Beverages, diet, and prevention of kidney stones.

Abstract

This month's discussion . . .The Journal Club focuses on a recent article entitled “Beverage Use and Risk for Kidney Stones in Women” (Annals of Internal Medicine 128:534-540, 1998) by Gary C. Curhan, Walter C. Willett, Frank E. Speizer, and Meir J. Stampfer.THE ROLE of diet in kidney stone formation has been studied extensively and is the subject of abundant advice given to stone formers. Stone formers themselves are particularly likely to seek dietary advice, correctly associating nephrolithiasis with the maladies caused (in part) by our society's well-publicized dietary excesses. The long-term and sporadic nature of stone disease also contributes to patients being reluctant to accept pharmacological therapy, optimistic that lightning will not strike again, and having heard about one more drug recall on the evening news.We therefore welcome another interesting study by Curhan and colleagues regarding the risk of stone formation associated with the ingestion of specific beverages.1Curhan GC Willett WC Speizer FE Stampfer MJ Beverage use and risk for kidney stones in women.Ann Intern Med. 1998; 128: 534-540Crossref PubMed Scopus (221) Google Scholar This prospective cohort study is an analysis of data gathered as part of the Nurses' Health Study, which includes data from 121,700 female nurses 30 to 55 years of age.2Colditz GA The Nurses' Health Study: A cohort of US women followed since 1976.J Am Med Womens Assoc. 1995; 50: 40-63PubMed Google Scholar These women were bienially questioned by mail about diet, lifestyle, and disease. The questionnaires administered were not identical at each interval, so detailed portion size and frequency information regarding 18 beverages, including water, was available only in 1986 and 1990. Elicitation of kidney stone diagnoses was performed in 1992 and 1994, and only cases that occurred between 1986 and 1994 were accepted. As a result of the timing of these questionnaires, and lacking some sense of the duration of preceding use of any individual beverage, there remains uncertainty regarding the relationship between the beverage history and the onset of nephrolithiasis. Care was taken to validate the dates of onset of stones and the legitimacy of the diagnoses. The availability of measures of dietary intake also allowed multivariate analysis controlled for energy-adjusted nutrient intake. After eliminating women with a previous history of kidney stones, there remained 81,093 women with appropriate data for analysis, and 719 incident symptomatic stones. No measures of urinary composition were made.The results were especially notable for the apparent protective effect of coffee, tea, and wine, and an adverse effect of grapefruit juice ingestion on stone formation. Although physiological explanations for these effects can be offered, the results cannot be wholly understood without detailed measures of urinary composition and lithogenicity over long periods, the sort of study that has never been performed. Short-term studies of urine composition may fail to correlate with clinical effects of foods or beverages, and the effects of food and beverages in turn may vary with time, particularly as epithelial transporters and serum levels of hormones respond to changes in intake.Conversely, the expected beneficial effect of total fluid intake on stone formation was observed. A relative risk of stone formation of 0.62 was shown in the comparison of the highest quintile of fluid intake to the lowest. This benefit of increased ingested volume correlates with the reduction in urinary supersaturation of calcium oxalate that arises from the resultant increase in urinary volume.3Coe FL Parks JH Asplin JR The pathogenesis and treatment of kidney stones: Medical Progress.N Engl J Med. 1992; 327: 1141-1152Crossref PubMed Scopus (620) Google Scholar This finding, in close agreement with our pathophysiologic understanding of the primacy of supersaturation as a risk factor for stone disease, helps validate the authors' data and conclusions.The finding of an increased risk of stones with ingestion of grapefruit juice more than once per week, and the protective effects of coffee, tea, and wine, are especially interesting because the authors' previous study of beverage use in men showed similar associations.4Curhan 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: 240-247Crossref PubMed Scopus (247) Google Scholar In that article, using data from the Health Professional Follow-up Study, the authors examined the association of stones and 21 beverages in more than 45,000 previously