Advertisement

An association between kidney stone composition and urinary metabolic disturbances in children

      Abstract

      Objective

      To determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors.

      Patients and methods

      We studied 135 pediatric patients with upper urinary tract lithiasis in whom excreted or extracted stones were available for analyses. Composition of stones was analyzed. A 24-hour urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate.

      Results

      Calcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. The calcium oxalate content in calculi showed a strong relationship with calciuria, and moderate association with oxaluria, magnesuria and acidification of urine. The percent content of struvite presented reverse and lower correlations with regard to the above parameters. Calcium phosphate stone proportion had low associations with urinary risk factors.

      Conclusions

      Calciuria, oxaluria, magnesuria and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. Relationships of urinary risk factors with calculi calcium phosphate content were of unclear significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.

      Keywords

      Introduction

      Evaluation of urinary stone composition is an important diagnostic step in determining the possible etiology and pathophysiologic mechanisms of stone formation. Effective crystal formation takes place when urine is supersaturated with stone-forming salts and, thus, the calculi composition should correspond with specific admixture's urine saturation [
      • Parks J.H.
      • Coward M.
      • Coe F.L.
      Correspondence between stone composition and urine supersaturation in nephrolithiasis.
      ,
      • Asplin J.
      • Parks J.
      • Lingeman J.
      • Kahnoski R.
      • Mardis H.
      • Lacey S.
      • et al.
      Supersaturation and stone composition in a network of dispersed treatment sites.
      ].
      In cases of struvite (MgNH4P) and cystine stones, these associations with chronic infection of the urinary tract with urea-splitting organisms and cystinuria, respectively, are clearly shown. However, for most common calcium stones, the presence of several risk factors, including hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria was reported [
      • Kourambas J.
      • Aslan P.
      • Teh C.L.
      • Mathias B.J.
      • Preminger G.M.
      Role of stone analysis in metabolic evaluation and medical treatment of nephrolithiasis.
      ,
      • Pak C.Y.
      • Poindexter J.R.
      • Adams-Huet B.
      • Pearle M.S.
      Predictive value of kidney stone composition in the detection of metabolic abnormalities.
      ]. Moreover, the composition of most of the calculi is not homogeneous. In developed countries, calcium oxalate (CaOx) is the predominant stone constituent usually admixed with small amounts of calcium phosphate (CaP) and/or uric acid (UA), which may form the initial nidus of the CaOx stone. Only in a limited number of cases do substances different from CaOx constitute the main stone phase [
      • Worcester E.M.
      • Coe F.L.
      Nephrolithiasis.
      ,
      • Daudon M.
      • Dore J.C.
      • Jungers P.
      • Lacour B.
      Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach.
      ].
      In children, the reported compositions of stones slightly differ from those in adults. They are often made of a larger number of constituents reflecting a specific complex structure. Another important feature of pediatric urinary stone disease is the prevalent proportion of cases with coincident metabolic disturbances in urine. Excretion rates of calcium, oxalate, citrate and uric acid are higher when adjusted for urine creatinine. Calcium oxalate supersaturation is similar to that in adults, but calcium phosphate supersaturation is usually higher whereas uric acid is lower because of higher urine pH at pediatric age [
      • Battino B.
      • DeFoor W.
      • Coe F.
      • Tackett L.
      • Erhard L.
      • Wacksman J.
      • et al.
      Metabolic evaluation of children with urolithiasis: are adult references for supersaturation appropriate?.
      ,
      • Cameron M.A.
      • Sakhaee K.
      • Moe O.W.
      Nephrolithiasis in children.
      ,
      • DeFoor W.
      • Asplin J.
      • Jackson E.
      • Jackson C.
      • Reddy P.
      • Sheldon C.
      • et al.
      Results of a prospective trial to compare normal urine supersaturation in children and adults.
      ,
      • DeFoor W.
      • Asplin J.
      • Jackson E.
      • Jackson C.
      • Reddy P.
      • Sheldon C.
      • et al.
      Urinary metabolic evaluations in normal and stone forming children.
      ,
      • VanDervoort K.
      • Wiesen J.
      • Frank R.
      • Vento S.
      • Crosby V.
      • Chandra M.
      • et al.
      Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome.
      ,
      • Sarica K.
      Pediatric urolithiasis: etiology, specific pathogenesis and medical treatment.
      ].
      In fact, only few reports to date have focused on the association between different stone components and biochemical urinary risk factors in children [
      • DeFoor W.
      • Asplin J.
      • Jackson E.
      • Jackson C.
      • Reddy P.
      • Sheldon C.
      • et al.
      Urinary metabolic evaluations in normal and stone forming children.
      ,
      • VanDervoort K.
      • Wiesen J.
      • Frank R.
      • Vento S.
      • Crosby V.
      • Chandra M.
      • et al.
      Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome.
      ]. Therefore, the purpose of this study was to define the correlations between stone constituents and urinary pH, and accompanying metabolic abnormalities in urine in pediatric kidney stone formers.

      Patients and methods

      Study population

      This retrospective study was carried out using the data of 135 patients with upper urinary tract lithiasis (71 boys, 64 girls), aged 2–18 years (median 14.6 years), treated in the University Children's Hospital in Bialystok, Poland during 2002–2011. There were two main inclusion criteria for the study: availability of the stone for chemical analysis and appropriate 24-hour urine collection. There were no other exclusion criteria if complete urinary metabolic and stone composition results were attainable. The study included 36% of urolithiasis patients registered in the hospital records during that period. In the remaining children, stones were not excreted or were unavailable because of loss/unnoticed spontaneous passage.
      Calculi were obtained intact from spontaneous passage (81), open surgery (26) or fragmented form after ureterorenoscopic lithotripsy (15), extracorporeal shock wave lithotripsy (12) or percutaneous nephrolithotripsy (1). In 26 traditionally operated children, 10 had staghorn calculi and concomitant pyeloureteral junction obstruction was suspected in 11. Twenty-one patients submitted more than one stone during that time, but only primary stone analyses and urinary chemical profiles were considered in the study. Thirteen stone formers presented with urinary tract infection at admission, and the another 17 had positive history of recurrent infections of urinary system. Ten participants in the study had neurogenic bladder because of myelomeningocele.

      Stone analysis and urine assessment

      Composition of stones was analyzed by laboratory commercial test (DiaSys Diagnostic Systems GmbH, No 131399990351, Holzheim, Germany) assessing the presence and relative proportions of the seven most frequent natural chemical components. The stone phase was considered to be the major component if it reached at least 50% of the total calculus composition. Four to eight weeks after passing/retrieving the stones and recovery from urinary infection, if present, the 24-hour urine collections were provided while patients were on their usual diet and fluid intake. After voiding, urine samples were kept refrigerated at 4 °C and all measurements were conducted at the end of collection periods within 4 h. Urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate. Urinary metabolites were assessed in an identical manner to that described in our previous publication [
      • Porowski T.
      • Zoch-Zwierz W.
      • Konstantynowicz J.
      • Taranta-Janusz K.
      A new approach to the diagnosis of children's urolithiasis based on the Bonn Risk Index.
      ]. