Marshall L. Stoller, Maxwell V. Meng-Urinary Stone Disease

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Chapter 15 / Diet and Urolithiasis 287

mg/d (13). The antibacterial effects of cranberry juice ingestion has been debated (14);

however, dietary cranberry juice lowers urinary pH, increases urinary oxalate, and

increases the urinary saturation of uric acid (15). In contrast, ingestion of blackcurrant

juice increases urinary pH, increases urinary citrate, and could be useful in metaphylaxis

of uric acid stones (15).

The consumption of soft drinks and oxalate-containing sodas has long been associated

with stone formation. Nevertheless, controlled studies have been unable to show a sig-

nificant increased risk with cola consumption (10). Many sodas contain caffeine and

induce diuresis from both fluid ingestion and an antidiuretic effect. Skim and whole milk

both have been shown to reduce stone formation risk likely secondary to the binding of

intestinal oxalate.

In summary, the intake of nearly all beverages is useful in reducing the risk of recur-

rent kidney stones. Fluid consumption should be encouraged in all patients with uroli-

thiasis. Any type of beverage is acceptable in moderation, however water is probably the

preferred fluid given its availability and lack of stone enhancing solutes.

PROTEIN

A diet high in protein is associated with an increased risk of urinary stone formation.

Epidemiological studies relate a high socioeconomic status with stone formation attrib-

utable to diets high in protein (16). Curhan et al., in a prospective study of male healthcare

workers, reported a 1.33 relative risk of stone formation for the group with the highest

animal protein consumption vs individuals on an animal protein free diet (17). Multiple

metabolic changes are induced by dietary protein consumption including hypercalciuria,

hyperuricosuria, hypocitraturia and possibly hyperoxaluria (Fig. 1). These changes in

urinary milieu predispose individuals to the formation of both calcium and uric acid

stones.

The mechanism by which dietary protein increases the risk of calcium stones is

complex and involves changes in calcium metabolism and other ions influencing cal-

cium stone formation. Dietary proteins possess sulfur-containing amino acids that, on

oxidation, yield sulfate. Sulfate represents an acid load and promotes a state of metabolic

acidosis. The presence of sulfate and metabolic acidosis promotes hypercalciuria by

increasing calcium resorption from bone and decreasing tubular calcium resorption

caused by binding of urinary calcium with sulfate. This increase in filtered calcium,

Fig. 1. Effects of dietary protein.

288 Johnston and Low

coupled with decrease in tubular resorption, account for the increase in urinary calcium.

In normal subjects, the addition of 75 g of protein raises urinary calcium excretion

approx 100 mg/d (18). The metabolic acidosis caused by protein consumption also

decreases urinary citrate. Lastly, hepatic metabolism of sulfur-containing amino acids

produces uric acid. The resultant increase in urinary uric acid excretion can also increase

the risk of calcium oxalate stone formation through heterogeneous nucleation. An

increase in urinary oxalate following high dietary protein ingestion has been demon-

strated in adult females but not in adult males (19). The explanation for an increase in

urinary oxalate may be owing to an increase in production of glycolate, a precursor to

oxalate. In summary, dietary protein adversely influences multiple urinary solutes

important to calcium oxalate stone formation. Consumption of large amounts of dietary

protein should be avoided in all patients with a history of calcium nephrolithiasis.

Dietary protein ingestion not only increases the risk of calcium stones but also uric

acid stones. Protein consumption is associated with both hyperuricosuria and urinary

acidification, factors known to promote uric acid stone formation. Dietary protein is a

source of amino acids, which on hepatic metabolism, increase endogenous production

of uric acid. In addition, the previously described metabolic acidosis resulting from

protein ingestion promotes urinary acidification. Hyperuricosuria and an acidic urinary

environment are two important factors adversely influencing the risk of uric acid stone

formation. Protein restriction is beneficial in those with a history of uric acid stones and

hyperuricosuric calcium nephrolithiasis, often attributable to dietary indulgence of ani-

mal protein.

