Renal Ammonium Excretion and Urinary Ph in Idiopathic Uric Acid Lithiasis

Demography and biochemistry of 2800 patients from a renal stones clinic

“…Stone formers may have deliberately increased their fluid intake or have decreased renal water re-absorption. Others have reported falling pH with age in normal individuals 39 and stone formers. 14,15 The explanation is unknown.…”

Urinary Ammonium Excretion in Primary Gout*

“…[In renal tubular acidosis and allied disorders, the urinary elimination of ammonium is meager, but this is associated with a relatively high urine pH, not with a markedly reduced renal capacity to produce ammonia (19).] More recently, Henneman, Wallach, and Dempsey (20) described a specific renal defect in excretion of ammonium associated with uric acid stone formation in nongouty subjects, an observation confirmed in some such cases (21) but not in others (16).…”

“…It has long been known that the urinary excretion of ammonium is substantially reduced in patients with advanced kidney disease, such as chronic glomerulonephritis with uremia (13,14), despite elimination of distinctly acid urine, although even in such circumstances renal production of ammonia may be surprisingly well preserved (15). A significant reduction in urinary ammonium excretion has been reported to occur in association with aging (16). Relatively minor injury due to pyelonephritis, it is said, may cause an appreciable decrease in renal production of ammonia, but when this impression was recently tested by Steinmetz, Eisinger, and Lowenstein (17), they could detect no specific tubular defect in ammonia production in such cases tuiless the functioning nephron mass was substantially reduced, as reflected in an unequivocally lower glomerular filtration rate.…”

The Kinetics of Intramolecular Distribution of 15N in Uric Acid after Administration of [15N]Glycine A REAPPRAISAL OF THE SIGNIFICANCE OF PREFERENTIAL LABELING OF N-(3 + 9) OF URIC ACID IN PRIMARY GOUT

“…The three elements of the hypothesis of abnormal gltutamine metabolism in primary (idiopathic) gout are: first, disproportionate labeling of N-(3 + 9) in urate overproducers after ingestion of ['3N]glycine (6,10); second, reduced production of urinary NH3 at a given acid load (15)(16)(17); and third, hyperglutamatemia (18, 19) that appears to be independent of dietary protein level (18). The disproportionate labeling of N-(3 + 9) has now been shown to be a general feature of accelerated purine biosynthesis, and therefore this finding does not specifically favor a defect of glutamine metabolism in primary gout.…”

“…Since N-3 and N-9 of uric acid are derived from the amide-N of glutamine (7-9), Gutman and Yu (6,10) proposed a defect in glutamine metabolism as the basis for excessive purine biosynthesis in primary gout. Since urinary ammonium, which arises principally from glutamine (11)(12)(13)(14), is reduced in many gouty subjects (15)(16)(17), they further postulated that the defect was a reduction of glutaminase activity (6,10). The recent finding of hyperglutamatemia in gout has shifted attention toward a possible defect of glutamate metabolism, resulting in diversion of glutarnic acid toward glutamine and purine biosynthesis (18)(19)(20).…”