non–stone-forming men. In men, as opposed to women, apple juice consumption was directly correlated with stone formation, and beer was protective. The effects of coffee, tea, wine, and grapefruit juice were similar in both studies. The congruency between these two studies performed in distinct populations, though with similar ascertainment methods for dietary recall and incidence of stones, strengthens the credibility of these associations.Nonetheless, the findings regarding grapefruit juice in both of these studies are unexpected. Other studies of urinary lithogenicity after short-term ingestion (no more than 1 week) of citrus fruit juices, though not grapefruit juice, have suggested that other citrus juices may prevent, not stimulate, kidney stone formation. Orange juice5Coe FL Parks JH Webb DR Stone-forming potential of milk or calcium-fortified orange juice in idiopathic hypercalciuric adults.Kidney Int. 1992; 41: 139-142Crossref PubMed Scopus (22) Google Scholar, 6Wabner CL Pak CY Effect of orange juice consumption on urinary stone risk factors.J Urol. 1993; 149: 1405-1408PubMed Google Scholar and diluted lemon juice,7Seltzer MA Low RK McDonald M Shami GS Stoller ML Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis.J Urol. 1996; 156: 907-909Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar are associated with either no change or an increase in urinary oxalate excretion, which is largely negated by increased urinary citrate excretion and decreased urinary calcium excretion. If grapefruit juice stimulates stone formation, it must be that either it has significantly different effects on urinary composition than other citrus juices, or that the measurements of urinary composition in these short-term studies fail to accurately predict long-term outcomes. If this is true, it might be because of changes in urinary analytes other than those currently measured and understood.Is there a basis for thinking that grapefruit juice would lead to an effect different from that of other juices? Grapefruit juice has peculiar properties that have recently been elucidated.8Lown KS Bailey DG Fontana RJ Janardan SK Adair CH Fortlage LA Brown MB Guo W Watkins PB Grapefruit juice increased felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.J Clin Invest. 1997; 99: 2545-2553Crossref PubMed Scopus (598) Google Scholar It is well known to increase absorption of many drugs such as cyclosporin, terfenadine, calcium channel blockers, and others. The juice appears to cause a significant reduction in enterocyte content of CYP3A4, a P450 cytochrome enzyme also present in the liver. The enzyme is responsible for substantial drug metabolism and thereby diminishes the amount of drug available for absorption. Diminished enterocyte content of the enzyme is found within 4 hours of ingestion of grapefruit juice,9Schmiedlin-Ren P Edwards DJ Fitzsimmons ME He K Lown KS Woster PM Rahman A Thummel KE Fisher JM Hollenberg PF Watkins PB Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents.Drug Metab Dispos. 1997; 25: 1228-1233PubMed Google Scholar and increased drug absorption is demonstrable at that interval. This effect is magnified after 1 week of persistent grapefruit juice ingestion.8Lown KS Bailey DG Fontana RJ Janardan SK Adair CH Fortlage LA Brown MB Guo W Watkins PB Grapefruit juice increased felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.J Clin Invest. 1997; 99: 2545-2553Crossref PubMed Scopus (598) Google Scholar Efforts to determine the juice constituent responsible for this effect have focused on a number of novel substances, including flavonoids such as naringin10Ameer B Weintraub RA Drug interactions with grapefruit juice.Clin Pharmacokinet. 1997; 33: 103-121Crossref PubMed Scopus (269) Google Scholar and furanocoumarins.9Schmiedlin-Ren P Edwards DJ Fitzsimmons ME He K Lown KS Woster PM Rahman A Thummel KE Fisher JM Hollenberg PF Watkins PB Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents.Drug Metab Dispos. 1997; 25: 1228-1233PubMed Google Scholar, 11Fukuda K Ohta T Oshima Y Ohashi N Yoshikawa M Yamazoe Y Specific CYP3A4 inhibitors in grapefruit juice: Furocoumarin dimers as components of drug interaction.Pharmacogenetics. 1997; 7: 391-396Crossref PubMed Scopus (192) Google Scholar One recent study showed that 6′,7′-dihydroxybergamottin, the major grapefruit juice constituent of the latter class, has significant activity accelerating CYP3A4 degradation.9Schmiedlin-Ren P Edwards DJ Fitzsimmons ME He K Lown KS Woster PM Rahman A Thummel KE Fisher JM Hollenberg PF Watkins PB Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents.Drug Metab Dispos. 1997; 25: 1228-1233PubMed Google Scholar Most recent studies of grapefruit juice effects on pharmacokinetics did not include other citrus juices as controls. Despite these many interesting observations, any role of CYP3A4 on net intestinal transport of oxalate or other substances relevant to stone formation has not been specifically determined and therefore cannot yet explain the association of grapefruit juice and stone formation.The abilities of coffee and tea in both the authors' studies to protect against stone formation are also unexplained. This result highlights the difficulty of translating food and beverage oxalate content into stone risk. The authors speculate that caffeine contributes to the reduction in stone formation by causing urinary dilution. But these beverages, particularly tea, are reported to contain enough oxalate that they appear on most lists of restricted items given patients with calcium oxalate stone disease.12Massey LK Sutton RAL Modification of dietary oxalate and calcium reduces urinary oxalate in hyperoxaluric patients with kidney stones.J Am Diet Assoc. 1993; 93: 1305-1307Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar However, the methods by which oxalate are measured are flawed; both enzyme-dependent and colorimetric methods suffer from lack of specificity and interference by endogenous substances. In addition, not all oxalate in food is available for absorption, much of it being complexed by calcium and in other insoluble forms.13Heaney RP Weaver CM Recker RR Calcium absorbability from spinach.Am J Clin Nutr. 1988; 47: 707-709PubMed Google Scholar, 14Massey LK Roman-Smith H Sutton RAL Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate stones.J Am Diet Assoc. 1993; 93: 901-906Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar The method of food preparation affects the oxalate content and the proportion that is soluble as well. Many of the fruits and vegetables with moderate oxalate content that appear on lists of restricted food also contain citrate and other organic anions that lead to increases in urinary citrate excretion. Many studies of oxalate excretion fail to measure urine citrate, organic anions, supersaturation, or the upper limit of calcium oxalate metastability concomitantly. They therefore fail to measure the real effect of various foods on lithogenicity. A final practical problem with oxalate restriction is that patients who need to reduce their risk of cardiovascular mortality are confused and exasperated when the standard oxalate restriction list further narrows the range of fruits and vegetables they are permitted.The current study identifies prospective dietary risk factors for stone formation, and the authors reasonably suggest that their results be used to counsel patients who have already formed stones. The recent experience of the Modification of Diet in Renal Disease study made quite clear the time-consuming and costly effort required to stimulate a modest level of compliance with a chronic alteration in dietary regimen.15Klahr S Levey AS Beck GJ Caggiula AW Hunsicker L Kusek JW Striker G The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease: Modification of Diet in Renal Disease Study Group.N Engl J Med. 1994; 330: 877-884Crossref PubMed Scopus (2028) Google Scholar That effort was intended to ward off chronic renal failure, a clearly more ominous and life-threatening eventuality than recurrent stone disease. We doubt that dietary modification, with the exception of augmenting fluid intake, for stone disease is durable. Adequate randomized trials of dietary interventions for stone disease, with stone recurrence, not changes in urinary composition, as the primary end point, will probably never be performed given these realities. We therefore can continue to choose between the results of well-designed epidemiologic studies such as this one, and short-term measures of urinary composition. On the evidence we have thus far, the theoretic bases for moderate protein and salt restriction and increased fluid intake appear sound. We also can acknowledge that safe, inexpensive pharmacological therapy has been proved effective for many patients and may make dietary therapy less compelling for patients with recurrent stones.16Parks JH Coe FL The financial effects of kidney stone prevention.Kidney Int. 1996; 50: 1706-1712Crossref PubMed Scopus (107) Google Scholar This month's discussion . . .The Journal Club focuses on a recent article entitled “Beverage Use and Risk for Kidney Stones in Women” (Annals of Internal Medicine 128:534-540, 1998) by Gary C. Curhan, Walter C. Willett, Frank