eMedicine Specialties > Urology > Stones

Hypocitraturia: Treatment & Medication

Author: George Bennett Stackhouse IV, MD, Clinical Fellow in Endourology, Urology, University of California, San Francisco
Coauthor(s): Howard H Woo, MD, Consulting Staff, Clinical Instructor, Department of Urology, Ochsner Urology Institute
Contributor Information and Disclosures

Updated: Jun 16, 2006

Treatment

Medical Care

Treatment should be aimed toward correcting the underlying disorder that reduces urine citrate. If the patient has idiopathic hypocitraturia, induce a mild metabolic alkalosis to increase urine citrate.

• Uric acid nephrolithiasis
  • Uric acid stones can form whenever elevated urinary uric acid is present or if the urinary pH drops consistently below recommended levels. Overly acidic urine can cause uric acid stones to form even with normal urinary uric acid excretion. Potassium citrate can maintain an optimal urinary pH of 6.5-7.0 to both dissolve existing stones and prevent recurrences. In these cases, monitoring the urinary pH frequently when trying to dissolve existing stones is important. Potassium citrate dosages should be adjusted accordingly and serum potassium levels checked to identify any hyperkalemia that may develop. Total urinary citrate excretion levels are less important in these situations than the pH.
  • Prophylaxis for uric acid lithiasis often may consist of a nighttime dose of potassium citrate to simulate the nightly alkaline tide that may be diminished or absent in these patients. Allopurinol can be used if the patient has gout, hyperuricemia, or hyperuricosuria.
• Distal RTA - Potassium citrate is administered in large doses. Often, patients require as much as 120 mEq/d.
  • Chronic diarrheal syndrome In mild-to-moderate severity of fluid loss and hypocitraturia, potassium citrate 40-60 mEq is administered in 3 or 4 divided doses in a liquid form or as needed to optimize urinary citrate and pH. The liquid form is preferred because of better absorption compared to slow-release tablets in conditions where rapid gastrointestinal transit may exist.
  • Severe hypocitraturia requires high doses of potassium citrate, often as much as 320 mEq/d. In these cases, care should be taken to monitor the patient for hyperkalemia while optimizing urinary citrate excretion without increasing the urinary pH beyond 7.0-7.2.
• Thiazide-induced hypokalemia
  • Potassium citrate 10-30 mEq PO is administered 2-4 times daily or as needed to optimize urinary citrate excretion without overly alkalinizing the urine.
  • For patients treated with a thiazide, potassium citrate has the added advantage of preventing or reducing hypokalemia by supplementing potassium. Potassium citrate attenuates the drop in urinary citrate associated with thiazide therapy by preventing the hypokalemia-induced intracellular acidosis that leads to hypocitraturia. Therefore, consider concurrent treatment with potassium citrate in normocitraturic stone-forming patients who are on a thiazide for hypercalciuria. Although potassium chloride also can prevent a reduction in urinary citrate because it also maintains normokalemia, urinary citrate levels are maintained only at baseline; potassium citrate increases urinary citrate above the baseline level, thereby improving the urinary stone risk profile.
• Idiopathic hypocitraturic calcium nephrolithiasis
  • The stones formed are composed predominantly of calcium oxalate.
  • Potassium citrate 10-30 mEq PO is administered 2-4 times daily or as needed to optimize the urinary citrate excretion without exceeding the recommended urinary pH levels.
  • Maintain urinary pH at 6.5-7.0.

Consultations

Consider long-term medical treatment for a patient with recurrent stone disease. Consider consultation with a urologist or a nephrologist for further management of stone disease.

