0022-5347/96/1552-0432%03.00/0 "HE JOURNAL OF UROLOCV Copyright 0 1996 by h E A l C A N URotoclCrrL ASSOCIATION, INC.

Vol. 155.432-440. February 1996 Printed In U S A .

Review Article

THE INFLUENCE OF DIET ON URINARY STONE DISEASE FARHAD PARIVAR, ROGER K. LOW AND MARSHALL L. STOLLER*

From the Department of Urology, University of California School of Medicine, San Francisco, California

ABSTRACT

Purpose: Conflicting data on the role of diet in the pathogenesis of nephrolithiasis prompted us to review the relevant literature regarding the impact of diet on urinary stone disease.

Materials and Methods: MEDLINE searches were obtained from 1966 to date using a variety of key words, including urolithiasis, nephrolithiasis, diet, protein, carbohydrate, fat, calcium, oxalate, phosphate, magnesium, sulfate, citrate, sodium, potassium, fiber, fluids, alcohol and vitamins. References earlier than 1966 were obtained through bibliographies of these MEDLINE searches. The search included in vitro and in vivo animal and human studies.

Results: Of the extracted articles 83% addressed the issue of nephrolithiasis and diet, and were included in this report. All articles were independently reviewed by each of us. The reviews were summarized and compiled according to each dietary component.

Conclusions: Appropriate dietary manipulation may be beneficial in the prevention of recur- rent urolithiasis in only a select group of patients.

KEY WORDS: urinary calculi, urolithiasis, diet

Diet impacts a wide variety of pathological processes. It is common and not unreasonable for stone patients to inquire how diet affects urinary stone formation. While surgery can render a patient stone-free, nonoperative treatment modali- ties are required to help decrease the risk of recurrent nephro- lithiasis. Long-term pharmacological therapy and its poten- tial side effects o h n lead to noncompliance and subsequent failure. Diet influences urinary constituents and pH, which may affect stone nucleation and growth. Random daily diet changes perceived to be beneficial may be detrimental. Di- etary intervention should be based upon objective evidence of a metabolic derangement. Much work has been reported on the influence of individual dietary components on urolithia- sis risk. We reviewed the existing literature to generate dietary guidelines for patients and medical practitioners.

METHODS

MEDLINE searches were obtained from 1966 to date using key words of urolithiasis, nephrolithiasis, diet, protein, car- bohydrate, fat, calcium, oxalate, phosphate, magnesium, sul- fate, citrate, sodium, potassium, fiber, fluids, alcohol and vitamins. Pertinent references earlier than 1966 were ob- tained through bibliographies of these MEDLINE searches. Only English language studies that included in vitro, animal and human studies were reviewed. All articles were indepen- dently reviewed by each of us. Many of these studies suffered from lack of control data. Due to their nature, outpatient clinical studies suffer from lack of control on the subjects and, therefore, may be flawed. Despite some of these inadequa- cies, the body of evidence was adequate to enable us to draw a generalized consensus. "he reviews were summarized and compiled according to each dietary component.

FLUIDS

The association of urolithiasis with chronic dehydration and/or low fluid intake is well recognized.'-" Beach lifeguards

* Reyes+s for reprints.: Department ofurology, U-575, University of Cali omia, San rancisco, California 94143-0738.

and marathon runners have a higher incidence of urinary These observations have led to the notion that a high

fluid intake will decrease the incidence of urinary calculi. Ob- jective supporting evidence is lacking, except for 1 study.6 The mean daily intake ofwater7 and urine output8 have been shown to be identical in renal stone formers and controls.

Chronic dehydration raises urine specific gravity and uric acid saturation, and decreases urinary pH.9 During dehydra- tion urinary urate crystals act as epitaxial templates for growth of calcium containing stones.10 Hydration may decrease the risk of urolithiasis thruugh multiple mechanisms, such as in- creasing crystalline product transit through the nephron and thus decreasing contact time with potential adsorptive sur- faces." Urinary dilution in vitro and in vivo lessens urinary saturation of calcium phosphate, calcium oxalate and monoso- dium urate.12 On the other hand, hydration potentially may be counterproductive by diluting some inhibitors, such as citrate and magnesium. However, the minimum supersaturation re- quired to elicit spontaneous nucleation of calcium oxalate crys- tals is significantly increased during urinary dilution despite dilution of these stone inhibitors. I t has been postulated that this finding may be due to the dilutional effect on unknown urinary stone promoters during hydration.12

There is consensus that an oral fluid intake to produce a t least 2 1. urine output a day is adequate hydration for stone patients.13 In contrast, there is no consensus on the type of recommended fluid. Preferably, oral fluids should be non- dairy and contain minimal oxalate. There is no evidence that "hard" water (nonfiltered, containing calcium and magne- sium salts) is more lithogenic than "soft" water.14 Ljunghall et a1 recommended 250 ml. fluid every 4 hours plus 250 ml. with each meal.15 Hosking et al noted that drinking 2,500 ml. fluids per day prevented new stones or growth of existing stones in 70% of hypercalciuric and 40%' of hyperurico- suric stone formers.16 These results have been attributed to the "stone clinic effect." Home urine specific gravity dipstick tests may be helpful in patients gauging adequate urinary ~ u t p u t . ' ~ Simply recommending a high fluid intake is too

432

INFLUENCE OF DIET ON URINARY STONE DISEASE 433 subjective to achieve the necessary urinary dilution. A min- imum voided volume of2 1. per day is required to achieve the dilutional goals (specific gravity less than l.010).17 Based on these data, 250 ml. nondairy fluid with each meal, between meals, a t bedtime and after arising a t night to void are recommended. Nighttime voiding indicates adequate hydra- tion during previous hours. I t is particularly important to maintain adequate levels of hydration during sleep hours when urine is normally most concentrated.

SODIUM

Most agents that promote natriuresis (for example furo- semide and bumetanide) stimulate calcium excretion due to a similar renal tubular handling of calcium and sodium.18 A high sodium intake normally increases urinary calcium ex- cretion. 19.20 Conversely, a low sodium diet decreases calcium excretion.z(J.21 Hypercalciuric patients are more sensitive to the calciuric effect of a sodium load.Z2 In fact, addition of sodium to the diet of hypercalciuric patients on a low calcium diet accen- tuates the hypercalciuria.23 Therefore, when measuring 24- hour urine calcium it is critical to emphasize the importance of a low sodium diet before and during urine collection.

Sodium intake of stone formers and controls has been simi- lar.24,z5 Urinary sodium excretion, however, is elevated in some stone patients.20,24.26 A high sodium diet not only increases urinary sodium but also urinary calcium and saturation of monosodium urate.Ig Monosodium urate crystals can act as an epitaxial nidus for calcium crystallization.1° High urinary so- dium excretion also increases the relative saturation of calcium phosphate and decreases urinary citrate.lg These factors can all contribute to a higher incidence of stone formation. Al- though we found no controlled studies demonstrating a de- creased incidence of urolithiasis with a sustained low sodium diet, based on the aforementioned laboratory and clinical data one must recommend a low sodium diet to all stone patients, particularly those with hypercalciuria.