E. Speizer, and Meir J. Stampfer. This month's discussion . . .The Journal Club focuses on a recent article entitled “Beverage Use and Risk for Kidney Stones in Women” (Annals of Internal Medicine 128:534-540, 1998) by Gary C. Curhan, Walter C. Willett, Frank E. Speizer, and Meir J. Stampfer. This month's discussion . . . The Journal Club focuses on a recent article entitled “Beverage Use and Risk for Kidney Stones in Women” (Annals of Internal Medicine 128:534-540, 1998) by Gary C. Curhan, Walter C. Willett, Frank E. Speizer, and Meir J. Stampfer. THE ROLE of diet in kidney stone formation has been studied extensively and is the subject of abundant advice given to stone formers. Stone formers themselves are particularly likely to seek dietary advice, correctly associating nephrolithiasis with the maladies caused (in part) by our society's well-publicized dietary excesses. The long-term and sporadic nature of stone disease also contributes to patients being reluctant to accept pharmacological therapy, optimistic that lightning will not strike again, and having heard about one more drug recall on the evening news. We therefore welcome another interesting study by Curhan and colleagues regarding the risk of stone formation associated with the ingestion of specific beverages.1Curhan GC Willett WC Speizer FE Stampfer MJ Beverage use and risk for kidney stones in women.Ann Intern Med. 1998; 128: 534-540Crossref PubMed Scopus (221) Google Scholar This prospective cohort study is an analysis of data gathered as part of the Nurses' Health Study, which includes data from 121,700 female nurses 30 to 55 years of age.2Colditz GA The Nurses' Health Study: A cohort of US women followed since 1976.J Am Med Womens Assoc. 1995; 50: 40-63PubMed Google Scholar These women were bienially questioned by mail about diet, lifestyle, and disease. The questionnaires administered were not identical at each interval, so detailed portion size and frequency information regarding 18 beverages, including water, was available only in 1986 and 1990. Elicitation of kidney stone diagnoses was performed in 1992 and 1994, and only cases that occurred between 1986 and 1994 were accepted. As a result of the timing of these questionnaires, and lacking some sense of the duration of preceding use of any individual beverage, there remains uncertainty regarding the relationship between the beverage history and the onset of nephrolithiasis. Care was taken to validate the dates of onset of stones and the legitimacy of the diagnoses. The availability of measures of dietary intake also allowed multivariate analysis controlled for energy-adjusted nutrient intake. After eliminating women with a previous history of kidney stones, there remained 81,093 women with appropriate data for analysis, and 719 incident symptomatic stones. No measures of urinary composition were made. The results were especially notable for the apparent protective effect of coffee, tea, and wine, and an adverse effect of grapefruit juice ingestion on stone formation. Although physiological explanations for these effects can be offered, the results cannot be wholly understood without detailed measures of urinary composition and lithogenicity over long periods, the sort of study that has never been performed. Short-term studies of urine composition may fail to correlate with clinical effects of foods or beverages, and the effects of food and beverages in turn may vary with time, particularly as epithelial transporters and serum levels of hormones respond to changes in intake. Conversely, the expected beneficial effect of total fluid intake on stone formation was observed. A relative risk of stone formation of 0.62 was shown in the comparison of the highest quintile of fluid intake to the lowest. This benefit of increased ingested volume correlates with the reduction in urinary supersaturation of calcium oxalate that arises from the resultant increase in urinary volume.3Coe FL Parks JH Asplin JR The pathogenesis and treatment of kidney stones: Medical Progress.N Engl J Med. 1992; 327: 1141-1152Crossref PubMed Scopus (620) Google Scholar This finding, in close agreement with our pathophysiologic understanding of the primacy of supersaturation as a risk factor for stone disease, helps validate the authors' data and conclusions. The finding of an increased risk of stones with ingestion of grapefruit juice more than once per week, and the protective effects of coffee, tea, and wine, are especially interesting because the authors' previous study of beverage use in men showed similar associations.4Curhan 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: 