Urological Research

, Volume 33, Issue 2, pp 73–79 | Cite as

Preventive treatment of nephrolithiasis with alkali citrate—a critical review

Invited Review

Abstract

Using the keywords “urolithiasis and citrate treatment”, “nephrolithaisis and citrate treatment”, “kidney stones and citrate treatment”, a Medline search revealed 635 articles published between 1 January 1966 and 1 December 2004. For the present analysis, only studies meeting all of the following criteria were included: (1) publications in English or German, (2) studies on preventive alkali citrate treatment in patients with calcium oxalate, uric acid and infection stone disease, (3) clinical studies including at least ten subjects, and (4) treatment phases of at least 1 week duration. A total of 43 studies met the inclusion criteria and were further subclassified according to intermediate or ultimate endpoints as well as to study design. With stone recurrence as the ultimate endpoint, 21 uncontrolled studies in almost 1,000 patients demonstrated a reduction in stone forming rate by 47–100%. In four randomized controlled trials including 227 patients, 53.5% on alkali citrate vs 35% on placebo remained stone-free after at least 1 year of treatment (P<0.0005). Similar values (66% vs 27.5% for alkali citrate vs placebo, P<0.0005) were obtained in 104 patients from two randomized trials with dissolution/clearance of residual stones as endpoint. Unfortunately, up to 48% of alkali citrate treated patients left the studies prematurely, primarily due to adverse effects such as eructation, bloating, gaseousness or frank diarrhea.

Keywords

Urolithiasis Nephrolithiasis Calcium oxalate Uric acid Citrate Alkali citrate treatment 