CALCIUM

Traditionally oral calcium restriction has been the main dietary recommendation for the prevention of calcium neph- rolithiasis. The linear relationship between calcium con- sumption and calci~ria27.2~ has been interpreted such that increasing calcium consumption increases the risk of neph- rolithiasis and decreasing calcium consumption lowers the risk. However, there is now evidence that a global recommen- dation for dietary calcium restriction may actually increase the risk of nephrolithiasis in some stone formers. Low levels of alimentary calcium cause preferential intestinal absorp- tion of oxalate and hyperoxaluria,2931 which may promote stone formation. Bataille et a1 noted that dietary calcium restriction decreased calciuria in all men but this was only significant in men with dietary dependent absorptive hyper- calciuria (type 2).31 The benefits of decreased calciuria were offset by significant increases in oxaluria and a 10%- in- creased risk of stone formation.31 Calcium restriction also may increase stone risk by stimulating vitamin D3 secretion, which increases bone resorption and promotes c a l ~ i u r i a . : ~ ~ . ~ ~ More recently, an epidemiological study by Curhan et al demonstrated that men on a high calcium diet had a 34% lower incidence of stone occurrence.2s This study was done in normal healthy subjects and the findings may not relate to patients with stones who may have select metabolic abnor- malities. It is mandatory to differentiate hypercalciuria into types 1 (dietary independent), 2 (dietary dependent) and 3 (secondary to a renal phosphate leak).34.35 Dietary calcium restriction decreases urinary calcium in patients with types 1 and 2 hypercalciuria but this level only normalizes in those with type 2 disease. Therefore, only patients with type 2 absorptive hypercalciuria benefit from a low calcium and low oxalate diet. A concomitant decrease in oxalate is needed to

avoid secondary hyperoxaluria. Dietary calcium restriction is unnecessary in patients with other types of hypercalciuria.

The role of calcium supplementation in postmenopausal women with urolithiasis has been debated. In premeno- pausal women calcium supplementation is associated with calciuria only during the first few months of therapy. ARRr this period, suppression of parathormone and 1,25-dihy- droxyvitamin D3 synthesis decreases the fractional calcium absorption from the guP and minimizes the effect of addi- tional oral ~a lc ium."~ Intestinal absorption of calcium is also decreased with age.3H Postmenopausal women with osteopo- rosis have impaired vitamin D and parathormone metabo- lism further blunting the response to oral calcium supple- mentati0n.3~83~ Based on this information, postmenopausal women are unlikely to have an increased risk of urolithiasis with calcium supplementation. There potentially may be an increased risk of nephrolithiasis during the first few months of calcium supplementation. I t would be prudent to recom- mend increasing fluid intake during this period. Postmeno- pausal women with type 2 absorptive hypercalciuria should be treated with a low calcium and low oxalate diet as with others with type 2 disease.

OXALATE

Since the majority of urinary calculi contain oxalate, it seems logical that decreasing urinary oxalate will lessen the risk of stone disease. Approximately 60% of urinary oxalate is derived from endogenous metabolism of glycine, glycolate and hydroxyproline, and 25 to 30% is the end product of dietary ascorbate metabolism. The remaining 10 to 15% comes from dietary 0xalate.~"-42 There are no means of de- creasing endogenous oxalate production. One may assume that decreasing exogenous oxalate intake may lessen urinary oxalate levels. In an unconfirmed report 45% of the patients with hyperoxaluria responded to dietary oxalate restric- tion.43 No difference in the dietary oxalate intake has been found in stone formers versus controls.44 However, many stone formers have hyperoxaluria. Dietary sources of oxalate are listed in Appendix l.45

Normally, only 8 to 12% of dietary oxalate is absorbed.46 Intestinal oxalate absorption is passive, and dependent on concentration and intraluminal calcium content.J7 Intestinal bacteria have been described that degrade oxalate, and their absence or deficiency correlated with increased oxalate ab- sorption.48 Unbound calcium in the gut complexes with ox- alate restricting its absorption. Decreasing dietary calcium increases intestinal absorption of unbound oxalate and sub- sequent h y p e r ~ x a l u r i a . ~ ~ Intestinal oxalate absorption and hyperoxaluria are also pronounced in patients with fat mal- absorption syndromes.49 These patients may benefit from dietary oxalate reduction or from administration of oral cal- cium to decrease absorption of unbound oxalate. Considering the low oxalate content of most common foods and the low percentage of absorption, the impact of oxalate restriction in nonenteric hyperoxaluric stone formers is questionable.

PROTEIN

Epidemiological studies show a correlation between afflu- ence and nephrolithiasis.so.sl The high protein diets of affluent societies have been implicated.52.53 Studies demon- strate an association between a high protein diet and an increased incidence of nephroli~hiasis.44."4 A vegetarian diet devoid of animal protein, despite being high in oxalate, has been associated with a lower risk of urolithiasis.""

The mechanism by which dietary protein increases uroli- thiasis incidence is complex. Stone promoters and inhibitors may have a role. Following a protein load there is a brief period of increased glomerular filtration calciuria,56 0xaluria,5~ uricosuria52, 57 and metabolic acidosis, and de- creased urinary citrate excretion.58 Typically, after a protein

434 INFLUENCE OF DIET ON URINARY STONE DISEASE

load there is a transient increase in endogenous acid produc- tion and excretion in the urine. Although no significant in- crease in ionized serum calcium has been observed after protein loading,% it is postulated that the transient meta- bolic acidosis may increase calcium resorption of bone and increase filtered calcium through the glomerulus. In addi- tion, increased renal acid excretion causes inhibition of cal- cium reabsorption from distal tubular ~ e l l s . ~ ~ . ~ 9 ~ 6 0 The calci- uric effect of dietary protein is greater in stone formers than controls.22

The hypercalciuric effect of protein is pronounced when methionine or other sulfur-containing amino acids are prin- cipal constituents (animal protein).61 A low protein diet is associated with low urinary sulfates." Decreased urinary sulfate may be another contributing factor in the lower inci- dence of urolithiasis observed in vegetarians. I t is postulated that urinary sulfate promotes calciuria by forming a complex with calcium, preventing its absorption by the renal tu- bules.62 Other sources of dietary sulfate (Appendix 1) may have a similar effect on urinary calcium but we found no data supporting dietary sulfate alone as a risk factor for urolithi- asis. These observations indicate that there must be factors other than urinary pH, calcium and sulfate responsible for the higher incidence of nephrolithiasis associated with a high protein diet.

Oxaluria associated with a high protein intake52.56 also contributes to recurrent calcium oxalate stone formation. A decrease in animal protein consumption has been associated with a slight decrease in urinary oxalate.54 The uricosuria associated with a high protein diet increases the risk of calcium oxalate lithiasis.52.56.57 The association of hyperuri- cosuria and calcium lithiasis has been demonstrated by oth- ers.10.63.64 Uric acid crystals adsorb glutamic acid and other organic compounds that in turn promote calcium oxalate crystal growth by epitaxy.10 Tubular reabsorption of citrate increases following a protein load and its associated acido- S ~ S . ~ ~ The resultant decrease in urinary citrate increases the risk of calcium crystallization.

In summary, a high protein diet increases the risk of neph- rolithiasis by increasing urinary levels of stone constituents (calcium, oxalate and uric acid) and facilitating an optimal environment for stone growth (low citrate and low pH). A decrease in dietary protein, in particular, animal protein, is a global recommendation for all stone formers.

CITRATE

Citrate is a naturally occurring urinary stone inhibitor that chelates calcium in solution forming a highly soluble calcium-citrate complex that decreases ionic concentration of calcium and, therefore, the relative saturation of calcium oxalate and calcium phosphate in urine.6"67 Virtually all absorbed intestinal citrate is converted to bicarbonate.68 The resultant metabolic alkalosis leads to increased urinary ci- trate excretion. Renal excretion of citrate is dependent on serum pH. Acidosis decreases urinary citrate (chronic diar- rheal syndromes, renal tubular acidosis, strenuous exercise, hypokalemia, high protein diet and so forth) and alkalosis increases citrate ex~retion.6~.~O The incidence of hypocitratu- ria in calcium stone formers is 15 to 50%.71.72 Some have been unable to demonstrate a difference in citrate excretion in stone formers compared to controls.24

Supplemental potassium citrate (60 to 80 mEq. per day] significantly increases urinary citrate and pH, and decreases the incidence of recurrent stone formation.65.7s76 A single nightly dose of 3.5 to 5 gm. potassium sodium citrate is more beneficial in decreasing stone risk than equivalent divided doses within 24 hours because of increased protection at- tained during sleep when urine is most concentrated.77 These studies use pharmacological sources of citrate supplementa- tion. Large volumes of natural citrate sources would be re-

quired to equal these pharmacological levels. Intake of large volumes of citrate containing fruits and vegetables is likely to result in hyperoxaluria, which may offset the benefits of increased dietary itr rate.^^ The merits of a high natural citrate diet are yet to be investigated.

