Abstract
Citrate is the most abundant organic anion in human urine. Its urinary excretion rate mainly depends on acid–base status: Alkalosis induces an increase in urinary citrate excretion, whereas acidosis has the opposite effect. It is important to note that citrate utilization by renal cells and urinary citrate excretion are mainly affected by intracellular changes in acid base homeostasis of proximal tubular cells. Even small acid loads such as meat protein-rich meals decrease urinary excretion of citrate. Low urinary citrate (hypocitraturia) is defined as daily urinary citrate excretion rates below 1.70 mmol (320 mg) in men and 1.90 mmol (350 mg) in women. Hypocitraturia occurs in 20–60% of calcium stone formers. Sufficient citrate in urine is important because citrate retards the crystallization of stone-forming calcium salts, mediates inhibitory effects of macromolecular modulators of calcium oxalate crystallization and – due to its alkalinizing effect – reduces rates of uric acid stone formation. Treatment with alkali citrate, usually in the form of potassium citrate or magnesium potassium citrate, is widely used to increase urinary citrate and reduce rates of stone formation in patients with hypocitraturic calcium nephrolithiasis as well as uric acid stone disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Amberg S, McClure WB. Occurrence of citric acid in urine. Am J Physiol. 1917;44:453-462.
Östberg O. Studien über Zitronensäureausscheidung der Menschenniere in normalen und pathologischen Zuständen. Scand Arch Physiol. 1931;62:81-222.
Boothby WM, Adams M. Occurrence of citric acid in urine and body fluids. Am J Physiol. 1934;107:471-479.
Scott WW, Huggins C, Selman BC. Metabolism of citric acid in urolithiasis. J Urol. 1943;50:202-209.
Conway NW, Maitland ATK, Rennie JB. The urinary citrate excretion in patients with renal calculi. Br J Urol. 1949;21:30-38.
Hodgkinson A. Citric acid excretion in normal adults and in patients with renal calculus. Clin Sci. 1962;23:203-212.
Chen SM, Chung LC, Lee YH, Young TK. Renal excretion of citrate in patients with chronic renal failure or nephrolithiasis. J Formos Med Assoc. 1991;90:41-47.
Baruch SB, Burich RL, Eun CK, King VF. Renal metabolism of citrate. Med Clin North Am. 1975;59:569-582.
Hamm LL, Hering-Smith KS. Pathophysiology of hypocitraturic nephrolithiasis. Endocrinol Metab Clin N Am. 2002;31:885-893.
Unwin RJ, Capasso G, Shirley DG. An overview of divalent cation and citrate handling by the kidney. Nephron. 2004;98:15-20.
Simpson DP. Citrate excretion: a window on renal metabolism. Am J Physiol. 1983;244:F223-F234.
Pak CYC. Citrate and renal calculi: new insights and future directions. Am J Kidney Dis. 1991;17:420-425.
Rodgers A, Allie-Hamdulay S, Jackson G. Therapeutic action of citrate in urolithiasis explained by chemical speciation: increase in pH is the determinant factor. Nephrol Dial Transplant. 2006;21:361-369.
Erwin DT, Kok DJ, Alam J, et al. Calcium oxalate stone agglomeration reflects stone-forming activity: citrate inhi-bition depends on macxromolecules larger than 30 kilodalton. Am J Kidney Dis. 1994;24:893-900.
Hess B, Jordi S, Zipperle L, Ettinger E, Giovanoli R. 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. 2000;15:366-374.
Moe OW, Abate N, Sakhaee K. Pathophysiology of uric acid nephrolithiasis. Endocrinol Metab Clin N Am. 2002;31:895-914.
Wang Y-H, Grenabo L, Hedelin H, Pettersson S. The effects of sodium citrate and oral potassium citrate on urease-induced crystallization. Br J Urol. 1994;74:409-415.
Hess B, Hasler-Strub U, Ackermann D, Jaeger Ph. Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis. Nephrol Dial Transplant. 1997;12:1362-1368.
Hess B. Acid-base metabolism: implications for kidney stone formation. Urol Res. 2006;34:134-138.
Hess B, Michel R, Takkinen R, Ackermann D, Jaeger Ph. 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. 1994;9:642-649.
Mattle D, Hess B. Preventive treatment of nephrolithiais with alkai citrate – a critical review. Urol Res. 2005;33:73-79.
Cicerello E, Merlo F, Gambaro G, et al. Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and in-fection nephrolithiasis patients. J Urol. 1994;151:5-9.
Soygür T, Akbay A, Kupeli S. 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. 2002;16:149-152.
Shekarriz B, Stoller ML. Cystinuria and other noncalcareous calculi. Endocrinol Metab Clin N Am. 2002;31:951-977.
Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997;158:2069-2073.
Pak CY, Koenig K, Khan R, Haynes S, Padalino P. Physicochemical action of potassium-magnesium citrate in nephrolithiasis. J Bone Miner Res. 1992;7:281-285.
Wabner CL, Pak CY. Effect of orange juice consumption on urinary stone risk factors. J Urol. 1993;149:1405-1408.
Kessler T, Hesse A. 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. 2000 Dec;84(6):865-871.
Premgamone A, Sriboonlue P, Disatapornjaroen W, Maskasem S, Sinsupan N, Apinives C. A long-term study on the efficacy of a herbal plant, ortho-siphon grandiflorus, and sodium potassium citrate in renal calculi treatment. Southeast Asian J Trop Med Public Health. 2001;32:654-660.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer London
About this chapter
Cite this chapter
Hess, B. (2010). Urinary Citrate and Citrate Metabolism. In: Rao, N., Preminger, G., Kavanagh, J. (eds) Urinary Tract Stone Disease. Springer, London. https://doi.org/10.1007/978-1-84800-362-0_14
Download citation
DOI: https://doi.org/10.1007/978-1-84800-362-0_14
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-84800-361-3
Online ISBN: 978-1-84800-362-0
eBook Packages: MedicineMedicine (R0)