articulo 3.pdf

1. Optimum Nutrition for Kidney Stone Disease Ita P. Heilberg and David S. Goldfarb We summarize the data regarding the associations of individual dietary components with kidney stones and the effects on 24- hour urinary profiles. The therapeutic recommendations for stone prevention that result from these studies are applied where possible to stones of specific composition. Idiopathic calcium oxalate stone-formers are advised to reduce ingestion of animal protein, oxalate, and sodium while maintaining intake of 800 to 1200 mg of calcium and increasing consumption of citrate and potassium. There are few data regarding dietary therapy of calcium phosphate stones. Whether the inhibitory effect of citrate sufficiently counteracts increasing urine pH to justify more intake of potassium and citrate is not clear. Reduction of sodium intake to decrease urinary calcium excretion would also be expected to decrease calcium phosphate stone recurrence. Con- versely, the most important urine variable in the causation of uric acid stones is low urine pH, linked to insulin resistance as a component of obesity and the metabolic syndrome. The mainstay of therapy is weight loss and urinary alkalinization provided by a more vegetarian diet. Reduction in animal protein intake will reduce purine ingestion and uric acid excretion. For cystine stones, restriction of animal protein is associated with reduction in intake of the cystine precursor methionine as well as cystine. Reduction of urine sodium results in less urine cystine. Ingestion of vegetables high in organic anion content, such as citrate and malate, should be associated with higher urine pH and fewer stones because the amino acid cystine is soluble in more alkaline urine. Because of their infectious origin, diet has no definitive role for struvite stones except for avoiding urinary alkalinization, which may worsen their development. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. Key Words: Calcium, Citrate, Oxalate, Protein, Nephrolithiasis Introduction Many data of various sorts, from epidemiology to urine chemistry, demonstrate that diet is an important contributor to the prevalence of kidney stones. Al- though many other variables, such as genetics, contribute, the composition of urine is largely determined by diet composition. Therefore, treatment of stone recurrence with dietary modification is appealing to patients and physicians because it is also relatively inexpensive and safe. Nevertheless, the long-term adherence of patients to diet and the effectiveness of diet are sup- ported more by short-term metabolic studies and epidemiological observations than by randomized controlled trials (RCTs). Comparisons of diet with pharma- cologic therapy have not been made so that their relative efficacy and the ability of patients to adhere to these regimens is unknown. Given these uncer- tainties, it is not possible to stress enough the importance of increasing fluid intake to increase urine volume and reduce the concentrations of stone- forming salts, a therapy of proven effectiveness.1 In the present review, we summarize the data regarding individual dietary components thought to be causa- tive in the pathophysiology of kidney stones. The therapeutic recommendations for stone prevention that result are based on stone type (Table 1) and 24-hour urinary profile (Table 2). Calcium Oversaturation of urine with calcium is one of the most important risk factors for calcium nephrolithiasis. Idio- pathic hypercalciuria (IH) represents a complex, primary metabolic alteration in at least half of calcium nephrolithiasis patients.2 Although higher dietary calcium intake may augment intestinal absorption of calcium and cause increased urinary calcium excretion,3 the net effect of calcium restriction on risk of stones in patients with IH is not established. Support for dietary calcium restriction has waned as doubts about efficacy, clinical trial evidence, and concerns about bone health have supervened. Cal- cium absorption is higher in IH cases at all levels of calcium intake, reflecting an increase in active calcium transport by the intestine. When challenged by an ex- tremely low calcium diet, patients with IH excrete more calcium in the urine than was ingested, suggesting that some of the urine calcium must derive from bone.4 In- creased urinary calcium excretion on a low-calcium diet in genetic hypercalciuric stone-forming rats also indicates an increase in bone resorption or a defect in kidney calcium reabsorption.5,6 In patients with IH, decreased bone mineral density, high bone resorption, and reduced bone formation are also commonly observed.7-9 From the Nephrology Division, Universidade Federal de S~ ao Paulo, S~ ao Paulo, Brazil; and Nephrology Division, New York University Langone Medi- cal Center, New York, NY, and Nephrology Section, New York Harbor V A Health Care System, New York, NY. I.P.H. reports nothing to disclose. D.S.G. Takeda and Keryx: He has served as a consultant to Quintiles. He has received honoraria from Amgen, Reata, and Hospira. He has served as a site principal investigator for clinical trials. He has received research funding from the National Institute of Diabetes and Digestive and Kidney Disease and the Office of Rare Diseases Research. Address correspondence to David S. Goldfarb, Department of Nephrology, New York V A Medical Center, 423 E 23rd St./111G, New York, NY 10010. E-mail: dsgold@verizon.net Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. 1548-5595/$36.00 http://dx.doi.org/10.1053/j.ackd.2012.12.001 Advances in Chronic Kidney Disease, Vol 20, No 2 (March), 2013: pp 165-174 165