FIBER

Supplemental dietary fiber is commonly consumed for a variety of ailments. There are conflicting epidemiological studies on the role of fiber intake on urolithiasis risk. Some studies note a lower28 and some a higher fiber intake$4 and others note no difference24 in stone patients compared to controls. These differences could well be due to methodolog- ical differences in calculating fiber consumption. Controlled studies have shown a significant decrease in new stone for- mation in hypercalciuric patients treated with rice bran,79 or wheat and soy bran.80 Bran ingestion has been shown to decrease urinary ~a lc ium,79*8~-~~ and i n c r e a ~ e ~ ~ . ~ ' and not change82383 urinary oxalate and phosphate. The mechanism by which bran exerts these effects is controversial. Postu- lated theories are bran phytic acid binding intestinal calcium and preventing its absorption, mechanical binding of bran to intestinal calcium and increased intestinal transit time.82.m Different sources of bran vary in oxalate content. Wheat bran has the highest oxalate content (240 mg./lOO gm.), followed by rice bran (123 mg./100 gm.), soy bran (17 mg./100 gm.) and corn bran (7 mg./100 gmJ.83 These differences in oxalate content may be responsible for the reported inconsistencies in bran induced oxaluria. The decrease in calciuria, however, has been a consistent finding. Consumption of 10 to 15 gm. bran per day is associated with a decreased incidence of new stone formation in hypercalciuric p a t i e n t ~ . ~ ~ . 8 0 . ~ ~ Whether dietary bran protects normal healthy subjects against uroli- thiasis is unknown.

CARBOHYDRATES

There are no studies demonstrating an association be- tween dietary carbohydrate and nephrolithiasis. Dietary car- bohydrate consumption has been shown to be similar in stone formers and normal control~.2~.~4 High carbohydrate intake is normally followed by transient hypercalciuria caused by an insulin surge, which impairs renal tubular reabsorption of calcium. However, patients on prolonged high carbohydrate diets do not have an increased risk of urolithiasis.85

FAT

There are conflicting studies regarding the role of dietary fat and the risk of nephrolithiasis. Dietary fat consumption by stone formers has been reported to be similar to that of controls by some24 and significantly higher by Greenland Eskimos have a low incidence of nephrolithiasis, which may be attributable to the high fish oil diet, although this finding also has been attributed to the low dietary salt intake.87 Experimental nephrocalcinosis and urinary calcium excretion are decreased in rats fed eicosapentaenoic acid.88 A 10 gm. per day eicosapentaenoic acid diet in hypercalciurk stone patients significantly decreases urinary c a l c i ~ m ~ ~ . ~ ~ and oxalate.88 A simultaneous decrease in urinary magne- sium and citrate (powerful inhibitors of stone formation) was noted in another study and, therefore, eicosapentaenoic acid had limited impact on the overall risk of u ro l i t h i a~ i s .~~ These representative studies indicate a close relationship between dietary fat and urinary solutes but the mechanism remaim poorly understood and the impact on urolithiasis risk unde- fined. Further studies are warranted.

MAGNESIUM

In vitro studies demonstrate that magnesium decreases nucleation and growth of calcium oxalate crystals."0,"' Ani- mal studies show that magnesium deficient rats on a hyper-

INFLUENCE OF DIET ON URINARY STONE DISEASE 435

oxaluric regimen have pronounced intratubular calcium ox- based antacids decrease intestinal phosphate absorption and alate monohydrate crystal depo~ition.~z-~4 Magnesium urinary excretion,112-' 14 which may be useful in the treat- supplementation decreases the rate of stone formation, ment of patients with struvite stones.11". 116

which may be due partly to the increased citrate excretion Dietary phosphate intake of stone formers and controls is associated with high dietary m a g n e ~ i u m . ~ ~ Magnesium sup- similar.24.44 Controlled studies investigating the effect of plementation does not decrease urinary oxalate or calcium phosphate on urolithiasis are lacking. It appears prudent to oxalate relative supersaturation in hyperoxaluric rats.9" increase the dietary intake of phosphate in patients with

A lower urinary magnesium level has been detected in calcium stones and hypercalciuria. I t is unclear whether some stone patient^.*^,^^ However, the magnesium intake of dietary sources of phosphate have the same effect as phar- these 2 groups has not been compared. Other studies have macological sources. Decreasing the oral intake of phosphate noted similar absolute concentrations of urinary magnesium and calcium supplementation may lessen the risk of stone between controls and stone formers, with a decreased mag- formation in patients with struvite stones. The main dietary nesium-to-calcium ratio in stone patients secondary to high sources of phosphate are listed in Appendix 1. urinary calcium level^.^^-^^ In clinical practice, oral admin- istration of magnesium oxide or magnesium citrate increases urinary magnesium and ~ i t r a t e .9~ In contrast to animal studies, it also decreases urinary oxalate, calcium oxalate supersatura- tion"" and the incidence of stone recurrence.1~. 101

~~~~~i~~ decreases the risk of urolithiasis by multiple mechanisms, ~~~~~i~~ binds to intestinal and urinary ox- alate, producing a more soluble magnesium-oxalate complex than calcium oxalate. 102 ~~~~~i~~ lowers the urinary sat- uration of calcium oxalate99 and increases urinary ,.itrate. 103

Magnesium supplementation in deficient patients helps de- the incidence of stone recurrence.95. 100. 1 0 1 It is not

clear whether dietary of magnesium provide ade- quate urinary levels to attain the desired protective effect (Appendix 1).

ALCOHOL

Alcohol ingestion alters several stone forming factors. Al- coholic beverages commonly contain calcium, oxalate and guanosine, which is metabolized to uric acid. Acute elevation of blood alcohol is associated with hypercal~iuria,~17 hyper- m a g n e ~ u r i a ~ ' ~ and hypercortisolism,11" which leads to accel- erated skeletal wasting. 119 Hypercalciuria and hyperphos- phaturia become more prominent with chronic alcohol intake."' Serum calcium and inorganic phosphate do not change.lZ0 There is a linear relationship between alcohol consumption and hyperuricemia or hyperuricosuria.120.121 Urinary PH, which in stone patients is consistently higher than in controls, is transiently lowered after an ethanol load.122 On the other hand, the diuresis associated with al- cohol ingestion may have beneficial effects on preventing stone disease by decreasing the concentration of urinary con- stituents. Alcoholic diuresis is also associated with magnes- una. The incidence of stone disease in chronic alcoholics has not been studied. Fellstrom et al found a higher alcohol con- sumption in 20 stone patients compared to controls.24 However,

in moderation is not a significant risk factor for urolithiasis.

POTASSIUM

~~~~~~i~~ dietary potassium intake is uncOmmOn but tass.um supplements are common~y for patients on potassium wasting diuretics. No difference in potassium intake has been found in stone formers to con- tro1s,24 epidemio~ogical study a lower new stone inti-

urinary calcium excretion with supplementa~ potassium car- bonate and potassium citrate.7". 104 Potassium deprivation

versely the administration of potassium carbonate and PO- tassium chloride decreases urinary calcium'os a t least in the short term. These studies investigated healthy subjects. A large part of dietary potassium is Provided from citrus Prod- ucts, which by virtue of producing an alkali load can increase urinary citrate and P H . ~ ~ The effect of potassium manipuh- tion on stone formers is unknown. We found no ProsPective studies demonstrating a decreased stone risk with Potassium supplementation. Based on the limited available data, it appears that supplemental potassium administration does not have an increased risk for stone disease. POtaSSiUm de- ficiency may potentially increase the risk because of its as- sociated calciuria.

