The Response of Normal Subjects to the Short Ammonium Chloride Test: The Modifying Influence of Renal Ammonia Production

Abstract

I. The response to the short ammonium chloride acidification procedure in seventeen normal young men was carefully defined by performing this test with rigid control.2. Wide variation in the response was observed, emphasizing the difficulty of interpretation of small changes when using this procedure.3. After ingestion of ammonium chloride, urine pH correlated positively with both net acid and ammonium excretion contrary to present concepts. It is suggested that the renal capacity to produce ammonia dictates the relation of urine pH to net acid and ammonium excretion, respectively. done under highly controlled conditions. Considering the variety of factors that might influence urine acidification, such information should be of value.During a series of studies designed to investigate some of the factors affecting urine acidification, I day ammonium chloride tests were performed on a number of normal men under rigidly controlled conditions. The normal response to the test was carefully defined and an unexpected relationship between urine pH, net acid and ammonium excretion was observed.A modified short ammonium chloride test was performed on eighteen occasions in seventeen men aged 19-31 years with normal renal function. All subjects were volunteers who gave informed consent. Six had malaria with apparent cure 1-2 months before the study. Two of them had a transient increase in blood urea nitrogen to approx. 35 mg/lOO ml with mild proteinuria during the acute malaria. One subject had idiopathic hypercalciuria without evidence of renal calculi. None of the remaining subjects had any significant illnesses. At the time of study every subject had a normal blood pressure, urinalysis and creatinine clearance and a negative urine culture.For 3 days before the test all subjects ingested a formula diet (Meade Johnson Low Electrolyte Food Powder 700(1) supplemented with sodium chloride and potassium chloride solutions which provided daily: 35 cal, 30 ml of water, 2 mmo1 of sodium and 0·75 mmol of potassium/kg body wt. This diet is deficient in magnesium and although a significant amount of magnesium depletion would not be expected in 3 days (Dunn & Walser, 1966;Fitzgerald & Fourman, 1956), mean serum magnesium concentration measured in eight subjects decreased from 0·75 to 0·66 mmol/l after 3 days of diet. In four studies the diet was supplemented with magnesium chloride (4 mmol/day). These subjects responded in the same way as those who did not receive a magnesium supplement. Therefore it is unlikely that the small change in magnesium influenced the study significantly.On the day of the test the subjects were awakened at 6.30 a.m. and from that time to the completion of the test they remained in the upright position and fasted except for the ingestion of water. A water load of 300-400 ml was ingested from 6.30 to 7.30 a.m. and approx. 100 mljh thereafter, in an attempt to maintain a urine flow rate between 1 and 3 ml/min, After the collection of two control hourly urine samples, NH 4Cl in gelatin capsules (2 mmol/kg) was sw...

Acute Metabolic Acidosis

“…In contrast to prior human reports that described either a tendency to (4,5,17) or a significant increase in [K] p during AMA (2,13), we found no appreciable change in [K] p . The major methodologic differences between these and the present study are the use of demonstrably arterialized plasma (versus venous serum or plasma) and the wider range of plasma bicarbonate values achieved in the present study.…”

“…In human studies reporting venous plasma or serum (2,4,5,17) potassium values after a small acute NH 4 Cl load, a tendency to elevated values was observed, with statistical significance in only one study (2), but interpretation was precluded by high variance and modest degrees of acidosis. Importantly, no arterial or arterialized plasma or serum potassium values have been reported in normal human subjects with experimentally induced AMA of any cause.…”

A Short Duration Renal Acidification Test Using Calcium Chloride

“…The decrease in serum bicarbonate concen tration produced by all of these salts is inversely proportional to the increase in serum chloride concentration [12,13]. Thus, chloride can be considered to displace bicarbonate from the blood; total serum cation concentration remains about the same [14,15].…”

“…mEq per mEq same effect as hydro chloric acid), the acidifying properties of CaCl2are substantially less; about 40% of the dose acts as an acid [14]. In addition, calcium salts when given intravenously do not produce systemic acidosis [10,25] although they may result in increases in renal acid excretion, presumably by a direct tubular effect [25], CaCl2 ingestion produces a decrease in urine pH [2,3,13,14,[16][17][18] and increments in renal ammonium [2,3,13,14,16,20], titratable acid [2,3,14,17], and sodium and potassium [12][13][14]16,17,20,21] excretion similar to that following the use of NH4CI [1,10,14,15,[26][27][28]. As expected, urinary calcium excretion is enhanced [13,14,16,17,20] to a greater extent by CaCl¿ than by NH4CI, but phosphorus excretion may [17] or may not [16] be increased since calcium phosphate salts are believed to be precipitated in the gut and excreted in the feces after the ingestion of CaCU [10,…”

Incomplete Renal Tubular Acidosis: some Clinical and Physiological Features

“…All patients were ingesting a normal diet prior to the day of the NH4CI study. The NH4CI study was performed in a fashion similar to that described pre viously for normal subjects [13] with the exception of five patients who ingested food during the study, two of whom were given the NH4CI in liquid form.…”