July 23, 2017
Ammonium Chloride Acidification Test for Renal Tubular Acidosis Minimize

Ammonium chloride acidification test for Renal Tubular Acidosis

  • This test is potentially very dangerous and must be undertaken with great care.
  • It should NOT be performed if the urine is alkaline in the presence of a metabolic acidosis (as above)
  • It should NOT be performed in patients with liver disease.
  • This test should not be performed if the patient is taking alkali replacement.
  • Bacterial urine infection may give a falsely high pH due to urea hydrolysis.
  • This test should not be performed in hypokalaemia or hypercalcaemia as these conditions interfere with tubular function and may mimic RTA.

Indication

Renal tubular acidosis is characterised by an hyperchloraemic acidosis with a normal anion gap. The diagnosis is already established if there is alkaline urine (pH > 5.5) despite a metabolic acidosis (plasma bicarbonate < 17.5 mmol/L) in the presence of a normal GFR. 

Principle of the test

The ammonium chloride is converted in the liver to urea with the consumption of bicarbonate. The bicarbonate is replaced by renal synthesis with excretion of hydrogen ions. This test stresses the ability of the kidneys to excrete acid and any failure will result in a metabolic acidosis.

Side effects

Most patients who take ammonium chloride will feel a degree of nausea, abdominal discomfort and mild diarrhoea. Some patients will vomit but this can be reduced by allowing a longer ingestion period of 2 hours.

Preparation

No specific preparation is required though the patient must fast on the morning prior to the test.

Requirements

  1. Ammonium chloride
  2. 6 urine collecting vessels
  3. 2 lithium heparin blood tubes

Procedure

General management

If possible keep the patient upright or ambulant during test. Food and drink may be given as required. From the moment the test is started, all urine must be collected for at least the next 8 hours. Each specimen must be placed in a separate container and clearly labelled with name and time of collection. Each specimen should be sent to the laboratory immediately.

 

The patient should be fasting at the onset of the test and weighed prior to the onset of the test. The first urine passed should be collected for pH. Out-patients may need to be given 300-400mL water to obtain this specimen. pH < 5.5 excludes almost all subjects with type 1 RTA. This result should be obtained prior to the onset of this test.

0900

collect a mid stream urine specimen and an anaerobic heparinised free-flowing venous blood sample (as for blood gas determination) and send to the laboratory on ice for estimation of pH and bicarbonate. It is important that forearm exercise and venous occlusion are avoided since they both result in a raised pH.

0905

patient should eat breakfast with ammonium chloride (0.1g/kg body weight). This may be given disguised with syrup or jam or in solution with iced water. The total dose should be taken over a period of 2 hours to reduce the degree of gastric irritation. If the total dose cannot be consumed note the exact quantity on the request card. It will be necessary to repeat test if the patient vomits all/the majority of the ammonium chloride.

1315

take a second venous blood sample (as above) and send to the laboratory on ice.

0915-1515

collect all urine passed. Samples should be collected at hourly intervals and periods of longer than 2 hours should be avoided - this should be achieved by ensuring that approximately 200 mL are drunk hourly. Any spillages should be accurately recorded.

Interpretation

Normal subjects should produce at least one urine specimen with a pH < 5.3 and have a rate of ammonia excretion in the region of 1mmol / min / kg. The plasma CO2 should fall by approximately 4 mmol/L and the pH by 0.05 units.

In neonates, it is normal for the urine pH to be 6-7 for the first week of life and a more adult pattern develops afterwards. During the first year of life the renal threshold for bicarbonate is relatively low at approximately 17-19 mmol/L whereas in adults it is 20-26 mmol/L.

RTA type 1 is due to a distal tubular inability to excrete hydrogen ions against a gradient. This results in loss of potassium and hypokalaemia. Chronic acidosis results in calcium wasting and consequently renal stones. This form of RTA may be secondary to other disorders eg nephrocalcinosis and galactosaemia.

  • The urinary pH does not fall below 5.3 during the ammonium chloride test.

RTA type 2 is often part of a generalised proximal tubular dysfunction (ie Fanconi syndrome) and is due to a failure to reabsorb bicarbonate (fractional clearance may be > 15%). Bicarbonate concentration falls to the level at which the tubules are able to absorb (c16-20mmol/L). Hypokalaemia is a feature. Hypercalciuria occurs but renal stones are unusual.  The urine is often not alkaline in the steady state (reduced filtered load due to low plasma bicarbonate).

  • The urinary pH does fall below 5.3 during the ammonium chloride test.

Diagnostic features include low plasma bicarbonate, alkaline urine, ability to acidify urine & requirement for high doses of bicarbonate to correct acidosis. It may be necessary to infuse bicarbonate to measure the threshold.

RTA type 4 is probably a distal tubular disorder. It is characterised by an acid urine during a metabolic acidosis. There is little bicarbonate wasting but poor urinary ammonia production and a high plasma potassium. Renal calcium stones do not develop and there is no Fanconi syndrome. It is often secondary to diabetic or hypertensive nephropathy. There is hyporeninaemic hypoaldosteronism even during extracellular volume depletion.

References:

  • Caldas A, Broyer M, Dechaux M, Kleinknecht C. Primary distal tubular acidosis in childhood: clinical study and longterm follow-up of 28 patients. J Pediatr 1992;121:233-241.
  • Oleesky D, Penny MD. Renal tubular acidosis. Ann Clin Biochem 1998 in press
  • Tannen RL. The response of normal subjects to the short ammonium chloride test. Clin Sci 1971;41:583-95.
  • Tannen RL, Falls WF Jr, Brackett NC Jr. Incomplete renal tubular acidosis: some clinical and physiological features. Nephron 1975;15:111-123
  • Wrong O, Davies HEF. The excretion of acid in renal disease. Q J Med 1959;28:259-313

  

Home|Paediatric|Endocrinology|Renal & electrolytes|Metabolic|Investigation protocols|Misc
Comments about this site to julian.barth@nhs.net Terms Of Use Privacy Statement