Ammonium Chloride Loading Test Protocol
The standard ammonium chloride loading test protocol involves oral administration of ammonium chloride at a dose of 0.15 g/kg body weight for 3 consecutive days, with urine pH measurements to assess renal acidification capacity. 1
Preparation and Administration
Standard Protocol
- Dosage: 0.15 g/kg body weight per day 1
- Duration: 3 consecutive days
- Administration forms:
- Whole tablets
- Crushed tablets
- Capsules
- Solution 2
Alternative Protocol
For patients who cannot tolerate ammonium chloride due to gastrointestinal side effects:
- Furosemide/Fludrocortisone Test: Simultaneous oral administration of furosemide and fludrocortisone
- This alternative is equally effective but better tolerated than ammonium chloride
- No reported vomiting with this method compared to NH4Cl 3
Specimen Collection and Measurements
Blood Measurements
- Collect arterialized capillary blood samples before and after NH4Cl administration
- Measure:
- Blood pH
- Bicarbonate
- Base excess
- Plasma electrolytes (especially potassium) 1
Urine Collection
- Collect 24-hour urine specimens:
- One day before acid loading (baseline)
- On the third day of acid loading 4
- For more detailed assessment, collect urine samples at regular intervals during the test
Urine Analysis
- Measure:
- Urine pH (primary outcome)
- Titratable acid
- Ammonium ions (NH4+)
- Urinary electrolytes (sodium, potassium, chloride)
- Urinary anion gap (sodium + potassium - chloride) 5
Interpretation of Results
Normal Response
- Urine pH decreases to below 5.3 3
- Base excess reaches approximately -6 mmol/L or lower 2
- Negative urinary anion gap (typically around -27 mmol/L) 5
- Increased urinary ammonium excretion
Abnormal Response (Distal Renal Tubular Acidosis)
- Inability to lower urine pH below 5.3 despite systemic acidosis 3
- Positive urinary anion gap 5
- Inadequate increase in urinary ammonium excretion
Monitoring and Safety Considerations
During the Test
- Monitor for:
- Vomiting (common side effect)
- Hyperkalaemia
- Excessive acidosis
- Dehydration due to increased urine flow rate 1
Contraindications
- Severe liver disease
- Severe kidney disease
- Pre-existing metabolic acidosis
- Severe electrolyte disturbances
Practical Tips
- Store collected blood at 4°C before centrifugation
- Centrifuge blood samples within 2 hours of collection
- If centrifugation must be delayed, refrigerate samples (but no more than 24 hours)
- Avoid direct contact of blood tubes with ice to minimize cell lysis 6
Alternative Testing Methods
When ammonium chloride cannot be tolerated:
Furosemide/Fludrocortisone Test:
- Increases distal tubular sodium delivery
- Enhances principal cell sodium reabsorption
- Stimulates alpha-intercalated cell proton secretion
- Produces equivalent diagnostic results to NH4Cl with fewer side effects 3
Urinary Anion Gap Assessment:
- Can be used as a rough index of urinary ammonium
- Negative anion gap suggests normal acidification
- Positive anion gap suggests altered distal urinary acidification 5
The ammonium chloride loading test remains the gold standard for diagnosing renal tubular acidosis, but the furosemide/fludrocortisone combination offers a well-tolerated alternative with equivalent diagnostic accuracy.