Urine Anion Gap (UAG): Key Tool for Metabolic Acidosis Workup:
Urine Anion Gap (UAG) calculator: Differentiate renal vs. extrarenal causes of normal anion gap metabolic acidosis using urine electrolytes. Essential for nephrology and critical care.
Urine Anion Gap (UAG) Calculation:
UAG =
(Urine Na+ + Urine K+) – Urine Cl–
Units: mmol/L or mEq/L (equivalent for monovalent ions)
Key Components:
• Urine Na+: Sodium concentration in urine (mmol/L)
• Urine K+: Potassium concentration in urine (mmol/L)
• Urine Cl–: Chloride concentration in urine (mmol/L)
• Normal Range: -20 to -10 mmol/L
• Critical Value: Positive UAG in metabolic acidosis
• Urine K+: Potassium concentration in urine (mmol/L)
• Urine Cl–: Chloride concentration in urine (mmol/L)
• Normal Range: -20 to -10 mmol/L
• Critical Value: Positive UAG in metabolic acidosis
Clinical Utility:
• Differentiates types of metabolic acidosis
• Assesses renal acid excretion capacity
• Detects renal tubular acidosis (RTA)
• Evaluates ammonium (NH4+) excretion
• Useful in unexplained normal anion gap acidosis
• Estimates unmeasured urine anions
• Assesses renal acid excretion capacity
• Detects renal tubular acidosis (RTA)
• Evaluates ammonium (NH4+) excretion
• Useful in unexplained normal anion gap acidosis
• Estimates unmeasured urine anions
Calculation Example:
• Urine Na+: 40 mmol/L
• Urine K+: 30 mmol/L
• Urine Cl–: 80 mmol/L
• Urine K+: 30 mmol/L
• Urine Cl–: 80 mmol/L
UAG =
(40 + 30) – 80
= 70 – 80 =
-10 mmol/L
• Interpretation: Appropriate renal acid excretion
Interpretation Guide:
• Negative UAG (< -10 mmol/L): Gastrointestinal HCO3– loss
• Slightly Negative (-10 to 0 mmol/L): Normal acid excretion
• Positive UAG (> 0 mmol/L): Renal tubular acidosis
• Strongly Positive (> 20 mmol/L): Type 1 RTA
• Diuretic use: May affect interpretation
• Urine pH: Critical for interpretation
• Slightly Negative (-10 to 0 mmol/L): Normal acid excretion
• Positive UAG (> 0 mmol/L): Renal tubular acidosis
• Strongly Positive (> 20 mmol/L): Type 1 RTA
• Diuretic use: May affect interpretation
• Urine pH: Critical for interpretation
Sampling Protocol:
• Spot urine sample preferred
• Simultaneous serum electrolytes recommended
• Avoid contamination
• Process within 2 hours of collection
• Measure with ion-selective electrodes
• Note concurrent medications
• Simultaneous serum electrolytes recommended
• Avoid contamination
• Process within 2 hours of collection
• Measure with ion-selective electrodes
• Note concurrent medications
Limitations:
• Less reliable if urine pH > 6.5
• Affected by diuretic therapy
• Not valid in ketoacidosis
• Requires normal renal function
• Interference from bromide intoxication
• Unreliable in volume depletion
• Affected by diuretic therapy
• Not valid in ketoacidosis
• Requires normal renal function
• Interference from bromide intoxication
• Unreliable in volume depletion
Critical Clinical Notes:
• UAG estimates urine ammonium excretion (negative UAG = high NH4+)
• Always correlate with serum anion gap and blood pH
• Positive UAG in metabolic acidosis → renal acidification defect
• Negative UAG in metabolic acidosis → extrarenal cause (e.g., diarrhea)
• Combine with urine osmolal gap for better accuracy
• UAG estimates urine ammonium excretion (negative UAG = high NH4+)
• Always correlate with serum anion gap and blood pH
• Positive UAG in metabolic acidosis → renal acidification defect
• Negative UAG in metabolic acidosis → extrarenal cause (e.g., diarrhea)
• Combine with urine osmolal gap for better accuracy
🧪 Urinary Anion Gap (UAG)
📐 Formula:
UAG =
Urine Na⁺ + Urine K⁺ − Urine Cl⁻
🖊️ Enter the Following Values:
Core Formula:
Urine Anion Gap (UAG) Calculation:
UAG =
(Urine Na+ + Urine K+) – Urine Cl–
Units: mmol/L or mEq/L (equivalent for monovalent ions)
Interpretation & Clinical Significance:
| UAG Result | Implication | Mechanism | Common Causes |
|---|---|---|---|
| Negative | Extrarenal HCO₃⁻ Loss | ↑ NH₄⁺ excretion (as NH₄Cl) | Diarrhea, Pancreatic Fistula |
| Positive | Renal Acidification Defect | ↓ NH₄⁺ excretion | RTA (Type 1, 4), CKD |
| Near 0 | Indeterminate/Volume Expansion | Mixed Factors | Early Diuretic Use |
🔑 Critical Insight: UAG estimates ammonium (NH₄⁺) excretion – the kidney’s primary acid-excreting mechanism.
