need 3-month renal function check and nephrology referral if abnormal. Risk of CKD is 15-30%.

Model Answers

Q: A 72-year-old presents with oliguria 48 hours post-major abdominal surgery. Describe your approach.

Model Answer:

"I would approach this systematically using the prerenal, intrinsic renal, and postrenal framework.

Assessment: First, I would perform a focused clinical assessment to determine volume status, examining for signs of hypovolemia (tachycardia, hypotension, reduced JVP) versus overload (elevated JVP, pulmonary edema). I would review the perioperative fluid balance, blood loss, and vital sign trends. I would ensure the urinary catheter is patent by flushing it.

Investigations: I would send urgent bloods including urea and electrolytes to assess creatinine, potassium, and urea:creatinine ratio. I would request urinalysis with microscopy looking for casts, and urinary biochemistry including sodium and osmolality to calculate FENa. I would arrange urgent renal ultrasound to exclude obstruction, particularly important post-abdominal surgery where ureteric injury is possible.

Interpretation: If FENa less than 1%, urine osmolality >500 mOsm/kg, and there is clinical evidence of hypovolemia, this suggests prerenal oliguria from inadequate resuscitation or ongoing losses. I would perform a fluid challenge with 250-500 mL crystalloid and monitor response. If FENa >2% with muddy brown casts, this suggests ATN, likely from perioperative hypotension or nephrotoxin exposure.

Management: For prerenal oliguria, I would optimize fluid resuscitation and hemodynamics, targeting MAP >65 mmHg. I would review and stop any nephrotoxins such as NSAIDs or gentamicin. For established ATN, management is supportive with careful fluid balance, monitoring for complications such as hyperkalemia and metabolic acidosis, and adjusting drug doses for reduced renal function. I would consider nephrology referral if there is diagnostic uncertainty, severe AKI (KDIGO Stage 3), or if complications develop requiring RRT.

I would monitor urine output hourly and check daily creatinine to assess trajectory. The patient requires close monitoring for indications for RRT using the AEIOU criteria: severe acidosis, refractory hyperkalemia, pulmonary overload, or uremic complications."

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Q: What are the indications for renal replacement therapy in AKI?

Model Answer:

"The indications for RRT can be remembered using the AEIOU mnemonic, representing absolute indications:

A - Acidosis: Severe metabolic acidosis with pH less than 7.1-7.2 that is refractory to medical management with sodium bicarbonate.

E - Electrolytes: Life-threatening hyperkalemia, typically potassium >6.5 mmol/L with ECG changes or refractory to medical therapy with insulin-dextrose, salbutamol, and resonium.

I - Intoxication: Dialyzable poisons including methanol, ethylene glycol, lithium, and salicylates.

O - Overload: Pulmonary edema refractory to diuretics, causing respiratory compromise.

U - Uremia: Symptomatic uremia including encephalopathy, pericarditis, or uremic bleeding.

Relative indications include severe oliguria or anuria persisting beyond 72 hours, or very high biochemical values such as urea >40 mmol/L or creatinine >500 μmol/L, though these alone are not absolute indications.

Evidence base: Recent large RCTs including AKIKI (2016), IDEAL-ICU (2018), and STARRT-AKI (2020) have shown that early or preemptive RRT based on biochemical thresholds alone does not improve mortality and may subject patients to unnecessary dialysis. [28-30] Therefore, current practice favors indication-based initiation when absolute indications develop. However, clinical judgment is important, and earlier RRT may be considered in severe oliguria with fluid overload compromising other organ systems or in anticipated deterioration."

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Q: How do you differentiate prerenal from intrinsic renal oliguria?

Model Answer:

"I would differentiate these using a combination of clinical assessment, urinary indices, and response to treatment.

Clinical Assessment: Prerenal oliguria typically occurs with evidence of hypovolemia—history of fluid losses (bleeding, vomiting, diarrhea), orthostatic symptoms, examination findings of tachycardia, hypotension, reduced JVP, dry mucous membranes. Intrinsic renal oliguria may have recent hypotensive episode, nephrotoxin exposure, or signs of vasculitis/glomerulonephritis such as hematuria and rash.

Urinary Indices: Prerenal oliguria shows intact tubular function with avid sodium and water reabsorption: FENa less than 1%, urine sodium less than 20 mEq/L, urine osmolality >500 mOsm/kg, urine:plasma creatinine >40:1. This occurs because the kidney responds appropriately to perceived volume depletion by activating RAAS and ADH.

Intrinsic renal oliguria from ATN shows impaired tubular function: FENa >2%, urine sodium >40 mEq/L, urine osmolality less than 350 mOsm/kg (isosthenuria), due to tubular injury preventing sodium reabsorption and urine concentration.

Important caveat: FENa is unreliable if the patient is on diuretics, which cause natriuresis even in prerenal states. In this case, I would use FEUrea, where less than 35% suggests prerenal and >50% suggests intrinsic renal. [15]

Urinalysis: Prerenal: benign sediment, perhaps hyaline casts from concentrated urine. ATN: muddy brown granular casts (pathognomonic), tubular epithelial cell casts.

Response to Treatment: Prerenal oliguria typically reverses within 1-2 hours of fluid resuscitation with urine output increasing to >0.5 mL/kg/hr. ATN shows minimal response to fluids and requires 7-21 days for tubular regeneration.

Key teaching point: The distinction is not always clear-cut. Prolonged prerenal oliguria (>24-48 hours) leads to ischemic tubular injury and progression to ATN. Critically ill patients often have mixed pictures with both inadequate perfusion and established tubular damage."

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