Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis

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1 Kidney Interntionl, Vol. 57 (2000), pp Effects of low niml protein or high-fiber diets on urine composition in clcium nephrolithisis MICHEL ROTILY, FRANÇOISE LÉONETTI, CECILIA IOVANNA, PATRICE BERTHEZENE, PATRICIA DUPUY, ALAIN VAZI, nd YVON BERLAND Centre d Investigtions Clinique, Sinte Mrguerite, APHM-INSERM; ORS PACA-INSERM U379; Service de Néphrologie, Hôpitl Sinte-Mrguerite; nd INSERM U315, Mrseille, Frnce Effects of low niml protein or high-fiber diets on urine composition in clcium nephrolithisis. Bckground. The purpose of this rticle is to evlute the impct of low protein nd high fiber intkes on risk fctors of stone recurrence in idiopthic clcium stone formers (ICSFs). Methods. Ninety-six ICSFs were rndomly ssigned low niml protein diet ( 10% of totl energy), high-fiber diet ( 25 g/dy), or usul diet (control group); ll ptients were recommended to increse their fluid intke. Their dily urine compositions were nlyzed t bseline nd t four months. Complince with dietry recommendtions ws checked by vlidted food frequency questionnires. Complince with totl nd niml protein intkes ws ssessed by 24-hour ure nd sulfte outputs, respectively. The nutritionl intervention (orl instructions, written leflet, phoning) nd food ssessment were crried out by reserch dietitin. Results. At bseline, diets nd the dily urine composition did not differ between the three groups. At four months, while diets differed significntly, the 24-hour output of clcium nd oxlte did not differ significntly within nd between groups fter djustment for potentil confounders (ge, sex, nd per- sonl nd fmily history of clcium stones) nd bseline vlues. However, s mny s 12 out of 31 ICSFs (95% CI, 22 to 58%) ssigned to low niml protein diet chieved reduction in the urine ure excretion rte of more thn 50 mmol/dy nd lso exhibited significnt decrese in urinry clcium excretion tht verged 1.8 mmol/dy. A significnt correltion between ure nd clcium outputs ws observed only mong ptients with hyperclciuri. Conclusions. These results show tht only ICSFs who mrkedly decrese their niml protein intke, especilly those with hyperclciuri, cn expect to benefit from dietry recommend- tions. Nephrolithisis hs incresed drmticlly since the Second World Wr [1] nd is recognized s public Key words: renl stones, urinry lithisis, fiber diet, kidney clculi, idiopthic stone formers. Received for publiction Februry 4, 1999 nd in revised form October 7, 1999 Accepted for publiction October 11, by the Interntionl Society of Nephrology helth problem [2, 3]. Estimtes of its prevlence rnge from 1% to s high s 5% in the generl popultion of industrilized countries [4, 5]. The nnul incidence ws estimted to be between 1 nd 3 per 1000 inhbitnts [4, 6], with 50% of relpses every four yers [7]. Clcium stones, the most prevlent type of nephrolithisis, result from severl metbolic defects. The combined role of genetic nd nutritionl fctors, especilly protein nd dietry fiber, in the formtion of clcium oxlte kidney stones hs been suggested in metbolic investigtions [8 12], cse control studies [3, 13 17], nd interntionl ecologic correltion studies [18 20]. Only one prospective study hs been published so fr, nd it showed tht dietry intkes of niml protein nd, bove ll, clcium were directly nd independently ssocited with the risk of stone formtion [21]. However, lthough idiopthic clcium stone formers (ICSFs) re encourged to reduce niml protein in their diet [6, 22, 23], the protective effect of such diet hs not been demonstrted by controlled clinicl trils. One tril showed tht the risk of stone recurrence in the dietry intervention group ws 5.6 [95% confidence intervl (CI), 1.2 to 26.1], reltive to the control group, fter djustment for possible con- founding effects of ge, sex, eduction, nd bseline pro- tein nd fluid intke [24]. The uthors concluded tht the dvice for ICSFs to follow low niml protein, high-fiber, high-fluid diet hs no dvntge over dvice to increse only fluid intke. However, in tht study, the decrese in 24-hour output of ure ws not significnt, which mkes it unlikely tht the diet hd ny impct. Also, the incidence of recurrent stone ws not significntly different mong the 32 ICSFs who reported men protein intke lower thn 70 g/dy (6.6 vs. 3 out of 100 person yers, P 0.24); ptients did not significntly increse their dietry fiber intke, which did not differ significntly between the intervention group nd the control group. Furthermore, the uthors did not tke into ccount clcium intke, which is considered protective fctor by Curhn et l [21]. 1115