2. Finally, Worcester and colleagues demonstrated a greater decrease in kidney calcium reabsorption in IH stone- formers after meals.10 Therefore, most individuals with IH appear to have a more generalized systemic abnor- mality in calcium homeostasis in which simultaneous dysregulation of calcium transport in the intestine, kidney, and bone takes place. Attempts to classify hypercalciuria on the basis of pathophysiology have not been shown to lead to superior therapeutic efficacy and are not recommended in clinical practice.11,12 Large prospective observational studies show that low calcium intake is associated with a 34% higher risk of kidney stones in young men,13 with similar findings in youn- ger14 and older women.15 The inverse association between dietary calcium and incident kidney stones has been ascribed to a secondary increase in urinary oxalate, which results from hyperabsorption of free oxalate dur- ing low calcium intake. This then leads to reduction of the formation of insoluble, nonabsorbable calcium oxalate complexes in the intestinal lumen. When the relation between diet and kidney stones in the Health Professionals Follow-Up Study was re-evaluated after 14 years of follow-up, the inverse association between dietary calcium and the risk of kidney stone formation was limited to men younger than 60 years.16 Al- though the cause of this age- specific difference remains unclear, vitamin D deficiency and a diminished ability to absorb dietary calcium, more prevalent in older people, might account for this observation. More available luminal calcium would then result in more oxalate being bound in poorly absorbable complexes so that additional dietary calcium would not have further effect. In contrast, supplemental calcium is associated with a slight but significantly higher risk of incident stones in older but not younger women.15,17 The inconsistent findings regarding the effect of dietary versus supplemental calcium might be due to different timing of ingestion of the latter. Ingestion of supplements without food may lead to increased calcium absorption and urinary excretion with little or no effect on the absorption and excretion of oxalate. Therefore, calcium supplements should be administered as calcium citrate and preferentially taken with, or shortly after, meals by stone-forming individuals.18 It is also possible that dairy products (the major source of dietary calcium) may contain other inhibitory factors. The protective effect of increased dietary calcium to reduce stone recurrence was tested in an RCT that compared the effect of a diet containing 1200 mg of calcium per day (30 mmol/day), but reduced amounts of animal protein (52 g/day) and salt (50 mmol/day), with a lower calcium diet (400 mg/day ¼ 10 mmol/day) in 120 hypercalciuric men with recurrent calcium oxalate stones.19 Both groups were counseled to reduce oxalate intake. Urinary calcium levels presented a marked and significant decrease in both groups, whereas urinary oxalate excretion was significantly decreased in the participants assigned to the higher calcium diet and nonsignificantly increased in the low-calcium diet group. The higher calcium intake was associated with a 49% lower unadjusted relative risk of recurrence of stone disease at 5 years. Because dietary sodium and animal protein may contribute to the causation of calcium stones,20 this trial, although suggestive, did not directly address the independent role of dietary calcium in the pathogenesis of kidney stones.21 No such study has been performed in women. In conclusion, the consen- sus is that dietary calcium restriction is no longer considered appropriate therapy for hypercalciuria because there is no evidence thatlowercalciumintakepre- vents stones and because of the threat of bone dem- ineralization.7,22 Instead, a moderate increase in calcium intake (800–1200 mg, approximately 3-4 servings of dairy per day) by subjects with low calcium intake appears appropriate, whereas those with moderate calcium intake can continue that practice. Oxalate Urinary oxalate derives from dietary sources and endogenous metabolism, with the relative proportions contrib- uted by each source varying among individuals.23 In metabolic studies with controlled oxalate intake, as expected, urinary oxalate excretion increases as dietary oxalate intake increases.24 The mean contribution of dietary oxalate to urinary oxalate excretion ranged from approximately 24 to 42% on a 10- to 50-mg/day diet. When the calcium content was also reduced from 1002 mg to 391 mg, the dietary contribution of oxalate further increased to 53%. This finding further emphasizes that oxalate absorption is also highly dependent on calcium intake.25,26 The proportion of oxalate absorbed from an oral load, as CLINICAL SUMMARY " Idiopathic calcium oxalate stone-formers are advised to reduce ingestion of animal protein, oxalate, and sodium while maintaining intake of 800 to 1200 mg of calcium and increasing consumption of citrate and potassium. " Reduction of sodium intake to decrease urinary calcium excretion would also be expected to decrease calcium phosphate stone recurrence. " The most important urine variable in the causation of uric acid stones is low urine pH, which is linked to insulin resistance as a component of obesity and the metabolic syndrome. " The mainstay of therapy for uric acid stones is weight loss and urinary alkalinization provided by a more vegetarian diet. Heilberg and Goldfarb 166

3. Table 1. Dietary Recommendations According to Stone Type Stone Type Nutrient Intake Recommendation Calcium Calcium Oxalate Sodium* Potassium† Animal Protein Citrate Fructose Fluids " Idiopathic calcium oxalate 800-1200 mg Avoid oxalate-rich foods Reduce to ,100 mEq Increase to .120 mEq Reduce to ,1.2 g/kg Increase Reduce Increase " Calcium phosphate 800-1200 mg Reduce to ,100 mEq ? Reduce to ,1.2 g/kg ? Increase Uric acid Increase Reduce (also purines) Increase Increase Cystine Reduce to 100 mEq Increase Reduce to ,1.2 g/kg Increase Increase Struvite 800-1200 mg Reduce to ,100 mEq Increase Empty box indicates that nutrient intake is not considered relevant; ? indicates unclear if dietary modification is beneficial or adverse. *100 mEq Na corresponds to 2.3 g Na, about 6 g NaCl. †120 mEq K corresponds to 4.7 g K. Table 2. Dietary Recommendations According to the Level of 24-h Urinary Excretion Level of 24 h Urinary Parameters Nutrient Intake Recommendation Calcium Oxalate Sodium Potassium Animal Protein Citrate Fructose Fluids High calcium 800-1200 mg Avoid oxalate-rich foods Reduce Increase Reduce Increase Reduce Increase High oxalate 800-1200 mg or more Reduce Reduce ? Reduce Increase Reduce Increase High sodium 800-1200 mg Reduce Increase Reduce Increase Increase High uric acid 800-1200 mg Reduce Increase Reduce (also purines) Increase Reduce Increase Low pH 800-1200 mg Adequate Increase Reduce Increase Reduce Increase Low citrate 800-1200 mg Reduce Increase Reduce Increase Reduce Empty box indicates that nutrient intake is not considered relevant; ? indicates unclear if dietary modification is beneficial or adverse. Optimum Nutrition for Stone Disease 167