Step-by-Step Calculation Example
Patient Values:
- Urine Na⁺: 50 mmol/L
- Urine K⁺: 25 mmol/L
- Urine Cl⁻: 100 mmol/L
UAG = (50 + 25) – 100 = 75 – 100 = -25 mmol/L
Interpretation: Negative UAG → Extrarenal cause (e.g., diarrhea)
When to Use UAG
- Normal Anion Gap Metabolic Acidosis (Serum AG 8-12 mmol/L)
- Suspected Renal Tubular Acidosis (RTA):
- Type 1 RTA: UAG >0 + Urine pH >5.5
- Type 4 RTA: UAG >0 + Urine pH <5.5 + Hyperkalemia
Limitations & Caveats
| Scenario | Effect on UAG | Workaround |
|---|---|---|
| Diuretic Use | Falsely Negative | Wait 48h after last dose |
| Severe Volume Depletion | Unreliable | Correct volume first |
| Ketones/Light Chains | Falsely Positive | Measure urine anions |
| UTI with Urea-Splitters | Alters pH | Treat infection → retest |
Urine Anion Gap vs Urine Osmolar Gap
For equivocal UAG results, Urine Osmolar Gap better estimates NH₄⁺:
Estimated Urinary Ammonium (NH4+) Calculation:
Est. NH4+ =
Urine Osmolality – 2×(Urine Na+ + K+) – Urea – Glucose
2
Units: Osmolality (mOsm/kg), Electrolytes (mmol/L), Urea & Glucose (mmol/L)
Key Components:
• Urine Osmolality: Total solute concentration (mOsm/kg)
• Urine Na+: Sodium concentration (mmol/L)
• Urine K+: Potassium concentration (mmol/L)
• Urine Urea: Urea nitrogen concentration (mmol/L)
• Urine Glucose: Glucose concentration (mmol/L)
• Normal Range: 15-40 mmol/L in healthy individuals
• Urine Na+: Sodium concentration (mmol/L)
• Urine K+: Potassium concentration (mmol/L)
• Urine Urea: Urea nitrogen concentration (mmol/L)
• Urine Glucose: Glucose concentration (mmol/L)
• Normal Range: 15-40 mmol/L in healthy individuals
Clinical Utility:
• Estimates renal ammonium excretion
• Differentiates renal vs. extrarenal acidosis
• Diagnoses renal tubular acidosis (RTA)
• Assesses kidney’s acidification ability
• Evaluates response to acidosis treatment
• Useful when direct NH4+ measurement unavailable
• Differentiates renal vs. extrarenal acidosis
• Diagnoses renal tubular acidosis (RTA)
• Assesses kidney’s acidification ability
• Evaluates response to acidosis treatment
• Useful when direct NH4+ measurement unavailable
Calculation Example:
• Urine Osmolality: 650 mOsm/kg
• Urine Na+: 40 mmol/L
• Urine K+: 30 mmol/L
• Urine Urea: 300 mmol/L
• Urine Glucose: 5 mmol/L
• Urine Na+: 40 mmol/L
• Urine K+: 30 mmol/L
• Urine Urea: 300 mmol/L
• Urine Glucose: 5 mmol/L
Est. NH4+ =
=
=
= 102.5 mmol/L
• Interpretation: High ammonium excretion650 – 2×(40 + 30) – 300 – 5
2
650 – 140 – 300 – 5
2
205
2
Interpretation Guide:
• < 20 mmol/L: Low excretion (suggests RTA)
• 20-40 mmol/L: Moderate excretion
• 40-80 mmol/L: High excretion
• > 80 mmol/L: Very high excretion
• In metabolic acidosis: >75 mmol/L indicates appropriate response
• Values vary with urine concentration
• 20-40 mmol/L: Moderate excretion
• 40-80 mmol/L: High excretion
• > 80 mmol/L: Very high excretion
• In metabolic acidosis: >75 mmol/L indicates appropriate response
• Values vary with urine concentration
Sampling Protocol:
• Spot urine sample preferred
• Collect in sterile container
• Process within 2 hours of collection
• Simultaneous serum electrolytes recommended
• Measure osmolality by freezing point depression
• Note concurrent medications
• Collect in sterile container
• Process within 2 hours of collection
• Simultaneous serum electrolytes recommended
• Measure osmolality by freezing point depression
• Note concurrent medications
Limitations:
• Assumes other anions are negligible
• Less accurate with high organic anion excretion
• Requires accurate measurement of all components
• Affected by urine concentration/dilution
• Urea conversion needed if in mg/dL
• Glucose should be near zero in healthy individuals
• Less accurate with high organic anion excretion
• Requires accurate measurement of all components
• Affected by urine concentration/dilution
• Urea conversion needed if in mg/dL
• Glucose should be near zero in healthy individuals
Critical Clinical Notes:
• Use when direct NH4+ measurement is unavailable
• In metabolic acidosis, low NH4+ (<40 mmol/L) suggests renal acidification defect
• High NH4+ (>75 mmol/L) indicates appropriate renal response to acidosis
• Always correlate with blood pH and serum bicarbonate
• Combine with urine anion gap for comprehensive assessment
• Use when direct NH4+ measurement is unavailable
• In metabolic acidosis, low NH4+ (<40 mmol/L) suggests renal acidification defect
• High NH4+ (>75 mmol/L) indicates appropriate renal response to acidosis
• Always correlate with blood pH and serum bicarbonate
• Combine with urine anion gap for comprehensive assessment
Clinical Pearls
- Sample Timing: Collect urine before bicarbonate therapy
- Confirm with pH:
- UAG >0 + pH >5.5 → Type 1 RTA
- UAG >0 + pH <5.5 → Type 4 RTA
- Drug Interference: Avoid testing while on acetazolamide or amphotericin
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