Understanding of acid excretion in kidney disease

Mirna Aleckovic-Halilovic and Mirha Pjanic
University Clinical Center Tuzla, Bosnia and Herzegovina

Fully understanding renal aspects of acid-base regulation has always been a challenge. A landmark paper that paved the way to current knowledge on acid excretion in different renal diseases and became a citation classic in 1979 was written by Oliver Wrong and H.E.F. Davies and published in 1959 (1).

At the time, knowledge on acid excretion variation in different renal diseases was limited and there was a clear need for the development of a clinically useful test to detect impairment of kidney acid elimination. The authors devised a test, still widely used today, using ammonium chloride as an external acidification stimulus. They tested 10 subjects with normal renal function and 58 patients with different renal conditions. The cut-off point of pH 5.3 became the accepted criterion for defining a defect in renal acid excretion.

Contrary to accepted belief, they found that renal ability to acidify urine was not impaired in subjects with renal failure, and that systemic acidosis was, in fact, the result of greatly

reduced excretion of ammonium and, to a lesser extent, reduced excretion of buffer and therefore reduced excretion of titratable acid, all due to reduced renal mass and nephron number.

On the other hand, they found that renal ability to acidify urine in renal tubular acidosis (RTA) was greatly impaired, and although buffer excretion was reduced, reflecting the reduced hydrogen ion secretion, urinary ammonium excretion was relatively well-preserved; this gave an explanation as to why many patients with RTA were not acidotic and had what the authors named “incomplete RTA”.

The authors further recognized that the form of RTA associated with features of renal Fanconi syndrome was different from the classical form, known today as distal RTA, and suggested an abnormality of proximal nephron function (2).

This first major work by Oliver Wrong, (1) as well as his very last paper, (3) was on RTA, a clinical disorder he returned to throughout his life. He was rightly named a ‘salt and water’ physician and a prize for innovative research in nephrology at the University College of London is named in his honor.


  1. Wrong O, Davies HE. The excretion of acid in renal disease. Q J Med. 1959;28(110):259-313.
  2. Unwin, RJ (2012). "Back to the future: renal tubular acidosis then and now". QJM. 105 (9): 915–916. doi:10.1093/qjmed/hcs134. PMID 22855286.
  3. Khositseth S, Bruce LJ, Walsh SB, Bawazir WM, Ogle GD, Unwin RJ, et al. Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients. Q J Med 2012;105:861–77.

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