Diet

• High fluid intake - Sufficient to produce 1.5 L or more of urine per day
• Sodium restriction - Patients should avoid saltshakers and processed or salty foods.
• Oxalate restriction (may be advised) - Patients should avoid nuts, dark roughage, chocolate, tea, and vitamin C.
• Restriction of animal proteins - Limited servings of meat products, especially at the same meal
• Increased citrus fruits, potassium-rich products, and alkalinizing foods
  • Orange juice is a good source of dietary citrate. Orange juice contains potassium citrate (approximately 50 mEq of potassium per L and 160 mEq of citrate per L). Wabner and Pak (1993) studied the value of orange juice consumption in kidney stone prevention in 8 healthy men and in 3 men with documented hypocitraturic nephrolithiasis. Consumption of 1.2 L of orange juice (containing 60 mEq of potassium per d and 190 mEq of citrate per d) was compared to potassium citrate tablets (60 mEq/d). Compared to potassium citrate, orange juice delivered an equivalent alkali load and caused a similar increase in urinary pH (6.48 versus 6.75 from 5.71) and urinary citrate (962 versus 944 from 571 mg/d). However, orange juice increased urinary oxalate and did not alter calcium excretion, whereas potassium citrate decreased urinary calcium without altering urinary oxalate.
  • Similarly, Seltzer et al (1996) used lemonade therapy in 12 patients who could not or would not take potassium citrate. Ingestion of 4 o. of lemon juice in 2 L of water daily raised urinary citrate levels from an average pretreatment level of 142 mg/d to 346 mg/d (P <.001). Daily total urinary volumes were similar (2.7 L pretreatment vs 2.9 L on lemonade therapy). Seven of 12 patients developed normal citrate levels while consuming lemonade. Urinary calcium excretion decreased an average of 39 mg while on lemonade. No change in urinary oxalate excretion was seen.
  • Kessler and Hesse evaluated the effects of bicarbonate-rich mineral water versus sodium potassium citrate in an equimolar fashion regarding alkali load in 24 healthy male volunteers using a crossover design study and found that the alkali load was sufficient to raise urinary citrate and pH levels regardless of the treatment arm. Urinary sodium levels were not reported in this study, so whether sodium levels were elevated in the mineral-water arm is unclear.

Activity

No limitation of activity level is necessary, but dehydration should be avoided, especially with outdoor activities in warm dry environments.

Medication

Currently, preferred treatment of hypocitraturia is with potassium citrate (eg, Urocit-K, Polycitra-K) supplementation. The sodium-containing forms of citrate (eg, Bicitra, Polycitra) and sodium bicarbonate do not have the same beneficial effects because the excess sodium in these preparations actually aggravates both hypercalciuria and hyperuricosuria.

Calcium citrate may be used in patients with enteric hyperoxaluria and hypocitraturia, as the calcium is available to bind oxalate in the intestinal lumen. This therapy can raise urinary citrate levels and lower urinary oxalate levels but can raise urinary calcium levels. Potassium citrate is often used in addition to calcium citrate in these patients to further elevate urinary citrate and pH levels.

Calcium citrate is often recommended for calcium supplementation in postmenopausal women and others at risk for osteoporosis. It increases urinary citrate levels in non–stone-forming patients but also raises urine calcium excretion and does not significantly increase or decrease the relative supersaturation of calcium oxalate. Calcium citrate has not been well studied as therapy for hypocitraturia in idiopathic calcium oxalate stone formers and is not typically used for this purpose. Natural sources of citrate are citrus fruits. Lemons contain the most concentrated form of citrate and, when provided as lemonade, can increase both fluid volume and citrate excretion.

Two agents have been used for the treatment of hypocitraturia—sodium potassium citrate, which commonly is used in Europe, and potassium citrate, either in liquid form or as a wax matrix tablet, which is used in the United States. The usual therapeutic dose is 30-60 mEq/d, administered in 3 divided doses or as a single evening dose. Potassium citrate is preferred because it appears to decrease urinary calcium excretion. Sodium citrate does not lower urinary calcium excretion, perhaps because of the increased sodium load associated with therapy.

