An appraisal of the in vivo role of phosphate as a modulator of urinary ammonium and titratable acid excretion in the acidotic rabbit

Previous studies have shown that the intravenous infusion of inorganic phosphate increased urinary ammonium excretion 8- to 10-fold in the acidotic rabbit. This was considered to be a very important observation at the time and to be unique to the rabbit. While investigating this finding, we discovered that the formol titration procedure, used to measure urinary ammonium by this research group, is subject to interference by phosphate, casting doubt on the validity of the urinary ammonium excretion data reported by them in the literature. In order to re-assess the importance of phosphate as a potential modulator of urinary ammonium excretion in the acidotic rabbit, renal net acid excretion studies were carried out in phosphate-loaded acidotic animals. We observed that while urinary ammonium excretion increased significantly (p < 0.05) after 50 min of phosphate infusion, the maximum concentrations excreted were substantially less than previously reported in the literature. However, through its urinary buffering capacity, we observed that inorganic phosphate, via an experimentally induced phosphaturia, could substantially enhance titratable acid excretion. Contrary to earlier reports, we demonstrated that phosphate plays a relatively minor in vivo modulator role in enhancing renal net acid excretion through the vehicle of ammonium during acute metabolic acidosis in the hyperphosphataemic rabbit. The findings reported in this study constitute an important update on ammonia metabolism in the acidotic rabbit.