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Epidemiology and clinical pathophysiology of uric acid kidney stones

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Abstract

There is global diversity in the prevalence of uric acid (UA) nephrolithiasis. UA nephrolithiasis comprises 8–10 % of all kidney stones in the United States. However, its prevalence is higher in patients with type 2 diabetes mellitus and those with obesity. Three significant urinary abnormalities have been described as the main etiologic factors for the development of UA nephrolithiasis; low urinary pH, hyperuricosuria and low urinary volume. However, an unduly acidic urine below the ionization constant of uric acid (pKa < 5.5) increases the urinary content of undissociated uric acid and thereby uric acid precipitation. Previous studies have shown the two major pathogenic mechanisms for unduly urinary pH are increased net acid excretion (NAE) and reduced renal ammonium (NH4 +), with a combination resulting in overly acidic urine. The impaired ammonium excretion has been demonstrated in a steady state in 24-hour urine and also following an oral ammonium chloride (NH4Cl) challenge to amplify ammoniogenic defects in this population. Similar abnormalities have been disclosed in normal populations and also in T2DM populations without kidney stones. To date, the underlying mechanism of increased acid production, source and nature of putative organic acid anions have not been fully elucidated. One plausible mechanism is the production of organic acid by intestinal and aerobic metabolism. This may occur in obese, diabetic and uric acid stone formers due to the differences in gut microflora.

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References

  1. Rafique M, Bhutta RA, Rauf A, Chaudhry IA (2000) Chemical composition of upper renal tract calculi in Multan. J Pak Med Assoc 50(5):145–148

    CAS  PubMed  Google Scholar 

  2. Herbstein FH, Kleeberg J, Shalitin Y, Wartski E, Wielinski S (1974) Chemical and X-ray diffraction analysis of urinary stones in Israel. Israel J Med Sci 10(12):1493–1499

    CAS  PubMed  Google Scholar 

  3. Hossain RZ, Ogawa Y, Hokama S, Morozumi M, Hatano T (2003) Urolithiasis in Okinawa, Japan: a relatively high prevalence of uric acid stones. Int J Urol 10(8):411–415

    Article  PubMed  Google Scholar 

  4. Sakhaee K (2011) Uric acid metabolism and uric acid stones. In: Rao PP, Kavanagh J (eds) Urinary tract stone disease. Springer, Manchester, pp 185–193

    Google Scholar 

  5. Portis AJ, Hermans K, Culhane-Pera KA, Curhan GC (2004) Stone disease in the Hmong of Minnesota: initial description of a high-risk population. J Endourol 18(9):853–857

    Article  PubMed  Google Scholar 

  6. Portis AJ, Laliberte M, Tatman P, Moua M, Culhane-Pera K, Maalouf NM, Sakhaee K (2010) High prevalence of gouty arthritis among the Hmong population in Minnesota. Arthr Care Res (Hoboken) 62(10):1386–1391

    Article  Google Scholar 

  7. Sakhaee K, Adams-Huet B, Moe OW, Pak CY (2002) Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int 62(3):971–979

    Article  CAS  PubMed  Google Scholar 

  8. Daudon M, Lacour B, Jungers P (2005) High prevalence of uric acid calculi in diabetic stone formers. Nephrol Dial Transplant 20(2):468–469

    Article  PubMed  Google Scholar 

  9. Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K (2006) Urine composition in type 2 diabetes: predisposition to uric acid nephrolithiasis. J Am Soc Nephrol 17(5):1422–1428

    Article  CAS  PubMed  Google Scholar 

  10. Prasongwatana V, Sriboonlue P, Suntarapa S (1983) Urinary stone composition in North–East Thailand. Br J Urol 55(4):353–355

    Article  CAS  PubMed  Google Scholar 

  11. Pak CY, Sakhaee K, Moe O, Preminger GM, Poindexter JR, Peterson RD, Pietrow P, Ekeruo W (2003) Biochemical profile of stone-forming patients with diabetes mellitus. Urology 61(3):523–527

    Article  PubMed  Google Scholar 

  12. Lieske JC, de la Vega LS, Gettman MT, Slezak JM, Bergstralh EJ, Melton LJ 3rd, Leibson CL (2006) Diabetes mellitus and the risk of urinary tract stones: a population-based case-control study. Am J Kidney Dis 48(6):897–904

    Article  PubMed  Google Scholar 

  13. Ekeruo WO, Tan YH, Young MD, Dahm P, Maloney ME, Mathias BJ, Albala DM, Preminger GM (2004) Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients. J Urol 172(1):159–163

    Article  PubMed  Google Scholar 

  14. Daudon M, Lacour B, Jungers P (2006) Influence of body size on urinary stone composition in men and women. Urol Res 34(3):193–199

    Article  PubMed  Google Scholar 

  15. Daudon M, Traxer O, Conort P, Lacour B, Jungers P (2006) Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol 17(7):2026–2033

    Article  CAS  PubMed  Google Scholar 

  16. Maalouf NM, Cameron MA, Moe OW, Sakhaee K (2004) Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens 13(2):181–189

    Article  PubMed  Google Scholar 

  17. Deren JJ, Porush JG, Levitt MF, Khilnani MT (1962) Nephrolithiasis as a complication of ulcerative colitis and regional enteritis. Ann Intern Med 56:843–853

    Article  CAS  PubMed  Google Scholar 

  18. Gelzayd EA, Breuer RI, Kirsner JB (1968) Nephrolithiasis in inflammatory bowel disease. Am J Dig Dis 13(12):1027–1034

