Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder - PubMed (original) (raw)

Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder

Michael R Wiederkehr et al. Clin Rev Bone Miner Metab. 2011 Dec.

Abstract

Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form.

Keywords: Acid urine; Alkaline; Ammonium; Gout; Hyperuricosuria; Metabolic syndrome; Potassium citrate; Uric acid nephrolithiasis; Urine buffer; pH.

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Figures

Fig. 1

Fig. 1

Events leading to titration of urate to uric acid in urine. Acid generation is increased in obesity, metabolic syndrome, and type 2 diabetes mellitus. The excess H+ is excreted in the urine but the increase in net acid excretion is not entirely mediated by increased ammonia synthesis and ammonium excretion. This leaves excess H+ to titrate other buffers, which fulfills acid–base balance. However, one such buffer is urate, which can precipitate when protonated to the highly insoluble uric acid. Additional but yet unidentified factor(s) enable uric acid crystals to become uric acid stones

Fig. 2

Fig. 2

The relative effects of urine pH and total uric acid on undissociated uric acid (modified from Maalouf et al. with permission). The quantitative relationship of urate, uric acid, and pH are determined by the pKa of 5.3. The dashed line denotes the solubility of uric acid. At a urine pH of 6.5, even a high level of uricosuria does not significantly elevate undissociated uric acid. At a urine pH of 5.5, even a modest concentration of uric acid within the clinical normal range will lead to an undissociated uric acid level that far exceeds its solubility. With permission from Maalouf N et al. (Credit to: Maalouf N, Gaska MA, Abate N, Sakhaae K, Moe OW. New insights in the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens 13:181–189, 2004)

Fig. 3

Fig. 3

Acid base parameters in normal individuals and uric acid stone formers.TA Titratable acidity, NAE Net acid excretion, estimated as NH4+ + TA—base (citrate and others)

Fig. 4

Fig. 4

Diurnal variation of urine pH and volume. In the early hours of the morning, both urine pH and urine volume are lowest, rendering this a particular vulnerable period for uric acid precipitation

References

    1. Balinsky JB. Phylogenetic aspects of purine metabolism. S Afr Med J. 1972;46(29):993–7. - PubMed
    1. Campbell JW. Comparative biochemistry of nitrogen metabolism. In: Campbell JW, editor. The vertebrates. Vol. 2. New York: Academic Press; 1970.
    1. Moe OW. Uric acid nephrolithiasis: proton titration of an essential molecule? Curr Opin Nephrol Hypertens. 2006;15(4):366–73. - PubMed
    1. Shoemaker VH, et al. Uricotelism and low evaporative water loss in a South American frog. Science. 1972;175(25):1018–20. - PubMed
    1. Christen P, et al. Urate oxidase in primates. Folia Primatol (Basel) 1970;13(1):35–9. - PubMed

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