Updated: Oct 05, 2015
  • Author: Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
  • Print

Overview of Hypocitraturia

Hypocitraturia, a low amount of citrate in the urine, is an important risk factor for kidney stone formation. Citrate in the urine has long been recognized as an inhibitor of calcium salt crystallization. Citrate is the dissociated anion of citric acid, a weak acid that is ingested in the diet and produced endogenously in the tricarboxylic acid cycle. The mean urinary citrate excretion is 640 mg/d in healthy individuals.

Defining hypocitraturia

Hypocitraturia usually is defined as citrate excretion of less than 320 mg per day, but this definition has been challenged as inadequate for recurrent stone formers. Severe hypocitraturia is citrate excretion of less than 100 mg per day, and mild to moderate hypocitraturia is citrate excretion of 100-320 mg per day. Other definitions include a urine citrate level of less than 220 mg per day for both men and women, regardless of age, or less than 115 mg per day in men and less than 200 mg per day in women.

These definitions have been called into question by several kidney stone experts and researchers. They feel that these reference range values were selected somewhat arbitrarily from statistical models and large populations of healthy subjects and do not necessarily indicate the optimal level for a calcium stone former. While hypocitraturia currently is defined as the excretion of less than 320 mg of citrate per day, most healthy people actually will have daily urinary citrate excretions of over 600 mg.

Researchers believe that the current definition ignores urinary citrate concentration, which may be far more important than the gross total 24-hour urinary citrate excretion. Further, they argue that optimal urinary citrate levels for calcium stone formers are likely to be closer to the statistical average or median of the reference group than to the lower limits of the healthy range. Using this logic, optimal daily urinary citrate levels for calcium stone formers would probably range from 500-800 mg, and one group uses 450 mg/d in men and 550 mg/d in women as cutoff values in stone formers.

Treatment considerations

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

When necessary, inpatient care should be directed only at the stone disease. Treatment of underlying hypocitraturia is best accomplished on an outpatient basis after convalescence. Diet and medication should be modified in an atmosphere as close as possible to the patient's normal environment.

Consider long-term medical treatment for a patient with recurrent stone disease. [1]


Importance of Citrate

Citrate plays several important roles in the mechanism of urinary stone formation. First, citrate complexes to calcium ions in the urine, reducing calcium ion activity, which results in lowering the urinary supersaturation of calcium phosphate and calcium oxalate. This complexing action is not completely understood, but it has been shown to involve the formation of a calcium-citrate-phosphate species. [2]

This process is pH-dependent, and increases in urinary pH levels appear to be more important in the formation of this complex than are increases in available citrate per se. Second, citrate has a direct inhibitory effect on the crystallization and precipitation of calcium salts.

Citrate also increases the calcium oxalate aggregation inhibitory activity of urine macromolecules (eg, Tamm-Horsfall protein) and may reduce the expression of urinary osteopontin, which is an important component of the protein matrix of urinary stones. [3] In addition, urinary citrate excretion can increase urinary pH, which is a factor in uric acid crystallization and uric acid stone formation, as well as in the calcium-citrate-phosphate complex formation described above.


Risk Factors in Hypocitraturia

Diet and fluid intake

High meat intake increases the urinary excretion of calcium, oxalate, and uric acid and decreases urinary pH and citric excretion. The use of high-protein, low-carbohydrate diets for weight loss has led to concern about increased risk of stone formation, as these diets have been shown to be associated with decreased urinary citrate and pH levels and increased urine calcium and sodium levels in the induction and maintenance phases. [4]

An excessive amount of sodium can also result in hypocitraturia.

Stone-provoking medications

Hypercalciuria can result from administration of corticosteroids, aluminum-containing antacids, loop diuretics, and vitamin D.

Hypocitraturia is often associated with thiazide diuretic or acetazolamide administration. Topiramate has also been found to be associated with an increased risk for urinary stones [5] and to cause hypocitraturia by its inhibition of renal carbonic anhydrases. [6]


Etiology of Hypocitraturia

The excretion of citrate in the urine is a function of filtration, reabsorption, peritubular transport, and synthesis by the renal tubular cell. The proximal tubule reabsorbs most (70-90%) of the filtered citrate, and citrate secretion is negligible.

Acid-base status plays the most significant role in citrate excretion. Alkalosis enhances citrate excretion, while acidosis decreases it. In acidosis, increased citrate utilization by the mitochondria in the tricarboxylic acid cycle occurs. This results in lower intracellular levels of citrate, facilitating citrate reabsorption and hence reducing citrate excretion. Citrate excretion is impaired by acidosis, hypokalemia (causing intracellular acidosis), a high–animal protein diet (with an elevated acid-ash content), and urinary tract infection (UTI).

In summary, hypocitraturia enhances urine calcium salt supersaturation and reduces calcium crystallization inhibition, increasing the risk of calcium nephrolithiasis. It also may play a role in uric acid solubility and uric acid stone formation.

Urinary calculi secondary to hypocitraturia are typically composed of some hydroxyapatite (calcium phosphate), along with calcium oxalate.

The following are causes of hypocitraturic calcium nephrolithiasis:

  • Distal renal tubular acidosis (RTA)
  • Chronic diarrheal syndrome
  • Thiazide diuretic or acetazolamide administration
  • Diet high in animal protein
  • Strenuous physical exercise
  • High sodium intake
  • Gout or gouty diathesis
  • Active UTI

Distal renal tubular acidosis

Renal tubular acidosis is a term applied to several clinical syndromes of metabolic acidosis that result from specific defects in renal tubular hydrogen ion secretion and urinary acidification.

One of the more common presentations of hypocitraturia is distal RTA, which can occur in a complete or incomplete form. The complete form is characterized by hyperchloremic metabolic acidosis, hypokalemia, and elevated urine pH, while the incomplete form exhibits normal serum electrolytes but the inability to acidify urine following an ammonium chloride load.

Both forms can be associated with hypercalciuria and profound hypocitraturia. Combined with alkaline urine, such abnormalities place patients at high risk for calcium phosphate or, less commonly, calcium oxalate stone formation.

Chronic diarrheal syndrome

Chronic diarrheal syndrome results in fluid loss and intestinal alkali loss. Patients with chronic diarrhea and inflammatory bowel disease frequently have hypocitraturia due to bicarbonate loss from the intestinal tract. Hypocitraturia caused by RTA or chronic diarrheal syndrome is associated with other metabolic abnormalities (eg, hypercalciuria, hyperuricosuria) or may occur alone. In chronic diarrheal syndrome, other risk factors for stone formation often are present (eg, low urinary volume, hyperoxaluria, hypomagnesuria, low urinary pH).

Thiazide diuretic or acetazolamide administration

Thiazide therapy may induce hypocitraturia owing to hypokalemia with resultant intracellular acidosis. Acetazolamide (a carbonic anhydrase inhibitor used in the treatment of glaucoma) produces changes in urine composition that are similar to those found in distal RTA. It results in hyperchloremic acidosis due to its action of inhibiting sodium bicarbonate reabsorption in the proximal tubule. Thus, hypocitraturia often occurs due to metabolic acidosis.


Therapy with topiramate (also a carbonic anhydrase inhibitor), a commonly used anti-seizure medication has also been associated with an increased risk of formation of calcium phosphate stones. Warner et al has shown that the use of topiramate has a ‘dose-dependent’ effect on renal excretion of citrate. There has been a 40% reduction in urinary citrate observed in patients on starting dose of topiramate; which can go up to as high as 65% reduction (in urinary citrate) at higher doses. [6, 7]

Angiotensin converting enzyme inhibitors

ACE inhibitors, by increasing adenosine triphosphate (ATP) citrate lyase activity, have also been shown to cause a reduction in urinary citrate. [8]

Diet high in animal protein

A diet rich in animal protein (from elevated acid-ash content) may produce hypocitraturia. Animal proteins contain sulfate and phosphate moieties that are excreted as acids.

Strenuous physical exercise

Strenuous physical exercise (which causes lactic acidosis) can likewise produce hypocitraturia.

Gout and gouty diathesis

Gout and gouty diathesis are conditions that involve excessive serum uric acid, which often is associated with nephrolithiasis. Controlling the uric acid problem and its potential contribution to stone formation may involve limiting purine intake, controlling hepatic uric acid production, monitoring urinary uric acid levels, and checking or altering urinary acidity.

Active urinary tract infection

UTI with bacteria that degrade citrate lowers urinary citrate levels.

Chronic Kidney Disease (CKD)

As glomerular filtration rate (GFR) decreases, there is a stepwise decrease in the amount of citrate that is filtered; however, in the early stages of CKD, the increased fractional excretion of citrate prevents an abrupt decline in urinary citrate, such that overt hypocitraturia is not usually observed until advanced stages of CKD. [9]

Primary Hyperaldosteronism

In this disease entity, both hypercalciuria and hypocitraturia occur via Na-dependent volume expansion and chronic hypokalemia. [10]


US Incidence

Hypocitraturia has been reported in 15-63% of all patients with nephrolithiasis, but it is probably a significant factor in the pathophysiology of nephrolithiasis in about a third of all kidney stone patients. This condition may exist as a single abnormality (10%) or in conjunction with other metabolic disorders of calcium nephrolithiasis (50%).


International Incidence

The incidence of nephrolithiasis varies among populations. Ramello et al reported rates of 1-5% in Asia, 5-9% in Europe, 13% in North America, and 20% in Saudi Arabia. [11] The incidence of hypocitraturia in these regions has not been reported.

In a cross-sectional study from the United Kingdom of 2861 patients with kidney stones (2016 of them male), the prevalence of hypocitraturia was 23%, The prevalence other risk factors was 5.6% for low urine volume, 38% for hypercalciuria, 7.9% for hyperoxaluria, and 18% for hyperuricosuria. [12]


Epidemiology of Hypocitraturia

Morbidity and mortality in hypocitraturia

Hypocitraturia commonly is observed in patients with nephrolithiasis, metabolic acidosis, and chronic diarrheal syndromes. Hypocitraturia itself may not be associated with significant mortality or morbidity; however, potential complications of nephrolithiasis secondary to hypocitraturia can be significant. Potential morbidity due to nephrolithiasis includes hematuria, ureteral obstruction, UTI, urosepsis, and loss of kidney function.

Race predilection

In general, epidemiologic studies have shown that blacks in the United States experience less stone disease than whites by a ratio of approximately 1:4. However, a review of 1,141 stone formers showed similar rates of hypocitraturia among whites, blacks, and Asians. [13]

Sex predilection

Calcium-containing stones occur 3 times more often in men than in women. The 24-hour measurement of urinary citrate in non–stone-forming subjects is higher in women (mean value of 710 mg) than in men (mean value of 531 mg). However, hypocitraturia is more common in stone-forming women than in men.

Age predilection

The incidence of stone diseases is highest in persons aged 30-50 years. Hypocitraturia is more common in premenopausal women with stone disease than in postmenopausal stone-forming women. Geriatric stone patients have a higher incidence of isolated hypocitraturia (29%) than do younger stone formers (17%).


Patient History

Medical history

The patient’s personal history of nephrolithiasis, including previous stone passage, interventional procedures, and previous stone composition are important in history taking. A history of multiple stone passages and rapid recurrent stone formation may indicate a fundamental metabolic cause, such as primary hyperparathyroidism or renal tubular acidosis.

The necessity for multiple interventional procedures, whether endoscopic or open surgical, implies the growth of larger stones. This may be indicative of a more malignant form of stone disease, such as infected lithiasis.

Chronic diarrhea, inflammatory bowel disease, ileostomy, and colostomy (fluid loss due to diarrhea) are important to note, as is recurrent UTI. (As many as 30% of patients with calcium oxalate stones have a history of Escherichia coli infection.)

A history of systemic disease, such as renal tubular acidosis, is another important consideration.

The presence of horseshoe kidney can also be diagnostically important. Stones in patients with horseshoe kidney have previously been attributed solely to urinary stasis. However, a review has since indicated that predisposing metabolic stone risk factors exist in most nephrolithiasis patients with horseshoe kidney and that more than 50% of patients with horseshoe kidney and stones have hypocitraturia. [14]

Surgical history

A past history of shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, or open stone surgery is important to note. [15]

Patients who have undergone enterocystoplasty (augmentation cystoplasty) or who have an intestinal urinary reservoir (neobladder, continent urinary diversion) are usually prone to infection stones but have also been found to have hypocitraturia associated with uninfected stone formation. [16]

Obesity is related to an increased risk for calcium oxalate stone formation but not specifically to a risk for hypocitraturia. However, many surgical treatments for obesity, including jejunoileal bypass and roux-en-Y procedures, lead to hyperoxaluria and hypocitraturia, resulting in urinary stone disease.

