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Update on the Pathophysiology and Management of Uric Acid Renal Stones

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Abstract

Idiopathic uric acid nephrolithiasis appears to be increasing in prevalence. While it has long been known that low urine pH is associated with uric acid stones, only recently has the pathophysiological basis for this disease emerged. Excessively acidic urine is the decisive risk for uric acid lithogenesis, and patients with diabetes and the metabolic syndrome often hold the company of low urine pH. While association does not imply causation, interesting insights have been made regarding insulin’s influence on acid-base physiology. We review recent evidence from both the molecular and clinical realms to underline the importance of [H+] in the development and treatment of uric acid nephrolithiasis.

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References

Papers of particular interest, published recently have been highlighted as: • Of importance •• Of major importance

  1. Maalouf NM, Cameron MA, Moe OW, Sakhaee K: Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens 2004, 13:181–189.

    Article  PubMed  Google Scholar 

  2. Taylor EN, Curhan GC: Body size and 24-hour urine composition. Am J Kidney Dis 2006, 48:905–915.

    Article  CAS  PubMed  Google Scholar 

  3. •• Maalouf NM, Cameron MA, Moe OW et al: Low urine pH: a novel feature of the metabolic syndrome. Clin J Am Soc Nephrol 2007, 2:883–888.

    Article  CAS  PubMed  Google Scholar 

  4. Daudon M, Lacour B, Jungers P: High prevalence of uric acid calculi in diabetic stone formers. Nephrol Dial Transplant 2005, 20:468–469.

    Article  PubMed  Google Scholar 

  5. Maalouf NM, Sakhaee K, Parks JH et al: Association of urinary pH with body weight in nephrolithiasis. Kidney Int 2004, 65:1422–1425.

    Article  PubMed  Google Scholar 

  6. Flegal KM, Carroll MD, Ogden CL, Johnson CL: Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002, 288:1723–1727.

    Article  PubMed  Google Scholar 

  7. • Asplin JR: Obesity and urolithiasis. Adv Chronic Kidney Dis 2009, 16:11–20.

    Article  PubMed  Google Scholar 

  8. Lemann J, Jr., Pleuss JA, Worcester EM et al: Urinary oxalate excretion increases with body size and decreases with increasing dietary calcium intake among healthy adults. Kidney Int 1996, 49:200–208.

    Article  CAS  PubMed  Google Scholar 

  9. Yamashita S, Matsuzawa Y, Tokunaga K et al: Studies on the impaired metabolism of uric acid in obese subjects: marked reduction of renal urate excretion and its improvement by a low-calorie diet. Int J Obes 1986, 10:255–264.

    CAS  PubMed  Google Scholar 

  10. Nowicki M, Kokot F, Surdacki A: The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure. Nephrol Dial Transplant 1998, 13:2566–2571.

    Article  CAS  PubMed  Google Scholar 

  11. Goldfarb DS: In the clinic. Nephrolithiasis. Ann Intern Med 2009, 151:ITC2.

  12. Eisner BH, Reese A, Sheth S, Stoller ML: Ureteral stone location at emergency room presentation with colic. J Urol 2009,

  13. Singh K, Bonaa KH, Jacobsen BK et al: Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study : The Tromso Study. Am J Epidemiol 2001, 154:236–244.

    Article  CAS  PubMed  Google Scholar 

  14. Shahinfar S, Simpson RL, Carides AD et al: Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia. Kidney Int 1999, 56:1879–1885.

    Article  CAS  PubMed  Google Scholar 

  15. Mandel NS, Mandel GS: Urinary tract stone disease in the United States veteran population. II. Geographical analysis of variations in composition. J Urol 1989, 142:1516–1521.

    CAS  PubMed  Google Scholar 

  16. Hossain RZ, Ogawa Y, Hokama S et al: Urolithiasis in Okinawa, Japan: a relatively high prevalence of uric acid stones. Int J Urol 2003, 10:411–415.

    Article  PubMed  Google Scholar 

  17. Hesse A, Schneider HJ, Berg W, Hienzsch E: Uric acid dihydrate as urinary calculus component. Invest Urol 1975, 12:405–409.

    CAS  PubMed  Google Scholar 

  18. Cameron MA, Sakhaee K: Uric acid nephrolithiasis. Urol Clin North Am 2007, 34:335–346.

    Article  PubMed  Google Scholar 

  19. Rafey MA, Lipkowitz MS, Leal-Pinto E, Abramson RG: Uric acid transport. Curr Opin Nephrol Hypertens 2003, 12:511–516.

    Article  CAS  PubMed  Google Scholar 

  20. Asplin JR: Uric acid stones. Semin Nephrol 1996, 16:412–424.

    CAS  PubMed  Google Scholar 

  21. Pak CY, Barilla DE, Holt K et al: Effect of oral purine load and allopurinol on the crystallization of calcium salts in urine of patients with hyperuricosuric calcium urolithiasis. Am J Med 1978, 65:593–599.

    Article  CAS  PubMed  Google Scholar 

  22. Fellstrom B, Danielson BG, Karlstrom B et al: The influence of a high dietary intake of purine-rich animal protein on urinary urate excretion and supersaturation in renal stone disease. Clin Sci (Lond) 1983, 64:399–405.

    CAS  Google Scholar 

  23. Alvarez-Nemegyei J, Medina-Escobedo M, Villanueva-Jorge S, Vazquez-Mellado J: Prevalence and risk factors for urolithiasis in primary gout: is a reappraisal needed? J Rheumatol 2005, 32:2189–2191.