2 1116 Rotily et l: Diet nd idiopthic clcium stones Consequently, further reserch, including sttisticl servtive. The smples were stored t 80 C, nd ll modeling, is needed to re-exmine the vlidity nd the mesurements were crried out t the sme time by effectiveness of current dietry recommendtions [1]. two trined technicins. Smples were ll mesured by We thus sought to determine whether decrese in protein DAX utonlyzer (Byer Dignosis ) for sodium, intke or n increse in totl dietry fiber cn pre- potssium, phosphte, clcium, ure, cretinine, nd vent recurrence in ICSFs during the four yers following urte. Oxlte ws mesured by n enzymtic method n episode of urinry clcium lithisis. We nlyzed the (Biore ) [25, 26], citrte by spectrophotometer (Boehringer-Mnnheim influence of low niml protein diet, high-fiber diet kit) [27]; sulfte ws mesured turinfluence (HFD), nd control diet on urinry solute excretion bidometriclly [28]. Urinry solutes were expressed in t four months. mmol/dy. The ccurcy of the individul dily urine collection ws evluted on the bsis of their cretinine content in reltionship to body weight [29] nd to creti- METHODS nine content predicted on the bsis of ge, sex, nd body Prticipnt selection weight through the Cockroft nd Gult formuls [30]. Prticipnts were recruited mong ptients ttending The net gstrointestinl bsorption of lkli (expressed our nephrology outptient clinic between Jnury 1996 in meq/24 h), subsequently referred to s GI-lkli, nd Jnury ICSFs were included regrdless of ws derived from 24-hour urine excretions of noncom- the number of stone episodes. The dignosis of clcium bustible ctions nd nions ccording to the formul: stones ws bsed on spontneous or surgicl stone elimintion (N K C Mg) (Cl 1.8 P), where electrolyte or bdominl rdiogrph nd ultrsound exmi- excretions re in meq/dy, except for P, which is in ntion. All ptients were evluted in our center for mmol/dy, with n verge vlence of 1.8 [9]. The reltive clinicl investigtions to exclude those with metbolic COx sturtion rtio ws clculted with EQUIL93 or urologicl cuse of stone formtion. Persons eligible softwre [31]. for the tril hd to be over 18 nd less thn 70 yers of ge, spek French, understnd dietry instructions, live Dietry ssessment close to our center, nd hve no pln to move in the All prticipnts were interviewed bout their diet over next months. Ptients on diet for other metbolic disorders the lst month by reserch dietitin using stndrdized or for urinry lithisis were lso excluded. Written semiquntittive food frequency questionnire [32, 33]. informed consent ws obtined from ech prticipnt, Nutrients were clculted from the ntionl food compo- nd the ethics committee pproved the tril. sition tble [34, 35]. Questionnire results were compred Among the 108 idiopthic ICSF included in our study, with seven-dy diet records collected simultne- 12 (11%) left the tril during the four months of follow- ously with the bseline evlution nd t four months. up (3 moved nd 9 did not succeed in stying on the The two methods were significntly correlted for the diet). The proportion of ptients who dropped out of nutrient mesures: energy, totl protein, niml protein, the study did not differ significntly between the three totl fiber, nd clcium intke. Correltion coefficients groups (5 in the control group, 4 in the LAPD, nd 3 in rnged from 0.47 for clcium to 0.63 for dietry fiber the HFD group, P 0.56). These 12 ptients did not (P 10 3 ). In this nlysis, we used nutrient intkes differ in ge, sex, eduction, personl nd fmily history evluted by the food frequency questionnires. of clcium stones, nd dily lcohol consumption. However, they hd higher body mss index (25.5 vs., 23.5, Nutritionl intervention P 0.03) nd lower outputs of clcium (4.94 vs. 6.26, P After giving informed consent, prticipnts were rndomized 0.04), oxlte (0.20 vs. 0.31, P 0.03), nd