Rodgers, AL

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The influence of SouthAfrican mineral water onreduction of risk of calciumoxalate kidney stoneformationA L RodgersObjectives. This study was undertaken to identify a SouthAfrican mineral water containing relatively highconcentrations of calcium and magnesium and toinvestigate its effect on urinary biochemical andphysicochemical risk factors associated with calciumoxalate kidney stone formation.Design. The study followed a change-over design inwhich each subject followed a randomised sequence ofthree water-drinking protocols involving their normal diet,a calcium and magnesium-rich mineral water and amineral water deficient in these elements.Setting. University of Cape Town.Subjects. 54 volunteers without any previous history ofstone disease (27 men, 27 women) in the age group 21 -35 years and 31 with a history of calcium oxalate kidneystones (24 men, 7 women) in the age group 25 - 45 yearsparticipated in the study.Outcome measures. Both mineral waters favourablyaltered several risk factors. However, the effect of thecalcium- and magnesium-rich water was shown to besignificantly greater as it altered a larger number of thesefactors and induced several unique changes that were notachieved by the other water.Conclusions. The risk of calcium oxalate stone formationcan be significantly reduced by consumption of mineralwater which is rich in calcium and magnesium.S Afr Med J 1998; 88: 448-451.In a recent study, the risk of calcium oxalate (CaOx) stoneformation was shown to decrease significantly afterconsumption of a French mineral water. 1 The prophylacticeffect of the water was attributed to its high calcium andmagnesium content as it has recently been proposed thatcalcium binds free oxalate in the gut, thereby reducing theamount of the latter which is absorbed; this reduces itsconcentration in the urine and thus reduces the risk of CaOxurolithiasis 2 On the other hand, magnesium has beenrecognised as an inhibitor of CaOx stone formation for manyyears by virtue of its ability to form soluble magnesiumDepartment of Chemistry, University of Cape TownA L Rodgers, MSc, PhDoxalate which is excreted harmlessly in the urine.' Thepresent study was undertaken to identify a South Africanmineral water containing levels of calcium and magnesiumsimilar to those in the French water and to investigatewhether it, too, would reduce the risk of CaOx kidney stoneformation.Subjects and methodsSix commercially available South African mineral waters(Baden, Caledon, Ceres, LaVie, Schoonspruit and Valpre)were randomly selected for analysis. The magnesium andcalcium concentrations in each water were measured with aVarian 1275 Model flame atomic absorption spectrometer.Fifty-four subjects with no previous history of stonedisease (27 men, 27 women) in the age group 21 - 35 yearsand 31 with a history of CaOx stone formation (24 men, 7women) in the age group 25 - 45 years participated in thestudy. All of the latter had suffered a stone episode in themonth prior to participation in the project; confirmation ofstone type was achieved by X-ray powder diffraction.Subjects were required to supply a 24-hour urine samplewhile on their free unrestricted diets as well as after twodrinking protocols involving a mineral water with a highmagnesium and calcium content and one containingrelatively low concentrations of these two components. Ineach of the water-drinking protocols, 1.5 litres per day wereconsumed for a period of 3 days. Urine was collected duringthe final 24 hours. Glass bottles (2.5 litres), which had beenthoroughly washed with 5M hydrochloric acid and rinsedwith distilled water, were used for this purpose. Nopreservative was present. During the collection period thebottle and contents were refrigerated.Urines were tested for the presence of blood and infection(Combur 10 test strip; Boehringer Mannheim). Samples inwhich haematuria was detected or which were found to benitrite-positive were discarded. Thereafter, volume and pHwere recorded. Urines were analysed for