The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers

Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary acid-base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and uric acid stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 uric acid stone formers on fixed metabolic diets to study the diurnal pattern of urinary acidification. All showed clear diurnal trends in urinary acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric acid stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric acid stone formers excreted more acid (normalized to acid ingestion), with the excess excreted primarily as titratable acid rather than ammonium. Urine base excretion was also lower in uric acid stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated uric acid throughout the day and consequently an increased risk of uric acid stones.