Potassium citrate is available in 5- or 10-mEq tablets (eg, Urocit-K) or as a liquid, powder, or syrup combining potassium citrate and citric acid (eg, Polycitra-K). The powder and syrup are mixed with water before ingestion. The tablet formulation has been shown to produce less variability in the level of urinary citrate throughout the day, but the liquid form is better in short bowel syndromes where absorption is a problem and in more severe cases because of its higher citrate dose.

Alkalinizing agents

The increase in urinary pH decreases calcium ion activity by increasing calcium complexation to dissociated anions and increases ionization of uric acid to more soluble urate ion.

Potassium citrate is an excellent alkalinizing agent for the treatment of patients with uric acid stones. The urinary pH should be checked regularly with Nitrazine paper and drug dosages adjusted to maintain a urinary pH of 6.5-7.0. Uric acid stones can be dissolved completely using this regimen, but dissolution may require 3-4 months of intensive medical therapy.

Increased citrate complexation of calcium is opposed by the rise in pH-dependent dissociation of phosphate; thus, urinary saturation of calcium phosphate is unaltered by potassium citrate therapy. Calcium phosphate stones are more stable in alkaline urine, such as pH 8. Therefore, a urinary pH is checked regularly and drug dosages adjusted to avoid calcium phosphate precipitation.

Potassium citrate (Urocit-K)

Citrate salt of potassium. Empirical formula is K₃ C₆ H₅ O₇.H₂ 0. White, granular, water-soluble powder (154 g/100 mL) that is almost insoluble in alcohol and is insoluble in organic solvents. Urocit-K is supplied as wax matrix tablets containing 5 mEq (ie, 540 mg) potassium citrate and 10 mEq (ie, 1080 mg) potassium citrate each for oral administration. Also available as the following: Cystopurin (England), K-Lyte (Canada), Kajos (Sweden, Norway), Kation (Italy), Nitrocit (United States).
Administered orally. Absorbed citrate is metabolized to produce an alkaline load that, in turn, increases urinary pH and raises urinary citrate by augmenting citrate clearance without measurably altering ultrafiltrable serum citrate. Urinary potassium is increased by approximately the amount contained in the medication, and some patients experience a transient reduction in urinary calcium. Potassium citrate produces urine that is less conducive to crystallization of stone-forming salts (eg, calcium oxalate, calcium phosphate, uric acid).
The increased citrate in the urine complexes with calcium, decreasing its ion activity and reducing saturation of calcium oxalate. Citrate also inhibits the spontaneous nucleation of calcium oxalate and calcium phosphate (brushite).

Polycitra-K crystals

Polycitra-K crystals is a pleasant-tasting oral systemic alkalizer containing potassium citrate and citric acid in a sugar-free base.
Each unit dose packet contains potassium citrate monohydrate 3300 mg and citric acid monohydrate 1002 mg. Each unit dose packet, when reconstituted, supplies the same amount of active ingredients as is contained in 15 mL (1 tablespoonful) Polycitra-K oral solution and provides 30 mEq potassium ion and is equivalent to 30 mEq bicarbonate.
Potassium citrate is absorbed and metabolized to potassium bicarbonate, thus acting as a systemic alkalizer. The effects are essentially those of chlorides before absorption and those of bicarbonates subsequently. Oxidation is virtually complete so that <5% of the potassium citrate is excreted in the urine unchanged.
Polycitra-K crystals is highly concentrated and, when administered after meals and before bedtime, allows one to maintain an alkaline urinary pH at all times, usually without the necessity of a 2 am dose. Polycitra-K crystals alkalinizes the urine without producing a systemic alkalosis in recommended dosage.

Polycitra-K oral solution

Polycitra-K is a stable and pleasant-tasting oral systemic alkalizer containing potassium citrate and citric acid in a sugar-free base.
Each teaspoonful (5 mL) contains potassium citrate monohydrate 1100 mg and citric acid monohydrate 334 mg. Each mL contains 2 mEq potassium ion and is equivalent to 2 mEq bicarbonate.

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