References

  1. 1.
    Pak CY (1991) Citrate and renal calculi: new insights and future directions. Am J Kidney Dis 17: 420PubMedGoogle Scholar
  2. 2.
    Erwin DT, Kok DJ, Alam J, Vaughn J, Coker O, Carriere BT et al. (1994) Calcium oxalate stone agglomeration reflects stone-forming activity: citrate inhibition depends on macxromolecules larger than 30 kilodalton. Am J Kidney Dis 24: 893PubMedGoogle Scholar
  3. 3.
    Hess B, Jordi S, Zipperle L, Ettinger E, Giovanoli R (2000) Citrate determines calcium oxalate crystallization kinetics and crystal morphology—studies in presence of Tamm-Horsfall protein of a healthy subject and a severely recurrent calcium stone former. Nephrol Dial Transplant 15: 366PubMedGoogle Scholar
  4. 4.
    Hamm LL, Hering-Smith KS (2002) Pathophysiology of hypocitraturic nephrolithiasis. Endocrinol Metab Clin North Am 31: 885PubMedGoogle Scholar
  5. 5.
    Hess B, Michel R, Takkinen R, Ackermann D, Jaeger P (1994) Risk factors for low urinary citrate in calcium nephrolithiasis: low vegetable fibre intake and low urine volume to be added to the list. Nephrol Dial Transplant 9: 642PubMedGoogle Scholar
  6. 6.
    Simpson DP (1983) Citrate excretion: a window on renal metabolism. Am J Physiol 244: F223PubMedGoogle Scholar
  7. 7.
    Churchill DN (1987) Medical treatment to prevent recurrent calcium urolithiasis. Mineral Eletrolyte Metab 13: 294Google Scholar
  8. 8.
    Wang Y-H, Grenabo L, Hedelin H, Pettersson S (1994) The effects of sodium citrate and oral potassium citrate on urease-induced crystallization. Br J Urol 74: 409PubMedGoogle Scholar
  9. 9.
    Kollwitz AA (1966) Die Behandlung und Prophylaxe von Harnsäuresteinen der Niere durch orale Alkalisierung. Dtsch Med Wochenschr 28: 1257Google Scholar
  10. 10.
    Uhlir K (1970) The peroral dissolution of renal calculi. J Urol 104: 239PubMedGoogle Scholar
  11. 11.
    Petritsch PH (1977) Uric acid calculi: results of conservative treatment. Urology 10: 536PubMedGoogle Scholar
  12. 12.
    Bach D, Hesse A, Strenge A, Vahlensieck W (1980) Harnstein-Prophylaxe mit einer Benzbromaron-Zitrat-Kombination. Fortschr Med 44: 1752Google Scholar
  13. 13.
    Butz M (1982) Oxalatsteinprophylaxe durch Alkali-Therapie. Urologe A 21: 142PubMedGoogle Scholar
  14. 14.
    Pak CY, Sakhaee K, Fuller CJ (1983) Physiological and physicochemical correction and prevention of calcium stone formation by potassium citrate therapy. Trans Assoc Am Physicians 96: 294PubMedGoogle Scholar
  15. 15.
    Nicar MJ, Peterson R, Pak CY (1984) Use of potassium citrate as potassium supplement during thiazide therapy of calcium nephrolithiasis. J Urol 131: 430PubMedGoogle Scholar
  16. 16.
    Pak CY, Peterson R, Sakhaee K, Fuller C, Preminger G, Reisch J (1985) Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis. Am J Med 79: 284PubMedGoogle Scholar
  17. 17.
    Pak CY, Fuller C, Sakhaee K, Preminger GM, Britton F (1985) Long-term treatment of calcium nephrolithiasis with potassium citrate. J Urol 134: 11PubMedGoogle Scholar
  18. 18.
    Preminger GM, Peterson R, Peters PC, Pak CY (1985) The current role of medical treatment of nephrolithiasis: the impact of improved techniques of stone removal. J Urol 134: 6PubMedGoogle Scholar
  19. 19.
    Pak CY, Fuller C (1986) Idiopathic hypocitraturic calcium-oxalate nephrolithiasis successfully treated with potassium citrate. Ann Int Med 104: 33PubMedGoogle Scholar
  20. 20.
    Pak CY, Peterson R (1986) Successful treatment of hyperuricosuric calcium oxalate nephrolithiasis with potassium citrate. Arch Intern Med 146: 863PubMedGoogle Scholar
  21. 21.
    Pak CY, Sakhaee K, Fuller C (1986) Successful management of uric acid nephrolithiasis with potassium citrate. Kidney Int 30: 422PubMedGoogle Scholar
  22. 22.
    Nicar MJ, Hsu MC, Fetner C (1986) Urinary response to oral potassium citrate therapy for urolithiasis in a private practice setting. Clin Ther 8: 219PubMedGoogle Scholar
  23. 23.
    Higashihara E, Nutahara K, Niijima T (1988) Renal hypercalciuria and metabolic acidosis associated with medullary sponge kidney: effect of alkali therapy. Urol Res 16: 95PubMedGoogle Scholar
  24. 24.
    Hauser W, Frick J, Kunit G (1990). Alkali citrate for preventing recurrence of calcium oxalate stones. Eur Urol 17: 248PubMedGoogle Scholar
  25. 25.
    Lindberg J, Harvey J, Pak CY (1990) Effect of magnesium citrate and magnesium oxide on the crystallization of calcium salts in urine: changes produced by food-magnesium interaction. J Urol 143: 248PubMedGoogle Scholar
  26. 26.
    Rodman JS (1991) Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts. J Urol 145: 97PubMedGoogle Scholar
  27. 27.
    Herrmann U, Schwille PO, Schwarzlaender H, Berger I, Hoffmann G (1992) Citrate and recurrent idiopathic calcium urolithiasis: a longitudinal pilot study on the metabolic effects of oral potassium sodium citrate administered as short-, medium- and long-term to male stone patients (version I). Urol Res 20: 347PubMedGoogle Scholar
  28. 28.
    Schwille PO, Herrmann U, Wolf C, Berger I, Meister R (1992) Citrate and recurrent idiopathic calcium urolithiasis: a longitudinal pilot study on the metabolic effects of oral potassium citrate administered over the short-, medium- and long-term medication of male stone patients (version II). Urol Res 20: 145PubMedGoogle Scholar
  29. 29.
    Pak CY, Koenig K, Khan R, Haynes S, Padalino P (1992) Physicochemical action of potassium-magnesium citrate in nephrolithiasis. J Bone Miner Res 7: 281PubMedGoogle Scholar