ure (305.9 from list of rndom numbers to receive in- vs , P 0.02). Hence, 96 ICSFs were followed up. struction either on low niml protein diet (LAPD group) or on high fiber diet (HFD group). No dietry Dt collection recommendtion ws given to persons included in the All ptients recruited with dignosis of idiopthic control group. clcium stone disese were invited in our center for clini- The LAPD group ws instructed to decrese their cl investigtions, where food questionnires were given, intke of niml protein by limiting their consumption urine ws collected, nd biochemicl prmeters were of met, fish, nd cooked pork to three servings per week nlyzed by trined stff t bseline nd fter four nd milk products (milk, cheese, nd yogurt) to 100 g months for the three diets. The initil interview included per dy (milk nd cheese). The trget ws to obtin fmily nd personl history of stone formtion, eduction, dily contribution of niml protein to energy of less nd lcohol nd tobcco consumption. thn 10%. Insted of protein, they were counseled to We collected the 24-hour urinry output of urine t et refined cerels (tht is, pst nd rice). bseline nd t four months. Thymol ws the urine pre- The HFD group ws instructed to increse their intke

3 Rotily et l: Diet nd idiopthic clcium stones 1117 of rw nd dried fruit, vegetbles, nd to substitute their the lst episode of urinry lithisis, nd dily lcohol usul cerels with whole grin dietry products in order consumption (Tble 1). Only the proportion of men ws to limit the increse in energy. The trget ws to obtin higher in the LAPD group thn in the control nd in the dily totl fiber intke of more thn 25 g. HFD groups. Eighty eight percent of men were mrried; The dietitin instructed ll prticipnts in the LAPD 46% of men nd 45% of women reported tht they hd nd HFD groups nd, for men, their spouses or fmily, eten t lest twice week outside. When they hd eten by describing llowble niml protein intke or sources outside their homes, 27% hd prepred their mel t of fiber nd how to follow the diet. Leflets with detiled home. The others hd eten in stff cfeteri (30%) informtion on clcium stone disese, dietry recom- or resturnt (35%), or they hd eten snck (8%). mendtions, nd pproprite recipes were given to these Of the 96 prticipnts, 37% hd hyperclciuri ( 0.1 ptients. The sme dietitin clled them four times dur- mmol/kg/dy); tht proportion did not differ mong the ing the four months to help them chnge their dietry three groups. The proportion of ptients recruited during hbits, to counsel them, nd to check the complince summer time (June through September) did not differ with dietry instructions. significntly between the control, LAPD, nd HFD groups All prticipnts, including those in the control group, (29, 29, nd 44%, respectively). In the sme wy, the were recommended to mintin high-wter intke. proportion of ptients exmined t four months during They were given leflet with informtion bout the the summer months did not differ significntly (48, 28, benefits of dily wter intke nd how to increse it by nd 25%, respectively, P 0.22). drinking eight glsses of tp wter (2 L per dy) t fixed times; the clcium concentrtion of tp wter vilble Dietry intke ssessments in Mrseille is 100 mg/l. The ttending physicin did Dietry intke ssessment t bseline did not differ not recommend ny modifiction in dietry hbits but significntly between the three groups (Tble 2). After did insist on n increse in fluid intke. four months, the nutrient intke did not chnge significntly in the control group, but it chnged drmticlly Sttisticl nlysis in the LAPD nd HFD groups. In the LAPD group, Results re presented s group mens nd stndrd totl nd niml protein intke decresed significntly; devitions. Proportions were compred by the 2 Person 31 out of 34 subjects chieved the intervention trget sttistic. The citrte output nd the time elpsed since ( 10% of clories from niml proteins). In the HFD the lst episode of urinry lithisis, neither of which were group, energy nd totl fiber nd clcium intkes incresed normlly distributed, were nturl-log trnsformed for significntly; 27 out of 31 subjects chieved the Person correltion nlyses nd significnce testing of intervention trget (totl fiber intke 25 g/dy). Totl differences between