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Kidney stones in adults: Prevention of recurrent kidney stones

Kidney stones in adults: Prevention of recurrent kidney stones
Author:
Gary C Curhan, MD, ScD
Section Editor:
Glenn M Preminger, MD
Deputy Editor:
Albert Q Lam, MD
Literature review current through: Dec 2022. | This topic last updated: May 12, 2022.

INTRODUCTION — Kidney stone disease (nephrolithiasis) is a common problem in primary care practice.

This topic will review the prevention of recurrent kidney stones in adults. Other aspects of kidney stones in adults are discussed separately:

(See "Kidney stones in adults: Epidemiology and risk factors".)

(See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis".)

(See "Kidney stones in adults: Evaluation of the patient with established stone disease".)

(See "Kidney stones in adults: Surgical management of kidney and ureteral stones".)

The prevention of recurrent kidney stones in children is also presented separately. (See "Kidney stones in children: Prevention of recurrent stones".)

GENERAL PRINCIPLES — In adults with established kidney stone disease, the goal of preventive therapy is to prevent the future recurrence of kidney stones as well as to prevent growth of existing kidney stones. Prevention is guided by the following general principles:

Preventive therapy generally consists of lifestyle changes (eg, increased fluid intake, dietary modification, weight loss), drug therapy, or a combination of these. The approach to preventive therapy for an individual patient depends upon a comprehensive evaluation of the patient's dietary and metabolic risk factors for stone formation as well as the patient's stone composition, if known. For calcium oxalate and calcium phosphate stones, we generally try dietary modification before initiating drug therapy. However, for other stone types, such as uric acid or cystine stones, drug therapy is frequently initiated at the same time as dietary changes. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Approach to evaluation'.)

While certain preventive measures are applicable to all patients with kidney stones, other measures are specific to certain stone types and should not be considered generalizable to all stone types. (See 'Preventive measures for all stone types' below and 'Preventive measures for specific stone types' below.)

All patients receiving treatment to prevent recurrent kidney stones should be regularly monitored to assess the response to therapy. Such monitoring consists of a metabolic evaluation (ie, 24-hour urine collection for analysis of urine composition) and imaging. (See 'Monitoring the response' below.)

Patients should be informed that these recommended changes are treatments that need to be continued long term. If they are stopped, the urine composition and therefore the stone risk would likely return to the pretreatment levels.

PREVENTIVE MEASURES FOR ALL STONE TYPES — Certain preventive measures are applicable to all patients with kidney stones, independent of their stone type or individual risk.

Fluid intake — For all patients with kidney stones, we suggest sufficient fluid intake to consistently produce at least 2 liters of urine per day. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Fluid intake'.)

To reach this goal, the best strategy is to recommend how much additional fluid the patient should drink based upon his or her 24-hour urine volume. As an example, if the total urine volume is 1.5 liters, then we recommend two additional 8 ounce (240 mL) glasses of fluid each day to reach the goal of at least 2 liters of urine output per day. We advise the patient to distribute the fluid intake throughout the day.

The risk of stone formation might be affected by the type of beverage consumed, with certain types of beverages being more or less beneficial for the prevention of kidney stones. Water is an ideal choice, but other non-calorie-containing beverages are also effective. We advise patients to avoid calorie-containing beverages, such as sweetened soda, to avoid weight gain with the general increase in fluid intake. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Type of fluid'.)

Increasing fluid intake, spread throughout the day (although it is not essential that the patient wake up several times per night to urinate), will increase the urine flow rate and lower the urine solute concentration, both of which may protect against stone formation [1]. In one prospective trial, 199 patients with a first calcium oxalate stone were randomly assigned either to no therapy or to a recommendation of a high fluid intake to produce at least 2 liters of urine per day [2]. At five years, the incidence of new stone formation was significantly lower in the treated patients than in those in the control group (12 versus 27 percent).

Similar findings were noted in a prospective clinical series [3]. Stone formers who remained free of stones were noted to have a greater increase in urine volume than those who had recurrent disease (320 mL/day versus no change). This study emphasizes that even small increases in fluid intake can reduce the risk of new stone formation.

Diet and lifestyle measures

Limit sodium intake — For all patients with kidney stones, we suggest limiting dietary sodium intake to below 100 mEq (2300 mg) per day. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Sodium'.)

Calcium is reabsorbed passively in the proximal tubule down the favorable concentration gradient created by the reabsorption of sodium and water (see "Diuretics and calcium balance"). Thus, a low-sodium diet (80 to 100 mEq/day) can enhance proximal sodium and calcium reabsorption, leading to a reduction in calcium excretion [4,5]. In one study, for example, lowering sodium intake from 200 to 80 mEq/day diminished calcium excretion by as much as 100 mg/day (2.5 mmol/day) [5]. Although the independent contribution of lowering dietary sodium intake on actual stone formation is unknown, limiting sodium intake is likely an important component of a regimen that has been demonstrated to reduce recurrent stone formation [4,6].

Increase fruit and vegetable intake — For all patients with kidney stones, we suggest increasing dietary fruit and vegetable intake. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Potassium'.)

Foods that are rich in potassium, particularly fruits and vegetables, may be beneficial. Increasing intake of fruits and vegetables, regardless of 24-hour urine values, may reduce the risk of calcium oxalate stone formation, particularly in patients who self-select a diet that is low in fruits and vegetables. This benefit is primarily the result of increasing citrate excretion [7]. Observational studies have consistently found a substantially lower risk of incident stone formation in those with diets rich in potassium [8].

Weight loss — Weight control may be helpful in preventing stone recurrence, since obesity and weight gain are risk factors for kidney stones, particularly in females [9]. However, there are no clinical trials that have shown that weight loss reduces the risk of recurrent stones. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Medical conditions'.)

PREVENTIVE MEASURES FOR SPECIFIC STONE TYPES — Patients with specific stone types may require additional preventive measures, in addition to general preventive measures for all stone types. (See 'Preventive measures for all stone types' above.)