dence was noted in men with high potassium diets,25 which is this fininding W a S not observed by others.'" Based On available consistent with previous studies demonstrating a decreased physiological it that alcohol consumption

increases fasting and 24-hour urinary calcium, and con- ASCORBIC ACID

The popularity of consuming large daily doses of vitamin c ( 10 to 20 times the recommended daily allowance) has led to an interest in its potential role in urolithiasis, Vitamin c is metabolized to oxalate. The extensive data have conflicting results. Much of the controversy arises from the difficulty in assaying urinary oxalate in the presence of ascorbate.123 Additionally, most studies implemented commercially avail- able vitamin C tablets instead of pure ascorbic acid. These tablets frequently contain large amounts of sucrose and tar- taric acid, which are also converted to oxalate. 124.125 Some repods demonstrate elevated urinary oxalate levels with vi- tamin c ingestion,1". 127 while others fail to demonstrate any changes.128. 129 Daily ingestion of 5 to 10 gm. of commercially available ascorbic acid results in a modest urinary oxalate elevation, which is accounted for by the nonenzymatic con- version of ascorbate to oxalate in ufine.130 Stone formers absorb significantly less intestinal a ~ c o r b a t e ' ~ ~ and have an enhanced production of oxalate from ascorbate in the intes- tine compared to controls.1"' Absorption of oxalate in stone formers without enteric hyperoxaluria is normal.". 1 9 3 Intra- venous ascorbate administration is not associated with ox- aluria. 132 In conclusion, evidence for associating vitamin C supplementation with calcium urolithiasis is still lacking.

PHOSPHATE

The influence of dietary phosphate on urolithiasis varies with stone composition (phosphate Containing versus non- phosphate containing calculi). A high phosphate intake in- creases urinary phosphate,106-10H which decreases urinary calcium'"". 1 ' ~ 1''" through a decrease in vitamin D and subse- quent intestinal calcium absorption.'"j This effect forms the basis for treating absorptive and rend hypercalciuric Patients with phosphate supplementation (neutral PhosPhates).lw On the other hand, dietary phosphate restriction increases calcium excretion, which may promote stone formation in patients with nonphosphate containing calcium stones."'

A low urinary phosphate level is desirable in patients with magnesium ammonium phosphate stones (struvite). A high calcium diet decreases urinary phosphate and inhibits stru- vite stone formation in rats."' We found no data to support a similar effect in man. Phosphate binders and aluminum

PY RI DOXl N E

Vitamin B6 is a cofactor in the oxalate metabolic path- way. Vitamin B6 deficiency increases oxalate production and oxaluria in animals134. 135 and humans.13" However, we found no studies correlating vitamin B6 deficiency with an in- creased incidence of stone formation.

436

t

Ston€ Risk

INFLUENCE OF DIET ON URINARY STONE DISEASE

Relative stone risk with different dietary components

APPENDIX 1: MAIN DIETARY SOURCES AND APPROXIMATE RECOMMENDED DAILY ALLOWANCE FOR ADULTS OF ELEMENTS INFLUENTIAL IN DEVELOPMENT OF UROLITHIASIS

Recommended Daily Allowance (mg.) Element

Calcium 1,000 Oxalate Not established Sulfate Not established

Magnesium 300

Potassium Not established

Phosphate 1,000 Vitamin C 60

Pyridoxine 2 Vitamin D 10 Data obtained &om Rodwell, W. S.: Renal disease

Publishing, pp. 866-875, 1989.

Main Dietary Sources

Dairy products, meat, green leafy vegetables Rhubarb, spinach, beet, peanut, chocolate, parsley, celery, tea, coffee Egg, milk, beef, wheat flour, chicken, liver, peanuts, preservatives in canned

meat, vegetables and wines Milk, meat, chicken, peanut, whole grain, cauliflower, corn, spinach, salmon,

canned crab, shrimp, tuna Milk, dates, banana, apricot, prunes, tomato, avacado, kiwi fruit, orange juice,

brussel sprouts, carrots, chicken, lima beans, spinach, yogurt Milk, cheese, meat, fish, poultry, egg, whole grain, nuts, beans Kiwi fruit, orange, pineapple, lemon, strawberry, tomato, broccoli, brussel

Wheat, seeds, corn, meat, liver, kidney Milk

sprouts

, nutrition and clinical care. In: Nutrition and Diet Therapy. Edited by P. Coryell. St. Louis: Mosby College

APPENDIX 2: GUIDELINES FOR DIET MODIFICATION BASED ON STONE CHEMISTRY

Guidelines General Specific:

Calcium oxalate

Diet Modifications Increase fluids, decrease protein and sodium chloride

Increase phosphate, magnesium and citrate if urinary level is low, decrease oxalate and calcium for type 2 absomtive hvDercakiufia -.

Calcium phosphate*

Struvite (magnesium ammonium phosphate)

Uric acid Alkalize urine (pharmacologically)

Increase magnesium and citrate if urinary levei is low”, decrease

Increase magnesium and citrate only if urinary level is low, de- oxalate, calcium and phosphate

crease phosphate

After primary cause has been treated.

VITAMIN D (tubular leak) have a vitamin D mediated increase in intes- tinal calcium absorption.1” In an epidemiological study, a lower incidence of urolithiasis was observed in men with a high intake of vitamin D.Z5 Despite the direct correlation between plasma vitamin D and calcium excretion, we found no conclusive evidence linking excessive dietary vitamin D or exposure to prolonged sunlight with a higher incidence of urolithiasis.

Calcium homeostasis is self-regulated by parathormone, calcitonin and vitamin D. Subjects exposed to prolonged sun- light have increased vitamin D production.’”7 Vitamin D synthesis is normal in absorptive hypercalciurics indicating a vitamin D independent mechanism for hyperabsorption of calcium.13R In contrast, patients with renal hypercalciuria

INFLUENCE OF DIET ON URINARY STONE DISEASE 437 CONCLUSIONS

Urolithiasis is a systemic disease. Successful treatment cannot rely on surgery or medical therapy alone. Structural or morphological factors, and concurrent medical conditions clearly predispose some individuals to stone formation. Ex- cluding these patients, the majority of stone formers in 1 way or another have a disturbance in the uptake, metabolism or excretion of stone constituents, promoters or inhibitors and urinary pH. Whether these derangements are acquired or inherited is unknown. We now have adequate knowledge to alter some of the chain of events leading to stone disease by changing some environmental factors, such as diet. Given the inadequacies of surgical and medical therapy to rid man of renal calculi, dietary manipulation may be useful as adjunc- tive therapy. The influence of dietary factors is summarized in the figure.

Recommended dietary modifications are summarized in Appendix 2. All stone formers should limit protein intake (maximum 1 gm./kg. per day) and sodium intake (100 mEq. per day), and increase urine output to more than 2 1. per day (nondairy, minimal oxalate containing fluids). Low oxalate bran consumption (15 gm. per day) is recommended, al- though the long-term effects on calcium balance are uncer- tain. Dietary sources of magnesium and citrate inadequately alter urinary levels for a significant impact on urinary stone disease. Additionally, with ingestion of high volumes of citrus fruits, oxalate intake is also increased, which may be detri- mental. Pharmacological supplementation of magnesium and citrate has proved beneficial in patients with docu- mented deficiencies. Patients with excessively high oxalate containing diets should decrease the intake, and those with absorptive hypercalciuria type 2 should decrease the oral calcium load. Patients with other types of hypercalciuria need not restrict calcium intake. More than 1 metabolic de- rangement may be responsible for stone formation. Dietary modification to correct 1 risk factor may be detrimental for another. Comprehensive evaluation of a stone patient should include a thorough dietary history.

REFERENCES

1. Pierce, L. W. and Bloom, B.: Observations on urolithiasis among American troops in a desert area. J. Urol., bl: 466, 1945.

2. Blacklock, N. J.: The pattern of urolithiasis in the Royal Navy. In: Proceedings of the Renal Stone Research Symposium. Ed- ited by A. Hodgkinson and B. E. C. Nordin. London: J & A Churchill, pp. 33-47, 1969.