4. measured by radiolabeled oxalate ingestion in calcium stone-formers, is higher than in nonstone-formers: 9.2 versus 6.8%.27 On the basis of these studies, it is possible that dietary oxalate restriction might be most efficacious if prescribed for those with hyperoxaluria and hyperabsorption, although this test has not been used prospectively in this manner to selectively prescribe an oxalate-restricted diet. The method of food preparation and local agricultural variables may contribute to varia- tion in oxalate content, but questions remain about what proportion of dietary oxalate is soluble and bio- available versus insoluble.28 Fat malabsorption is also responsible for increased intestinal oxalate absorption in many conditions in which reducing dietary fat might be considered.29-31 In epidemiological studies in 3 cohorts of men and women, oxalate intake assessed by food frequency ques- tionnaires (FFQs) surprisingly did not differ between stone-formers and nonstone-formers. The relative risks for stones in participants were 1.22 for men, 1.21 for older women, and not significant for younger women, compar- ing the highest versus the lowest quintiles of dietary oxalate intake.32 Overall, the effect was small. In addition, no trial of oxalate lowering with stone formation as the outcome has been performed. Newer data on food oxalate content would be important in the design of an RCT (see https://regepi.bwh.harvard.edu/health/ Oxalate/files). Therefore, the efficacy of restricting dietary oxalate intake for stone prevention remains un- proven, except for special conditions such as bariatric surgery.29,33 It is possible that increasing calcium intake, especially if low, is a more useful means of reducing urine oxalate excretion than reducing oxalate intake alone.19 Another variable of uncertain significance in deter- mining the importance of dietary oxalate is colonization with Oxalobacter formigenes, an obligate oxalate- degrading anaerobe in the normal intestinal micro- biome. Its presence in the colon is associated with lesser urine oxalate excretion.34 The organism may also be ca- pable of stimulating oxalate secretion from the host’s blood to the intestinal lumen, thereby offering another mechanism of reducing the host’s urine oxalate load.35 Other intestinal commensals such as Enterococcus faeca- lis, Eubacterium lentum, and some lactic acid bacteria present in various food products may also use oxalate as an energy source and lead to decreasing oxaluria. Several studies have assessed the effects of oral admin- istration of different probiotic preparations on oxaluria with variable results.34,36 However, individuals characterized by high oxalate absorption were most likely to experience clinically significant reductions in urinary oxalate in response to acute probiotic ingestion, which suggests that dietary oxalate plays a key role as a determinant of urinary oxalate excretion in response to the use of probiotics. Protein The nutrient that clearly has universal effects on most of the urinary parameters involved in stone formation is animal protein (meat, fish, poultry, eggs; dairy products are not included).20 The combination of a low-calcium diet with a high-animal-protein diet is particularly harmful because it also induces negative calcium balance.22 High animal protein intake, a source of purines, contrib- utes to hyperuricosuria, a risk factor for calcium stones.37 The accompanying acid load leads to hypocitraturia because of reduced tubular citrate reabsorption.38,39 The effect of dietary protein on urinary oxalate is controversial, with some studies showing an increase40-42 whereas others report no change.43 Increased protein intake on a controlled oxalate diet increased urinary glycolate but did not affect total daily oxalate excretion in normal subjects, suggesting that endogenous oxalate synthesis was not increased.44 Finally, the effect of dietary protein on urinary excretion of calcium is clear and well established. Animal protein-induced hypercalciuria occurs from more bone resorption and lower tubular calcium reabsorption. The presence of nonresorbable calcium sulfate in the tubular lumen consequent to sulfate production from oxidation of excessive sulfur-containing amino acids may also contribute.45,46 In addition, acidosis has an effect on calcium absorption by TRPV5 channels and their expression in the distal tubule, leading to increased urine calcium excretion.47 However, a very recent study concluded that hypercalciuria associated with high dietary protein intake was not due to the acid load.48 Epidemiological data reveal a positive association between animal protein consumption and new kidney stone formation in men but not women.13,15,17 The risk associated with animal protein intake varied with body mass index (BMI) only in men with a BMI of less than 25 kg/m2 .16 The lack of association in overweight men remains unexplained. Short-term dietary protein restriction (0.8 g/kg/day) for 2 weeks significantly reduced urinary excretion of calcium, phosphate, hydroxyproline, uric acid, and oxalate and increased citrate excretion in patients with nephrolithiasis.41 Patients with recurrent nephrolithiasis may be more sensitive to the calciuric action of protein.49 Despite poor adherence to a 4-month period of low animal protein intake, 38.7% of stone-formers exhibited a reduction in urine urea and calcium excretion. Significant correla- tions between urea and calcium outputs were detected only among those with hypercalciuria.50 Few clinical trials have definitively evaluated the effect of animal protein restriction on calcium oxalate stone formation. An RCT of a low-animal-protein, high-fiber diet was conducted in calcium oxalate stone-formers followed regularly for up to 4.5 years with FFQs and urine chemistry measurements.51 The intervention group had Heilberg and Goldfarb 168

5. an increase in the relative risk of recurrent stones, leading the authors to conclude that the diet had no advantage over advice to increase fluid intake alone. Measurement of urea excretion suggested that the intervention group had difficulty adhering to the diet. On the other hand, in the trial of Borghi and colleagues the reduction of dietary protein as prescribed was confirmed by a lower urinary urea and sulfate and might have been partly responsible for the reduction of stone recurrence by decreasing oxalate and calcium excretion.19 Finally, a more recent 4-year randomized trial of low-animal-protein compared with high-fiber diets revealed no change in urinary calcium levels and recurrence rates despite a significant decrease in 24-hour urinary sulfate in the low- protein group.52 Again, there was imperfect adherence, so that the effectiveness of protein restriction in clinical practice may either be considered not definitively tested or as a manipulation not likely to find more enthusiastic adherents. Despite well described effects of increased animal protein to increase stone risk as assessed by adverse changes in urine chemistry, no protein-restricted diet has been shown to reduce stone recurrence rates except one that included higher calcium intake and restricted sodium intake. Given the difficulty that modern, Western popula- tions have with protein restriction, the importance of such a dietary prescription has not been demonstrated but might be worthwhile for patients with high protein intake suggested by history or by 24-hour urine results. Sodium High sodium intake and a subsequent decrease in proximal sodium reabsorption reduce kidney tubular calcium reabsorption. The effect of sodium intake on increasing calcium excretion is well established. Every 100-mEq increase in daily dietary sodium leads to an approximate 25- to 40-mg increase in urinary calcium excretion per day.53 In kidney stone-forming subjects, daily urinary calcium excretion varied directly with moderate changes in dietary sodium intake.54,55 Although epidemiological studies revealed a positive, independent association between sodium consumption and new kidney stone formation in women,13,17 the interpretation of the results may be limited by the inaccuracy of the assessment of sodium intake by semiquantitative FFQs. Recently, a cross-sectional study aimed at delineating associations between dietary and urinary factors with 24-hour urinary calcium excretion found that participants in the highest quartiles of urinary sodium excreted 37 mg/day more urinary calcium than participants in the lowest quartile.56 The adverse effects of a high sodium chloride (NaCl) intake (assessed by 24-hour sodium excretion) on calcium excretion and bone loss have also been reported in stone-formers.57 Af- ter adjustment for calcium and protein intakes; age, weight, BMI, urinary calcium, citrate, and uric acid excretion; and duration of stone disease, a multiple regression analysis showed that a high NaCl intake was the single variable that was most predictive of risk of low bone density. No RCTs addressing sodium restriction as a sole therapy have been performed. Nevertheless, in the RCT by Borghi and colleagues the reduction in sodium intake accompanying higher calcium intake may have been important to reduce calciuria.19 Citrate and Potassium The primary mechanisms of action of urine citrate are to increase the solubility of stone-forming calcium salts and inhibit calcium oxalate crystal growth. Modulation of citrate excretion in the kidney is influenced by multiple factors, but systemic acid-base variables have the strongest effect.58 Whereas acid loads and acidosis increase kidney tubule reabsorption of citrate, alkali loads and alkalosis reduce it, hence increasing urinary citrate excretion. In addition, the systemic alkalinization that occurs with citrate supplementation reduces calcium excretion. This effect is also important in increasing urine pH, reducing the risk of uric acid and cystine-based calculi. However, com- pliance with potassium citrate preparations can be diffi- cult, especially in the older population, because of gastrointestinal side effects. Substitution of increased animal protein intake with high intake of fruits and vegetables among stone-formers is associated with increased urine pH and volume (because of the water content of fruits and vegetables) and increases of 68% in urinary citrate and potassium with concomitant reductions in am- monium excretion.59 Citrus fruits such as oranges, lemons, limes, and some tangerines are natural sources of dietary citrate and may be a nonpharmacological, dietary alternative therapy to potassium citrate supplementation for the management of hypocitraturia or uric acid and cystine stones. Numerous short-term studies of urinary chemistry measures have demonstrated that urinary citrate levels increased after consumption of either grapefruit60,61 or orange juice61-63 or lemonade64-67 whereas a few yielded no improvements in citraturia with lemonade.63,68 Citrate in orange and grapefruit juices is complexed mainly by potassium, thus also increasing urinary pH. However, citrate in lemon juice, with high citric acid content, is largely accompanied by protons, hence not conferring the alkalinizing load that orange juice provides.63 Nevertheless, some citraturic effect of oral citric acid may be attributed to some of the absorbed citrate escaping liver oxidation and degradation.69 Be- cause any organic anion that causes a systemic alkalosis increases citrate excretion, malate may also increase urinary citrate.70 The significant caloric load that accom- panies the ingestion of large volumes of orange juice is a major concern that is not shared by freshly squeezed Optimum Nutrition for Stone Disease 169