Calcium oxalate stones — Prevention of recurrent calcium oxalate stones is aimed at decreasing the concentrations of the lithogenic factors (calcium and oxalate) and increasing the concentrations of inhibitors of stone formation, such as citrate. Achieving these goals may require an increase in fluid intake (see 'Fluid intake' above), dietary modification, and the administration of appropriate medications. Specific recommendations should be based upon the results of 24-hour urine collection results, which should be performed before dietary modification or drug therapy is attempted. In addition, any medical conditions that are associated with calcium stones (eg, primary hyperparathyroidism) should be addressed as appropriate. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on '24-hour urine collections'.)

Dietary modification — From the viewpoint of diet, increasing the intake of fluid, dietary calcium, potassium, and phytate may be beneficial. In addition, decreasing the intake of oxalate, animal protein, sucrose, fructose, sodium, supplemental vitamin C, and supplemental calcium (as opposed to dietary calcium) may reduce the risk of calcium oxalate stones [10]. (See "Kidney stones in adults: Epidemiology and risk factors".)

Maintain adequate calcium intake — For all patients with calcium oxalate stones, we suggest against a low calcium diet. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Calcium'.)

We generally encourage patients to consume several servings of dairy or other calcium-rich foods to reach 800 to 1000 mg/day. Some plant-based milk alternatives are calcium enriched and low in oxalate and may be suitable options in place of traditional dairy offerings [11].

Calcium supplements should not be routinely used to achieve adequate dietary calcium intake in patients with calcium oxalate stones, as they do not appear to be effective in preventing recurrent stones and may even slightly increase risk [12,13]. In patients with a history of stones who require calcium supplements (eg, for the treatment of osteoporosis, or as an oxalate binder in patients with gastrointestinal malabsorption), a suggested approach is to measure urinary calcium excretion before and approximately one month after starting the calcium supplement. If there is a clinically important increase in urinary calcium excretion, the supplement should be discontinued or the dose should be reduced. In this setting, the initiation of a thiazide diuretic may be useful to reduce urinary calcium excretion (and to help maintain bone density). In addition, if a calcium supplement is used, it should be taken with a meal. (See 'High urine calcium' below.)

Higher urine calcium is a common finding in stone formers, but restricting dietary calcium intake is not generally recommended unless it is excessive (more than 1500 mg/day). Although urine calcium excretion may decrease with restriction, the decrease in free intestinal calcium can lead to increased absorption of dietary oxalate and enhanced oxalate excretion, due to decreased binding of oxalate by calcium in the intestinal lumen. The net effect may be increased supersaturation of the urine with respect to calcium oxalate and an enhanced tendency to stone formation. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Dietary factors'.)

The ability to help prevent new stone formation with adequate calcium intake was shown in part by a five-year randomized trial that compared two diets among males with idiopathic hypercalciuria and recurrent calcium oxalate stones [4]. In this trial, 120 such males were randomly assigned to either a diet consisting of calcium (1200 mg/day [30 mmol/day]) and low amounts of animal protein (52 g/day) and salt (2900 mg/day [50 mmol/day] of sodium chloride) or a diet containing a low amount of calcium (400 mg/day [10 mmol/day]). At five years, the group assigned to the adequate calcium, low-animal protein, low-salt diet had a lower risk of stone recurrence (unadjusted relative risk 0.49, 95% CI 0.24-0.98). However, the independent effect of calcium is unclear given that the amounts of animal protein and salt ingested among those in the low-calcium diet differed from that of patients in the normal-calcium diet group. Nonetheless, the low-calcium intervention was not beneficial and is not recommended.

In addition to increasing stone formation, a low-calcium diet may have a second deleterious effect in patients with idiopathic hypercalciuria: development of negative calcium balance [10,14]. This extra loss of calcium can exacerbate the already diminished bone density in some of these patients [14,15], a complication that may be due to enhanced bone resorption.

Reduce nondairy animal protein intake — For all patients with calcium oxalate stones, we suggest reducing nondairy animal protein intake. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Protein'.)

Adverse changes in urinary calcium and citrate excretion can be induced by a high-protein diet since the metabolism of sulfur-containing amino acids increases the daily acid load by generating sulfuric acid (figure 1). Nondairy animal protein is much more likely to induce this effect than vegetable protein since it has a higher sulfur content and therefore generates more acid [16]. How acid loading produces these changes is discussed elsewhere. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Protein'.)

Thus, lowering animal protein intake will produce favorable changes in the urine [10]. However, it has not been proven that this will reduce the incidence of stone formation. In one randomized trial, for example, reduced animal protein in association with higher dietary calcium and lower dietary sodium reduced the risk of stone recurrence [4], but the individual impact of animal protein could not be determined. A subsequent randomized trial found that, compared with a high fluid intake plus a diet rich in calcium, a low animal protein intake does not reduce stone recurrence [17]. In addition, observational studies have been inconsistent, suggesting that a high-animal protein diet was a risk factor for incident kidney stones in males and older females but not in younger females [8]. Based upon the available data, it would be prudent to avoid excessive nondairy animal protein intake for all calcium stone formers.

Limit oxalate intake — For all patients with calcium oxalate stones, we suggest limiting intake of high oxalate foods and supplemental vitamin C. However, excessive restriction of oxalate is not likely to be helpful; patients should continue to consume a wide variety of fruits and vegetables while avoiding those very high in oxalate. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine oxalate' and "Kidney stones in adults: Epidemiology and risk factors", section on 'Oxalate'.)

Some foods contain very large amounts of oxalate, and those should be avoided (eg, spinach, rhubarb, potatoes). In addition, some nuts and legumes are also high in oxalate, and the intake should be limited (eg, peanuts, cashews, almonds). High-oxalate foods should be avoided regardless of urine oxalate since there may be a period of very high urinary oxalate excretion soon after the food is consumed. If a low-oxalate diet is recommended, it should only be continued if there is documented evidence that the urine oxalate excretion has fallen. The oxalate content of foods is available at the following website.

However, there is scant evidence that low-oxalate diets reduce the risk of stone formation. In prospective observational studies of individuals who had never had a stone, higher dietary oxalate only slightly increased the risk of incident stone formation in males and older females; there was no association in younger females [18]. The risk was higher with increasing oxalate intake among those with calcium intake below the median, again demonstrating that adequate dietary calcium intake may reduce the risk of stone formation. Because of the documented health benefits of many foods that are traditionally considered high in oxalate (but still contain 10 mg or less of oxalate per serving), strict oxalate restriction does not seem to be supported. As noted above, some foods traditionally believed to be high in oxalate, such as tea, do not increase the risk of stone formation.

High-dose supplemental vitamin C appears to increase urine oxalate excretion in certain individuals [19,20] and the risk of stone formation [21]; thus, high-dose supplements should be avoided in those with calcium oxalate stones.

Limit sucrose and fructose intake — For all patients with calcium oxalate stones, we suggest limiting intake of sucrose and fructose. Sucrose intake increases urine calcium independent of calcium intake and has been associated with an increased risk of stones [22]. Fructose intake also is associated with an increased risk of stone formation [23]. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Sucrose'.)

Drug therapy for specific metabolic abnormalities — Drug therapy is indicated if the stone disease remains active (as evidenced by the formation of new stones, enlargement of old stones, or the ongoing passage of gravel) or if there is insufficient improvement in the urine chemistries despite attempted dietary modification over a three- to six-month period (see 'Monitoring the response' below). The aim of therapy is to prevent further calcium oxalate precipitation; dissolution of already existing calcium stones is highly unlikely (in comparison to uric acid or cystine stones). Thus, passage of an existing stone does not necessarily reflect a therapeutic failure in a patient known to have a kidney stone prior to the institution of therapy.

Initial drug therapy varies with the metabolic abnormality that is present:

Thiazide diuretics to reduce urine calcium

Allopurinol for high urine uric acid

Potassium citrate or potassium bicarbonate for low urine citrate

High urine calcium — For patients with recurrent calcium oxalate stones who have higher than desired urine calcium, we suggest treatment with a thiazide diuretic to lower urinary calcium excretion. The definition of high urine calcium is arbitrary, and the urinary calcium level at which one should consider treatment is not clear because the relation between urine calcium and risk of stone formation is continuous; if there is evidence of ongoing stone formation, then the urine calcium should be lowered. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine calcium'.)

We generally start chlorthalidone at 12.5 to 25 mg/day, hydrochlorothiazide at 25 mg/day, or indapamide at 2.5 mg/day to minimize diuretic-induced complications. However, many patients will require 50 to 100 mg/day of chlorthalidone or hydrochlorothiazide to achieve adequate lowering of the urine calcium. In our experience, patients who do not respond to 50 mg/day are unlikely to respond to higher doses. Chlorthalidone can be given once daily, but hydrochlorothiazide at doses above 25 mg/day may need to be given twice daily because of its short half-life. The serum potassium level should be checked one week after starting a thiazide. Hypokalemia should be avoided since low potassium levels reduce urinary citrate excretion. (See 'Low urine citrate' below.)

All patients receiving a thiazide diuretic should maintain a low-sodium diet, which is essential for the diuretic to effectively lower urinary calcium. (See 'Limit sodium intake' above.)

Urinary calcium and sodium excretion should be monitored after the institution of thiazide therapy (see 'Metabolic surveillance' below). A repeat 24-hour urine collection should be performed one to two months after initiating therapy. If the urine calcium remains higher than desired, a high sodium intake may be responsible, and efforts should be made to reduce sodium excretion below 100 mEq (2300 mg) per day. The potassium-sparing diuretic amiloride (5 to 10 mg/day) can also be added since this drug may increase calcium reabsorption in the cortical collecting tubule, further lowering calcium excretion [24], and may also prevent hypokalemia, which could lead to lower citrate excretion (see "Diuretics and calcium balance", section on 'Cortical collecting tubule and potassium-sparing diuretics'). Triamterene is typically avoided because of the rare possibility of precipitation.

If the urine calcium does not fall as desired or the thiazide is not well tolerated, an alternative therapy is administration of 40 to 60 mEq of alkali per day as potassium bicarbonate or potassium citrate (citrate is rapidly metabolized to bicarbonate) [25]. Potassium supplements should not routinely be given with amiloride, since the combination can lead to potassium retention and hyperkalemia.

Thiazide therapy can lower calcium excretion by as much as 50 percent. This is primarily by inducing mild volume depletion, leading to a compensatory rise in the proximal reabsorption of sodium and therefore of passive calcium reabsorption [26,27]. The net effect may be a 90 percent reduction in the incidence of new stones (although there is also an appreciable improvement of 50 to 65 percent in placebo-treated patients) [28-31]. In a meta-analysis of five trials of thiazide diuretics compared with standard treatment, thiazide therapy was associated with a significant reduction in the number of new stone recurrences (relative risk 0.52, 95% CI 0.39-0.69) [32]. The full benefit may not be seen unless sodium intake is also restricted [26]. (See "Diuretics and calcium balance".)

The tendency toward positive calcium balance with a thiazide diuretic may have an additional beneficial effect: increasing bone mineralization and decreasing the incidence of hip fracture in older patients (see "Drugs that affect bone metabolism"). This will also be helpful in patients who have mistakenly been on a low-calcium and/or high-sodium diet, both of which can lead to negative calcium balance and osteopenia in patients with higher urine calcium. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine calcium'.)

Via an unknown mechanism, raising the plasma bicarbonate concentration increases calcium reabsorption and lowers calcium excretion [33,34]. For this to occur, however, the potassium salt must be given; the volume expansion induced by sodium bicarbonate or sodium citrate will increase sodium and therefore calcium excretion, counteracting the effect of the elevation in the plasma bicarbonate concentration [33-35]. The administration of potassium citrate or potassium bicarbonate may have an additional beneficial effect by increasing the urinary excretion of citrate, a potent inhibitor of calcium stone formation. (See 'Low urine citrate' below.)

Low urine citrate — For patients with recurrent calcium oxalate stones who have low urine citrate, we suggest potassium citrate or potassium bicarbonate therapy to increase urinary citrate excretion. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Low urine citrate'.)

We typically start with potassium citrate 30 to 40 mEq/day given in two to three divided doses or potassium bicarbonate 25 to 50 mEq/day given in two divided doses. We titrate the dose according to the change in urine citrate, as well as to the serum potassium level in patients with impaired potassium excretory capacity.