Social history

Take note of strenuous exercise or high sodium intake by the patient.


Physical Examination

No specific physical findings are related to hypocitraturia. However, patients with nephrolithiasis often experience acute and extremely painful episodes of renal colic, with associated costovertebral angle tenderness. Abdominal tenderness may develop during renal colic, but peritoneal signs are not found. Renal colic due to kidney stone disease prompts one of the most common reasons for visits to the emergency department for urologic care.


Differentials in Hypocitraturia

Symptoms that mimic those of hypocitraturia can result from the following:

Hypomagnesuria is another metabolic abnormality contributing to nephrolithiasis.


Laboratory Studies in Hypocitraturia

24-hour urine collection

Hypocitraturia, defined as less than 320 mg of citrate excreted per 24-hour urine collection, is diagnosed by 24-hour urine collection for metabolic stone risk analysis. (Many laboratories, however, have their own definition of normal citrate levels.)

The collection should be undertaken in recurrent stone formers, children, patients with solitary kidneys, and, selectively, in first-time stone formers with either increased risk (eg, family history of stones, bone or bowel disease, gout, chronic UTI, nephrocalcinosis) or who are sufficiently motivated to follow long-term therapy for stone prophylaxis.

A 24-hour urine sample is obtained for analysis of a full stone risk profile while patients maintain their customary activity level, diet and fluid intake. Some practitioners always use 2 separate 24-hour urine collections for initial evaluation, to avoid clinical confusion due to spurious variations in diet or activity. Patients should not have a metabolic stone risk profile while on a controlled diet in the hospital or while they are experiencing an acute renal colic attack.

Several commercial laboratories provide metabolic kidney stone prevention profiles, including Dianon, LabCorp, Litholink, Mission, Nichols, and Urocor. Some analyze only 24-hour urine data, while others include serum data and/or patient-reported clinical history and medications in their analysis. They calculate the total volume from the dilution of the volume marker and analyze metabolic risk factors (eg, calcium, oxalate, uric acid, citrate, pH), as well as total volume, sodium, phosphorus, and magnesium. Supersaturation ratios are calculated, and the risk of specific stone types is presented.

The 24-hour urine collection usually is deferred for several weeks after stone passage, although several studies have suggested that this may be unnecessary as long as the patient is following the regular routine diet and activity.

If the evaluation results are normal, the 24-hour collection may be repeated twice. If the evaluation results of metabolic stone workups remain normal after 2 separate 24-hour urine collections, idiopathic nephrolithiasis is suspected. False-positive 24-hour urine collection results can be caused by the patient altering the usual diet while being tested.

The issue of defining what may be within the reference range versus what is optimal for a stone former also may exist. Increased fluid output almost always is recommended for recurrent stone formers, regardless of the measured amount on a 24-hour urine testing.

In a large database of over 20,000 stone-forming patients with computerized analysis of the urinary and serum laboratory data, less than 1% demonstrated no urinary or serum chemistry abnormality related to possible kidney stone disease.

Other studies

Other useful studies include the following:

  • Urine analysis and culture
  • Sequential multiple analysis of 20 chemical constituents - Serum calcium, phosphorus, electrolyte, uric acid, and creatinine levels
  • Parathyroid hormone
  • Urinary stone/sediment analysis

Clinical Examples of Laboratory Results

Complete type I RTA

This condition is characterized by a urine pH of greater than 6.9, a high serum chloride level, a low serum potassium level, low bicarbonate levels, and, in some cases, hypercalciuria.

Incomplete type I RTA

Patients with incomplete type I RTA have normal electrolytes but demonstrate a poor response to acid load (NH4 Cl 100 mg/kg administered PO, and urine pH does not fall below 5.3). In some cases, hypercalciuria may be present.

Chronic diarrhea

Test results in chronic diarrhea include a urine pH of less than 5.5, low urine volume, hypokalemia, hypomagnesemia, hypocalciuria, and hypomagnesuria.

Uric acid lithiasis

Some patients with uric acid stones may demonstrate unusually acidic urine and normal or near-normal uric acid excretion levels. In these cases, appropriate levels of potassium citrate should be used to alkalinize the urine sufficiently to prevent uric acid stone formation. (See Overview of Potassium and Calcium Citrate, below.)


