Alkali citrate

Alkali citrate (also known as alkaline citrate) is an inhibitor of kidney stones.[1] It is used to increase urine citrate levels - this prevents calcium oxalate stones by binding to calcium and inhibiting its binding to oxalate.[2] It is also used to increase urine pH (alkalinize urine) - this prevents uric acid stones and cystine stones (which form in cystinuria).[2]

It is different than citric acid which is citrate bonded by hydrogen ions (or protons) making it acidic.[3] Citric acid does not alkalinize urine as alkali citrate does.[4] Alkali citrate replaces the protons with a non-acid positively charged ion like sodium, potassium or magnesium.

Available forms

Alkaline citrate can be prescribed (K-citrate) or found as an over-the-counter (OTC) pill, liquid, or powder.[2] For kidney stone prevention or alkalinization, it is most often accompanied by mineral(s) sodium or potassium. Less frequently, magnesium citrate may be included.[2] This results in compounds like Trimagnesium citrate,[5] Tripotassium citrate[6][7][8] and Trisodium citrate:[9]

Citrus based beverages like lemon juice and orange juice may raise urine citrate, but much of the citrate is citric acid; without a cation like sodium, potassium or magnesium these beverages will have less effect on urine chemistry and therefore not aid in prevention of kidney stones as alkali citrate will.[12]

Biological effects

Alkaline citrates are used to prevent recurrent calcium stone formation.[13][14][15][5] This is one of the major types of kidney stones.[16][17] The citrate salts can increase urine citrate, which binds with urine calcium, reduces supersaturation of calcium salts, and inhibits crystal formation.[18][8] This helps prevent kidney stones.[18][8]

Oral alkali supplementation can also slow the rate of kidney function decline and “potentially reduce the risk of end stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) and metabolic acidosis.”[19]

The compound also raises urine pH.[18] When citrate is metabolized by the liver, it essentially generates bicarbonate, an important buffer. This reduces uric acid supersaturation and prevents uric acid stones and cystine stones.[18][8]

References

  1. Berg, C.; Larsson, L.; Tiselius, H. G. (1992). "The effects of a single evening dose of alkaline citrate on urine composition and calcium stone formation". The Journal of Urology. 148 (3 Pt 2): 979–985. doi:10.1016/s0022-5347(17)36795-2. ISSN 0022-5347. PMID 1507355.
  2. "Educate Your Patients about Kidney Stones" (PDF). National Kidney Foundation.
  3. PubChem. "Citric acid". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-08-24.
  4. "Citric Acid and Kidney Stones" (PDF). UW Health.
  5. Schwille, P. O.; Schmiedl, A.; Herrmann, U.; Fan, J.; Gottlieb, D.; Manoharan, M.; Wipplinger, J. (1999-05-01). "Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis". Urological Research. 27 (2): 117–126. doi:10.1007/s002400050097. ISSN 1434-0879. PMID 10424393. S2CID 1506052.
  6. Wong, Daniel G.; Elson, Lauren; Nottingham, Charles U.; Desai, Alana C. (2022-05-01). "Pharmaceutical versus Over-the-Counter Potassium Citrate: A Benchtop Comparison". Urology Practice. 9 (3): 205–211. doi:10.1097/UPJ.0000000000000300. S2CID 246716306.
  7. "The Impact of Alternative Alkalinizing Agents on 24-Hour Urine Parameters" (PDF). University of Wisconsin Department of Urology.
  8. Rao, Nagarja (2011). Urinary Tract Stone Disease. Springer London. p. 183. ISBN 9781848003620.
  9. PubChem. "Sodium citrate". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-08-24.
  10. PubChem. "Potassium citrate". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-08-24.
  11. PubChem. "Magnesium citrate". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-08-24.
  12. Goodman, Jeffrey W.; Asplin, John R.; Goldfarb, David S. (2009). "Effect of two sports drinks on urinary lithogenicity". Urological Research. 37 (1): 41–46. doi:10.1007/s00240-008-0166-0. ISSN 1434-0879. PMID 19066876. S2CID 24253323.
  13. Hauser, W.; Frick, J.; Kunit, G. (1990). "Alkali citrate for preventing recurrence of calcium oxalate stones". European Urology. 17 (3): 248–251. doi:10.1159/000464049. ISSN 0302-2838. PMID 2190842.
  14. Berg, Clas; Larsson, Lasse; Tiselius, Hans-Göran (1992-09-01). "The Effects of a Single Evening Dose of Alkaline Citrate on Urine Composition and Calcium Stone Formation". The Journal of Urology. 148 (3, Part 2): 979–985. doi:10.1016/S0022-5347(17)36795-2. ISSN 0022-5347. PMID 1507355.
  15. Achilles, W.; Schulze, D.; Schalk, C.; Rodeck, G. (1990). "The in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate and other parameters in human urine". Urological Research. 18 (1): 1–6. doi:10.1007/BF00294572. ISSN 0300-5623. PMID 2316065. S2CID 27047307.
  16. Phillips, Rebecca; Hanchanale, Vishwanath S.; Myatt, Andy; Somani, Bhaskar; Nabi, Ghulam; Biyani, C Shekhar (2015). "Citrate salts for preventing and treating calcium containing kidney stones in adults". Cochrane Database of Systematic Reviews. 2015 (10): CD010057. doi:10.1002/14651858.CD010057.pub2. PMC 9578669. PMID 26439475. Retrieved 2022-08-24.
  17. MBA, Kevin R. Loughlin, MD (2019-05-17). "What causes kidney stones (and what to do)". Harvard Health. Retrieved 2022-08-24.{{cite web}}: CS1 maint: multiple names: authors list (link)
  18. "CITRATE TO PREVENT CALCIUM AND URIC ACID STONES | Kidney Stone Evaluation And Treatment Program". kidneystones.uchicago.edu. Retrieved 2022-08-24.
  19. Navaneethan, Sankar D.; Shao, Jun; Buysse, Jerry; Bushinsky, David A. (2019-07-05). "Effects of Treatment of Metabolic Acidosis in CKD". Clinical Journal of the American Society of Nephrology. 14 (7): 1011–1020. doi:10.2215/CJN.13091118. ISSN 1555-9041. PMC 6625635. PMID 31196951.
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