3. Robertson, W. G. and Peacock, M.: Epidemiological factors in the genesis of calcium-containing urinary stones. In: Metabolic Phisico-Chemical Therapeutical Aspects of Urolithiasis. Pro- ceedings of the 2nd International Symposium, Turin, Novem- ber 27-28, 1981. Edited by F. Linari, M. Bruno, B. Fruttero and M. Marangella. Milano: Wichtig Editore srl, pp. 5-20, 1983.

4. Better, 0. S., Melamud, A., Shabtai, M., Berenheim, J. and Chaimowitz, C.: Studies in the pathogenesis of increased inci- dence of nephrolithiasis (N) in lifeguards (LG) in Israel. Clin. bs., 26 1264 1978.

5. Milvy, P., Colt, E. and Thornton, J.: A high incidence of urolithi- asis in male marathon runners. J. Sports Med. Phys. Fitness, 3: 295,1981.

6. Frank, M. and De Vries, A.: Prevention of urolithiasis. Education to adequate fluid intake in a town situated in the Judean Desert Mountains. Arch. Environ. Health, 13 625, 1966.

7. Power, C., Barker, D. J., Nelson, M. and Winter, P. D.: Diet and renal stones: a case-control study. Brit. J. Urol., S& 456,1984.

8. Ljunghall, S. and Waern, A. U.: Urinary electrolytes in renal stone formers and healthy subjects. A population study of 60-year-old men. Scand. J. Urol. Nephrol., Suppl. 41, 11: 55,

Mineral. Electrolyte Metab., 13 251, 1987. 11. Finlayson, B.: Symposium on renal lithiasis. Renal lithiasis in

review. Urol. Clin. N. Amer., 1: 181, 1974. 12. Pak, C. Y., Sakhaee, K, Crowther, C. and Brinkley, L.: Evidence

justifying a high fluid intake in treatment of nephrolithiasis. Ann. Intern. Med., 93 36,1980.

13. Consensus conference. Prevention and treatment of kidney stones. J.A.M.A., 280: 977, 1988.

14. Singh, P. P. and Kiran, R.: Are we overstressing water quality in urinary stone disease? Int. Urol. Nephrol., 25: 29, 1993.

15. Ljunghall, S., Backman, U., Danielson, B. G., Fellstriim, B., Johansson, G. and Wikstriim, B.: Prophylactic treatment of renal calcium stones. Experiences with dietary advice, cellu- lose, phosphate, and thiazides. Scand. J. Urol. Nephrol., suppl., 63: 239, 1980.

16. Hosking, D. H., Erickson, S. B., Van Den Berg, C. J., Wilson, D. M. and Smith, L. H.: The stone clinic effect in patients with idiopathic calcium urolithiasis. J. Urol., 130 1115, 1983.

17. McCormack, M., Dessureault, J. and Guitard, M.: The urine specific gravity dipstick a useful tool to increase fluid intake in stone forming patients. J. Urol., 146: 1475,1991.

18. Agus, Z. S., Goldfarb, S. and Wasserstein, A: Calcium transport in the kidney. Rev. Physiol. Biochem. Pharmacol., 90. 155, 1981.

19. Sakhaee, K, Harvey, J. A, Padalino, P. K, Whitson, P. and Pak, C. Y. C.: The potential role of salt abuse on the risk for kidney stone formation. J. Urol., 1M). 310, 1993.

20. Silver, J., Rubinger, D., Friedlaender, M. M. and Popovtzer, M. M.: Sodium-dependent idiopathic hypercalciuria in renal- stone formers. Lancet, 2 484,1983.

21. Wasserstein, A. G. and Agus, 2. S.: How extensive should the work-up for hypercalciuric patients with nephrolithiasis be: the case for a limited evaluation. In: Controversies in Nephrol- ogy and Hypertension. Edited by R. G. Narins. New York Churchill Livingstone, chapt. 8B, pp. 303328,1984.

22. Wasserstein, A. G., Stolley, P. D., Soper, K A., Goldfarb, S., MaisLin, G. and Agus, Z.: Case-control study of risk factors for idiopathic calcium nephrolithiasis. Mineral. Electrolyte Metab., 13 85, 1987.

23. Muldowney, F. P., Freaney, R. and Moloney, M. F.: Importance of dietary sodium in the hypercalciuria syndrome. Kidney Int., 2 2 292, 1982.

24. Fellstrom, B., Danielson, B. G., Karlstriim, B., Lithell, H., Ljunghall, S. and Vessby, B.: Dietary habits in renal stone patients compared with healthy subjects. Brit. J . Urol., 83: 575, 1989.

25. Curhan, G. C., Willett, W. C., Rimm, E. B. and Stampfer, M. J.: A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. New Engl. J. Med., 328: 833, 1993.

26. Pak, C. Y., Britton, F., Peterson, R., Ward, D., Northcutt, C., Breslau, N. A., McGuire, J., Sakhaee, K, Bush, S., N i w , M., Norman, D. A. and Peters, P.: Ambulatory evaluation of neph- rolithiasis. Classification, clinical presentation and diagnostic criteria. Amer. J. Med., gg: 19, 1980.

27. Bleich, H. L., Moore, M. J., Lemann, J., Jr., Adams, N. D. and Gray, R. W.: Urinary calcium excretion in human beings. New Engl. J. Med., 301: 535, 1979.

28. Robertson, W. G.: Diet and calcium stones. Mineral. Electrolyte Metab., 1 3 228, 1987.

29. Marshall, R. W., Cochran, M. and Hodgkinson, A: Relationships between calcium and oxalic acid intake in the diet and their excretion in the urine of normal and renal-stone-forming sub jects. Clin. Sci., 43: 91, 1972.

30. Barilla, D. E., Notz, C., Kennedy. D. and Pak, C. Y.: Renal oxalate excretion following oral oxalate loads in patients with ileal disease and with renal and absorptive hypercalciurias. Effect of calcium and magnesium. h e r . J. Med., 64: 579, 1978.

31. BatailIe. P., Charraneol, G., Gregoire, I., Daigre, J. L., Coevoet, B., Makdassi, R., Pruna, A, Loquet, P., Sueur, J. P. and Foumier, A: Effect of calcium restriction on renal excretion of oxalate and the probability of stones in the various pathophys- iological groups with calcium stones. J . Urol., 130: 218, 1983.

32. Coe, F. L., Favus, M. J., Crockett, T., Strauss, A. L., Parks, J. H., Porat, A., Gantt, C. L. and Sherwood, L. M.: Effect of low- calcium diet on urine calcium excretion, parathyroid function and serum 1.25(OH)2D3 levels in oatients with idiooathic

abstract, 1977. 9. Borghi, L., Meschi, T., Amato, F., Novarini, A, Romanelli, A. and

Cigala, F.: Hot occupation and nephrolithiasis. J. Urol., 1M): 1757, 1993.

10. Sang. S.: The hyperuricosuric calcium oxalate stone former. ~

438 INFLUENCE OF DIET ON URINARY STONE DISEASE

hypercalciuria and in normal subjects. Amer. J. Med., 7 2 25, 1982.

33. Maierhofer, W. J.. Gray. R. W., Cheung. H. S. and h m a n n , J.. Jr.: Bone resorption stimulated by elevated serum 1,25-(OH12- vitamin D concentrations in healthy men. Kidney Int.. 2 4 555. 1983.

34. Pak. C. Y.. Oata. M.. Lawrence, E. C. and Snyder, W.: The hypercalciurias. Causes. parathyroid functions, and diagnostic criteria. J. Clin. Invest., 54: 387, 1974.

35. Zenvekh, J. E.: Pathogenesis of hypercalciuria. In: Renal Stone Disease: Pathogenesis, Prevention and Treatment. Edited by C. Y. C. Pak. Boston: Martinus Nijhoff Publishers, chapt. 2, pp. 25-46, 1987.