Imaging Studies in Hypocitraturia

Kidneys, ureters, and bladder (KUB) radiography, intravenous pyelography (IVP), renal ultrasonography, and noncontrast spiral computed tomography (CT) scans are available to diagnose nephrolithiasis.

KUB radiography

On plain radiography, radiopaque stones imply the presence of calcium oxalate, calcium phosphate, struvite, or cystine.

Radiolucency may implicate uric acid stones. Nephrocalcinosis may lead to consideration of type I RTA. Large branching stones are more likely to be infection stones or cystine stones. No imaging modality is sensitive or specific for hypocitraturia as an etiology for detected stones.

KUB radiography is the least specific, but most available and inexpensive, imaging modality for stone detection. KUB radiography is commonly used for follow-up of stone therapies or to screen for recurrence.

Renal ultrasonography

This operator-dependent modality is widely available and noninvasive and does not use ionizing radiation. Renal ultrasonography is typically used in pregnant women, in acute screening, and in follow-up in conjunction with KUB radiography.

Intravenous pyelography or intravenous urography

These are widely available. The sensitivity and specificity of these modalities are better than those of plain KUB radiography. However, IVP and intravenous urography (IVU) are invasive and entail increased radiation exposure. Contrast allergy and nephropathy are associated risks.

Noncontrasted spiral computed tomography scanning

The availability of this modality is increasing throughout the world. The radiation in exposure in noncontrasted spiral CT scanning is greater than it is in KUB radiography, but the modality also has the best sensitivity and specificity for stone detection.

In addition, cross-sectional imaging allows for evaluation of non–stone-related causes of flank or abdominal pain. Noncontrasted spiral computed tomography is typically used in the immediate evaluation of patients with colic.


Overview of Potassium Citrate and Calcium Citrate

Potassium citrate

Currently, the preferred treatment for 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 hypercalciuria and hyperuricosuria. [17, 18]

The objective of treatment with Urocit-K or Polycitra-K is to provide potassium citrate in sufficient dosage to restore normal urinary citrate (ie, >320 mg/d and as close to the normal mean of 640 mg/d as possible) and to increase urinary pH to a level between 6.0 and 7.0. Urinary citrate and/or urinary pH measurements should be evaluated every 4 months. Those results should be used to determine the adequacy of the initial dosage and to evaluate the effectiveness of any dosage change.

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, in which absorption is a problem, and in more severe cases because of its higher citrate dose.

Note that doses of Urocit-K greater than 100 mEq/d have not been studied and should be avoided when possible. Obviously, the risk of hyperkalemia is increased when these higher dosages are used, so serum potassium levels should be monitored, particularly in cases of renal failure.

The pH change after institution of potassium citrate therapy generally is small, although reduced doses may be required, with frequent pH monitoring, to maintain the pH below 7.0-7.2. At pH levels above 7.2, the risk of calcium phosphate crystallization increases significantly. Calcium phosphate can coat an otherwise dissolvable uric acid stone and prevent it from dissolving, so avoiding overalkalinization when trying to dissolve pure uric acid calculi is particularly important.

Potassium-containing medications should be used with caution in patients with renal insufficiency or in those receiving potassium-sparing diuretics.

Citrate therapy may be counterproductive in patients with infection stones.

Meta-analysis shows that up to 48% of patients in long-term studies discontinue oral potassium citrate therapy because of side effects.


Potassium-magnesium-citrate has been investigated and may be more effective than potassium citrate in the prevention of stones, because it increases not only urinary citrate but also urinary magnesium, which is another well-known inhibitor of stone formation. It is available over-the-counter and on the Internet but has not yet been widely embraced by the urologic community.