groups. Anlysis of vrince ws protein intke did not chnge fter four months in the used to compre nutrient intkes nd urinry prmeters HFD group. In contrst, their niml protein intke decresed t bseline nd t four months mong the three groups. significntly, but tht decrese ws significntly Anlysis of covrince tht took into ccount the bse- greter in the LAPD group. line vlues ws used to compre nutrient intkes nd urinry prmeters t four months only in controls nd Dily urine composition t bseline nd t four months ptients who complied with either of the diets (less thn Both t bseline nd t four months, the cretinine 10% of totl energy brought by niml proteins in the excretion rtes for ll urine collected by the 96 ptients LAPD group; dietry fiber intke greter thn 25 per were significntly correlted with their body weights (r dy in the HFD group). Pired t-test nd Wilcoxon test 0.64, P 10 4 ) nd with predicted urinry cretinine were used to compre the differences in urinry prme- content (r 0.55, P 10 4 ). These dt indicte tht ters within intervention groups between bseline nd t the prticipnts collected their urine smples with re- four months. Multiple regression nlyses were per- sonble ccurcy. formed to explin the vrince of urinry prmeters by The mens of dily urine composition for ech group nutrient intke nd personl chrcteristics. P vlues of re shown in Tble 3. On the whole, there ws no significnt lower thn 0.05 were considered significnt. All nlyses difference in urinry solute excretion between were done with SPSS softwre (version 8.0). groups both t bseline nd t four months mong subjects who complied with the nutritionl recommendtions (Tble 3). RESULTS Wheres 24-hour urinry volume did not chnge in Smple chrcteristics the LAPD group, it decresed significntly in the control The LAPD, HFD, nd control groups did not differ in ge, eduction, weight, height, body mss index, personl nd fmily history of clcium stones, time elpsed since nd the HFD groups. As expected, the LAPD group showed significnt decrese in ure nd sulfte excretion nd to some extent in cretininuri. Citrturi lso

4 1118 Rotily et l: Diet nd idiopthic clcium stones Tble 1. Demogrphic chrcteristics nd history of study subjects with t lest one documented kidney stone Vrible Control group LAPD group HFD group Totl P Smple size Men % Age yers (men SD) Eduction yers; % 12 y y y Weight kg (men SD) Height cm (men SD) Body mss index kg/m 2 (men SD) Fmily history of kidney stones % No One prent More thn one prent Personl history of kidney stones (%) Hyperclciuri 0.1 mmol/kg/d % Elpsed time since the lst episode of urinry lithisis 2 months months months Smokers % Dily lcohol consumption g/d (men SD) Abbrevitions re: LAPD, low niml protein diet; HFD, high fiber diet; SD, stndrd devition. Sttisticl significnce of the nlysis of vrince fter djustment for sex decresed significntly in this group. For the three groups, to 1.65 L/dy nd 3.74 to 1.84 mmol/dy, respectively. we observed no chnge in clcium, oxlte, sodium, nd Decreses in urine clcium were not observed in the potssium urinry excretion, nd COx sturtion index. other two subsets, with no decrese in urine ure or However, ptients with hyperclciuri in the LAPD decrese of less thn 50 mmol/dy. group showed slight but not significnt decrese in clcium output from 8.7 to 7.4 mmol/dy (Tble 4). Such Reltionships between dietry intke nd urinry decrese ws not observed mong ptients with normoclciuri. solute excretion t bseline The bseline 24-hour urinry volume did not vry csolute We divided the HFD group into three subsets of equl cording to ge, sex, personl nd fmily history of urinry size, ccording to the sttisticl distribution of increse lithisis, nd time elpsed since the lst episode of uriin totl dietry fiber ( 14 g/dy, 14 to 23 g/dy, 23 g/dy). nry lithisis. Although the bseline 24-hour urinry vol- No chnge in urinry clcium nd oxlte outputs ws ume ws not correlted with the outputs of cretinine, observed within ech subset. We lso divided the LAPD clcium, ure, nd urte, it ws significntly correlted group into three subsets ccording to the sttisticl distri- with the outputs of sulfte (r 0.25, P 0.04) nd bution of the decrese in urine ure: no decrese, de- citrte (r 0.27, P 0.03; Tble 6). Bseline urinry crese 