Nonalkalinizing salts such as potassium chloride should not be used. In contrast with potassium citrate or potassium bicarbonate, potassium chloride does not increase citrate excretion in normokalemic subjects [36].

Increasing urinary citrate excretion is the goal in patients with low urine citrate since citrate inhibits calcium stone formation by forming a poorly dissociable but soluble complex with calcium, thus reducing the amount of calcium available for binding with oxalate or phosphate. Citrate excretion can be enhanced by alkalinizing the plasma by the daily administration of 30 to 80 mEq of potassium citrate or potassium bicarbonate [36,37]. In a controlled trial of 57 patients, for example, the incidence of new stone formation was lower in patients with low urine citrate treated with potassium citrate (0.1 versus 1.1 events per patient-year in the placebo group) [37]; this benefit was associated with an approximate doubling of citrate excretion. In a meta-analysis of four trials of citrate therapy compared with placebo or no treatment, citrate significantly reduced the incidence of stone recurrence (relative risk 0.25, 95% CI 0.14-0.44) [32].

Although orange juice is a good source of potassium and citrate, it has some undesirable effects: It does not lower calcium excretion, it modestly raises oxalate excretion, and the increase in caloric intake could lead to weight gain [38]. By comparison, lemon juice has been proposed to be an effective source of citrate [39,40]. In one report, for example, the ingestion of 4 ounces of lemon juice concentrate per day (mixed with tap water as lemonade for a total volume of 2 liters) resulted in increased urinary citrate levels in 11 of 12 patients (average increase of 142 to 346 mg/day, although it remained in the low range) who were either noncompliant or intolerant of conventional citrate replacement therapy [39]. Active therapy also decreased urinary calcium excretion and did not alter urinary oxalate excretion. However, other citrate-containing, low-calorie beverages (particularly diet soft drinks that contain large amounts of citrate such as diet Sunkist, diet 7Up) do not appear to be therapeutically useful [41,42]. The actual alkali content of these beverages was less than 10 mEq/L, including the lemonade recipe above containing 6 mEq/L [41]. Further studies of the impact on actual stone formation are required before this approach can be routinely recommended to prevent stone recurrence.

Contrary to popular belief, cranberry juice does not seem to increase urinary citrate levels. This was demonstrated in a study of 24 individuals (12 of whom had prior calcium oxalate stones), in which urinary citrate excretion was the same during water (the control intervention) and cranberry juice intake [43]. A possible explanation for the lack of effect is the low potassium content of cranberry juice.

Alkalinization raises citrate excretion by diminishing the uptake of filtered citrate by the proximal tubular cells [44]. The mechanism by which this occurs is related in part to the chemical form of citrate that is present in the lumen. Citrate can exist at a physiologic pH either as a divalent or trivalent anion. Proximal citrate reabsorption (via a sodium-citrate cotransporter in the luminal membrane) preferentially occurs as the divalent anion. Raising the pH in the tubular lumen converts the divalent form into the less reabsorbable trivalent form:

 Citrate(2-) + HCO3-  →  Citrate(3-) + CO2 + H2O

Increasing the systemic pH may enhance citrate excretion by a second mechanism. The associated intracellular alkalosis will diminish citrate metabolism within the cells. The ensuing elevation in the cell citrate concentration will create a less favorable concentration gradient for passive citrate movement from the tubular lumen into the cell [43,45].

The net effect is decreased citrate uptake and increased citrate excretion. In addition to the effect on pH, some of the administered citrate may be excreted directly before being metabolized to bicarbonate [46]. Thus, potassium citrate has a slightly greater citraturic effect than potassium bicarbonate [36,46].

On the other hand, metabolic acidosis diminishes citrate excretion due to enhanced citrate reabsorption [44]. This effect is mediated both by conversion of citrate(3-) to the more reabsorbable citrate(2-) and by increased citrate metabolism (due to upregulation of the enzyme ATP citrate lyase) within the cells [45]. Hypocitraturia probably contributes to the stone formation that is relatively common in patients with untreated distal renal tubular acidosis (see "Nephrolithiasis in renal tubular acidosis"). Care must be taken when providing alkali supplements in patients with calcium phosphate stones (see below).

Hypokalemia, as may be produced by a thiazide diuretic for example, has a similar stimulatory effect on citrate reabsorption. Potassium moves out of the proximal tubule cells to repair the extracellular deficit and electroneutrality is maintained in part by the movement of extracellular hydrogen into the cells. The intracellular acidosis will enhance citrate metabolism, thereby lowering the cell citrate concentration and creating a more favorable gradient for citrate reabsorption [46,47]. It is therefore essential to correct hypokalemia in recurrent stone formers.

High urine oxalate — High urine oxalate can result from ingestion of a diet high in oxalate or factors that can be converted to oxalate (eg, high-dose supplemental vitamin C), increased gastrointestinal absorption of dietary oxalate (enteric hyperoxaluria), or increased endogenous production of oxalate (eg, primary hyperoxaluria). (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine oxalate'.)

Enteric hyperoxaluria – Treatment in individuals with enteric hyperoxaluria is directed toward diminishing intestinal oxalate absorption [28,48]. The initial regimen consists of oral calcium carbonate or citrate (1 to 4 g/day) with meals to bind oxalate in the intestinal lumen. Although some of the calcium is absorbed, there is a proportionately greater fall in oxalate excretion (see "Kidney stones in adults: Epidemiology and risk factors"). These patients may also have increased gastrointestinal losses of fluid and alkali, so they may benefit from a high fluid intake and potassium alkali salt to correct metabolic acidosis and/or low urine citrate.

A low-fat, low-oxalate diet is another modality that may be helpful in patients with enteric hyperoxaluria by reducing the quantity of fatty acids and free oxalate in the colon. Importantly, reliable data on the oxalate content of foods are available, and a diet that is too restrictive should be avoided, because it may lead to inadequate nutrition in these patients who have malabsorption and/or a short bowel syndrome. (See 'Limit oxalate intake' above.)