Calcium citrate

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 it can also raise urinary calcium levels. Potassium citrate is often used in addition to calcium citrate in patients with enteric hyperoxaluria and hypocitraturia 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 fluid volume and citrate excretion. [19]


Treatment With Potassium Citrate

Approximately 80-90% of patients with hypocitraturia are treated successfully with potassium citrate to raise their urine citrate levels. This reduces the risk of recurrent stone formation. [20, 21]

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 dissolve existing stones and prevent recurrences. It is important to frequently monitor the urinary pH when trying to dissolve existing stones. Potassium citrate dosages should be adjusted accordingly and serum potassium levels should be checked to identify any hyperkalemia that may develop. Total urinary citrate excretion levels are less important in these situations than is the pH. In a study of patients with urolithiasis who had hypocitraturia and low urine pH, Astroza and colleagues found that patients with a higher body mass index (BMI) had lower increases in citrate excretion and urine pH levels after being started on potassium citrate and they needed more frequent adjustments of their therapy. [22]

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 patients.

Allopurinol is reserved for cases in which potassium citrate supplementation is insufficient to stop uric acid stone formation or is not tolerated for some reason. It also can be used in cases of calcium nephrolithiasis, gout, hyperuricemia, and hyperuricosuria, particularly when alkalinization alone has been inadequate to stop stone formation.

Distal renal tubular acidosis

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 with slow-release tablets, in conditions in which 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.



Consider consultation with a urologist or nephrologist for the management of stone disease.


Dietary Considerations

High fluid intake

The patient’s fluid intake should be 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

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 should be consumed, especially at the same meal.

Increased citrus fruits, potassium-rich products, and alkalinizing foods

Orange juice is a good source of dietary citrate, containing approximately 50 mEq of potassium per L and 160 mEq of citrate per L.

In a study of the value of orange juice consumption in kidney stone prevention, Wabner and Pak found that compared with 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. [23]

Another retrospective study tried to compare patient outcomes in those receiving lemonade therapy (120 mL concentrated lemon juice diluted to 2L with water) vs. potassium citrate (40 meqs/day). Although there was a significant increase in the amount of urinary citrate in both groups, those taking potassium citrate had greater increases in urinary citrate, as well as increases in urine pH. Lemonade therapy did not alter urine pH. [24]

Using ion chromatography, a group of researchers tried to quantify the amount of citrate in natural and commercially available fruit juices. Natural lemon and lime juice contained the highest amount of citric acid, followed by lemon and lime juice concentrates. Among low-calorie beverages, grapefruit juice and orange juice had the highest content of citrate. [25]


Severity-based Treatment Specifications

Severe hypocitraturia

Severe hypocitraturia (< 100 mg/d) is treated with the following:

  • Chronic diarrheal states - Liquid formulation of potassium citrate
  • Complete distal RTA - Potassium citrate 20-40 mEq PO 2-4 times daily as needed to optimize urinary citrate excretion
  • Infection stones (magnesium and ammonium phosphate or carbonate apatite) - Potassium citrate, antibiotics, stone removal

With regard to struvite (infection) stones, potassium citrate should be used cautiously in these situations, because alkalinization will increase the formation of these stones.

Mild to moderate hypocitraturia

The recommended therapy in cases of mild to moderate hypocitraturia (100-320 mg/d) caused by diet is the administration of supplemental potassium citrate (initial dose 20 mEq PO bid-tid) and dietary restriction of animal protein. The dose is adjusted based on urinary pH and citrate levels obtained at 2-3 months of treatment.

Once stabilized, repeat testing can be performed at 4- to 6-month intervals and then yearly if stable. Performing a complete, 24-hour urine metabolic screening that includes serum potassium, as well as urinary volume, calcium, uric acid, oxalate, phosphate, sodium, and magnesium, in addition to citrate, is important.

New problems may develop as the patient’s diet is adjusted. An adequate fluid volume needs to be maintained, even if this means dilution of the citrate concentration. When this occurs, appropriate adjustment of the potassium citrate dosage should be achieved to ensure an optimal concentration of roughly 300 mg of citrate per liter.

When hypocitraturia results from incomplete RTA, potassium citrate supplementation should be employed as appropriate.

Low-normal urinary citrate level

In patients with a low-normal urinary citrate level (320-400 mg/d), administer potassium citrate (10 mEq PO bid-tid). Consider optimizing 24-hour citrate to 600 mg per 24 hours.



No limitation of the patient’s activity level is necessary, but dehydration should be avoided, especially when the patient is engaging in outdoor activities in a warm, dry environment.


Patient Information

Educate the patient in the following:

  • Diet and behavioral modification
  • Risks and benefits of treatment with potassium citrate

For patient education information, see eMedicineHealth's Kidney Stones.