sodium, potassium,calcium and magnesium content by means of flame atomicabsorption spectrometry. Oxalate content was determinedwith oxalate decarboxylase. For these analyses an ascorbateoxidase spatula was used to remove L-ascorbic acid. Citratecontent was determined by citrate lyase conversions tooxalo-acetate. Inorganic phosphorus level was determinedwith ammonium molybdate; creatinine content wasdetermined with picric acid and uric acid level wasdetermined with uricase. Analytical kits manufactured byBoehringer Mannheim were used for these determinations.The metastable limit (MSL) of urine is a measure of howreadily it supports crystallisation! The method for itsdetermination has been described elsewhere.' Briefly,successive aliquots of aqueous sodium oxalate (NaOx) areadded in progressively increasing concentrations to theurine, until CaOx crystallisation (as detected by turbiditymeasurements) is initiated. The concentration of exogenousNaOx required to produce detectable crystallisation is takenas the MSL. It follows that an increase in the MSL (e.g. afteradministration of a therapeutic protocol) corresponds to adecrease in the likelihood of stone formation.Several physicochemical quotients, ratios and indices,which have been empirically derived and which have beenVolume 88 No.4 April 1998 SAMJSAMJArt c I e 5Table I. Biochemical and physicochemical risk factors determinedin the urine of all subjects in this studyStatistical design and analysisThe study was statistically planned to follow a Latin squarecross-over design9 in which each subject participated in arandomised sequence of the three protocols (i.e. normaldiet, calcium- and magnesium-rich water, calcium- andwidely used by stone researchers in assessing the efficacyof treatment regimens, were determined prior to and afterthe water-drinking protocols. Among the most important ofthese were the CaOx relative supersaturation," the 'riskindex" and the standardised activity product.s Allincorporate urinary component concentrations inmathematical functions, the output of which (in each case) isa number which indicates the potential for stone formation.The higher the relative value of the number, the higher therisk. Risk index and activity product values for all urineswere calculated by means of the published equations,"swhile relative supersaturation values were determined withthe speciation computer program, EQUIL.s A summary of thebiochemical and physicochemical risk factors which weredetermined in this study is given in Table I.Ca ConcentrationLaVie Schoonspruit ValpreCeresCaledon_ Mg ConcentrationBadenThe concentrations of magnesium and calcium of sixrandomly selected South African mineral waters arepresented in the histogram in Fig. 1. On the basis of theseresults, Schoonspruit (calcium- and magnesium-rich) andCaledon (calcium- and magnesium-deficient) mineral waterswere selected for the trial. Tables 11 - V give those riskfactors for each of the four groups in which a statisticallysignificant change occurred (relative to normal diet values)as a result of either the Schoonspruit or Caledon protocols,or both. In this table a 't' symbol indicates a favourablechange (i.e. a shift towards lower stone risk). An asterisk Windicates that the effect of one protocol was more significantthan that of the other. Risk factors which were measured,but which did not change significantly in any group, were pHand calcium, sodium, potassium, uric acid and phosphateexcretions. However, because pH is an important indicatorof urine milieu, mean values are included in Tables 11 - V.Fig. 1. Mg and Ca concentrations (mg/l) in 6 randomly selectedSouth African mineral waters.Results4050 -;magnesium-deficient water). The data were analysed by themethod of analysis of variance; comparisons betweenprotocols were made with Student's t-test to establish whichof a multitude of risk factors might change significantly. Allanalyses were performed with the SAS statistical package.'o60-i1.1.Change indicatingreduced riskBiochemicalOxalate excretion"Citrate excretion '2Magnesium excretion'Uric acid excretion"Calcium excretion'Phosphate excretion"pH'SVolume"PhysicochemicalCalcium oxalate metastable limit'Risk index'Standardised activity product'Relaiive supersaturation'Risk factorTable 11. Male controls (N = 27) - mean risk factor values associated with each protocol, standard errors and pairwise P comparisonsDrinking protocol Pairwise P-valuesNormal (N) Caledon (C) Schoonspruit (S) N v. C N v. S Cv. SMSL 0.53 (0.08r 0.69 (0.08) 0.75 (0.08) 0.15 0.04 0.58Risk index 318 (30) 284 (29) 174 (30) 0.40 < 0.01 t 0.01CaOx RS 4.96 (0.36) 3.52 (0.34) 2.10 (0.35) < 0.01t < 0.01t· < 0.01Brush RS 1.35 (0.14) 0.93 (0.14) 1.04 (0.14) 0.04t 0.12 0.57UARS 2.11 (0.24) 1.20 (0.24) 1.15 (0.24) 0.011 0.011 0.88Vol (cm') 1 537 (116) 2203 (116) 1 973 (116) < 0.01t 0.C1t 0.16Cit (mmol/24 h) 2.18 (0.22) 2.83 (0.22) 2.82 (0.22) 0.04t 0.04t 0.97Ox (mmol/24 h) 0.29 (0.01) 0.30 (0.01) 0.17 (0.01) 0.61 < 0.01t < 0.01APS 1.32 (0.10) 1.28 (0.10) 0.78 (0.10) 0.79 < 0.01t < 0.01pH 6.00 (0.08) 6.21 (0.08) 6.23 (0.08) 0.07 0.05 0.90• More signifrcant effect of one protOCOl relative to the other.t Favourable change in the risk factor.MSL ; metastable limit (M NaOx); CaOx RS ; calcium oxalate relative supersaturation; Brush RS ; brushite relative supersaturation; UA RS ; uric acid relative supetSaturation;APS ; standardised CaOx activity product.SAMJ Volume 88 No.4 April 1998 __Table Ill. Men with stone formation (N =24) - mean risk factor values associated with each protocol, standard errors and pairwise PcomparisonsDrinking protocol Pairwise P-valuesNormal (N) Caledon (C) Schoonspruit (S) N v. C N v. S Cv. SRisk index 405 (32) 269 (32) 229 (32) < a.on < 0.01t 0.37CaOx RS 6.26 (0.39) 3.63 (0.38) 3.53 (0.37) < 0.01t < 0.01t 0.85Vol (cm') 1 359 (126) 1 877 (126) 1 829 (126) < 0.01t o.on 0.79Cit (mmoV24 h) 2.11 (0.24) 2.72 (0.24) 2.95 (0.24) 0.07 0.01t 0.51Ox (mmol/24 h) 0.32 (0.02) 0.26 (0.02) 0.20 (0.02) < 0.01t < o.on· 0.01Mg (mmol/24 h) 3.35 (0.31) 4.03 (0.31) 4.38 (0.31) 0.12 0.02t 0.42APS 1.52 (0.11) 1.33 (0.11) 1.03 (0.11) 0.21 < 0.01t 0.05pH 5.96 (0.09) 5.96 (0.09) 5.98 (0.09) 0.99 0.91 0.92• More significant effect of one protocol relative to the other.t Favourable change in the risk factor.CaOx RS = calcium oxalate relative supersaturation; APS = standardised CaOx activity product.Table IV. Female controls (N =27) - mean risk factor values associated with each protocol, standard errors and pairwise P comparisonsDrinking protocol Pairwise P-valuesNormal (N) Caledon (C) Schoonspruit (S) N v. C N v. S Cv. SRisk index 352 (29) 367 (29) 216 (29) 0.72 < 0.01t < 0.01CaOx RS 3.49 (0.35) 2.64 (0.34) 1.57 (0.34) 0.08 < 0.01t 0.03Vol (cm') 1 504 (116) 2342 (114) 2257 (116) < 0.01t < 0.01t 0.60Cit (mmol/24 h) 2.73 (0.22) 3.32 (0.22) 3.47 (0.22) 0.06 0.02t 0.63Ox (mmoV24 h) 0.23 (0.01) 0.25 (0.01) 0.15 (0.01) 0.44 < 0.01t < 0.01APS 0.91 (0.10) 1.07 (0.10) 0.60 (0.10) 0.25 0.03t < 0.01pH 6.20 (0.08) 6.23 (0.08) 6.32 (0.08) 0.77 0.29 0.44t Indicates a favourable change in the risk factor.CaOx RS = calcium oxalate relative supersaturation; APS ~ standardised CaOx activity product.Table V. Women with stone formation (N =7) - mean risk factor values associated with each protocol, standard errors and pairwise PcomparisonsDrinking protocol Pairwise P-valuesNormal (N) Caledon (C) Schoonspruit (S) N v. C N v. S Cv. SRisk index 409 (63) 325 (63) 215 (63) 0.32 0.02t 0.19CaOx RS 4.62 (0.72) 3.96 (0.72) 2.36 (0.72) 0.50 0.02t 0.10Ox (mmol/24 h) 0.26 (0.03) 0.24 (0.03) 0.15 (0.03) 0.72 0.01t 0.02pH 6.20 (0.08) 6.23 (0.08) 6.32 (0.08) 0.77 0.29 0.44t Indicates a favourable change in the risk factor.CaOx AS =calcium oxalate re1ative supersaturation.Discussion80th protocols indu.ced several favourable changes in theurinary risk factors. However, the number of factors alteredby the Schoonspruit protocol was greater than that affectedby the Caledon protocol. Furthermore, when both protocolsaltered the same risk factor, the effect of Schoonspruit wasmore significant in two of these - CaOx relativesupersaturation (Table 11) and oxalate