Cholestyramine, which binds both bile acids and oxalate, can also be used, but side effects may be limiting. Although it has been postulated that manipulation of enteric flora (as with lactic acid bacteria or Oxalobacter formigenes) may also reduce dietary oxalate absorption and urinary oxalate excretion, a randomized, placebo-controlled trial found that lactic acid bacteria failed to reduce urinary oxalate excretion; other bacterial formulations have also not been successful [49-51].

Primary hyperoxaluria – Treatment in individuals with primary hyperoxaluria is directed at reducing endogenous oxalate production, which is increased in patients with primary hyperoxaluria. This is discussed in more detail elsewhere. (See "Primary hyperoxaluria", section on 'Medical management'.)

High urine uric acid — For patients with recurrent calcium oxalate stones who do not respond to dietary modification and other drug therapies and who have high urine uric acid, we suggest treatment with allopurinol. We typically initiate allopurinol at 300 mg/day, given in two divided doses to improve tolerability. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine uric acid'.)

Elevated urinary excretion of uric acid has been thought to promote calcium oxalate stone formation [28,52,53], but there is controversy regarding the role of uric acid [54].

The lack of importance of uric acid excretion was suggested in a study of 3350 individuals, which revealed no difference in mean 24-hour uric acid excretion between individuals with and without a history of stones [54]. Multivariate analyses adjusting for other urinary factors revealed no higher likelihood of being a stone former among those with higher urine uric acid. To the contrary, there was a significant inverse association between 24-hour uric acid excretion and the likelihood of stone formation in males.

Despite the latter findings, two randomized trials and several observational studies have shown benefit from allopurinol in calcium stone formers with high urine uric acid [32,52,55,56]. In one trial, 60 patients with high urine uric acid and normocalciuria were assigned to allopurinol or placebo [52]. Allopurinol therapy significantly reduced the likelihood of calcium oxalate stone recurrence (0.12 versus 0.26 per patient per year with placebo) (figure 2). These two apparently conflicting findings raise the possibility that allopurinol may lower the risk through a mechanism other than reducing uric acid excretion.

In the past, it was suggested that uric acid may act as a nidus for calcium oxalate stone formation, and alkali therapy with potassium citrate (60 to 80 mEq/day) was proposed to be theoretically beneficial since raising the urine pH above 6.0 will convert insoluble uric acid to the much more soluble urate salt [36,57]. However, uric acid is no longer believed to act as a nidus. No trials address the benefits of alkali therapy in preventing recurrent calcium oxalate stone formation among patients with high urine uric acid.

No metabolic abnormality — Some patients with recurrent calcium stones have no identifiable metabolic abnormality [28,54,58,59]. However, careful analysis has shown that these patients frequently have more calcium, more oxalate, and/or less citrate in the urine than normal controls, although no value meets the traditional definition of abnormal [54,58]. The likely explanation for these patients with "no metabolic abnormality" is that the traditional definitions should be changed because there appears to be a graded increase in stone risk that begins when the rate of urinary excretion is still within the "normal" range. If a patient has evidence of stone growth or new stone formation, then one or more of the relevant urinary factors needs to be modified by diet and/or medication.

There is some suggestive evidence that lowering calcium excretion with a thiazide diuretic may be beneficial, even in patients who do not have high urine calcium [29,30]. The possible benefit of potassium alkali salts in this setting remains to be determined.

Calcium phosphate stones — In general, patients with calcium phosphate stones have the same risk factors as those with calcium oxalate stones (except for hyperoxaluria and higher urine pH); as a result, therapy for recurrent stone formation is similar in most cases [60]. (See 'Calcium oxalate stones' above.)

Most calcium phosphate stone formers have a persistently elevated urine pH (usually above 6.0); the reason is not always clear but in some patients may be due to overt or incomplete distal renal tubular acidosis. Calcium phosphate stones form when the urine pH is more alkaline; calcium oxalate stones are not pH sensitive. Although the administration of alkali (preferably potassium citrate or potassium bicarbonate) in this setting may diminish the frequency of stone growth or new formation by increasing urine citrate or reducing urine calcium, it could also increase the risk by raising the urine pH, thereby increasing the likelihood of calcium phosphate crystal formation. Thus, alkali therapy must be undertaken with caution. Urine pH and citrate should be monitored, and supplemental alkali should be discontinued if urine pH rises above 6.5 without a substantial increase in the urine citrate or decrease in the urine calcium (or a decrease in the supersaturation for calcium phosphate). (See "Nephrolithiasis in renal tubular acidosis".)

Uric acid stones — In addition to general preventive measures (see 'Preventive measures for all stone types' above), specific preventive measures for patients with uric acid stones include urinary alkalinization (with potassium citrate or potassium bicarbonate), which increases the solubility of uric acid, and in selected patients, treatment with a xanthine oxidase inhibitor. The treatment of uric acid stones is discussed in more detail elsewhere. (See "Kidney stones in adults: Uric acid nephrolithiasis", section on 'Treatment'.)

Cystine stones — In addition to general preventive measures (see 'Preventive measures for all stone types' above), specific preventive measures for patients with cystine stones include urinary alkalinization (with potassium citrate or potassium bicarbonate) and the use of thiol-containing drugs (eg, tiopronin, D-penicillamine) that reduce cystine precipitation. The treatment of cystine stones is presented separately. (See "Cystinuria and cystine stones", section on 'Treatment'.)

Struvite stones — In addition to general preventive measures (see 'Preventive measures for all stone types' above), specific preventive measures for patients with struvite (magnesium ammonium phosphate) stones include complete surgical stone removal, short- or long-term antimicrobial therapy, and administration of urease inhibitors (such as acetohydroxamic acid [AHA]). The treatment of struvite stones is discussed in more detail elsewhere. (See "Kidney stones in adults: Struvite (infection) stones", section on 'Approach to therapy'.)

Stone composition not known — For a patient with recurrent stone disease (but the type of stone is unknown), it is reasonable to assume that the stone is calcium oxalate or calcium phosphate. In this setting, certain disorders associated with calcium nephrolithiasis should be excluded as possible underlying causes. Although one cannot distinguish between calcium oxalate and calcium phosphate stones radiographically, this is less important, because the evaluation will be the same for both stone types.