    Article  CAS  PubMed  Google Scholar 

  19. Knudsen L, Marcussen H, Fleckenstein P, Pedersen EB, Jarnum S (1978) Urolithiasis in chronic inflammatory bowel disease. Scand J Gastroenterol 13(4):433–436

    Article  CAS  PubMed  Google Scholar 

  20. Bambach CP, Robertson WG, Peacock M, Hill GL (1981) Effect of intestinal surgery on the risk of urinary stone formation. Gut 22(4):257–263

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Fukushima T, Yamazaki Y, Sugita A, Tsuchiya S (1991) Prophylaxis of uric acid stone in patients with inflammatory bowel disease following extensive colonic resection. Gastroenterol Jpn 26(4):430–434

    CAS  PubMed  Google Scholar 

  22. Clarke AM, McKenzie RG (1969) Ileostomy and the risk of urinary uric acid stones. Lancet 2(7617):395–397

    Article  CAS  PubMed  Google Scholar 

  23. Obialo CI, Clayman RV, Matts JP, Fitch LL, Buchwald H, Gillis M, Hruska KA (1991) Pathogenesis of nephrolithiasis post-partial ileal bypass surgery: case-control study. The POSCH Group. Kidney Int 39(6):1249–1254

    Article  CAS  PubMed  Google Scholar 

  24. Rafey MA, Lipkowitz MS, Leal-Pinto E, Abramson RG (2003) Uric acid transport. Curr Opin Nephrol Hypertens 12(5):511–516

    Article  CAS  PubMed  Google Scholar 

  25. Asplin JR (1996) Uric acid stones. Semin Nephrol 16(5):412–424

    CAS  PubMed  Google Scholar 

  26. Finlayson B, Smith A (1974) Stability of first dissociable proton of uric acid. J Chem Eng Data 19(1):94–97

    Article  CAS  Google Scholar 

  27. Riese RJ, Sakhaee K (1992) Uric acid nephrolithiasis: pathogenesis and treatment. J Urol 148(3):765–771

    CAS  PubMed  Google Scholar 

  28. Sakhaee K, Nigam S, Snell P, Hsu MC, Pak CY (1987) Assessment of the pathogenetic role of physical exercise in renal stone formation. J Clin Endocrinol Metab 65(5):974–979

    Article  CAS  PubMed  Google Scholar 

  29. Reddy ST, Wang CY, Sakhaee K, Brinkley L, Pak CY (2002) Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis 40(2):265–274

    Article  CAS  PubMed  Google Scholar 

  30. Koka RM, Huang E, Lieske JC (2000) Adhesion of uric acid crystals to the surface of renal epithelial cells. Am J Physiol Renal Physiol 278(6):F989–F998

    CAS  PubMed  Google Scholar 

  31. Pak CY, Sakhaee K, Peterson RD, Poindexter JR, Frawley WH (2001) Biochemical profile of idiopathic uric acid nephrolithiasis. Kidney Int 60(2):757–761

    Article  CAS  PubMed  Google Scholar 

  32. Maalouf NM, Cameron MA, Moe OW, Sakhaee K (2010) Metabolic basis for low urine pH in type 2 diabetes. Clin J Am Soc Nephrol 5(7):1277–1281

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Sakhaee K (2009) Recent advances in the pathophysiology of nephrolithiasis. Kidney Int 75(6):585–595

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Nagami GT (1989) Ammonia production and secretion by the proximal tubule. Am J Kidney Dis 14(4):258–261

    CAS  PubMed  Google Scholar 

  35. Bobulescu IA, Di Sole F, Moe OW (2005) Na+/H+ exchangers: physiology and link to hypertension and organ ischemia. Curr Opin Nephrol Hypertens 14(5):485–494

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH (1994) Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships. Proc Natl Acad Sci USA 91(23):10878–10882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288(2):E462–E468

    Article  CAS  PubMed  Google Scholar 

  38. Bachmann OP, Dahl DB, Brechtel K, Machann J, Haap M, Maier T, Loviscach M, Stumvoll M, Claussen CD, Schick F, Haring HU, Jacob S (2001) Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. Diabetes 50(11):2579–2584

    Article  CAS  PubMed  Google Scholar 

  39. Weinberg JM (2006) Lipotoxicity. Kidney Int 70(9):1560–1566

    Article  CAS  PubMed  Google Scholar 

  40. Bobulescu IA, Dubree M, Zhang J, McLeroy P, Moe OW (2008) Effect of renal lipid accumulation on proximal tubule Na+/H+ exchange and ammonium secretion. Am J Physiol Renal Physiol 294(6):F1315–F1322

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40(6):1387–1395

    Article  PubMed  Google Scholar 

  42. Halperin ML, Kamel KS (1996) d-Lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int 49(1):1–8

    Article  CAS  PubMed  Google Scholar 

  43. Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sorensen SJ, Hansen LH, Jakobsen M (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5(2):e9085

    Article  PubMed Central  PubMed  Google Scholar 

  44. Iber FL, Parveen S, Vandrunen M, Sood KB, Reza F, Serlovsky R, Reddy S (1993) Relation of symptoms to impaired stomach, small bowel, and colon motility in long-standing diabetes. Dig Dis Sci 38(1):45–50

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The author was supported by NIH R01-DK081423 grant. He would like to acknowledge Ashlei L. Johnson for her primary role in the preparation and editorial review of this manuscript.

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The author declares that he has no conflict of interest.

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  1. Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8885, USA

    Khashayar Sakhaee

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Correspondence to Khashayar Sakhaee.

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Sakhaee, K. Epidemiology and clinical pathophysiology of uric acid kidney stones. J Nephrol 27, 241–245 (2014). https://doi.org/10.1007/s40620-013-0034-z

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