36. Norman, D. A., Fordtran. J. S., Brinkley, L. J., Zenvekh, J. E.. Nicar, M. J.. Strowig. S. M. and Pak, C. Y.: Jejunal and ileal adaptation to alterations in dietary calcium: changes in cal- cium and magnesium absorption and pathogenetic role of parathyroid hormone and 1.25-dihydroxy vitamin D. J . Clin. Invest., 67: 1589, 1981.

37. Sakhaee, K., Baker, S., Zerwekh, J.. Poindexter, J., Garcia-Hemandez, P. A. and Pak, C. Y. C.: Limited risk of kidney stone formation during long-term calcium citrate sup- plementation in nonstone forming subjects. J. Urol., 152 324, 1994.

38. Gallagher, J. C., Riggs, B. L., Eisman, J., Hamstra, A., Amaud, S. B. and Deluca, H. F.: Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteopo- rotic patients: effect of age and dietary calcium. J. Clin. In- vest., 64. 729. 1979.

39. Sakhaee, K., Nicar, M. J., Glass, K., Zerwekh, J. E. and Pak, C. Y.: Reduction in intestinal calcium absorption by hydrochlo- rothiazide in postmenopausal osteoporosis. J. Clin. Endocr. Metab., 5 9 1037, 1984.

40. Hagler, L. and Herman, R. H.: Oxalate metabolism. I. Amer. J. Clin. Nutr., 26: 758, 1973.

41. Williams, H. E.: Oxalic acid: absorption, excretion and metabo- lism. In: Urolithiasis Research. Edited by H. Fleisch, W. G. Robertson, L. H. Smith and W. Vahlensieck. New York: Ple- num Press Co., pp. 181-188, 1976.

42. Menon, M. and Mahle, C. J.: Oxalate metabolism and renal calculi. J. Urol., 127: 148, 1982.

43. Laminski, N. A., Meyers, A. M., Kruger, M., Sonnekus, M. I. and Margolius, L. P.: Hyperoxaluria in patients with recurrent calcium oxalate calculi: dietary and other risk factors. Brit. J. Urol., 68: 454, 1991.

44. Trinchieri, A., Mandressi, A., Luongo, P., Longo, G. and Pisani, E.: The influence of diet on urinary risk factors for stones in healthy subjects and idiopathic renal calcium stone formers. Brit. J. Urol.. 67: 230. 1991.

53. Robertson, W. G. and Peacock, M.: The pattern of urinary ston,, disease in Leeds and in the United l n g d o m in relation t,, animal protein intake during the period 1960-1980. Urol. I n t , , 37: 394, 1982.

54. Marangella. M., Bianco. O., Martini, C., Petrarw,la, M., Vitale. ( 7

and Linari, F.: Effect of animal and vegetable protein intak,, on oxalate excretion in idiopathic calcium stone disease Brit J. Urol., 63: 348, 1989.

55. Robertson, W. G., Peacock, M.. Heyburn, P. J . , Hanes. F. A , Ouimet, D., Rutherford. A. and Sergeant. V. J.: Should recur- rent calcium oxalate stone formers eat less animal protein? I ~ , Urolithiasis: Clinical and Basic Research. Edited hy 1,. I+ Smith, W. G. Robertson and B. Finlayson. New York: Plenun, Press, pp. 359-362, 1980.

the mechanism of protein-induced hypercalciuria in older mC.1, and women. J. Nutr., 110 305, 1980.

57. Coe. F. L.: Calcium-uric acid nephrolithiasis. Arch. Intern. Med ,

138 1090, 1978. 58. Deetjen, P.: The renal handling of citrate. In: Urolithiasis anti

Related Clinical Research. Edited by P. 0. Schwille, L. € 1 Smith, W. G. Robertson and W. Vahlensieck. New York: plrb. num Press, pp. 181-188, 1985.

59. Sutton, R. A,, Wong, N. L. and Dirks, J. H.: Effects of metabolic acidosis and alkalosis on sodium and calcium transport in thL. dog kidney. Kidney Int., 1 5 520, 1979.

60. Lemann, J., Jr., Gray, R. W., Maierhofer, W. J . and CheunK:. H. S.: The importance of renal net acid excretion as a dett.r- minant of fasting urinary calcium excretion. Kidney Int.. 29: 743, 1986.

61. Whiting, S. J. and Draper, H. H.: The role of sulfate in thca calciuria of high protein diets in adult rats. J. Nutr., 110: 212. 1980.

62. Arora, B., Selby, P. L. and Norman, R. W.: The effect of im increased intake of various constituents of a high animal pro- tein diet on the risk of calcium oxalate formation in men. In : Urolithiasis and Related Clinical Research. Edited by P. 0 Schwille, L. H. Smith, W. G. Robertson and W. Vahlensieck. New York: Plenum Press, pp. 85-88, 1985.

63. Pak, C. Y., Waters, 0. and Arnold, L.: Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersatu- ration of urine with respect to monosodium urate. J. Chn. Invest., 59 426, 1977.

64. Sang, S., Hirsch, D., Garti, N. and Goldwasser. B.: An extensinn of the concept of epitaxial growth. J. Crystal Growth, 69: 92, 1984.

65. Preminger, G. M., Sakhaee, K., Skurla, C. and Pak, C. Y. ( ' : Prevention of recurrent calcium stone formation with pot;i.;- sium citrate theraw in patients with distal renal tubultir

56. Schuette, S. A,, Zemel, M. B. and Linkswiler, H. M.: Studies

45. Kasidas, G. P. and Rose, G. A.: Oxalate content of some common foods: determination by an enzymatic method. J. Hum. Nutr., 34: 255. 1980.

46. Tiselius, H. G.: Oxalate and renal stone formation. Scand. J. Urol. Nephrol., suppl., 53: 135, 1980.

47. Binder, H. J.: Intestinal oxalate absorption. Gastroenterology, 67: 441, 1974.

48. Kleinschmidt, K., Mahlmann, A. and Hautmann, R. E.: Intes- tinal oxalate degrading bacteria decrease urinary oxalate in stone formers. J. Urol., part 2, 151: 425A, abstract 791, 1994.

49. Smith, L. H., Hofmann, A. F., Tacker, M. M., Fromm, H. and Thomas, P. J.: Acquired hyperoxaluria, nephrolithiasis and intestinal disease. In: Urinary Calculi: Recent Advances in Etiology, Stone Structure and Treatment. Edited by L. Cifuentes Delatte, A. Rapado and A. Hodgkinson. New York: S. Karger, pp. 31-40, 1973.

50. Andersen, D. A.: Environmental factors in the aetiology of uro- lithiasis. In: Urinary Calculi: Recent Advances in Aetiology, Stone Structure and Treatment. Edited by L. Cifuentes Delatte, A. Rapado and A. Hodgkinson. New York: S. Karger, pp. 130-144, 1973.

51. Robertson, W. G., Peacock, M., Heyburn, P. J. and Hanes, F. A,: Epidemiological risk factors in calcium stone disease. Scand. J. Urol. Nephrol., suppl., 53 15, 1980.

52. Robertson. W. G.. Heybum, P. J., Peacock, M., Hanes, F. A. and Swaminathan, R.: The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract. Clin. Sci., 57: 285, 1979.

acidosis. J. Urol., 1G: 20,' 1985. 66. Pak, C. Y. C., Fuller, C., Sakhaee, K., Preminger, G. M. a n d

Britton, F.: Long-term treatment of calcium nephrolithia.;is with potassium citrate. J. Urol., 134: 11, 1985.

67. Pak, C. Y.: Citrate and renal calculi. Mineral Electrolyte Metali.. 13: 257, 1987.

68. Wainer, L., Resnick, V. A. and Resnick, M. I.: Nutritional aspects of stone disease. In: Renal Stone Disease: Pathogenesis, Pve- vention and Treatment. Edited by C. Y. C. Pak. Boston: Martinus Nijhoff Publishing, chapt. 4, pp. 85-102, 1987.