However, if a patient is a recurrent stone former, then it should be made clear to the patient and the treating urologist that a stone must be sent for analysis if possible from the next stone episode. Information about stone composition will then allow for more tailored treatment recommendations. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Stone analysis'.)

If stone composition is unknown, then treatment recommendations to prevent future stone episodes will be influenced by the 24-hour urine results and the clinical picture:

High urine calcium – If the urine calcium is higher than desired, then attempts to lower the urine calcium concentration should be instituted (often a thiazide diuretic will be necessary). (See 'High urine calcium' above.)

Low urine citrate – If the citrate is low, then supplementing alkali intake (eg, potassium citrate or potassium bicarbonate) will increase urinary citrate excretion. However, this will also raise the urinary pH. If the predominant calcium salt is calcium phosphate, which forms more readily in an alkaline urine, supplementation with alkali such as citrate (which is metabolized to bicarbonate in the body) may, in fact, accelerate the rate of stone formation. In this case, the urine pH may be a useful guide. If the urine pH is 6.5 or higher, the use of citrate supplements should be used with caution. (See 'Low urine citrate' above.)

High urine oxalate – If high urine oxalate is present, a low-oxalate diet should be tried first. The primary foods to avoid are spinach, rhubarb, potatoes, and almonds. The following website contains the oxalate value for different foods. Even if the urine calcium is high, increasing dietary calcium or adding an over-the-counter calcium supplement with meals should be considered in addition to a low-oxalate diet if the low-oxalate diet alone is insufficient. However, the amount of urinary oxalate that is derived from the diet is quite variable; thus, if a patient adheres to a low-oxalate diet with adequate calcium intake and the urine oxalate does not fall, then the stricter oxalate restriction can be removed (though the very-high-oxalate-containing foods mentioned above should still be avoided). (See 'Limit oxalate intake' above.)

High urine uric acid – If high urine uric acid is present, lifestyle modification (ie, decreased nondairy animal protein intake and weight loss) to reduce uric acid production may be warranted. If dietary measures are insufficient to lower the urinary uric acid, allopurinol should be considered. (See 'High urine uric acid' above.)

Low urine volume – If the urine volume is less than 2 liters in 24 hours, then patients should increase their fluid intake with the goal of consistently producing at least 2 liters of urine per day. (See 'Fluid intake' above.)

MONITORING THE RESPONSE

Metabolic surveillance — The 24-hour urine is an essential component of the initial evaluation and guides recommendations for prevention for all stone types. The response to dietary or drug therapy is monitored by repeat 24-hour urine collections for calcium oxalate and calcium phosphate stones; this may also be done more selectively for patients with uric acid, cystine, or struvite stones. It is essential that all the relevant urinary factors be monitored in individuals with calcium oxalate and calcium phosphate stones as they often have more than one urinary abnormality. Although remnant stones may theoretically consume urinary constituents and lower their measured urinary concentration, the potential error from a stone being present is much less than the variability due to dietary intake [61,62]. Thus, the patient does not need to be stone free to perform a collection. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on '24-hour urine collections'.)

The goal of therapy is to reverse the abnormalities detected during the initial workup (eg, low urine volume, high urine calcium, high urine oxalate, and low urine citrate). We routinely obtain a 24-hour urine collection at six to eight weeks after therapy has begun to assess the impact of the intervention. If the desired changes in the urine values have taken place, repeat values are obtained at six months and then at yearly intervals [63]. If urinary abnormalities persist, additional therapy is required and 24-hour urine studies should be repeated. (See "Patient education: Collection of a 24-hour urine specimen (Beyond the Basics)".)

It is important to emphasize that it is urinary supersaturation that must be reduced, not simply the concentration of a particular reactant (such as calcium). Supersaturation can be calculated from the 24-hour urine collection when performed in an experienced laboratory. Although the supersaturation is not perfectly predictive, it can be used as a guide to monitor the overall impact of the interventions. The risk decreases as the supersaturation decreases [64]. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on '24-hour urine collections'.)

Imaging — Another component of monitoring is periodic imaging to detect new stone formation or growth of existing stones. This is discussed in more detail elsewhere. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on 'Monitoring for new stones'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney stones".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Kidney stones in adults (The Basics)")

Beyond the Basics topic (see "Patient education: Kidney stones in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

General principles – In adults with established kidney stone disease (nephrolithiasis), the goal of preventive therapy is to prevent the future recurrence of kidney stones as well as to prevent growth of existing kidney stones. Preventive therapy generally consists of lifestyle changes (eg, increased fluid intake, dietary modification, weight loss), drug therapy, or a combination of these. While certain preventive measures are applicable to all patients with kidney stones, other measures are specific to certain stone types and should not be considered generalizable to all stone types. (See 'General principles' above.)

Preventive measures for all stone types – Certain preventive measures are applicable to all patients with kidney stones, independent of their stone type or individual risk:

Fluid intake – For all patients with kidney stones, we suggest sufficient fluid intake to consistently produce at least 2 liters of urine per day (Grade 2C). (See 'Fluid intake' above.)

Sodium intake – For all patients with kidney stones, we suggest limiting dietary sodium intake to below 100 mEq (2300 mg) per day (Grade 2C). (See 'Limit sodium intake' above.)

Fruit and vegetable intake – For all patients with kidney stones, we suggest increasing dietary fruit and vegetable intake (Grade 2C). (See 'Increase fruit and vegetable intake' above.)

Weight loss – Weight control may be helpful in preventing stone recurrence; however, there are no clinical trials that have shown that weight loss reduces the risk of recurrent stones. (See 'Weight loss' above.)

Preventive measures for calcium oxalate or calcium phosphate stones – Prevention of recurrent calcium oxalate stones is aimed at decreasing the concentrations of the lithogenic factors (calcium and oxalate) and at increasing the concentrations of inhibitors of stone formation, such as citrate. Achieving these goals may require an increase in fluid intake, dietary modification, and the administration of appropriate medications. Specific recommendations should be based upon 24-hour urine collection results, which should be performed before dietary modification or drug therapy is attempted. In addition, any medical conditions that are associated with calcium stones (eg, primary hyperparathyroidism) should be addressed as appropriate.

