Urine organic anion increases with age and its effects on renal acid excretion vary with pKa

Findings of falling urine pH with age among stone formers have not been explained by changes in renal function or renal ammonia production with age. We collected and analyzed 245 urine samples from 190 stone-forming subjects (95 male) and 55 normal subjects (18 male) to expand on our previous study using urine titration to explore whether urine organic anion (Uoa) contributes to acid load and rises with age. We stratified our previous titration protocol to include three pKa subranges, 2.70-3.60, 3.61-4.30, and 4.31-7.40, to measure effects of Uoa of differing pKa values on renal acid excretion. We found that Uoa behaves as a metabolic acid, and associates independently and positively with ammonia (<i>P</i> < 0.001). Uoa in pKa range 2.70-3.60 is the principal acid component and rises with age (<i>P</i> < 0.001), whereas Uoa in pKa range 4.31-7.40 seems to reflect net alkali excretion when studied in a regression model with the kidney as a reporter organ. When factored per urine creatinine, we found significant age and sex effects of nearly all components of renal acid-base balance. Effects from subject type (stone former vs. normal) were minimal, though we are limited by the oldest tertile having few normals. As acid anions with pKa within 2.70-3.60 are used in the tricarboxylic acid cycle, markers of acid excretion may reflect mitochondrial abnormalities associated with aging.<b>NEW & NOTEWORTHY</b> When assessed using the kidney as a reporter organ, titrated urine anions behave overall as an acid load. However, those in the pKa range of 2.70-3.60 account for much of that behavior, whereas anions in the pKa ranges above 3.60 variably behave as alkali or acid, indicating that the urinary anions are heterogeneous. Despite their differences in function, they all rise with age. This may explain acid stress reported as part of the aging phenotype.