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Mitchell L. Halperin, MD, Laboratory No. 1, Research Wing, St. Michael’s Hospital, 38 Shuter Street, Toronto, Ont. (Canada) M5B 1A6 Dear Sir, I agree with Dr. Meregalli and coworkers that the rate of excretion of NHJ is the critical component of net acid excretion because it is the major adaptable component of net acid excretion during metabolic acidosis. Furthermore, I agree that the hallmark for the diagnosis of distal renal tubular acidosis is a low rate of NHJ excretion [ 1 ]. This only leaves me to define what is low and what is high for NHJ excretion rates and the optimal tests for assessing NHJ excretion at the bedside. Quantitative analysis: Normal adults on a typical western diet excrete close to 30 mmol of NHJ /day. In contrast, when metabolic acidosis is due to ingestion of NH4C1 and if it is chronic, the expected rate of excretion of NHJ is > 200 mmol/day [2, 3]. Accordingly, when faced with a patient who has chronic metabolic acidosis, a normal anion gap in plasma, and a normal glomerular filtration rates one should expect to find an NHJ excretion rate close to 200 mmol/day, if the renal capacity to excrete NHJ is normal; much lower values indicate a major defect in net acid excretion. Moreover, if the acidosis is strictly due to a renal defect in NHJ excretion, the rate of excretion of NHJ would have to be < 30-40 mmol/day; otherwise the acidosis would resolve spontaneously. Hence the crucial initial information about the rate of NHJ excretion is whether this rate is close to 200 mmol/day versus considerably less than 40 mmol/day. Bearing this in mind, let us return to the accuracy needed from the indirect measures of NHJ excretion. This will illustrate my disagreement with the interpretation of the data of Dr. Meregalli and colleagues. Tests to measure the rate of excretion of NH↕: The gold standard for assessing the concentration of NHJ in the urine is a direct assay, as pointed out in the letter. Conversely, three indirect techniques are commonly used. First, some authors rely heavily on the urine pH which is, in my opinion, an unreliable way to assess the concentration of NHJ [4]. The other two indirect techniques are the urine net charge [5] and the urine osmolal gap [6, 7]. Both require many individual measurements, and it goes without saying that if all of these measurements are not absolutely accurate, there could be considerable scatter in the data. More specifically, the urine net charge reflects the concentration of NHJ only if the anion excreted with NHJ is CF. The urine osmolal gap has the advantage that it will detect NHJ excreted with any anion. Pitfalls in the osmolal gap include excretion of unusual uncharged compounds such as alcohols, the excretion of polyvalent anions, or the excretion of cations such as Ca2+, Mg2+, or Li+. Since the excretion

Modified Urine Osmolal Gap: An Accurate Method for Estimating the Urinary Ammonium Concentration?