  30. 30.
    Ito H, Suzuki F, Yamaguchi K, Nishikawa Y, Kotake T (1992) Reduction of urinary oxalate by combined calcium and citrate administration without increase in urinary calcium oxalate stone formers. Clin Nephrol 37: 14PubMedGoogle Scholar
  31. 31.
    Berg C, Larsson L, Tiselius HG (1992) The effects of a single evening dose of alkaline citrate on urine composition and calcium stone formation. J Urol 148: 979PubMedGoogle Scholar
  32. 32.
    Khanniazi MK, Khanam A, Naqvi SA, Sheikh MA (1993) Study of potassium citrate treatment of crystalluric nephrolithiasis. Biomed Pharmacother 47: 25PubMedGoogle Scholar
  33. 33.
    Wabner CL, Pak CY (1993) Effect of orange juice consumption on urinary stone risk factors. J Urol 149: 1405PubMedGoogle Scholar
  34. 34.
    Abdulhadi MH, Hall PM, Streem SB (1993) Can citrate therapy prevent nephrolithiasis? Urology 41: 221PubMedGoogle Scholar
  35. 35.
    Barcelo P, Wuhl O, Servitge E, Rousaud A, Pak CY (1993) Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urology 150: 1761Google Scholar
  36. 36.
    Kocvara R, Louzensky G, Tuikova J (1994) Development of metaphylaxis in calcium urolithiasis: a restriction of conventional drug therapy. Int Urol Nephrol 26: 269PubMedGoogle Scholar
  37. 37.
    Hofbauer J, Hobarth K, Szabo N, Marberger M (1994) Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis—a prospective randomized study. Br J Urol 73: 362PubMedGoogle Scholar
  38. 38.
    Cicerello E, Merlo F, Gambaro G, Maccatrozzo L, Fandella A, Baggio B et al. (1994) Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients. J Urol 151: 5PubMedGoogle Scholar
  39. 39.
    Fine JK, Pak CY, Preminger GM (1995) Effect of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy. J Urol 153: 27PubMedGoogle Scholar
  40. 40.
    Whalley NA, Meyers AM, Martins M, Margolius LP (1996) Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia. Br J Urol 78: 10PubMedGoogle Scholar
  41. 41.
    Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A (1997) Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol 158: 2069PubMedGoogle Scholar
  42. 42.
    Grases F, Conte A, March JG, Garcia-Ferragut L (1998) Evolution of lithogenic urinary parameters with a low dose potassium citrate treatment. Int Urol Nephrol 30: 1PubMedGoogle Scholar
  43. 43.
    Fuselier HA, Moore K, Lindberg J, Husserl FE, Cole FE, Kok DJ et al. (1998) Agglomeration inhibition reflected stone forming activity during long-term potassium citrate therapy in calcium stone formers. Urology 52: 988PubMedGoogle Scholar
  44. 44.
    Lee YH, Huang WC, Tsai JY, Huang JK (1999) The efficacy of potassium citrate based medical prophylaxis for preventing upper urinary tract calculi: a midterm follow-up study. J Urol 161: 1453PubMedGoogle Scholar
  45. 45.
    Ruml LA, Pak CY (1999) Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Kidney Dis 34: 107PubMedGoogle Scholar
  46. 46.
    Premgamone A, Sriboonlue P, Disatapornjaroen W, Maskasem S, Sinsupan N, Apinives C (2001) A long-term study on the efficacy of a herbal plant, orthosiphon grandiflorus, and sodium potassium citrate in renal calculi treatment. Southeast Asian J Trop Med Public Health 32: 654PubMedGoogle Scholar
  47. 47.
    Soygür T, Akbay A, Kupeli S (2002) Effect of potassium citrate therapy on stone recurrence and residual fragments after shockwave lithotripsy in lower caliceal calcium oxalate urolithiasis: a randomized controlled trial. J Endourol 16: 149PubMedGoogle Scholar
  48. 48.
    Pak CY, Heller HJ, Pearle MS, Odvina CV, Poindexter JR, Peterson RD (2003) Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions. J Urol 169: 465PubMedGoogle Scholar
  49. 49.
    Siener R, Glatz S, Nicolay C, Hesse A (2003) Prospective study on the efficacy of a selective treatment and risk factors for relapse in recurrent calcium oxalate stone patients. Eur Urol 44: 467PubMedGoogle Scholar
  50. 50.
    Mardis HK, Parks JH, Muller G, Ganzel K, Coe FL (2004) Outcome of metabolic evaluation and medical treatment for calcium nephrolithiasis in a private urological practice. J Urol 171: 85PubMedGoogle Scholar
  51. 51.
    Jaipakdee S, Prasongwatana V, Premgamone A, Reungjui S, Toshukhowong P, Tungsanga K et al. (2004) The effects of potassium and magnesium supplementations on urinary risk factors of renal stone patients. J Med Assoc Thai 87: 255PubMedGoogle Scholar
  52. 52.
    Pearle MS, Roehrborn CG, Pak CY (1999) Meta-analysis of randomized trials for medical prevention of calcium oxalate nephrolithiasis. J Endourol 13: 679PubMedGoogle Scholar
  53. 53.
    Hesse A, Brändle E, Wilbert D, Köhrmann K-U, Alken P (2003) Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs 2000. Eur Urol 44: 709PubMedGoogle Scholar
  54. 54.
    Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63: 1817PubMedGoogle Scholar
  55. 55.
    Shekarriz B, Stoller ML (2002) Cystinuria and other noncalcareous calculi. Endocrinol Metab Clin N Am 31: 951Google Scholar
  56. 56.
    Kessler T, Hesse A (2000) Cross-over study of the influence of bicarbonate-rich mineral water on urinary composition in comparison with sodium potassium citrate in healthy subjects. Br J Nutr 84: 865PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Internal MedicineRegional Hospital
  2. 2.Department of Internal Medicine/NephrologyHospital Zimmerberg
  3. 3.Internal Medicine/NephrologyKlinik Im Park

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