excretion (Table Ill). Itis also noteworthy that Caledon had no effect on the riskfactors in women with a history of stone disease, whileSchoonspruit altered three of them (Table V).Three risk factors were favourably altered in all fourgroups: oxalate excretion, CaOx relative supersaturation andthe CaOx 'risk index'. Of these, oxalate excretion is Widelyregarded as the most crucial determinant in CaOx_urolithiasis." The results show that Schoonspruit uniquelyachieved a decrease in this risk factor in male controls,female controls and women with a history of stoneformation; in men who had experienced stone formation thedesired decrease was achieved by both waters, butSchoonspruit was significantly more effective. The CaOxrelative supersaturation and the CaOx risk index decreasedin the four groups after consumption of Schoonspruit, Le.favourable shifts occurred in all eight risk factors while asimilar effect occurred in only three of these factors afterconsumption of Caledon. It should be noted that one of theother risk quotients determined in this study - thestandardised CaOx activity product - decreasedsignificantly in male and female controls as well as in menwho had experienced stone formation, after theSchoonspruit protocol. In women who had had kidneyVolume 88 No.4 April1998 SAMJSAMJArt c e 5stones, the decreasing trend was evident but not significant(P = 0.0708). The standardised activity product was notaffected in any group by the Caledon protocol.Also worthy of comment is the significant increase incitrate excretion in three groups after mineral waterconsumption (Tables \I - IV) while in the fourth group (womenwho had experienced stone formation) an increasing (but notsignificant) trend occurred (normal: 2.08 (0.47); Caledon:1.99 (0.47); Schoonspruit: 2.74 (0.47)). These observationsare of great importance as they provide further evidence insupport of the risk-reducing effect of mineral water.However, it is intriguing that the increased citrate excretionwas not accompanied by increasing pH values. Themechanism by which this could have occurred is unknown.The results of this study have demonstrated that bothSchoonspruit and Caledon mineral water favourably alteredseveral biochemical and physicochemical risk factors relatedto CaOx kidney stone formation. However, the effect ofSchoonspruit was shown to be significantly greater, as italtered a larger number of risk factors and induced severalunique changes in key determinants which were notachieved by the Caledon protocol. Since the two watersdiffer markedly in respect of their calcium and magnesiumcontent (Fig. 1), it is suggested that these componentsafford Schoonspruit mineral water its inhibitory capacity inrespect of stone formation. This result supports thehypothesis that delivery of a large fluid volume containingrelatively high levels of calcium and magnesium reduces therisk of stone development.' Therefore, mineral waters suchas Schoonspruit, which satisfy this criterion, can beeffectively recommended as a therapeutic protocol in CaOxkidney stone disease.The author wishes to thank the Medical Research Council, theFoundation for Research and Development and the University ofCape Town for financial support.REFERENCES1. Rodgers AL Effect of mineral water containing calcium and magnesium oncalcium oxalate urolithiasis risk factors. Ufo/lnt 1997; 58: 93-99.2. Curhan GC, WilJett WC, Rimm EB, Stampfer MJ. A prospective study of dietarycalcium and other nutrients and the risk of symptomatic kidney stones. N Eogl JMed 1993; 328: 833-838.3. Ahfstrand C, Tiselius HG. Biochemical effects in patients with calcium oxalatestone disease during combined treatment with bendroflumethiazide and MgO.Br J Uro11984; 56: 125-130.4. Ryall RL, Hibberd CM, Marshall YR. A method for stUdying inhibitory activity inwhole urine. Urol Res 1985; 13: 285-289.5. Aodgers AL. Ball 0, Harper W. Urinary macromolecules are promoters of calciumoxalate nucleation in human urine: turbidimetric studies. elin Chim Acta 1993;220: 125-134.6. Werness PG, Brown CM, Smith LH, Finlayson 8. EQUIL 2: A basic computerprogram ;or the calculation of urinary saturation. J Uro11985; 134: 1242-1244.7. Tiselius HG. An improved method for the routine biochemical evaluation ofpatients with recurrent calcium oxalate stone disease. Clin Chim Acta 1982; 122:409-418.8. Tiselius HG. Standardized estimate of the ion activity product of calcium oxalatein urine from renal stone formers. Eur Uro/1989; 16: 48-50.9. Cochran WG, Cox GM. Experimental Designs. 