The type of dietary protein may influence stone risk. The highest risk is associated

with a diet high in animal protein, represented primarily by meats. Breslau et al. exam-

ined the urinary effects of three different types of dietary protein (20). Subjects were

evaluated after the ingestion of diets containing animal protein, soy protein, and a

combination of soy and egg protein. Calcium and uric acid excretion were highest and

urinary citrate lowest after the ingestion of the animal protein diet. This increased risk

associated with animal protein has been attributed to meats containing the highest

amounts of the sulfur rich amino acids: cystine and methionine.

CARBOHYDRATES

There is little evidence suggesting dietary carbohydrates significantly affect one’s

risk for urolithiasis. Carbohydrate consumption is similar in stone formers compared to

controls (21,22). In addition, patients on a prolonged high carbohydrate diet have not

been found to have an increased incidence of urolithiasis (23). Ingestion of carbohy-

drates has been associated with increased urinary calcium and oxalate. Dietary car-

bohydrates increase intestinal absorption and decrease renal tubular resorption of

calcium (24–27). An increase in urinary oxalate has been demonstrated in control

subjects following a glucose load, probably caused by an increase in endogenous

hepatic metabolism (26,28). The available literature suggests that although dietary

carbohydrates influence key urinary substrates, they do not definitively increase one’s

risk of urolithiasis.

FAT

The effect of dietary fat intake on the risk for urolithiasis is unclear. Most studies

demonstrate a similar dietary fat intake between stone formers and controls (17,21,29).

Chapter 15 / Diet and Urolithiasis 289

The focus on dietary fat and stone risk has centered on eicosapentanoic acid, an inhibitor

of arachidonic acid metabolism. Fish oil is high in eicosapentaenoic acid and a dietary

staple of Greenland Eskimos, who have a very low incidence of urinary stones (30).

Studies of stone formers who supplement their diet with fish oil have demonstrated a

reduction in both urinary calcium and oxalate (31,32). Additional clinical studies are

needed to verify the apparent benefit of fish oil in reducing the risk of urolithiasis.

CALCIUM

It is important to recognize that many urinary substrates influence calcium stone

formation including calcium, oxalate, citrate, sodium, and uric acid. The most common

identifiable abnormality in those with calcium stones is hypercalciuria related to dietary

hyperabsorption (33,34). It would seem logical that all patients with calcium stones

would benefit from limiting their dietary calcium intake. There is a linear relationship

between dietary calcium intake and urinary calcium (35,36). However, dietary calcium

restriction may result in higher levels of urinary oxalate, believed to be caused by a

decreased oxalate binding with calcium in the intestine (37). In addition, two cohort

studies by Curhan et al. suggest a protective rather than detrimental effect of a high

calcium intake on stone formation risk (17,29). These studies also found that supplemen-

tal calcium decreased, rather than increased, the risk of stone formation; this difference

was only statistically significant in women.

Recently, Borghi et al. published the only long-term study evaluating stone formation

risk associated with dietary calcium intake (38). They evaluated 120 men with unclas-

sified hypercalciuria and a history of calcium oxalate nephrolithiasis. Subjects were

assigned a specific diet for a period of at least 5 yrs. Patients were randomized to either

a low calcium diet (400 mg/d) or a normal calcium diet (1200 mg/d) with restricted

sodium (2900 mg/d) and animal protein (52 g/d). Both groups were instructed to limit

their oxalate intake and encouraged to drink fluids. A diet restricted in animal protein and

salt was chosen because both of these substances are associated with increased urinary

calcium; combining this diet with normal dietary calcium intake may minimize the risk

of hyperoxaluria. Patients were followed radiographically for development of stone

recurrences and metabolically with annual quantitative urinary chemistries.

At 5 yrs, the relative risk of forming recurrent stones was higher in the low dietary

calcium group vs the group on a normal calcium, restricted protein and sodium diet.