50 mmol/dy, decrese 50 mmol/dy (50 mmol/ concentrtions of clcium (r 0.62, P 10 4 ), oxlte dy ws the higher 33rd percentile). Among ptients (r 0.37, P 10 3 ), nd urte (r 0.71, P 10 4 ) with decrese in urine ure of more thn 50 mmol/ were significntly nd negtively correlted with the 24- dy, there ws significnt decrese in urine clcium, hour urinry volume. However, urinry concentrtions together with significnt decrese in cretinine, sulfte, of citrte, ure, nd cretinine were not correlted with urte, nd citrte (Tbles 4 nd 5). Such decreses were the 24-hour urinry volume. not observed in the other two subsets (no decrese or After the outputs of cretinine, citrte, sulfte, nd decrese 50 mmol/dy). In the entire series of 96 p- urte were controlled for, the correltion between the tients, 31 hd decrese in urine ure of more thn 50 output of clcium nd tht of ure ws significnt mong mmol/dy; mong these 31 ptients, there ws mrked ptients with hyperclciuri (r 0.83, P 0.003) but decrese in urine clcium (7.12 to 5.13 mmol/dy, P not mong those with normoclciuri (r 0.21, P 0.31) ), together with significnt decrese in cretinine, Mny urinry prmeters were ssocited t bseline sulfte, nd urte. Twenty-four hour urinry volume with individul chrcteristics nd nutrient intke, but nd citrte lso decresed significntly (P 10 3 ), 2.11 none with the time elpsed since the lst episode of

5 Rotily et l: Diet nd idiopthic clcium stones 1119 Tble 2. Dietry intke t Bseline (M0) nd t 4 months (M4) reported by the food frequency questionnire in the three nutritionl intervention groups Control group (N 31) LAPD group (N 34) HFD group (N 31) Contrsts between intervention groups (P vlue) b M0 M4 M0 M4 M0 M4 M4 Vrible men SD men SD P men SD men SD P men SD men SD P M0 M4 C vs. HFD C vs. LAPD HFD vs. LAPD Energy Kj/24 h Protein g/24 h Animl protein g/24 h Totl fiber g/24 h Clcium mg/24 h Abbrevitions re: LAPD, low niml protein diet; HFD, high fiber diet; SD, stndrd devition. P sttisticl significnce of pired t-test between M0 nd M4 b P sttisticl significnce of the inter-group comprison test; nlysis of vrince fter djustment for sex nd ge urinry lithisis (Tble 6). Multiple regression models explined smll prt of vrince of urinry prmeters (between 6 nd 24%). Citrturi ws significntly lower mong people who reported previous episodes of urinry lithisis. Energy intke ws negtively correlted with urinry oxlte nd GI-lkli. Urinry potssium, phosphte, cretinine, oxlte, ure, urtem, nd GI-lkli were significntly nd positively correlted with niml protein intke. Totl fiber intke ws not significntly correlted with ny urinry prmeter. COx sturtion ws independently ssocited with niml protein intke nd ws negtively ssocited with energy. At bseline, both in the smple including ll ptients nd in the LAPD group, the correltion between citrte nd ure ws not significnt (coeficient 0.02, P 0.84; coeficient 0.11, P 0.32). At four months, in the LAPD group, the correltion between citrte nd ure ws highly significnt (coeficient 0.62, P 10 3 ). In the control nd the HFD group, tht reltionship ws not significnt. DISCUSSION The min result of our rndomized nd controlled nutritionl intervention is tht decrese in niml protein intke, with urine ure output of more thn 50 mmol/dy, mong ICSFs cn led to decrese in dily urine clcium output. Our study hs lso shown tht n increse in dietry fiber intke did not succeed in modifying the min predictive fctors of clcium oxlte stone formtion, clcium, nd oxlte outputs. Our ptients were very similr to those evluted in previous studies for urinry output of ure, clcium, nd oxlte [3, 9, 14, 16] nd for the proportion of ptients with hyperclciuri (bout third) [3]. The men protein intke in our smple ws lso very close to tht reported for ICSFs dwelling in the sme geogrphic re, Mrseilles [3], nd those in other studies [21]. The proportion of ptients who left the tril between bseline nd t four months ws 11% (12 out of 108) nd did not vry between groups. This shows how difficult it is for these ptients to sty on diet in spite of the strong support given by the dietitin. In the sme wy, lrge increse in diuresis, recognized s bsic recommendtion in ICSFs [11, 22, 23], ws not obtined in spite of recommendtions by both the dietitin nd the ttending physicin. It hs been shown tht ICSFs with low urine volumes hve ltered thirst sensitivity nd vsopressin relese (bstrct; Hess et l, J Am Soc Nephrol 7:1802, 1996). The drmtic decrese in niml protein intke (bout third of the initil intke) between bseline nd t four months nd in the outputs of ure nd sulfte nd to some extent the decrese in cretinine show tht dietry hbits were drsticlly modified in the LAPD group. However, these modifictions were not homogeneous