    CAS  PubMed  Google Scholar 

  24. Sakhaee K, ms-Huet B, Moe OW, Pak CY: Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int 2002, 62:971–979.

    Google Scholar 

  25. Yu T, Gutman AB: Uric acid nephrolithiasis in gout. Predisposing factors. Ann Intern Med 1967, 67:1133–1148.

    CAS  PubMed  Google Scholar 

  26. Stamatelou KK, Francis ME, Jones CA et al: Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 2003, 63:1817–1823.

    Article  PubMed  Google Scholar 

  27. 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, 65:386–392.

    Article  CAS  PubMed  Google Scholar 

  28. Pak CY, Sakhaee K, Moe O et al: Biochemical profile of stone-forming patients with diabetes mellitus. Urology 2003, 61:523–527.

    Article  PubMed  Google Scholar 

  29. Chobanian MC, Hammerman MR: Insulin stimulates ammoniagenesis in canine renal proximal tubular segments. Am J Physiol 1987, 253:F1171–F1177.

    CAS  PubMed  Google Scholar 

  30. Nissim I, States B, Nissim I et al: Hormonal regulation of glutamine metabolism by OK cells. Kidney Int 1995, 47:96–105.

    Article  CAS  PubMed  Google Scholar 

  31. Vinay P, Lemieux G, Cartier P, Ahmad M: Effect of fatty acids on renal ammoniagenesis in in vivo and in vitro studies. Am J Physiol 1976, 231:880–887.

    CAS  PubMed  Google Scholar 

  32. Gesek FA, Schoolwerth AC: Insulin increases Na(+)-H + exchange activity in proximal tubules from normotensive and hypertensive rats. Am J Physiol 1991, 260:F695–F703.

    CAS  PubMed  Google Scholar 

  33. Klisic J, Hu MC, Nief V et al: Insulin activates Na(+)/H(+) exchanger 3: biphasic response and glucocorticoid dependence. Am J Physiol Renal Physiol 2002, 283:F532–F539.

    CAS  PubMed  Google Scholar 

  34. Nakagawa T, Hu H, Zharikov S et al: A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 2006, 290:F625–F631.

    Article  CAS  PubMed  Google Scholar 

  35. Cirillo P, Gersch MS, Mu W et al: Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol 2009, 20:545–553.

    Article  CAS  PubMed  Google Scholar 

  36. •• Bobulescu IA, Dubree M, Zhang J et al: Effect of renal lipid accumulation on proximal tubule Na+/H + exchange and ammonium secretion. Am J Physiol Renal Physiol 2008, 294:F1315–F1322.

    Article  CAS  PubMed  Google Scholar 

  37. Bobulescu IA, Dubree M, Zhang J et al: Reduction of renal triglyceride accumulation: effects on proximal tubule Na+/H + exchange and urinary acidification. Am J Physiol Renal Physiol 2009, 297:F1419–F1426.

    Article  CAS  PubMed  Google Scholar 

  38. Chen YD, Varasteh BB, Reaven GM: Plasma lactate concentration in obesity and type 2 diabetes. Diabete Metab 1993, 19:348–354.

    CAS  PubMed  Google Scholar 

  39. Bilobrov VM, Chugaj AV, Bessarabov VI: Urine pH variation dynamics in healthy individuals and stone formers. Urol Int 1990, 45:326–331.

    Article  CAS  PubMed  Google Scholar 

  40. Murayama T, Taguchi H: The role of the diurnal variation of urinary pH in determining stone compositions. J Urol 1993, 150:1437–1439.

    CAS  PubMed  Google Scholar 

  41. Rodman JS: Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts. J Urol 1991, 145:97–99.

    CAS  PubMed  Google Scholar 

  42. Rodman JS: Intermittent versus continuous alkaline therapy for uric acid stones and ureteral stones of uncertain composition. Urology 2002, 60:378–382.

    Article  PubMed  Google Scholar 

  43. Seltzer MA, Low RK, McDonald M et al: Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. Journal of Urology 1996, 156:907–909.

    Article  CAS  PubMed  Google Scholar 

  44. Odvina CV: Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin J Am Soc Nephrol 2006, 1:1269–1274.

    Article  CAS  PubMed  Google Scholar 

  45. Goldfarb DS, Asplin JR: Effect of grapefruit juice on urinary lithogenicity. J Urol 2001, 166:263–267.

    Article  CAS  PubMed  Google Scholar 

  46. Goodman JW, Asplin JR, Goldfarb DS: Effect of two sports drinks on urinary lithogenicity. Urol Res 2009, 37:41–46.

    Article  CAS  PubMed  Google Scholar 

  47. Becker MA, Schumacher HR, Jr., Wortmann RL et al: Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005, 353:2450–2461.

    Article  CAS  PubMed  Google Scholar 

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Disclosures

Dr. Goldfarb: medical advisory boards for Takeda and Sanofi-Aventis; consultant for Watson; research funding from NIDDK and Office of Rare Disease Research.

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Authors and Affiliations

  1. Department of Medicine, NYU Langone Medical Center, New York, NY, USA

    Jon-Emile S. Kenny & David S. Goldfarb

  2. Nephrology Section, New York Harbor VA Health Care System, New York, NY, USA

    David S. Goldfarb

  3. Nephrology Section/111G, New York DVAMC, 423 E. 23 St., New York, NY, 10010, USA

    David S. Goldfarb

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  1. Jon-Emile S. Kenny
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  2. David S. Goldfarb
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Correspondence to David S. Goldfarb.

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Kenny, JE.S., Goldfarb, D.S. Update on the Pathophysiology and Management of Uric Acid Renal Stones. Curr Rheumatol Rep 12, 125–129 (2010). https://doi.org/10.1007/s11926-010-0089-y

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  • DOI: https://doi.org/10.1007/s11926-010-0089-y

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