Twenty-three of 60 men on the low calcium diet vs only 12 of the 60 men on the normal

calcium diet developed stone recurrences. The relative risk of stone formation for those

patients on the normal calcium, low protein and sodium diet was 0.49 compared to the

men on the low calcium diet. Urinary chemistries documented lower urinary calcium

levels in both groups; however, a lower calcium oxalate product and saturation were

found in those patients on the normal calcium, low sodium and protein diet. This was

caused by urinary oxalate levels, which rose in the low calcium diet and fell in the normal

calcium, protein and sodium restricted diet. These results suggest that patients with

hypercalciuria and calcium oxalate stones benefit from a diet that allows a moderate

intake of dietary calcium but limits dietary protein and sodium. This study was per-

formed with men only and it would be beneficial if similarly validated with women. In

addition, some forms of hypercalciuria, such as resorptive and renal hypercalciuria,

require surgical or pharmacologic intervention to prevent stone recurrences; it is unclear

how many of these patients were classified in this way.

290 Johnston and Low

OXALATE

Calcium oxalate stones are the most common urinary calculi. Many patients with

calcium oxalate stones assume that lowering dietary oxalate consumption will curb

future stone formation. Literature supporting this practice is lacking. The dietary oxalate

intake of stone formers vs controls has been found to be similar (22). Urinary oxalate

originates from two sources, endogenous production from hepatic metabolism and

dietary oxalate resulting from intestinal absorption. Until recently, the endogenous

oxalate production from hepatic metabolism was thought to account for the majority of

urinary oxalate with dietary oxalate contributing only 10–15% (39,40).

Recent work by Holmes and Assimos suggests a much higher contribution of dietary

oxalate to urinary oxalate (41). They found a nonlinear relationship between dietary

oxalate intake and absorption with a 45% mean contribution of diet to urinary oxalate.

In addition, marked individual variance in absorption was observed ranging from 10–

72% (42). Much of the difficulty in determining the influence of dietary oxalate on

urinary oxalate relates to lack of information on oxalate content of dietary foodstuffs and

inaccurate methods of oxalate quantification. Previous methods used to quantify oxalate

content relied on indirect enzymatic and calorimetric assays, which underestimate

oxalate content. Evidence also suggests there may be a genetic component, which may

explain the variability among individuals (43).

The main dietary sources of oxalate are green leafy vegetables, chocolate, and tea. In

general spinach and rhubarb have abundant oxalate, however the actual content may

vary with source, location, brand, or even growth conditions (42). The oxalate contained

within tea can vary with type and producer (44,45). In addition to these variables, food

processing and preparation influence oxalate bioavailability (42). Intestinal oxalate

absorption is passive and affected by binding with intestinal cations, such as calcium and

magnesium. Intestinal oxalate complexes with calcium and magnesium and limits the

amount available for absorption. Patients with fat malabsorption syndromes are at high-

est risk for developing hyperoxaluria. Intestinal transit time and the presence of oxalate-

degrading bacteria may also influence oxalate availability. Oxalobacter formigenes is a

common colonic bacterium capable of degrading intestinal oxalate. Typically, 70% of

adults are colonized with the bacterium (46). Absence of intestinal O. formigenes has

been linked with hyperoxaluria and an increase in severity of stone disease (47,48).

Although the influence of dietary oxalate on urinary oxalate remains controversial,

the risk of hyperoxaluria on calcium oxalate urinary stone formation is well documented.

Most would agree that avoidance of foods that are high in oxalate is beneficial in those

with a history of calcium oxalate stone disease.

SODIUM

Sodium is an important dietary element influencing urolithiasis risk. An increase in

dietary sodium intake has been associated with hypercalciuria, hypocitraturia, and cysti-

nuria (Fig. 2). As a result, dietary sodium should be restricted in those patients at risk for

calcium and cystine stones.

Because of similar renal tubular handling of sodium and calcium, dietary sodium and

natriuresis are associated with calciuria (49). A 100 mmol increase in dietary sodium

intake increases urinary calcium an average of 25 mg/d (50). In addition, hypercalciuric

patients may have an increased sensitivity to the calciuric effects of dietary sodium (51).