6. lemon/lime juices that can be sweetened with artificial sweeteners, thereby minimizing increased calciuria associated with fructose ingestion71 or perhaps other carbohydrates.72 An additional benefit of citrus juice is the requisite increase in overall fluid consumption, thus increasing daily urine volume and reducing urine supersaturation. Noncitrus fruits such as pineapple and cranberry may also be rich in citrate. However, the effect of cranberry extracts on urine citrate excretion is variable and it may increase oxalate excretion73 (as also observed for orange juice63 ), probably because of the presence of a cer- tain amount of oxalate or conversion of ascorbic acid to oxalate in vivo.74 Fresh tomato juice is also reported to contain a considerable amount of citrate.75 Finally, various melons—noncitrus alkaline fruits rich in potassium, citrate, and malate—yield increases in urinary citrate excretion similar to those provided by orange, hence representing another dietary alternative for the treatment of hypocitraturic stone-formers.76 Despite the evidence of increased urinary citrate induced by citrus juice consumption, observational studies do not show a reduction of the risk for stone formation associated with orange juice. For reasons yet unexplained, stone risk increased up to 44% for each 240-mL serving of grapefruit juice consumed daily in men and women.77,78 In one observational study, the risk of stones increased by 35% with apple juice consumption77 despite its effect to increase urinary citrate excretion.61 On the other hand, observational studies show that higher potassium intake is inversely associated with incident kidney stones in men and older women, with the ex- ception of younger women.13,15,17 The effect of higher potassium intake would mostly relate to the cation being accompanied by an organic anion, such as citrate and malate, representing an alkaline load. However, potassium deficiency stimulates proximal tubular citrate reabsorption so that potassium intake per se might reduce stone risk regardless of the accompanying anion. Martini and colleagues have observed a significant correlation between urinary potassium and citrate.54 Patients whose self-assigned diets more closely resembled the Dietary Approaches to Stop Hypertension (DASH)-style diet, which is rich in fruits and vegetables, had a marked decrease in kidney stone risk.79 In a cross- sectional study of a large cohort of persons with and without nephrolithiasis, multivariate-adjusted 24-hour urinary citrate excretion was 16% greater in those exhib- iting the highest quintile of scores for diets resembling the DASH diet.80 Higher urine potassium and pH were also significantly associated with higher DASH score in all cohorts, confirming the benefits of the alkali and high potassium content of such diet. In 2 recent studies, quantitative analysis of citric acid in commercially available fruit juice products and beverages was performed with variable results.81,82 Lemon and lime juice from either fresh fruit or concentrates provided more citric acid per liter than ready-to-consume grapefruit or orange juice.82 In the nonjuice category of tested beverages, only lemonade-flavored Crystal Light presented a high concentration of citrate.81 However, consumption of diet orange soda to provide 60 mEq of citrate would have to be in excess of 2 L/day or more than 9 8-oz glasses per day.83 Finally, pH is an important determinant of alkali load in beverages containing organic anions such as citrate. The carboxyl groups of citrate will have no effect on urine pH if protonated, but if accompanied by other cations such as potassium or sodium, they will serve as net base. Commercial oral rehy- dration solutions that contain a higher pH and more citrate content led to an increase in citraturia and urinary pH.84 However, these sports drinks may contain too many calories and fructose to be preferred beverages for stone prevention. The amount of vitamin C added to juices is also a concern because of its conversion to oxalate, although the amount is not high if compared with vitamin C supplements.74 Other Beverages A prospective controlled study showed that increasing water intake to achieve a urinary volume of approximately 2.5 L/day was associated with reduced stone recurrence.1 Although the exact daily amount of fluids needed by stone-formers remains uncertain, advice on how much to drink to form at least 30 mL/kg of body weight of urine per day can be recommended. Achieving 2.5 to 3 L per day may be optimal. Although there is general agreement on the need to increase urinary volume in stone-formers, controversy ex- ists regarding the effect of water hardness on kidney stone incidence.85 The magnesium and bicarbonate content of some mineral waters may result in favorable changes in urinary pH, magnesium and citrate excretion, inhibitors of calcium oxalate stone formation, counterbal- ancing increased calcium excretion.86,87 The risk of uric acid precipitation may also decrease with bicarbonate- containing water intake. However, increased risk of calcium phosphate stone formation may be observed.88 Observational studies have found that caffeinated or decaffeinated coffee and tea reduce the risk of stone for- mation77,89 despite caffeine’s effect to increase urine calcium excretion.90 Alcohol in general, and beer specifi- cally, are consistently associated with protection against stone prevalence,1,2,75 possibly because of the inhibition of antidiuretic hormone secretion, leading to decreased urinary concentration.77,78,89 Beer was once said to contain sizeable oxalate content, but current methods do not confirm that supposition. However, beer may contain purines and contribute to hyperuricosuria. Although observational studies have not shown an adverse effect of cola consumption on stone Heilberg and Goldfarb 170