240-247Crossref PubMed Scopus (247) Google Scholar In that article, using data from the Health Professional Follow-up Study, the authors examined the association of stones and 21 beverages in more than 45,000 previously non–stone-forming men. In men, as opposed to women, apple juice consumption was directly correlated with stone formation, and beer was protective. The effects of coffee, tea, wine, and grapefruit juice were similar in both studies. The congruency between these two studies performed in distinct populations, though with similar ascertainment methods for dietary recall and incidence of stones, strengthens the credibility of these associations. Nonetheless, the findings regarding grapefruit juice in both of these studies are unexpected. Other studies of urinary lithogenicity after short-term ingestion (no more than 1 week) of citrus fruit juices, though not grapefruit juice, have suggested that other citrus juices may prevent, not stimulate, kidney stone formation. Orange juice5Coe FL Parks JH Webb DR Stone-forming potential of milk or calcium-fortified orange juice in idiopathic hypercalciuric adults.Kidney Int. 1992; 41: 139-142Crossref PubMed Scopus (22) Google Scholar, 6Wabner CL Pak CY Effect of orange juice consumption on urinary stone risk factors.J Urol. 1993; 149: 1405-1408PubMed Google Scholar and diluted lemon juice,7Seltzer MA Low RK McDonald M Shami GS Stoller ML Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis.J Urol. 1996; 156: 907-909Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar are associated with either no change or an increase in urinary oxalate excretion, which is largely negated by increased urinary citrate excretion and decreased urinary calcium excretion. If grapefruit juice stimulates stone formation, it must be that either it has significantly different effects on urinary composition than other citrus juices, or that the measurements of urinary composition in these short-term studies fail to accurately predict long-term outcomes. If this is true, it might be because of changes in urinary analytes other than those currently measured and understood. Is there a basis for thinking that grapefruit juice would lead to an effect different from that of other juices? Grapefruit juice has peculiar properties that have recently been elucidated.8Lown KS Bailey DG Fontana RJ Janardan SK Adair CH Fortlage LA Brown MB Guo W Watkins PB Grapefruit juice increased felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.J Clin Invest. 1997; 99: 2545-2553Crossref PubMed Scopus (598) Google Scholar It is well known to increase absorption of many drugs such as cyclosporin, terfenadine, calcium channel blockers, and others. The juice appears to cause a significant reduction in enterocyte content of CYP3A4, a P450 cytochrome enzyme also present in the liver. The enzyme is responsible for substantial drug metabolism and thereby diminishes the amount of drug available for absorption. Diminished enterocyte content of the enzyme is found within 4 hours of ingestion of grapefruit juice,9Schmiedlin-Ren P Edwards DJ Fitzsimmons ME He K Lown KS Woster PM Rahman A Thummel KE Fisher JM Hollenberg PF Watkins PB Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents.Drug Metab Dispos. 1997; 25: 1228-1233PubMed Google Scholar and increased drug absorption is demonstrable at that interval. This effect is magnified after 1 week of persistent grapefruit juice ingestion.8Lown KS Bailey DG Fontana RJ Janardan SK Adair CH Fortlage LA Brown MB Guo W Watkins PB Grapefruit juice increased felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.J Clin Invest. 1997; 99: 2545-2553Crossref PubMed Scopus (598) Google Scholar Efforts to determine the juice constituent responsible for this effect have focused on a number of novel substances, including flavonoids such as naringin10Ameer B Weintraub RA Drug interactions with grapefruit juice.Clin Pharmacokinet. 1997; 33: 103-121Crossref PubMed Scopus (269) Google Scholar and furanocoumarins.9Schmiedlin-Ren P Edwards DJ Fitzsimmons ME He K Lown KS Woster PM Rahman A Thummel KE Fisher JM Hollenberg PF Watkins PB Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents.Drug Metab Dispos. 1997; 25: 1228-1233PubMed Google Scholar, 11Fukuda K Ohta T Oshima Y Ohashi N Yoshikawa M Yamazoe Y Specific CYP3A4 inhibitors in grapefruit juice: Furocoumarin dimers as components of drug interaction.Pharmacogenetics. 