Uric acid nephrolithiasis

INTRODUCTION

Uric acid stones account for 5 to 10 percent of urinary tract stones in the United States and Europe. In contrast, they comprise 40 percent or more of stones in areas with hot, arid climates in which the tendency to a low urine volume and acid urine pH promote uric acid precipitation. The risk of both uric acid and calcium stones is also increased in patients with gout. (See "Clinical manifestations and diagnosis of gout", section on 'Nephrolithiasis' and 'Gout' below and "Risk factors for calcium stones in adults", section on 'Hyperuricosuria' and "Risk factors for calcium stones in adults", section on 'Other factors'.)

Issues related to uric acid stone disease will be reviewed here. The general approach to the patient with nephrolithiasis and other management issues related to hyperuricemia and gout are discussed separately. (See "Diagnosis and acute management of suspected nephrolithiasis in adults" and "Evaluation of the adult patient with established nephrolithiasis and treatment if stone composition is unknown" and "Clinical manifestations and diagnosis of gout" and "Asymptomatic hyperuricemia".)

PATHOGENESIS

The two major factors that promote uric acid precipitation are a high urine uric acid concentration and an acid urine pH, which drives the following reaction toward the right, converting the relatively soluble urate salt into insoluble uric acid [1,2].

     H+   +   Urate-    ↔    Uric acid

A low urine pH is the more significant of these two biochemical risk factors for the development of uric acid nephrolithiasis [3-9]. Uric acid solubility in the urine falls from approximately 200 mg/dL (1.2 mmol/L) at a urine pH of 7 (a setting in which 95 percent of uric acid is present as the more soluble urate anion) to 15 mg/dL (0.09 mmol/L) at a urine pH of 5 (a setting in which most of the uric acid is the less soluble, undissociated acid) [1,10].

             

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Literature review current through: Jun 2014. | This topic last updated: Oct 16, 2013.
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References
Top
  1. Coe FL. Uric acid and calcium oxalate nephrolithiasis. Kidney Int 1983; 24:392.
  2. Perez-Ruiz F, Hernando I, Herrero-Beites AM. Uricosuric therapy. In: Crystal-Induced Arthropathies, Wortmann RL, Schumacher HR Jr, Becker MA, Ryan LM (Eds), Taylor & Francis Group, New York 2006. p.369.
  3. Kenny JE, Goldfarb DS. Update on the pathophysiology and management of uric acid renal stones. Curr Rheumatol Rep 2010; 12:125.
  4. Pak CY, Sakhaee K, Peterson RD, et al. Biochemical profile of idiopathic uric acid nephrolithiasis. Kidney Int 2001; 60:757.
  5. Sakhaee K, Adams-Huet B, Moe OW, Pak CY. Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int 2002; 62:971.
  6. Negri AL, Spivacow R, Del Valle E, et al. Clinical and biochemical profile of patients with "pure" uric acid nephrolithiasis compared with "pure" calcium oxalate stone formers. Urol Res 2007; 35:247.
  7. Pak CY, Poindexter JR, Peterson RD, et al. Biochemical distinction between hyperuricosuric calcium urolithiasis and gouty diathesis. Urology 2002; 60:789.
  8. Yu TF. Urolithiasis in hyperuricemia and gout. J Urol 1981; 126:424.
  9. Falls WF Jr. Comparison of urinary acidification and ammonium excretion in normal and gouty subjects. Metabolism 1972; 21:433.
  10. Seegmiller JE. Xanthine stone formation. Am J Med 1968; 45:780.
  11. Riese RJ, Sakhaee K. Uric acid nephrolithiasis: pathogenesis and treatment. J Urol 1992; 148:765.
  12. Pak CY, Poindexter JR, Adams-Huet B, Pearle MS. Predictive value of kidney stone composition in the detection of metabolic abnormalities. Am J Med 2003; 115:26.
  13. Kramer HM, Curhan G. The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994. Am J Kidney Dis 2002; 40:37.
  14. Kramer HJ, Choi HK, Atkinson K, et al. The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study. Kidney Int 2003; 64:1022.
  15. Sperling O. Hereditary renal hypouricemia. Mol Genet Metab 2006; 89:14.
  16. Parks JH, Worcester EM, O'Connor RC, Coe FL. Urine stone risk factors in nephrolithiasis patients with and without bowel disease. Kidney Int 2003; 63:255.
  17. Abate N, Chandalia M, Cabo-Chan AV Jr, et al. The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int 2004; 65:386.
  18. Cameron MA, Maalouf NM, Adams-Huet B, et al. Urine composition in type 2 diabetes: predisposition to uric acid nephrolithiasis. J Am Soc Nephrol 2006; 17:1422.
  19. Pak CY, Sakhaee K, Moe O, et al. Biochemical profile of stone-forming patients with diabetes mellitus. Urology 2003; 61:523.
  20. Meydan N, Barutca S, Caliskan S, Camsari T. Urinary stone disease in diabetes mellitus. Scand J Urol Nephrol 2003; 37:64.
  21. Daudon M, Lacour B, Jungers P. High prevalence of uric acid calculi in diabetic stone formers. Nephrol Dial Transplant 2005; 20:468.
  22. Daudon M, Traxer O, Conort P, et al. Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol 2006; 17:2026.
  23. Maalouf NM, Cameron MA, Moe OW, et al. Low urine pH: a novel feature of the metabolic syndrome. Clin J Am Soc Nephrol 2007; 2:883.
  24. Taylor EN, Curhan GC. Body size and 24-hour urine composition. Am J Kidney Dis 2006; 48:905.
  25. Maalouf NM, Sakhaee K, Parks JH, et al. Association of urinary pH with body weight in nephrolithiasis. Kidney Int 2004; 65:1422.
  26. Shekarriz B, Stoller ML. Uric acid nephrolithiasis: current concepts and controversies. J Urol 2002; 168:1307.
  27. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med 2004; 350:684.
  28. Matlaga BR, Kawamoto S, Fishman E. Dual source computed tomography: a novel technique to determine stone composition. Urology 2008; 72:1164.
  29. Shimizu T, Hori H. The prevalence of nephrolithiasis in patients with primary gout: a cross-sectional study using helical computed tomography. J Rheumatol 2009; 36:1958.
  30. Asplin JR. Uric acid stones. Semin Nephrol 1996; 16:412.
  31. Pak CY, Sakhaee K, Fuller C. Successful management of uric acid nephrolithiasis with potassium citrate. Kidney Int 1986; 30:422.
  32. Trinchieri A, Esposito N, Castelnuovo C. Dissolution of radiolucent renal stones by oral alkalinization with potassium citrate/potassium bicarbonate. Arch Ital Urol Androl 2009; 81:188.
  33. Rodman JS. Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts. J Urol 1991; 145:97.
  34. Borghi L, Meschi T, Amato F, et al. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. J Urol 1996; 155:839.
  35. Becker MA, Kisicki J, Khosravan R, et al. Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers. Nucleosides Nucleotides Nucleic Acids 2004; 23:1111.
  36. Curhan GC, Taylor EN. 24-h uric acid excretion and the risk of kidney stones. Kidney Int 2008; 73:489.
  37. Ettinger B, Tang A, Citron JT, et al. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med 1986; 315:1386.
  38. Goldfarb DS, MacDonald PA, Gunawardhana L, et al. Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones. Clin J Am Soc Nephrol 2013; 8:1960.