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Alkali Citrates: Mechanism, Adverse Effects, Contraindications, and Dosage

Indications for Alkali Citrates

Pharmacologic Prevention of Recurrent Urolithiasis:

Alkaline citrates are used for pharmacologic prevention of recurrent urinary stones in patients with uric acid stones, calcium oxalate stones, calcium phosphate stones in the context of renal tubular acidosis, and cystine stones.

Metabolic Acidosis Due to Urinary Diversion:

Continent urinary diversions in particular (e.g., neobladder) can lead to hyperchloremic metabolic acidosis due to the intestinal absorption of urinary constituents: chloride (Cl⁻) is absorbed through the ileal mucosa in exchange for bicarbonate (HCO₃⁻), and sodium (Na⁺) in exchange for hydrogen ions (H⁺). Alkali citrate supplementation is indicated when the base excess in venous blood falls below −2.5 mmol/L (see section on follow-up after urinary diversion).

Mechanism of Action of Alkali Citrates

Metabolic Acidosis:

Alkaline citrates are the salts of citric acid (citrate ions). The citrate component is metabolized in the liver, kidney, and skeletal muscle via the citric acid cycle to carbon dioxide, water, and bicarbonate. The alkaline ions are excreted or retained depending on the body’s needs.

Prevention of Recurrent Urinary Stones:

Renal excretion of the alkali load (see above) increases the urine pH. This increase in urine pH raises the degree of dissociation and thereby the solubility of, for example, uric acid. Additional mechanisms include increased urinary citrate excretion and reduced urinary calcium excretion, which together reduce the formation of calcium oxalate and, under appropriately controlled pH conditions, calcium phosphate crystals (Rinnab, 2004).

Active Substances of Alkali Citrates

Prevention of Recurrent Urinary Stones:

Select the alkali citrate based on the sodium and potassium content and relevant comorbidities (e.g., arterial hypertension, heart failure, or glomerular filtration rate, and serum electrolyte concentrations).

• Calcium sodium hydrogen citrate (Acetolyt)
• Potassium sodium hydrogen citrate (Blanel, Uralyt)
• Citric acid, sodium citrate, and potassium hydrogen carbonate (Blemaren)
• Potassium citrate (Urocit)

Metabolic Acidosis:

Sodium bicarbonate–containing preparations (for example, Alkala, Bicanorm, Nephrotrans) are available as enteric-coated capsules and are generally associated with fewer adverse effects than the citrate-containing preparations listed above, particularly with respect to gastrointestinal symptoms.

Alkaline Citrates and Adverse Effects

• Gastrointestinal tract: Gastric or abdominal pain occurs frequently and is triggered by CO₂ release in the stomach. Diarrhea or nausea occurs less commonly. Rare case reports describe gastric rupture, particularly after excessive ingestion of effervescent tablets.
• Potassium-containing preparations carry an additional risk of hyperkalemia, especially in patients with pre-existing chronic kidney disease or concomitant use of potassium-sparing medications.
• Sodium-rich preparations can contribute to volume overload and hypernatremia.
• Urinary alkalinization may favor the formation of phosphate stones in the presence of urinary tract infections.

Alkali Citrates and Drug Interactions

Avoid concomitant intake of alkali citrates with aluminum-containing substances (e.g., antacids). If necessary, keep a minimum interval of two hours between the medications. Caution is warranted when using medications whose effects depend on serum potassium (e.g., cardiac glycosides) and with substances that alter potassium excretion (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or potassium-sparing diuretics such as spironolactone, eplerenone, amiloride, and triamterene). In at-risk patients, monitor serum potassium and creatinine after initiation of therapy and after dose adjustments.

Contraindications to Alkali Citrates

Severe chronic kidney disease with impaired renal potassium excretion, metabolic alkalosis, urinary tract infections with urease-producing bacteria, and a strictly sodium-restricted diet represent contraindications. Hyperkalemic periodic paralysis is a further contraindication. Caution in patients with pre-existing hyperkalemia, severe heart failure, or decompensated liver cirrhosis.

Dosage of Alkali Citrates

Titrate the alkali citrate dose stepwise, depending on the indication, using either urine pH or venous blood gas analysis as a guide. For further details, see the sections on metaphylaxis of kidney stones and on follow-up after urinary diversion for the treatment of metabolic acidosis caused by urinary diversion.

• Typical initial dosage for metaphylaxis of uric acid stones: potassium sodium hydrogen citrate 2.4 g every 8 hours; the evening dose can be increased if necessary. The urine pH before intake should be between pH 6.2 and 6.8.
• Typical initial dosage for the treatment of metabolic acidosis: 50 mg/kg body weight of sodium bicarbonate per day, divided into several single doses throughout the day; depending on the preparation, one capsule contains 500–1000 mg.

Before and during dose titration, regular laboratory monitoring is essential, particularly of serum electrolytes (potassium and sodium) and renal function (creatinine). In patients with metabolic acidosis, venous blood gas analysis should also be performed. The frequency of monitoring depends on the individual risk of electrolyte disturbances (caution in patients with kidney or liver disease, or those receiving angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or potassium-sparing diuretics).

References

Rinnab u.a. 2004 RINNAB, L. ; HAUTMANN, R. E. ; STRAUB, M.: [Alkaline citrates in urology. A status report].
In: Urologe A
43 (2004), Apr, Nr. 4, S. 429–439. -
URL https://dx.doi.org/10.1007/s00120-003-0515-0

T. Soygür, A. Akbay, and S. Küpeli, “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 Endourology, vol. 16, no. 3, pp. 149–152, 2002, doi: 10.1089/089277902753716098.

M. Straub, W. L. Strohmaier, W. Berg, B. Beck, B. Hoppe, N. Laube, S. Lahme, M. Schmidt, A. Hesse, und K. U. Koehrmann. Diagnosis and metaphylaxis of stone disease. consensus concept of the national working committee on stone disease for the upcoming german urolithiasis guideline.
World J Urol, 23 (5): 309–323, Nov 2005.

  Deutsche Version: Alkalizitrate für die Harnalkalisierung

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