7. prevalence,78,91 colas have lower citrate content than clear sodas and are variably associated with worsening of urine parameters, including an increase in oxalate excretion, suggesting an increased tendency to form calcium oxalate crystals at least in vitro.92 Phytate Phytate, or inositol hexaphosphate, inhibits calcium salt crystallization and stone growth in vitro.93 Phytate-rich foods include beans, cereals, whole grains, and rice. In fact, these foods also have significant oxalate content, and it is possible that their phytate content mitigates their oxalate-induced lithogenic potential.94 Although relatively nonabsorbable with less than 5% of ingested phytate appearing in the urine, increased dietary phytate content is associated with increases in urine excretion such that a clinically meaningful result is possible.95 Western diets contain progressively less phytate because of greater refinement of grains and rice, corresponding to increased stone prevalence. In prospectively followed cohorts of men and women, increased dietary phytate content, as estimated by FFQs, has been variably associated with reductions in stone risk.15 However, phytate intake was not associated with reduced stone risk in men in a multivariate analysis.16 Calories and Fructose Many observations and epidemiological studies link obesity, weight gain, insulin resistance, metabolic syndrome, and diabetes with increased prevalence of stones.96-98 Higher BMI is associated with lower urine pH99 and a higher prevalence of uric acid stones.100 However, alkalinization alone may fail in uric acid stone-formers because they appear to have increased net acid excretion and lower urine pH at any level of urine sulfate excretion (a surrogate of animal protein intake) compared with nonuric acid stone-formers.101 Because higher BMI is associated with higher urine oxalate excretion, calcium oxalate stones might also increase with obesity. Therefore, weight loss might be associated with reduced stone prevalence of any composition. However, low-carbohydrate diets rich in animal protein such as the Atkins diet reduce urine pH and citrate excretion while increasing uric acid excretion. Therefore, such diets are not recommended for stone-formers.45 Perhaps their negative effect could be overcome by ample potassium citrate supplementation. We would instead recommend a low-calorie DASH diet, also useful for diabetes and hypertension. Weight Watchers and other more balanced plans might also yield satisfactory results.79,102 Of note, stone-formers advised to decrease their intake of protein (or fat) should not increase their consumption of fructose-rich foods (especially high-fructose corn syrup). Fructose was independently associated with an increased risk of incident kidney stones whereas nonfructose carbohydrates Table 3. Dietary Recommendations for Adult Stone-Formers Nutrient Intake Recommendation Protein Calcium Oxalate Sodium Potassium Citrate Fructose Average daily intake 0.8-1.0 g/kg/d 1000-1200 mg/d* ,200 mg/d ,2.3 g/d* (100 mEq Na, about 6 g NaCl) .4.7 g/d* (120 mEq K) ND ND Main food sources Animal protein (meat, poultry, fish, eggs, and dairy [milk, cheese, yogurt, etc.]) Dairy products (milk, cheese, yogurt, etc.) Spinach, beetroot, potatoes, nuts† Processed foods to which NaCl/ benzoate/ phosphate added; salted meats, nuts, cold cuts; canned products; use of salt-shaker Fruits and vegetables, dried peas, dairy products, meats, and nuts Fruits (citrus and noncitrus potassium-rich) and vegetables High amounts in corn syrup Abbreviation: ND, not determined. *Recommended Dietary Allowances (recommendation varies according to life stage and gender): adapted from Dietary Reference Intakes reports from the National Academy of Sciences, Institute of Medicine, Food and Nutrition Board (http://www.nap.edu). †For more information see https://regepi.bwh.harvard.edu/health/oxalate/files. Energy requirements for a normal, healthy individual with sedentary lifestyle: 25-30 kcal/kg/d, with a percentage of total energy of 45-65% from carbohydrates, 20-35% from fat, and 10-15% from protein (50% of high biological value, as from meat, fish, poultry, eggs, milk, and soy). Optimum Nutrition for Stone Disease 171