Calcium intake – For all patients with calcium oxalate stones, we suggest against a low-calcium diet (Grade 2C). We generally encourage patients to consume several servings of dairy or other calcium-rich foods to reach 800 to 1000 mg/day. Calcium supplements should not be routinely used to achieve adequate dietary calcium intake, as they do not appear to be effective in preventing recurrent stones and may even slightly increase risk. (See 'Maintain adequate calcium intake' above.)

Protein intake – For all patients with calcium oxalate stones, we suggest reducing nondairy animal protein intake (Grade 2C). (See 'Reduce nondairy animal protein intake' above.)

Oxalate intake – For all patients with calcium oxalate stones, we suggest limiting intake of high oxalate foods and supplemental vitamin C (Grade 2C). However, excessive restriction of oxalate is not likely to be helpful; patients should continue to consume a wide variety of fruits and vegetables while avoiding those very high in oxalate. (See 'Limit oxalate intake' above.)

Sucrose and fructose intake – For all patients with calcium oxalate stones, we suggest limiting intake of sucrose and fructose (Grade 2C). (See 'Limit sucrose and fructose intake' above.)

High urine calcium – For patients with recurrent calcium oxalate stones who have higher than desired urine calcium, we suggest treatment with a thiazide diuretic to lower urinary calcium excretion (Grade 2C). (See 'High urine calcium' above.)

Low urine citrate – For patients with recurrent calcium oxalate stones who have low urine citrate, we suggest potassium citrate or potassium bicarbonate therapy to increase urinary citrate excretion (Grade 2C). (See 'Low urine citrate' above.)

High urine oxalate – Treatment in individuals with enteric hyperoxaluria is directed toward diminishing intestinal oxalate absorption. The initial regimen consists of oral calcium carbonate or citrate (1 to 4 g/day) with meals to bind oxalate in the intestinal lumen. Treatment in individuals with primary hyperoxaluria is directed at reducing endogenous oxalate production, which is increased in patients with primary hyperoxaluria. (See 'High urine oxalate' above.)

High urine uric acid – For patients with recurrent calcium oxalate stones who do not respond to dietary modification and other drug therapies and who have high urine uric acid, we suggest treatment with allopurinol (Grade 2B). We typically initiate allopurinol at 300 mg/day, given in two divided doses to improve tolerability. (See 'High urine uric acid' above.)

Preventive measures for other stone types – In general, patients with calcium phosphate stones have the same risk factors as those with calcium oxalate stones (except for hyperoxaluria and higher urine pH); as a result, therapy for recurrent stone formation is similar in most cases. In addition to general preventive measures, patients with uric acid, cystine, or struvite stones may require additional specific preventive measures. For a patient with recurrent stone disease (but the type of stone is unknown), it is reasonable to assume that the stone is calcium oxalate or calcium phosphate. (See 'Calcium phosphate stones' above and 'Uric acid stones' above and 'Cystine stones' above and 'Struvite stones' above and 'Stone composition not known' above.)

Monitoring – The 24-hour urine is an essential component of the initial evaluation and guides recommendations for prevention for all stone types. The response to dietary or drug therapy is monitored by repeat 24-hour urine collections for calcium oxalate and calcium phosphate stones; this may also be done more selectively for patients with uric acid, cystine, or struvite stones. Another component of monitoring is periodic imaging to detect new stone formation or growth of existing stones. (See 'Metabolic surveillance' above and 'Imaging' above.)