6 1120 Rotily et l: Diet nd idiopthic clcium stones Tble 3. Urinry excretion t bseline (M0) nd t 4 months (M4) in the three nutritionl intervention groups Control (N 31) LAPD group (N 31) HFD group (N 27) Comprisons between groups M0 M4 M0 M4 M0 M4 M0 M4 Vrible men SD men SD P men SD men SD P men SD men SD P P b P c Volume L/d ph Sodium mmol/d Potssium mmol/d Phosphte mmol/d Cretinine mmol/d Clcium mmol/d Oxlte mmol/d Sulphte mmol/d Ure mmol/d Urte mmol/d Citrte mmol/d GI-lkli d COx sturtion Abbrevitions re: LAPD, low niml protein diet; HFD, high fiber diet; SD, stndrd devition. P sttisticl significnce of pired t-test between M0 nd M4 b P Sttisticl significnce of inter-groups comprison tests; nlysis of vrince fter djustment for sex c P Sttisticl significnce of inter-groups comprison tests; nlysis of covrince (covrite sex nd vlue t bseline M0) d GI-lkli is the net gstrointestinl bsorption of lkli: (N K C Mg) [Cl (1.8 P)] Tble 4. Urinry excretion t bseline (M0) nd t 4 months (M4) ccording to the decrese in 24-h urine ure excretion in idiopthic clcium stone formers on low niml protein diet No decrese in urine ure excretion Decrese 50 mmol/d Decrese 50 mmol/d (N 11) (N 8) (N 12) Vrible M0 men M4 men P M0 men M4 men P M0 men M4 men P Volume L/d ph Sodium mmol/d Potssium mmol/d Phosphte mmol/d Cretinine mmol/d Clcium mmol/d Oxlte mmol/d Sulphte mmol/d Ure mmol/d Urte mmol/d Citrte mmol/d GI-lkli b COx sturtion P sttisticl significnce of Wilcoxon pired test between M0 nd M4 b GI-lkli is the net gstrointestinl bsorption of lkli: (N K C Mg) [Cl (1.8 P)] within the LAPD group, nd only 12 of 34 ptients suc- erl public [32]. In our study, the reserch dietitin noticed ceeded in decresing their ure output by more thn 50 tht the increse in totl dietry fiber intke mmol/dy nd their clcium output. In the HFD group, through incresed fruit, vegetble, nd cerel consumption fiber intke ssessments from food frequency questionnires ws esier to chieve thn the decrese in niml showed drmtic increse t four months. Unlike protein consumption. Thus, it is unlikely tht ptients in for protein intke, biomrkers of fiber intke re not the HFD group flsified their nswers to the dietitin to currently vilble, nd we cnnot scertin the compli- show their complince with the given recommendtions. nce of prticipnts with the high-fiber intke. The mesurement Some studies reported no difference in dily protein of fecl weight s check of dietry fiber intke intke between ICSF nd helthy subjects [3, 13 15, 36], is frught with problems nd is uncceptble to the gen- wheres others found significnt positive correltion

7 Rotily et l: Diet nd idiopthic clcium stones 1121 Tble 5. Urinry excretion t bseline (M0) nd t four months (M4) mong idiopthic clcium stone formers on low niml protein diet ccording to clciuri Normoclciuric (N 22) Hyperclciuric (N 9) Vrible M0 men M4 men P b M0 men M4 men P b Volume L/d ph Sodium mmol/d Potssium mmol/d Phosphte mmol/d Cretinine mmol/d Clcium mmol/d Oxlte mmol/d Sulphte mmol/d Ure mmol/d Urte mmol/d Citrte mmol/d GI-lkli c COx sturtion Hyperclciuri (24-h clcium urine excretion 0.1 mmol/kg/d) b P sttisticl significnce of Wilcoxon pired test between M0 nd M4 c GI-lkli is the net gstrointestinl bsorption of lkli: (N K C Mg) [Cl (1.8 P)] Tble 6. Multiple regression nlyses for 24-hour urinry solutes ccording to nutrient intke, 24-hour urinry volume, nd personl nd fmily history of lithisis t bseline [stndrdized coefficients (sttisticl significnce); N 96] Personl history Fmily history Animl 24-hour R 2 of lithisis of lithisis Energy protein Totl fiber Clcium urinry volume (percent) ph 0.06 (0.60) 0.15 (0.21) 0.14 (0.39) 0.24 (0.16) 0.15 (0.28) 0.08 (0.56) 0.19 (0.12) 12.0 Sodium 0.04 (0.73) 0.11 (0.39) 0.12 (0.49) 0.11 (0.51) 0.14 (0.30) 0.01 (0.97) 