69. Hodgkinson, A.: Citric acid excretion in normal adults and 111

patients with renal calculus. Clin. Sci., 23: 203, 1962. 70. Lang, F.: Renal handling of oxalate, urate, citrate, phosphate

and sulphate. In: Renal Tract Stone: Metabolic Basis and Clinical Practice. Edited by J. E. A. Wickham and A. Colin Buck. New York: Churchill Livingstone, pp. 183-213, 1990.

71. Menon, M. and Mahle, C. J.: Urinary citrate excretion in pix- tients with renal calculi. J. Urol., 129: 1158, 1983.

72. Nicar, M. J., Skurla, C., Sakhaee, K. and Pak. C. Y.: Low urinat?' citrate excretion in nephrolithiasis. Urology, 21: 8, 1983.

73. Sakhaee, K., Nicar, M., Hill, K. and Pak, C. Y.: Contrasting effects of potassium citrate and sodium citrate therapies 011 urinary chemistries and crystallization of stone-forming salt:. Kidney Int., 24: 348, 1983.

74. Nicar, M. J., Peterson, R. and Pak, C. Y. C.: Use of potassicin1 citrate as potassium supplement during thiazide therap!' of calcium nephrolithiasis. J. Urol., 131: 430. 1984.

75. Pak, C. Y., Skurla, C., Brinkley, L. and Sakhaee. K.: Augmen- tation of renal citrate excretion by oral potassium citrate ad-

439 INFLUENCE OF DIET ON URINARY STONE DISEASE

ministration: time course, dose frequency schedule, and dose- response relationship. J. Clin. Pharm., 24: 19. 1984.

76. Pak. C. Y.. Peterson, R., Sakhaee, K, Fuller, C., Preminger, G. and Fleisch, J.: Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithia- sis. Amer. J. Med., 79 284, 1985.

77. Berg, C., Larsson, L. and Tiselius. H.-G.: The effects of a single evening dose of alkaline citrate on urine composition and calcium stone formation. J. Urol., 148: 979, 1992.

78. Wabner, C. L. and Pak. C. Y. C.: Effect of orange juice consump- tion on urinary stone risk factors. J. Urol., 149: 1405, 1993.

79. Ebisuno. S.. Morimoto, S., Yasukawa, S. and Ohkawa, T.: Re- sults of long-term rice bran treatment on stone recurrence in hypercalciuric patients. Brit. J . Urol., 61: 237, 1991.

80 Schneider, H.J . : Reventing the recurrence of kidney stones with Furnolith bran preparation. In: Umlithiasis. Edited by V. R. Walker, R. A. L. Sutton. E. C. B. Cameron, C. Y. C. Pak und W. G. Robertson. New York: Plenum Press, pp. 871-888,

81. Jahnen. A.. Heynck. H.. Gertz. B.. Classen, A. and Heaee, A: I3ietnry fibre: the effectiveness of a high bran intake in reduc- ing renal calcium excretion. Urol. Res., w): 3, 1992.

8’2 Tizznni. A.. Casetta. G.. Piana. P. andvercelli, D.: Wheat bran in the sclective therapy of absorptive hypercalciuria: a study performed on 18 lithiaaic patients. J. Urol.. 142: 1018, 1989.

83 Kno. P. N.. Jenkins. 1. L.. Robertson. W. G., Peacock. M. and Hlacklock, N. J.: The effect of ‘high fiber biscuits’ on urinary r isk factors for atone formation. In: Urolithiasis and Related Clinical Research. Edited by P. 0. Schwille. L. H. Smith, W. G. Robertson and W. Vahlensieck. New York Plenum Press, pp. 42.5428. 1985.

81 Shah. P. J.. Green. N. A. and Williams. G.: Unprocessed bran and i t s effect on urinary calcium excretion in idiopathic hyper- calciuna. Brit. Med. J.. 281: 426. 1980.

85 Gnrg. A.. Bonanome. A., Grundy. S. M., Unger, R. H., Breslau, N. A. and Pak. C. Y.: E f f i of dietary carbohydrates on metabolism of calcium and other minerals in normal subjects and patients with noninsulindependent diabetes mellitus. J. Clin. Endocr. Metab., 70: 1007, 1990.

86. Grimth. H. M.. OShea, B.. Kevany, J. P. and McCormick, J. S.: A control study of l e t a r y factors in renal stone formation. Brit. J. Urol., 63: 416, 1981.

87 Modlin, M.: Urinary sodium and renal stone. In: Renal Stone Research Symposium. Edited by A. Hodgkinson and B. E. C. Nordin. London: J & A Churchill, pp. 209-220, 1969.

8H Buck. A. C.. Davies. R. L. L. and Hamson, T.: The protective role of eimsapentaenoic acid [EPA] in the pathogenesis of nephro- lithiasis. J. Urol.. lls: 188, 1991.

89 Rothwell, P. J. N.. Green. R.. Blacklock, N. J. and Kavanagh, J. P.: Does fish oil benefit stone formers? J . Urol., IW. 1391, 1993.

90 Li. M. K.. Blacklock, N. J. and Garside, J.: Effeds of magnesium on calcium oxalate crystallization. J. Urol.. 15s: 123, 1985.

91 Kohri. K. Garside. J. and Blacklock, N. J.: The role of magne- sium in calcium oxalate urolithiasis. Brit. J . Urol., 61: 107, 1988.

92 Faragalla. F. F. and Gershoff, S. N.: Interelations among mag- nesium, vitamin B6. sulfur and phosphorus in the formation of kidney stones in the rat. J. Nutr., 81: 60, 1963.

9.3 Borden, T. A. and Lyon, E. S.: The effects of magnesium and pH on experimental calcium oxalate stone dieease. Invest. Uml., 6: 412. 1969.

94 Rushton. H. G . and Spector, M.: Effect of magnesium deficiency on intratubular calcium oxalate formation and crystalluria in hypernxaluric rats. J. Urol.. 127 698. 1982.

9s Su. C . 4 . . Shevock. P. N.. Khan, S. R. and Hackett, R. L.: Effect of magnesium on calcium oxalate urolithiasis. J . Uml., 1- 1092. 1991.

R(i Orropnulos. D. G., Soyannwo, M. A. 0. and McCeown, M. G.: Mngnesium-calcium ratio in urine of patients with renal stnnea. Lancet. 2: 420. 1968.

iw.

48: 357, 1974. 99. Lindberg, J., Harvey, J. and Pak, C. Y. C.: Effect of magnesium

citrate and magnesium oxide on crystallization of calcium salts in urine: changes produced by food-magnesium interac- tion. J. Urol., 143: 248,1990.

LOO. Moore, C. A. and Bunce, G. E.: Fbduction in frequency of renal calculus formation by oral magnesium administration. A pre- liminary report. Invest. Urol., 2: 4, 1964.

101. Johansson, G., Backman, U., Danielson, B. G., Fellstriim, B., Ljunghall, S. and Wikstriim, B.: Biochemical and clinical ef- fects of prophylactic treatment of renal calcium stones with magnesium hydroxide. J . Uml., 124: 770,1980.

102. Danielson, B. G.: Drugs against kidney stones: effects of mag- nesium and alkali. In: Urolithiasis and Related Clinical Re- search. Edited by P. 0. Schwille, L. H. Smith, W. G. Robertson and W. Vahlensieck. New York Plenum Press, pp. 525-631, 1985.

103. Lindberg, J. S.. Zobitz, M. M., Poindexter, J. R. and Pak, C. Y.: Magnesium bioavailability from magnesium citrate and mag- nesium oxide. J. Amer. Coll. Nutr., 9: 48, 1990.

104. Lemann, J., Jr., Gray, R. W. and Pleuss, J. A.: Potassium bicarbonate, but not Bodium bicarbonate, reduces urinary cal- cium excretion and improves calcium balance in healthy men. Kidney Int., S. 688, 1989.