8. were not associated with increased risk in any cohort.71 On the other hand, short-term studies of varying, controlled fructose intake were not associated with changes in urinary excretion of calcium, oxalate, or uric acid.103 Therefore, the mechanisms linking the epidemiologic finding of an association between fructose and stones is not established. Summary Calcium Oxalate Stones Idiopathic calcium oxalate stone-formers are advised to reduce animal protein, oxalate, and sodium in their diets while maintaining adequate intakes of calcium and increasing their consumption of citrate and potassium (Table 1). Calcium Phosphate Stones Reduce sodium intake to reduce calcium excretion. Uric Acid Stones The mainstay of therapy is weight loss and urinary alkalinization provided by a more vegetarian diet, leading to an increase in urine citrate content and pH. Reduction in animal protein intake may further reduce purine ingestion and uric acid excretion. Cystine Stones Restrict animal protein to reduce cystine and methionine ingestion, and restrict sodium intake to further reduce excretion and supersaturation of cystine.104-106 Ingestion of vegetables high in content of organic anions, such as citrate, should be associated with higher urine pH.104,106 Struvite Stones Because of their infectious origin, diet has no definitive role for struvite stones. Conclusion Dietary modification can reduce the risk of stone recurrence. Although an individualized dietary prescription must be tailored according to stone type or urinary risk factors, almost all stone-formers should benefit from increased fluid intake and a diet containing 800 to 1200 mg of calcium; reduced amounts of sodium and animal protein; and higher intake of fruits, vegetables, and grains (excluding the high-oxalate ones). Reduced sugar intake, such as in the low-calorie DASH diet, is also recommended.107 Table 3 shows the adequacy for nutrients based on the Recommended Dietary Allowances. Dietary modifications (increase or reduction of nutrients), as pre- viously suggested in Tables 1 and 2, can be calculated from these recommendations. Acknowledgments The authors appreciate insightful conversations with Alessan- dra Baxmann, PhD. References 1. Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. J Urol. 1996;155(3):839-843. 2. Levy FL, Adams-Huet B, Pak CY. Ambulatory evaluation of nephrolithiasis: an update of a 1980 protocol. Am J Med. 1995;98(1):50-59. 3. Worcester EM, Coe FL. New insights into the pathogenesis of idiopathic hypercalciuria. Semin Nephrol. 2008;28(2):120-132. 4. Coe FL, Favus MJ, Crockett T, et al. Effects of low-calcium diet on urine calcium excretion, parathyroid function and serum 1,25(OH) 2D3 levels in patients with idiopathic hypercalciuria and in normal subjects. Am J Med. 1982;72(1):25-32. 5. Bushinsky DA, Frick KK, Nehrke K. Genetic hypercalciuric stone- forming rats. Curr Opin Nephrol Hypertens. 2006;15(4):403-418. 6. Tsuruoka S, Bushinsky DA, Schwartz GJ. Defective renal calcium reabsorption in genetic hypercalciuric rats. Kidney Int. 1997;51(5): 1540-1547. 7. Heilberg IP, Weisinger JR. Bone disease in idiopathic hypercalciuria. Curr Opin Nephrol Hypertens. 2006;15(4):394-402. 8. Gomes SA, dos Reis LM, Noronha IL, Jorgetti V, Heilberg IP. RANKL is a mediator of bone resorption in idiopathic hypercalciuria. Clin J Am Soc Nephrol. 2008;3(5):1446-1452. 9. Heller HJ, Zerwekh JE, Gottschalk FA, Pak CY. Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria. Kidney Int. 2007;71(8):808-815. 10. Worcester EM, Gillen DL, Evan AP, et al. Evidence that postpran- dial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis. Am J Physiol Ren Physiol. 2007;292(1):F66-F75. 11. Sakhaee K, Maalouf NM, Sinnott B. Clinical review. Kidney stones 2012: Pathogenesis, diagnosis, and management. J Clin Endocrinol Metab. 2012;97(6):1847-1860. 12. Worcester EM, Coe FL. Clinical practice. Calcium kidney stones. N Engl J Med. 2010;363(10):954-963. 13. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symp- tomatic kidney stones. N Engl J Med. 1993;328(12):833-838. 14. 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(6):2290-2298. 15. Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses’ Health Study II. Arch Intern Med. 2004;164(8):885-891. 16. 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(12):3225-3232. 17. Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ. 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(7):497-504. 18. Domrongkitchaiporn S, Sopassathit W, Stitchantrakul W, Prapaipanich S, Ingsathit A, Rajatanavin R. Schedule of taking calcium supplement and the risk of nephrolithiasis. Kidney Int. 2004;65(5):1835-1841. 19. 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(2):77-84. 20. Heilberg IP. Update on dietary recommendations and medical treatment of renal stone disease. Nephrol Dial Transplant. 2000; 15(1):117-123. Heilberg and Goldfarb 172