0.08 (0.54) 6.4 Potssium 0.27 (0.02) 0.03 (0.81) 0.10 (0.52) 0.44 (0.008) 0.15 (0.23) 0.12 (0.38) 0.03 (0.80) 11.9 Phosphte 0.15 (0.20) 0.06 (0.62) 0.06 (0.73) 0.38 (0.02) 0.07 (0.62) 0.04 (0.76) 0.18 (0.12) 9.5 Cretinine 0.09 (0.41) 0.00 (0.99) 0.07 (0.65) 0.50 (0.003) 0.02 (0.87) 0.23 (0.10) 0.02 (0.84) 19.8 Clcium 0.01 (0.93) 0.19 (0.10) 0.12 (0.47) 0.30 (0.08) 0.13 (0.36) 0.17 (0.23) 0.03 (0.83) 12.5 Oxlte 0.04 (0.72) 0.05 (0.69) 0.43 (0.009) 0.45 (0.007) 0.21 (0.10) 0.16 (0.25) 0.18 (0.11) 18.4 Sulphte 0.02 (0.89) 0.19 (0.11) 0.25 (0.13) 0.10 (0.56) 0.02 (0.90) 0.24 (0.10) 0.25 (0.04) 15.9 Ure 0.09 (0.44) 0.01 (0.92) 0.07 (0.68) 0.41 (0.01) 0.13 (0.31) 0.04 (0.77) 0.08 (0.51) 18.3 Urte 0.14 (0.23) 0.14 (0.23) 0.10 (0.54) 0.43 (0.01) 0.07 (0.62) 0.22 (0.13) 0.14 (0.24) 13.4 Citrturi 0.24 (0.04) 0.03 (0.83) 0.04 (0.80) 0.07 (0.66) 0.03 (0.85) 0.02 (0.90) 0.27 (0.03) 15.3 GI-lkli b 0.31 (0.007) 0.03 (0.77) 0.39 (0.01) 0.54 (0.001) 0.05 (0.68) 0.03 (0.80) 0.09 (0.41) 24.0 COx sturtion 0.05 (0.69) 0.02 (0.88) 0.34 (0.04) 0.44 (0.008) 0.18 (0.18) 0.22 (0.13) 0.18 (0.12) 16.8 R 2 is the percentge of vrince of the dependent vrible (tht is, sodium) explined by the multiple regression model b GI-lkli is the net gstrointestinl bsorption of lkli: (N K C Mg) [Cl (1.8 P)] protein intkes [21]. Rightly, tht study did not conclude tht dvice to decrese protein intke or increse clcium intke could reduce the stone recurrence rte. Results bout the protective role of dietry fiber in cl- cium stone formtion, estblished minly from metbolic nd retrospective studies, re lso discordnt [13, 20, 37]. Brker et l found significnt correltion between protein intke nd emergency rtes for renl stones nd colic in 72 res in Englnd nd Wles [20]. However, they did not djust for protein intke when nlyzing the correltion between fiber intke nd the emergency rte. Furthermore, since it ws n ecologic study, the results of their study cnnot be considered s estblishing cusl reltionship between protein intke nd renl stone formtion. Other rguments for decrese in protein intke mong ICSFs rely on correltions between niml pro- between the protein consumption nd the risk of stone disese [16, 37, 38]. These discrepncies were discussed by Robertson, who noted tht most studies mtched for socioeconomic bckground filed to find ny consistent difference between the dietry intke of the two groups, wheres the unmtched studies showed severl significnt differences [22]. We could dd tht in most studies, the risk fctors were not djusted for confounding fctors, nd smples were smll. Furthermore, even if cse control studies were to show significnt reltionships between niml protein intke nd clcium stones, they would not demonstrte tht restriction in niml protein intke would prevent recurrent stones mong ICSF. In support of role of nutrient intke in clcium stone formtion is the prospective study of Curhn et l, who found higher reltive risk of stone episodes in persons reporting low clcium intkes nd to some extent high

8 1122 Rotily et l: Diet nd idiopthic clcium stones tein intke nd clcium output, minly mong helthy nd totl fiber intke, but citrturi ws significntly people, or rely on experimentl studies in which nutrient nd independently correlted with personl history of intke levels were fr from the usul ones mong ICSF. urinry lithisis nd the 24-hour urine volume. This cor- Kok et l showed tht high niml protein intke de- reltion emphsizes the need for ICSFs to increse their cresed the bility of urine to inhibit the gglomertion wter intke nd highlights tht giving dietry recomof clcium oxlte crystls [10]. Those uthors suggested mendtions to ICSFs could be counterproductive: When tht this impirment ws possible physicochemicl ex- the recommendtion to these ptients is to reduce their plntion for the dverse effects of dietry hbits on niml protein intke, they tended not to increse their renl stone formtion. However, tht investigtion ws fluid intke. Tht grees with Hitt s study, which crried out mong helthy mle subjects, nd the mount showed tht the stone recurrence ws higher in the group of protein intke ws very high (2 g/kg/dy) reltive to on dietry regimen in comprison with the control usul diets mong ICSFs (in our smple, 1.25 g/kg/dy group [24]. t bseline). Another clinicl investigtion hs shown As reported by other studies [3, 9], we found signifitht high brn intke, rich in phytic cid, significntly cnt correltion between the clcium nd ure output. reduced renl clcium excretion [8]. First, in tht tril, However, fter we controlled for the output of cretithe fiber intke ws very high (36 g rice brn per dy) nine, citrte, sulfte, nd urte, tht correltion ws signd would not be fesible in long-term perspective. nificnt mong ptients with hyperclciuri but not those Furthermore, tht investigtion ws performed mong with normoclciuri. In the LAPD group, we lso found helthy women nd not mong ICSFs. Future studies smll but not significnt decrese in 24-hour output of should investigte the impct of different chievble recclcium mong ICSFs with hyperclciuri. One could ommendtions on dietry fiber (tht is, fiber brought by hypothesize tht ptients with hyperclciuri re metfruit nd vegetbles, usully soluble, or cerels, usully boliclly more sensitive to niml protein intke. If this not soluble) mong ICSFs. is confirmed, only ICSFs with hyperclciuri should be Correltions between nutrients nd urinry prmedvised to reduce their niml protein intke. It is very ters re difficult to interpret. Wheres our dietry ssesslikely tht some geneticlly cquired chrcteristics ply ment reflects the nutrient intke during the lst month, mesured urinry prmeters reflect the lst 24-hour meof clcium stones, nd tht nutrition could be stimulus more importnt role thn nutrition in the recurrence tbolism. This difference in timing cn explin some potentil discrepncies or lck of correltions between only in metboliclly sensitive subjects. dietry ssessment nd urinry output. For ure, cretiurinry risk fctors s end points does not support recom- In conclusion, our rndomized controlled tril using nine, nd sulfte, the estimted correltions with niml protein intke concur with the current knowledge. We mendtions to increse dietry fiber mong idiopthic did not, however, observe the correltion between the clcium stone formers. Among those ptients who were output of citrte nd fiber intke reported by Hess et l recommended to be on low niml protein diet, s [9]. Their smple ws smll (34 ptients), nd bove ll, mny s 12 out of 31 (95% CI, 22 to 58%) of ICSFs they did not djust tht correltion for other chrcteristics ssigned to low niml protein diet chieved reduc- nd nutrients, such s niml protein intke, which is tion in the urine ure excretion rte of more thn 50 often negtively correlted with fiber intke. It is eqully mmol/dy nd lso exhibited significnt decrese in possible tht the type of dietry fiber consumed by our urinry clcium excretion tht verged 1.8 mmol/dy, ptients differed from theirs. Tht issue will remin un- nd could expect to benefit from such diet. Furthersolved becuse the French food composition tble, s in more, ptients with hyperclciuri could drw more benmny countries, does not mke distinction between efit from low niml protein diet. The four-yer followsoluble nd nonsoluble dietry fibers. up of ptients included in tht tril will confirm whether Although Hitt et l did not consider the citrte output low niml protein or HFD hs n impct on the stone in their risk nlysis of recurrent clcium oxlte kidney recurrence rte. stones [24], hypocitrturi hs been considered by some uthors s risk fctor for clcium stone formtion [11]. In our study, reduction of niml protein intke did ACKNOWLEDGMENTS not significntly increse the output of citrte. On the We thnk Dr. Brny, G. Burkhrt, Dr. Brunet, J. Csnov, Pr. Coulnge, Pr. Dussol, Dr. Fbre-Monges, C. Guthier, Dr. Gugliott, contrry, citrte output ws decresed, nd trend to- Dr. Lechevllier, B.M. Mrgetts, Dr. Mornge, C. Portelli, Dr. Purgus, wrd reduction in men citrte excretion ws observed Dr. Rossi, Dr. Roubicek, nd Pr. Serment. in the whole smple. No cler explntion for tht reduc- Reprint requests to Michel Rotily, M.D., Center d Investigtions Clintion in men citrte excretion cn be proposed. The iques, Hôpitl Sinte Mrguerite, Boulevrd Sinte Mrguerite, nlysis of correltions t bseline showed tht citrturi Mrseille, Frnce. ws not correlted with energy, niml protein, clcium, E-mil: rotily@mrseille.inserm.fr

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