Although the sodium intake of stone formers has been found to be similar compared with

Chapter 15 / Diet and Urolithiasis 291

controls (21,17), dietary sodium restriction in hypercalciuric stone formers has been

shown to reduce urinary calcium (52,53). For these reasons, dietary sodium restriction

should be recommended to all hypercalciuric patients.

In addition to promoting hypercalciuria, dietary sodium intake influences calcium

stone formation through promotion of epitaxial calcium oxalate crystal growth and

reduction of urinary stone inhibitors. Natriuresis increases urinary supersaturation of

monosodium urate and heterogeneous nucleation of calcium oxalate (54). Dietary intake

of sodium also lowers urinary citrate levels (55). For all the above reasons, dietary intake

of sodium should be restricted in patients with a history of calcium stone disease. Patients

should be instructed to limit their intake of sodium to less than 200 mEq/d (11 g/d) (56).

Dietary sodium restriction is beneficial in those with calcium stones, and in cystinuric

patients. Dietary sodium intake increases dibasic amino acid excretion including urinary

cystine. Jaeger et al. demonstrated that a reduction of 150 mEq (8.8 g) in dietary sodium

chloride reduced urinary cystine by 156 mg/d (57). The cystinuric effect of sodium also

explains why potassium citrate preparations are preferred over sodium bicarbonate as an

alkalinizing agent for the treatment of cystinuria. Potassium citrate preparations lack the

sodium load and thereby minimize urinary cystine while still providing urinary alkalin-

ization.

VITAMINS AND SUPPLEMENTS

Nutritional supplementation is promoted by our health conscious society and aging

population concerned about senescence. Physicians must be aware of the potential risks

of vitamin and nutritional supplementation on stone formation risk. Much of the diffi-

culty in determining the risks of nutritional and herbal supplements is related to our lack

of formal education and federal regulation of commercially available products.

Fig. 2. Effects of salt on urinary constituents.

292 Johnston and Low

Much has been written about the potential risk of vitamin C intake. Dietary ascorbic

acid is metabolized in the liver to form oxalate, which is then excreted in the urine. The

recommended daily dose of vitamin C is 60 mg/d. Linus Pauling is responsible for

promoting the ingestion of supraphysiologic quantities of vitamin C to maintain health.

An increase in urinary oxalate has been shown in both stone formers and normal controls

after the ingestion of 1 g of ascorbic acid per day (58). Other studies have found either

a similar or decreased risk of stones in patients who take supplemental vitamin C (59,60).

In summary, vitamin C ingestion is associated with increasing urinary oxalate, however

if taken in moderate quantities (500 mg/d), its use probably does not significantly influ-

ence one’s risk for stone formation.

Nutritional supplementation to enhance muscle mass is in vogue predominantly in

athletes and young men. Unfortunately, many of these supplements contain large amounts

of protein. As discussed, dietary supplementation with many of these compounds can be

associated with a significant increased risk of stone formation. Protein supplementation

can be associated with hypercalciuria, hyperuricosuria, hypocitraturia, and possibly

hyperoxaluria. These associated urinary changes increase the risk for both calcium and

uric acid stones. Patients taking such supplements should be warned about the associated

risks of their usage and importance of fluid intake during exertional exercise.

The beneficial effect of cranberry juice in preventing urinary tract infections has been

popularized. Many health food stores offer cranberry extract tablets promoting its use as

being “healthy for the urinary tract”. Cranberries contain oxalate, and unfortunately

these supplements have been associated with the development of calcium oxalate stones

(61). Terris et al. found that use of cranberry extract tablets in five nonstone forming

adults increased their mean urinary oxalate level an average of 43% (61). Cranberry

extract tablets not only contain oxalate but also supplemental vitamin C.