  1. Qaseem A, Dallas P, Forciea MA, et al. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2014; 161:659.
  2. Borghi L, Meschi T, Amato F, et al. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. J Urol 1996; 155:839.
  3. Strauss AL, Coe FL, Deutsch L, Parks JH. Factors that predict relapse of calcium nephrolithiasis during treatment: a prospective study. Am J Med 1982; 72:17.
  4. Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 2002; 346:77.
  5. Muldowney FP, Freaney R, Moloney MF. Importance of dietary sodium in the hypercalciuria syndrome. Kidney Int 1982; 22:292.
  6. Eisner BH, Eisenberg ML, Stoller ML. Impact of urine sodium on urine risk factors for calcium oxalate nephrolithiasis. J Urol 2009; 182:2330.
  7. Meschi T, Maggiore U, Fiaccadori E, et al. The effect of fruits and vegetables on urinary stone risk factors. Kidney Int 2004; 66:2402.
  8. Ferraro PM, Mandel EI, Curhan GC, et al. Dietary Protein and Potassium, Diet-Dependent Net Acid Load, and Risk of Incident Kidney Stones. Clin J Am Soc Nephrol 2016; 11:1834.
  9. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA 2005; 293:455.
  10. Taylor EN, Curhan GC. Diet and fluid prescription in stone disease. Kidney Int 2006; 70:835.
  11. Borin JF, Knight J, Holmes RP, et al. Plant-Based Milk Alternatives and Risk Factors for Kidney Stones and Chronic Kidney Disease. J Ren Nutr 2022; 32:363.
  12. Curhan GC, Willett WC, Speizer FE, et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 1997; 126:497.
  13. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354:669.
  14. Bataille P, Achard JM, Fournier A, et al. Diet, vitamin D and vertebral mineral density in hypercalciuric calcium stone formers. Kidney Int 1991; 39:1193.
  15. Asplin JR, Donahue S, Kinder J, Coe FL. Urine calcium excretion predicts bone loss in idiopathic hypercalciuria. Kidney Int 2006; 70:1463.
  16. Breslau NA, Brinkley L, Hill KD, Pak CY. Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab 1988; 66:140.
  17. Hiatt RA, Ettinger B, Caan B, et al. Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones. Am J Epidemiol 1996; 144:25.
  18. Taylor EN, Curhan GC. Oxalate intake and the risk for nephrolithiasis. J Am Soc Nephrol 2007; 18:2198.
  19. Massey LK, Liebman M, Kynast-Gales SA. Ascorbate increases human oxaluria and kidney stone risk. J Nutr 2005; 135:1673.
  20. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003; 170:397.
  21. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004; 15:3225.
  22. Lemann J Jr, Piering WF, Lennon EJ. Possible role of carbohydrate-induced calciuria in calcium oxalate kidney-stone formation. N Engl J Med 1969; 280:232.
  23. Taylor EN, Curhan GC. Fructose consumption and the risk of kidney stones. Kidney Int 2008; 73:207.
  24. Alon U, Costanzo LS, Chan JC. Additive hypocalciuric effects of amiloride and hydrochlorothiazide in patients treated with calcitriol. Miner Electrolyte Metab 1984; 10:379.
  25. Pak CY, Peterson R, Sakhaee K, et al. Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis. Am J Med 1985; 79:284.
  26. Nijenhuis T, Hoenderop JG, Loffing J, et al. Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int 2003; 64:555.
  27. Nijenhuis T, Vallon V, van der Kemp AW, et al. Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest 2005; 115:1651.
  28. Coe FL, Parks JH, Asplin JR. The pathogenesis and treatment of kidney stones. N Engl J Med 1992; 327:1141.
  29. Ettinger B, Citron JT, Livermore B, Dolman LI. Chlorthalidone reduces calcium oxalate calculous recurrence but magnesium hydroxide does not. J Urol 1988; 139:679.
  30. Laerum E, Larsen S. Thiazide prophylaxis of urolithiasis. A double-blind study in general practice. Acta Med Scand 1984; 215:383.
  31. Escribano J, Balaguer A, Pagone F, et al. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane Database Syst Rev 2009; :CD004754.
  32. Fink HA, Wilt TJ, Eidman KE, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med 2013; 158:535.
  33. Lemann J Jr, Gray RW, Pleuss JA. Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men. Kidney Int 1989; 35:688.
  34. Sakhaee K, Nicar M, Hill K, Pak CY. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts. Kidney Int 1983; 24:348.
  35. Preminger GM, Sakhaee K, Pak CY. Alkali action on the urinary crystallization of calcium salts: contrasting responses to sodium citrate and potassium citrate. J Urol 1988; 139:240.
  36. Sakhaee K, Alpern R, Jacobson HR, Pak CY. Contrasting effects of various potassium salts on renal citrate excretion. J Clin Endocrinol Metab 1991; 72:396.
  37. Barcelo P, Wuhl O, Servitge E, et al. Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol 1993; 150:1761.
  38. Wabner CL, Pak CY. Effect of orange juice consumption on urinary stone risk factors. J Urol 1993; 149:1405.
  39. Seltzer MA, Low RK, McDonald M, et al. Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. J Urol 1996; 156:907.
  40. Penniston KL, Steele TH, Nakada SY. Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology 2007; 70:856.
  41. Eisner BH, Asplin JR, Goldfarb DS, et al. Citrate, malate and alkali content in commonly consumed diet sodas: implications for nephrolithiasis treatment. J Urol 2010; 183:2419.
  42. Sumorok NT, Asplin JR, Eisner BH, et al. Effect of diet orange soda on urinary lithogenicity. Urol Res 2012; 40:237.
  43. Gettman MT, Ogan K, Brinkley LJ, et al. Effect of cranberry juice consumption on urinary stone risk factors. J Urol 2005; 174:590.
  44. Hamm LL. Renal handling of citrate. Kidney Int 1990; 38:728.
  45. Melnick JZ, Srere PA, Elshourbagy NA, et al. Adenosine triphosphate citrate lyase mediates hypocitraturia in rats. J Clin Invest 1996; 98:2381.
  46. Sakhaee K, Alpern R, Poindexter J, Pak CY. Citraturic response to oral citric acid load. J Urol 1992; 147:975.
  47. Levi M, McDonald LA, Preisig PA, Alpern RJ. Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter. Am J Physiol 1991; 261:F767.
  48. Witting C, Langman CB, Assimos D, et al. Pathophysiology and Treatment of Enteric Hyperoxaluria. Clin J Am Soc Nephrol 2021; 16:487.
  49. Lieske JC, Goldfarb DS, De Simone C, Regnier C. Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int 2005; 68:1244.
  50. Hoppe B, Beck B, Gatter N, et al. Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1. Kidney Int 2006; 70:1305.
  51. Goldfarb DS, Modersitzki F, Asplin JR. A randomized, controlled trial of lactic acid bacteria for idiopathic hyperoxaluria. Clin J Am Soc Nephrol 2007; 2:745.
  52. Ettinger B, Tang A, Citron JT, et al. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med 1986; 315:1386.
  53. Ettinger B. Does hyperuricosuria play a role in calcium oxalate lithiasis? J Urol 1989; 141:738.
  54. Curhan GC, Taylor EN. 24-h uric acid excretion and the risk of kidney stones. Kidney Int 2008; 73:489.
  55. Favus MJ, Coe FL. The effects of allopurinol treatment on stone formation on hyperuricosuric calcium oxalate stone-formers. Scand J Urol Nephrol Suppl 1980; 53:265.
  56. Coe FL. Treated and untreated recurrent calcium nephrolithiasis in patients with idiopathic hypercalciuria, hyperuricosuria, or no metabolic disorder. Ann Intern Med 1977; 87:404.
  57. Pak CY, Peterson R. Successful treatment of hyperuricosuric calcium oxalate nephrolithiasis with potassium citrate. Arch Intern Med 1986; 146:863.
  58. Parks JH, Coe FL. A urinary calcium-citrate index for the evaluation of nephrolithiasis. Kidney Int 1986; 30:85.
  59. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 2001; 59:2290.
  60. Gault MH, Chafe LL, Morgan JM, et al. Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones. Medicine (Baltimore) 1991; 70:345.
  61. Laube N, Pullmann M, Hergarten S, Hesse A. Influence of urinary stones on the composition of a 24-hour urine sample. Clin Chem 2003; 49:281.
  62. Laube N, Pullmann M, Hergarten S, et al. The alteration of urine composition due to stone material present in the urinary tract. Eur Urol 2003; 44:595.
  63. Parks JH, Asplin JR, Coe FL. Patient adherence to long-term medical treatment of kidney stones. J Urol 2001; 166:2057.
  64. Prochaska M, Taylor E, Ferraro PM, Curhan G. Relative Supersaturation of 24-Hour Urine and Likelihood of Kidney Stones. J Urol 2018; 199:1262.
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