1997; 7: 391-396Crossref PubMed Scopus (192) Google Scholar One recent study showed that 6′,7′-dihydroxybergamottin, the major grapefruit juice constituent of the latter class, has significant activity accelerating CYP3A4 degradation.9Schmiedlin-Ren P Edwards DJ Fitzsimmons ME He K Lown KS Woster PM Rahman A Thummel KE Fisher JM Hollenberg PF Watkins PB Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents.Drug Metab Dispos. 1997; 25: 1228-1233PubMed Google Scholar Most recent studies of grapefruit juice effects on pharmacokinetics did not include other citrus juices as controls. Despite these many interesting observations, any role of CYP3A4 on net intestinal transport of oxalate or other substances relevant to stone formation has not been specifically determined and therefore cannot yet explain the association of grapefruit juice and stone formation. The abilities of coffee and tea in both the authors' studies to protect against stone formation are also unexplained. This result highlights the difficulty of translating food and beverage oxalate content into stone risk. The authors speculate that caffeine contributes to the reduction in stone formation by causing urinary dilution. But these beverages, particularly tea, are reported to contain enough oxalate that they appear on most lists of restricted items given patients with calcium oxalate stone disease.12Massey LK Sutton RAL Modification of dietary oxalate and calcium reduces urinary oxalate in hyperoxaluric patients with kidney stones.J Am Diet Assoc. 1993; 93: 1305-1307Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar However, the methods by which oxalate are measured are flawed; both enzyme-dependent and colorimetric methods suffer from lack of specificity and interference by endogenous substances. In addition, not all oxalate in food is available for absorption, much of it being complexed by calcium and in other insoluble forms.13Heaney RP Weaver CM Recker RR Calcium absorbability from spinach.Am J Clin Nutr. 1988; 47: 707-709PubMed Google Scholar, 14Massey LK Roman-Smith H Sutton RAL Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate stones.J Am Diet Assoc. 1993; 93: 901-906Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar The method of food preparation affects the oxalate content and the proportion that is soluble as well. Many of the fruits and vegetables with moderate oxalate content that appear on lists of restricted food also contain citrate and other organic anions that lead to increases in urinary citrate excretion. Many studies of oxalate excretion fail to measure urine citrate, organic anions, supersaturation, or the upper limit of calcium oxalate metastability concomitantly. They therefore fail to measure the real effect of various foods on lithogenicity. A final practical problem with oxalate restriction is that patients who need to reduce their risk of cardiovascular mortality are confused and exasperated when the standard oxalate restriction list further narrows the range of fruits and vegetables they are permitted. The current study identifies prospective dietary risk factors for stone formation, and the authors reasonably suggest that their results be used to counsel patients who have already formed stones. The recent experience of the Modification of Diet in Renal Disease study made quite clear the time-consuming and costly effort required to stimulate a modest level of compliance with a chronic alteration in dietary regimen.15Klahr S Levey AS Beck GJ Caggiula AW Hunsicker L Kusek JW Striker G The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease: Modification of Diet in Renal Disease Study Group.N Engl J Med. 1994; 330: 877-884Crossref PubMed Scopus (2028) Google Scholar That effort was intended to ward off chronic renal failure, a clearly more ominous and life-threatening eventuality than recurrent stone disease. We doubt that dietary modification, with the exception of augmenting fluid intake, for stone disease is durable. Adequate randomized trials of dietary interventions for stone disease, with stone recurrence, not changes in urinary composition, as the primary end point, will probably never be performed given these realities. We therefore can continue to choose between the results of well-designed epidemiologic studies such as this one, and short-term measures of urinary composition. On the evidence we have thus far, the theoretic bases for moderate protein and salt restriction and increased fluid intake appear sound. We also can acknowledge that safe, inexpensive pharmacological therapy has been proved effective for many patients and may make dietary therapy less compelling for patients with recurrent stones.16Parks JH Coe FL The financial effects of kidney stone prevention.Kidney Int. 1996; 50: 1706-1712Crossref PubMed Scopus (107) Google Scholar