RECOMMENDATIONS FOR SPECIFIC STONE TYPES (TABLE 1)

Calcium Stones

Known risk factors for calcium oxalate stones include: hypercalciuria, hyperoxaluria,

hypocitraturia, hyperuricosuria and unduly concentrated urine. In general, any abnor-

mality identified benefits from dietary restriction or dietary augmentation in the case of

hypocitraturia and dehydration.

Table 1

Recommended Diets

Stone type Recommendations

Calcium • Decrease meat consumption

• Minimize salt intake

• Moderate calcium intake (1200 mg/d)

Uric acid • Decrease meat consumption

• Encourage citrus juices

Cystine • Minimize salt intake

• Limit meat and milk intake

Struvite • Encourage fluid intake

Note: Meat = beef, poultry, or fish.

Chapter 15 / Diet and Urolithiasis 293

The most common identifiable abnormality in patients with calcium stones is

hypercalciuria related to intestinal absorption. Traditionally, extensive metabolic test-

ing has been recommended to classify patients and selectively treat patients accord-

ingly. General dietary measures are recommended to all patients. These measures

include dietary fluid intake to maintain a urine output of at least 2 L/d, avoidance of

dietary overindulgence of sodium and animal protein, and regulated amounts of cal-

cium. Patients with milder forms of absorptive hypercalciuria can be selectively man-

aged with a calcium restricted diet (400–600 mg/d). Borghi et al. demonstrated the

importance of dietary protein and sodium on influencing urinary calcium excretion.

Their findings suggest that dietary restriction of sodium and protein coupled with a

normal amount dietary calcium intake provides greater protection from recurrent cal-

cium stones than a low-calcium diet (38). Dietary calcium restriction may be detrimental

in some patients with hypercalciuria. Dietary calcium restriction in patients with renal

hypercalciuria can exacerbate the secondary hyperparathyroidism associated with a

renal calcium leak. In addition, growing children and postmenopausal women may be

at risk for bony loss from limiting their dietary calcium intake.

In summary, a high fluid intake along with dietary sodium and protein restriction is

beneficial in reducing the risk for recurrent calcium stones. These dietary modifications

in combination with a normal calcium intake have been shown to lower stone recurrence

rates in men with a history of hypercalciuria and calcium stones. Dietary calcium restric-

tion is capable of lowering urinary calcium in all forms of hypercalciuria, excluding

renal hypercalciuria, but must be practiced in conjunction with dietary oxalate restriction

to prevent hyperoxaluria. Specific groups at risk for negative calcium balance such as

growing children, post-menopausal women, or adults with documented bony loss are

best served by adhering to a diet with a normal amount of daily calcium but restricted

amounts of dietary sodium and animal protein. In addition, differentiation between the

various forms of hypercalciuria remains useful in identifying patients who would benefit

from additional pharmacologic intervention.

Uric Acid Stones

Urinary uric acid solubility relates to uric acid concentration and pH. Of these, urinary

pH is most important. Uric acid stones form in patients with unduly acidic urine (pH

<5.5). These include patients with gout, chronic diarrhea states, and those who partici-

pate in frequent exercise. As with all stone patients, patients with a history of uric acid

stones benefit from maintaining a high dietary fluid intake to maintain dilute urine. Fruit

juices, a source of alkali, may be particularly useful owing to their urinary alkalinizing

effects.

Uric acid is the end product of purine metabolism and is derived from three sources:

diet, de novo synthesis, and tissue catabolism. Diet normally contributes approximately

one-half (400 mg) of the uric acid produced by the body each day. The main dietary

source of purines comes from meat, poultry, and fish. Both serum and urinary levels of

uric acid reflect changes in dietary purine intake. Individuals placed on a low-purine diet

exhibit urinary uric acid levels of 300 mg/d as opposed to the normal 600 mg/d (62). As

a result, it is recommended that patients with uric acid stones limit their intake of animal

meat. Complete abstinence of meat is impractical, however reduction of the frequency

and size of meat portions is beneficial. It has been recommended that individuals limit

their dietary protein intake to 1 gm/Kg ideal body weight/d (63).