105. Lemann, J.. Jr., Pleuss, J . A., Gray, R. W. and Hoffmann, R. G.: Potassium administration increases and potassium depriva- tion reduces urinary calcium excretion in healthy adults. Kid- ney Int., 3% 973, 1991.

106. Van Den Berg, C. J., Kumar, R., Wilson, D. M., Heath, H., I11 and Smith, L. H.: Orthophosphate therapy decreases urinary calcium excretion and serum 1,25dihydroxyvitamin D concen- trations in idiopathic hypercalciuria. J. Clin. Endocr. Metab., 51: 998, 1980.

107. Portale, A. A, Halloran, B. P., Murphy, M. M. and Moms, R. C., Jr.: Oral intake of phosphorus can determine the serum con- centrations of 1.25-dihydroxyvitamin D by determining its production rate in humans. J. Clin. Invest., 71: 7, 1986.

108. Insogna, K. L., Ellison, A. S., Burtis, W. J., Sartori, L., Lang, R. L. and Broadus, A. E.: Trichlormethiazide and oral phos- phate therapy in patients with absorptive hypercalciuria. J. Urol., 141: 269,1989.

109. Breslau, N. A, Padalino, P., Kok, D. J., Kim, Y. G. and Pak, C. Y. C.: Physiochemical effect of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalci- uria. J . Bone Mineral Res., 10 394. 1995.

110. Roberts, D. H. and Knox, F. G.: Renal phosphate handling and calcium nephrolithiasis: role of dietary phosphate and phos- phate leak. Sem. Nephrol., 10: 24, 1990.

111. Takeuchi, H., Ueda, M., Satoh, M. and Yoshida, 0.: Effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in the urinary tract of rats. UmI. b., 19 305, 1991.

112. Pak, C. Y ., Delea, C. S. and Bartter, F. C.: Successful treatment of recurrent nephrolithiaais (calcium stones) with cellulose phosphate. New Engl. J. Med., aS0: 175, 1974.

113. Shields, H. M.: Rapid fall of serum phosphorus secondary to antacid therapy. Gastroenterology, 76 1137, 1978.

114. Cooke, N., Teitelbaum, S. and Avioli, L. V.: Antacid-induced osteomalacia and nephrolithiasis. Arch. Intern. Med., 138: 1007, 1978.

115. Shorr, E. and Carter, A. C.: Aluminum gels in management of renal phosphatic calculi. J.A.M.A., 144: 1549, 1960.

116. Lavengocd, R. W., Jr. and Marshall, V. F.: The prevention of renal phosphatic calculi in the presence of infection by the Shorr regimen. J . Urol., 108: 368, 1972.

117. Kalbfleisch, J. M., Lindeman, R. D., Ginn, H. E. and Smith, W. 0.: Effects of ethanol administration on urinary excretion of magnesium and other electrolytes in alcoholic and normal subjects. J. Clin. Invest.. 42: 1471, 1963.

118. Jenkins, J. S. and Connolly, J.: Adrenocortical response to ethanol in man. Brit. Med. J., 2: 804. 1968.

119. Nilsson, B. E. and Westlin, N. E.: Changes in bone maas in alcoholics. Clin. Orthop., 90: 229, 1973.

120. Zechner, O., Latal. D., Ptliiger, H. and Scheiber, V.: Nutritional risk factors in urinary stone disease. J . Urol., 1 s 51,1981.

121. Grunst, J., Dietze, G. and Wicklmayr, M.: Effect of ethanol on uric acid production of human liver. Nutr. Metab., suppl., 81: 138, 1977.

9; Takasaki. E.: Themagnesium:calcium ratio in the concentrated urines of patients with calcium oxalate calculi. Invest. Uml., 10: 147. 1972.

98. Hodgkinaon, A.: Relations between oxalic acid, calcium, rnagne- sium and creatinine excretion in normal men and male pa- tients calcium oxalate kidney stones. Clin. Sci. Mole. Med.,

440 INFLUENCE OF DIET ON URINARY STONE DISEASE

122. Zechner, 0.: Hyperuricosuric calcium oxalate lithiasis. In: Re- nal Tract Stone: Metabolic Basis and Clinical Practice. Edited by J. E. A. Wickham and A. Colin Buck. New York: Churchill Livingstone, pp. 285-293. 1990.

123. Kasidas, G. P.: Assay of oxalate and glycolate in urine. In: Oxalate Metabolism in Relation to Urinary Stone. Edited by G. A. Rose. New York Springer-Verlag, pp. 7-26.1988.

124. Fituri, N., Allawi, N., Bentley, M. and Castello, J.: The effect of h h intake of tartaric acid on urinary and plasma oxalate. In: Urnlithiasis and Related Clinical Research. Edited by P. 0. Schwille, L. H. Smith, W. G. Robertson and W. Vahlensieck. New York Plenum Press, pp. 379382, 1985.

125. Rofe, A. M., Bais, R. and Conyers, R. A.: The effect of dietary refined sugars and sugar alcohols on renal calcium oxalate deposition in ethylene glycol-treated rats. Food Chem. Toxi- col., 24: 397, 1986.

126. Kallner, A.: Serum bile acids in man during vitamin C supple- mentation and restriction. Acta Med. Scand., 202 283, 1977.

127. Urivetzky, M., Kessaris, D. and Smith, A. D.: Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis. J. Urol., 147: 1215, 1992.

128. Takiguchi, H., Furuyama, S. and Shimazono, N.: Urinary oxalic acid excretion by man following ingestion of large amounts of ascorbic acid. J. Vitaminol., 12: 307, 1966.

129. Fituri, N., AUawi, N., Bentley, M. and Castello, J.: Urinary and plasma oxalate during ingestion of pure ascorbic acid a re- evaluation. Eur. Urol.. 9: 312.1983.

J. Uml., 151: 834,1994. 131. Cowley. D. M., McWhinney, B. c., Brow, J. M. and Chalmers,

A. H.: Chemical factors important to nephrolithiasis: evidence for impaired hydroxycarboxylic acid absorption causing hyper- oxaluria. Clin. Chem., 33: 243, 1987.

132. Chalmers, A. H., Cowley, D. M. and Brown, J. M.: A possible etiological role of ascorbate in calculi formation. Clin. Chem,, 3 2 333, 1986.

133. Fegan, J., Khan, R., Poindexter, J. and Pak, C. Y. C.: Gastro- intestinal citrate absorption in nephrolithiasis. J. Urol., 147: 1212,1992.

134. Gershoff, S. N., Faragalla, F. F., Nelson, D. A. and Andrus, S. B.: Vitamin B6 deficiency and oxalate nephrocalcinosis in the cat. Amer. J. Med., 21: 72, 1959.

135. Hannett, B., Thomas, D. W. and Chalmers, A. J.: Formation of oxalate in pyridoxine or thiamin deficient rats during intrave- nous xylitol infusion. J. Nutr., 101: 458, 1977.

136. Tiselius, H. G. and AlmgHud, L. E.: The diurnal excretion of oxalate and the effect of pyridoxine and ascorbate on oxalate excretion. Em. Urol., 3: 41, 1977.

137. Parry, E. S. and Lister, I. S.: Sunlight and hrpercalciufia. Lancet, 1: 1063, 1975.

138. Zerwekh, J. E. and Pak, C. Y. C.: Vitamin D metabolism in idiopathic renal nephrolithiasis. In: Vitamin D: Basic and Clinical Aspects. Edited by R. Kumar. Boston: Martinus Nijhoff Publishing, chapt. 30, pp. 747-764, 1984.

139. Rodwell Williams, S.: Renal disease: nutrition and clinical C B ~ P

130. Wandzilak, T. R., D'&dre, S..D., Davis, P. A. and Williams, H. E.: Effect of high dose vitamin C on urinary oxalate levels.

In: Nutrition and Diet Therapy. St. Louis: Times Mi&;/ Mosby College Publishing, pp. 866-875, 1989.