9. 21. Taylor EN, Curhan GC. Diet and fluid prescription in stone disease. Kidney Int. 2006;70(5):835-839. 22. Martini LA, Heilberg IP. Stop dietary calcium restriction in kidney stone-forming patients. Nutr Rev. 2002;60(7 Pt 1):212-214. 23. Holmes RP, Assimos DG. The impact of dietary oxalate on kidney stone formation. Urol Res. 2004;32(5):311-316. 24. Holmes RP, Goodman HO, Assimos DG. Contribution of dietary oxalate to urinary oxalate excretion. Kidney Int. 2001;59(1):270-276. 25. von Unruh GE, Voss S, Sauerbruch T, Hesse A. Dependence of oxalate absorption on the daily calcium intake. J Am Soc Nephrol. 2004;15(6):1567-1573. 26. de O G Mendonça C, Martini LA, Baxmann AC, et al. Effects of an oxalate load on urinary oxalate excretion in calcium stone formers. J Ren Nutr. 2003;13(1):39-46. 27. Hesse A, Schneeberger W, Engfeld S, von Unruh GE, Sauerbruch T. Intestinal hyperabsorption of oxalate in calcium oxalate stone formers: application of a new test with [13C2]oxalate. J Am Soc Nephrol. 1999;10(Suppl 14):S329-S333. 28. Chai W, Liebman M. Assessment of oxalate absorption from al- monds and black beans with and without the use of an extrinsic label. J Urol. 2004;172(3):953-957. 29. Kumar R, Lieske JC, Collazo-Clavell ML, et al. Fat malabsorption and increased intestinal oxalate absorption are common after roux-en-y gastric bypass surgery. Surgery. 2011;149(5):654-661. 30. Worcester EM. Stones from bowel disease. Endocrinol Metab Clin North Am. 2002;31(4):979-999. 31. Ferraz RR, Tiselius HG, Heilberg IP. Fat malabsorption induced by gastrointestinal lipase inhibitor leads to an increase in urinary oxalate excretion. Kidney Int. 2004;66(7):676-682. 32. Taylor EN, Curhan GC. Oxalate intake and the risk for nephrolithiasis. J Am Soc Nephrol. 2007;18:2198-2204. 33. Froeder L, Arasaki CH, Malheiros CA, Baxmann AC, Heilberg IP. Response to dietary oxalate after bariatric surgery. Clin J Am Soc Nephrol. 2012;7:2033-2040. 34. Sidhu H, Schmidt ME, Cornelius JG, et al. Direct correlation between hyperoxaluria/oxalate stone disease and the absence of the gastrointestinal tract-dwelling bacterium Oxalobacter formigenes: possible prevention by gut recolonization or enzyme replacement therapy. J Am Soc Nephrol. 1999;10(Suppl 14):S334- S340. 35. Hatch M, Cornelius J, Allison M, Sidhu H, Peck A, Freel RW. Ox- alobacter sp. reduces urinary oxalate excretion by promoting en- teric oxalate secretion. Kidney Int. 2006;69(4):691-698. 36. Goldfarb DS, Heilberg IP. Oxalobacter formigenes, lactic acid bacteria and hyperoxaluria: an update NephSAP; Disorders of Divalent Ions, Renal Bone Disease, and Nephrolithiasis. 2012;11:231–235. 37. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine- rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004;350(11):1093-1103. 38. 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(1):140-146. 39. Kok DJ, Iestra JA, Doorenbos CJ, Papapoulos SE. The effects of dietary excesses in animal protein and in sodium on the composition and the crystallization kinetics of calcium oxalate monohydrate in urines of healthy men. J Clin Endocrinol Metab. 1990;71(4):861-867. 40. Nguyen QV, Kalin A, Drouve U, Casez JP, Jaeger P. Sensitivity to meat protein intake and hyperoxaluria in idiopathic calcium stone formers. Kidney Int. 2001;59(6):2273-2281. 41. Giannini S, Nobile M, Sartori L, et al. Acute effects of moderate dietary protein restriction in patients with idiopathic hypercalciuria and calcium nephrolithiasis. Am J Clin Nutr. 1999;69(2):267-271. 42. Holmes RP, Goodman HO, Hart LJ, Assimos DG. Relationship of protein intake to urinary oxalate and glycolate excretion. Kidney Int. 1993;44(2):366-372. 43. Marangella M, Bianco O, Martini C, Petrarulo M, Vitale C, Linari F. Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease. Br J Urol. 1989;63(4):348-351. 44. Knight J, Easter LH, Neiberg R, Assimos DG, Holmes RP. In- creased protein intake on controlled oxalate diets does not increase urinary oxalate excretion. Urol Res. 2009;37(2):63-68. 45. Reddy ST, Wang CY, Sakhaee K, Brinkley L, Pak CY. Effect of low- carbohydrate high-protein diets on acid-base balance, stone- forming propensity, and calcium metabolism. Am J Kidney Dis. 2002;40(2):265-274. 46. Frank H, Graf J, Amann-Gassner U, et al. Effect of short-term high-protein compared with normal-protein diets on renal hemo- dynamics and associated variables in healthy young men. Am J Clin Nutr. 2009;90(6):1509-1516. 47. Bonny O, Edwards A. Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow. Am J Physiol Ren Physiol. 2012 Nov 14 [Epub ahead of print]. doi: 10.1152/ajprenal.00493. 2012. 48. Maalouf NM, Moe OW, Adams-Huet B, Sakhaee K. Hypercalciu- ria associated with high dietary protein intake is not due to acid load. J Clin Endocrinol Metab. 2011;96(12):3733-3740. 49. Goldfarb S. The role of diet in the pathogenesis and therapy of nephrolithiasis. Endocrinol Metab Clin North Am. 1990;19(4): 805-820. 50. Rotily M, Leonetti F, Iovanna C, et al. Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis. Kidney Int. 2000;57(3):1115-1123. 51. Hiatt RA, Ettinger B, Caan B, Quesenberry CP, Duncan D, Citron JT. 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(1):25-33. 52. Dussol B, Iovanna C, Rotily M, et al. A randomized trial of low- animal-protein or high-fiber diets for secondary prevention of calcium nephrolithiasis. Nephron Clin Pract. 2008;110(3):c185-c194. 53. Bleich HL, Moore MJ, Lemann J Jr, Adams ND, Gray RW. Urinary calcium excretion in human beings. N Engl J Med. 1979;301(10): 535-541. 54. Martini LA, Cuppari L, Cunha MA, Schor N, Heilberg IP. Potas- sium and sodium intake and excretion in calcium stone forming patients. J Ren Nutr. 1998;8(3):127-131. 55. Muldowney FP, Freaney R, Moloney MF. Importance of dietary sodium in the hypercalciuria syndrome. Kidney Int. 1982;22(3): 292-296. 56. Taylor EN, Curhan GC. Demographic, dietary, and urinary factors and 24-h urinary calcium excretion. Clin J Am Soc Nephrol. 2009;4:1980-1987. 57. Martini LA, Cuppari L, Colugnati FA, et al. High sodium chloride intake is associated with low bone density in calcium stone- forming patients. Clin Nephrol. 2000;54(2):85-93. 58. Zuckerman JM, Assimos DG. Hypocitraturia: pathophysiology and medical management. Rev Urol. 2009;11(3):134-144. 59. Meschi T, Maggiore U, Fiaccadori E, et al. The effect of fruits and vegetables on urinary stone risk factors. Kidney Int. 2004;66(6):2402-2410. 60. Goldfarb DS, Asplin JR. Effect of grapefruit juice on urinary lithogenicity. J Urol. 2001;166(1):263-267. 61. Honow R, Laube N, Schneider A, Kessler T, Hesse A. Influence of grapefruit-, orange- and apple-juice consumption on urinary variables and risk of crystallization. Br J Nutr. 2003;90(6):295-300. 62. Wabner CL, Pak CY. Effect of orange juice consumption on urinary stone risk factors. J Urol. 1993;149:1405-1408. 63. Odvina CV. Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin J Am Soc Nephrol. 2006; 1(6):1269-1274. 64. Kang DE, Sur RL, Haleblian GE, Fitzsimons NJ, Borawski KM, Preminger GM. Long-term lemonade based dietary manipulation in patients with hypocitraturic nephrolithiasis. J Urol. 2007;177(4): 1358-1362. Optimum Nutrition for Stone Disease 173