294 Johnston and Low

The most effective method of preventing uric acid stones is urinary alkalinization.

First time stone formers are encouraged to make necessary dietary changes and to be

monitored closely. Urinary alkalinizing agents should be implemented in those who fail

dietary therapy.

Cystine Stones

The goal in prophylaxis against recurrent urinary cystine stones is to maintain urinary

cystine levels below its solubility limit of 200 mg/L. To this end, hydration to maintain

urinary volumes in excess of 2 L/d is a mainstay of therapy. Hydration alone has been

reported to be successful in preventing stone recurrences in up to two-thirds of cystinuric

patients (64). Continued hydration even throughout the night is recommended to main-

tain urinary cystine concentrations below its solubility limit. Hydration with any type of

beverage is probably useful; however, avoidance of milk due its methionine content and

sodium rich beverages are encouraged. Alkali-containing fruit juices are preferred given

their ability to augment urinary citrate and urinary alkalinizing effects.

Aside from hydration, avoidance of sodium is perhaps the most important dietary

principle for cystinuric patients. Dietary sodium increases urinary cystine excretion by

a poorly understood mechanism. Jaeger et al. demonstrated a reduction of dietary sodium

of 150 mEq/d could reduce urinary cystine by 156 mg/d (57). The main dietary source

of urinary cystine comes from methionine incorporated in protein. Common sources of

dietary methionine are animal meats, milk, eggs, wheat, and peanuts. It is impractical to

require dietary restriction of methionine containing foodstuffs because of poor palatabil-

ity; however, overindulgence of these foodstuffs should be avoided.

Struvite Stones

Dietary manipulation has a limited role in the prevention of stone recurrences in

patients with infection related stone disease. Rendering a patient stone and infection free

is the mainstay of therapy for those with either struvite or carbonate apatite stones. As

in patients with other stone types, hydration is encouraged to maximize ion solubility and

minimize bacterial colonization.

A low phosphorus diet in combination with aluminum hydroxide was popularized by

Shorr and colleagues. Aluminum hydroxide binds intestinal phosphate and, when

coupled with a low phosphorus diet, is capable of lowering urinary phosphorus (65).

Clinical trials in patients treated with this regimen demonstrate not only a reduction of

stone growth but enhanced stone dissolution in some patients (65,66). Unfortunately, the

Shorr regimen is poorly tolerated and dietary compliance difficult. Takeuchi et al. stud-

ied the effects of dietary magnesium and calcium in rats. They demonstrated that a low

magnesium diet resulted in decreased urinary magnesium excretion and decreased stone

growth. Similarly, a high calcium diet led to lower urinary phosphate and magnesium

levels thought to be related to intestinal calcium binding (67).

In theory, urinary acidification would be beneficial in those patients with infection

related stones. Urinary acidification would not only increase urinary solubility of mag-

nesium ammonium phosphate and carbonate apatite but also may increase the antimicro-

bial effects of some penicillins (68,69). Unfortunately, no dietary changes have been

found to be capable of providing sustained urinary acidification. Murphy et al. demon-

strated urinary acidification from ingestion of ascorbic acid when given in combination

with antimicrobials (70). Pharmacologic doses of ammonium sulfate and ammonium

Chapter 15 / Diet and Urolithiasis 295

nitrite are also capable of urinary acidification but are poorly tolerated and available only

in Europe.

CONCLUSION

Diet plays a major role in the majority of patients with urolithiasis. Excluding patients

with infection related stones, all patients benefit from a detailed dietary history, meta-

bolic evaluation, and dietary counseling on stone prevention. Dietary modification can

reduce and often prevent stone recurrences and is adjunctive in patients requiring phar-

macologic therapy. Physician’s awareness of the importance of diet and urolithiasis will

benefit patients who suffer from urinary stone disease (Figs. 3 and 4).

Fig. 4. Impact of major food groups.

Fig. 3. Dietary stone risk.

296 Johnston and Low

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