2nd ed. New York: John WHey,1957: 127-131.10. SAS Users Guide: Statistics. Cary, NC: SAS Institute Inc., 1990.11. Borsati A. Calcium oxalate nephrolithiasis; defective oxalate transport. Kidney Int1991; 39: 1283-1298.12. Pak eye, Fuller C, Sakahee K, Preminger GM, Britton F. Long-term treatment ofcalcium nephrolithiasis with potassium citrate. J UfOJ 1985; 134: 11-19.13. Cce FL, Lawton RL, Goldstein RB, Tembe V. Sodium urate acceleratesprecipitation of calcium oxalate in vitro. Proc Soc Exp BioI Med 1975; 149: 926-929.14. Rodgers Al, 8arbour LJ, Pougnet BM, Lombard CJ, Ryall AL. Re-evaluation ofthe 'weekend effect data'; possible role of urinary copper and phosphorus in thepathogenesis of renal calculi. J Trace Elements Med BioI 1995; 9: 150-155.15. Pak eye, FuHer C. Idiopathic hypocitraturia calcium oxalate nephrolithiasissuccessfully treated with potassium citrate. Ann Intern Med 1986; 104: 33-37.16. Pak cye, Sakhaee K, Crowther e, Brinkley L Evidence justifying a high fluidintake in treatment of nephrolithiasis. Ann Intern Med 1980; 93: 36-39.Accepted 4 Aug 1997.Do stroke patients realisethat a consequence ofhypertension is stroke?L A Hale, V U Fritz, C J EalesStudy objective. The specific objectives of the study wereto survey residual disability and handicap following stroke.Information on four risk factors, namely hypertension, age,smoking, and alcohol abuse, was obtained. Enquiry wasmade into the subjects' insight into the causes of theirproblems.Design. Descriptive survey.Setting. Baragwanath Hospital and Soweto.Participants. Stroke patients 12 - 14 weeks post-discharge.Outcome measures. Structured questionnaire.Results. A total of 361 patients were initially screened.Only 54 fulfilled all inclusion criteria, 38 (70%) over 50years of age and 16 (30%) under 50 years. Ninety-three ofthe 361 died within the first 3 months; 71 % of all patientsknew that they had suffered a stroke. Only 20% of thetotal group understood that hypertension had probablycaused their stroke, although 76% of the older group and56% ef the younger group had been told at some stagethat they were hypertensive. Of the older group 32% knewthe name of their medication, 21 % could not name theirmedication and 23% claimed they were on no medication.Similarly in the younger group, 19% could name theirmedication, 25% could not name their medication, and12% were on no medication. In addition, 16% ofthe oldergroup and 56% of the younger group admitted tosmoking. The abuse of alcohol in both groups was low,but this figure was taken from subjective assessment andmay not reflect the true extent of drinking as a risk factor.Conclusion. Most patients in this study appear wellaware of their hypertension and take medication. However,they seem unaware that their hypertension and stroke arecausally linked and their hypertension knowledge issuboptimal. It is also apparent that smoking is increasingas a major risk factor for stroke in the black population ofSouth Africa. Patients need more education regardinghypertension and its consequences.S Air Med J 1998; 88: 451-454.Departments of Physiotherapy and Neurology, University of theWitwatersrand, JohannesburgL A Hale, Postgraduate studentV U Fritz. "16 BCh. Fep (SA), PhD (Med)C J Eales. MSc (Phys)SAMJ Volume 88 No. 4 April 1998 __

The influence of South African mineral water on reduction of risk of calcium oxalate kidney stone formation

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The influence of South African mineral water on reduction of risk of calcium oxalate kidney stone formation

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