10. 65. Seltzer MA, Low RK, McDonald M, Shami GS, Stoller ML. Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. J Urol. 1996;156(3):907-909. 66. 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(5):856-860. 67. Aras B, Kalfazade N, Tugcu V, et al. Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study. Urol Res. 2008;36(6):313-317. 68. Koff SG, Paquette EL, Cullen J, Gancarczyk KK, Tucciarone PR, Schenkman NS. Comparison between lemonade and potassium citrate and impact on urine pH and 24-hour urine parameters in patients with kidney stone formation. Urology. 2007;69(6): 1013-1016. 69. Sakhaee K, Alpern R, Poindexter J, Pak CY. Citraturic response to oral citric acid load. J Urol. 1992;147(4):975-976. 70. Eisner BH, Asplin JR, Goldfarb DS, Ahmad A, Stoller ML. Citrate, malate and alkali content in commonly consumed diet sodas: im- plications for nephrolithiasis treatment. J Urol. 2010;183(6): 2419-2423. 71. Taylor EN, Curhan GC. Fructose consumption and the risk of kidney stones. Kidney Int. 2008;73(2):207-212. 72. 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(5):232-237. 73. Gettman MT, Ogan K, Brinkley LJ, Adams-Huet B, Pak CY, Pearle MS. Effect of cranberry juice consumption on urinary stone risk factors. J Urol. 2005;174(2):590-594. 74. Baxmann AC, De O G Mendonça C, Heilberg IP. Effect of vitamin C supplements on urinary oxalate and pH in calcium stone- forming patients. Kidney Int. 2003;63(3):1066-1071. 75. Yilmaz E, Batislam E, Basar M, Tuglu D, Erguder I. Citrate levels in fresh tomato juice: a possible dietary alternative to traditional citrate supplementation in stone-forming patients. Urology. 2008;71(3):379-383. 76. Baia LD, Baxmann AC, Moreira SR, Holmes RP, Heilberg IP. Non- citrus alkaline fruit: a dietary alternative for the treatment of hypocitraturic stone formers. J Endourol. 2012;26:1221-1226. 77. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. J Urol. 1996;155(6):1847-1851. 78. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Beverage use and risk for kidney stones in women. Ann Intern Med. 1998; 128(7):534-540. 79. Taylor EN, Fung TT, Curhan GC. DASH-style diet associates with reduced risk for kidney stones. J Am Soc Nephrol. 2009;20(10): 2253-2259. 80. Taylor EN, Stampfer MJ, Mount DB, Curhan GC. DASH-style diet and 24-hour urine composition. Clin J Am Soc Nephrol. 2010;5(12): 2315-2322. 81. Haleblian GE, Leitao VA, Pierre SA, et al. Assessment of citrate concentrations in citrus fruit-based juices and beverages: implica- tions for management of hypocitraturic nephrolithiasis. J Endourol. 2008;22(6):1359-1366. 82. Penniston KL, Nakada SY, Holmes RP, Assimos DG. Quantitative assessment of citric acid in lemon juice, lime juice, and commercially available fruit juice products. J Endourol. 2008;22(3):567-570. 83. Sumorok NT, Asplin JR, Eisner BH, Stoller ML, Goldfarb DS. Ef- fect of diet orange soda on urinary lithogenicity. Urol Res. 2012; 40(3):237-241. 84. Goodman JW, Asplin JR, Goldfarb DS. Effect of two sports drinks on urinary lithogenicity. Urol Res. 2009;37(1):41-46. 85. Caudarella R, Rizzoli E, Buffa A, Bottura A, Stefoni S. Compara- tive study of the influence of 3 types of mineral water in patients with idiopathic calcium lithiasis. J Urol. 1998;159(3):658-663. 86. Siener R, Jahnen A, Hesse A. Influence of a mineral water rich in calcium, magnesium and bicarbonate on urine composition and the risk of calcium oxalate crystallization. Eur J Clin Nutr. 2004;58(2):270-276. 87. Rodgers AL. Effect of mineral water containing calcium and magnesium on calcium oxalate urolithiasis risk factors. Urol Int. 1997;58(2):93-99. 88. Karagulle O, Smorag U, Candir F, et al. Clinical study on the effect of mineral waters containing bicarbonate on the risk of urinary stone formation in patients with multiple episodes of CaOx- urolithiasis. World J Urol. 2007;25(3):315-323. 89. Goldfarb DS, Fischer ME, Keich Y, Goldberg J. A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) registry. Kidney Int. 2005;67(3):1053-1061. 90. Massey LK, Sutton RA. Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers. J Urol. 2004;172(2):555-558. 91. Curhan GC, Willett WC, Rimm EB, Spiegelman D, Stampfer MJ. Prospective study of beverage use and the risk of kidney stones. Am J Epidemiol. 1996;143(3):240-247. 92. Rodgers A. Effect of cola consumption on urinary biochemical and physicochemical risk factors associated with calcium oxalate urolithiasis. Urol Res. 1999;27(1):77-81. 93. Saw NK, Chow K, Rao PN, Kavanagh JP. Effects of inositol hexaphosphate (phytate) on calcium binding, calcium oxalate crystallization and in vitro stone growth. J Urol. 2007;177(6):2366-2370. 94. Al-Wahsh IA, Horner HT, Palmer RG, Reddy MB, Massey LK. Ox- alate and phytate of soy foods. J Agric Food Chem. 2005;53(14): 5670-5674. 95. Grases F, March JG, Prieto RM, et al. Urinary phytate in calcium oxalate stone formers and healthy people–dietary effects on phytate excretion. Scand J Urol Nephrol. 2000;34(3):162-164. 96. Obligado SH, Goldfarb DS. The association of nephrolithiasis with hypertension and obesity: a review. Am J Hypertens. 2008;21(3): 257-264. 97. Lieske JC, de la Vega LS, Gettman MT, et al. Diabetes mellitus and the risk of urinary tract stones: a population-based case-control study. Am J Kidney Dis. 2006;48(6):897-904. 98. Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-462. 99. Maalouf NM, Sakhaee K, Parks JH, Coe FL, Adams-Huet B, Pak CY. Association of urinary pH with body weight in nephrolithiasis. Kidney Int. 2004;65(4):1422-1425. 100. Maalouf NM, Cameron MA, Moe OW, Sakhaee K. Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Neph- rol Hypertens. 2004;13(2):181-189. 101. Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric acid nephrolithiasis. J Am Soc Nephrol. 2006;17(5):1422-1428. 102. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005;293(1):43-53. 103. Knight J, Assimos DG, Easter L, Holmes RP. Metabolism of fructose to oxalate and glycolate. Horm Metab Res. 2010;42(12):868-873. 104. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and ca- pacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047. 105. Rodman JS, Blackburn P, Williams JJ, Brown A, Pospischil MA, Peterson CM. The effect of dietary protein on cystine excretion in patients with cystinuria. Clin Nephrol. 1984;22(6):273-278. 106. Rodriguez LM, Santos F, Malaga S, Martinez V. Effect of a low sodium diet on urinary elimination of cystine in cystinuric children. Nephron. 1995;71(4):416-418. 107. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH collaborative research group. N Engl J Med. 1997;336(16):1117-1124. Heilberg and Goldfarb 174

articulo 3.pdf

Vous êtes en train de lire un aperçu.

Consultez-les par la suite

articulo 3.pdf

Plus De Contenu Connexe

Similaire à articulo 3.pdf (20)

Plus récents (20)

articulo 3.pdf

articulo 3.pdf

Vous êtes en train de lire un aperçu.

articulo 3.pdf

Suggestions

Plus De Contenu Connexe

Similaire à articulo 3.pdf (20)

Plus récents (20)

articulo 3.pdf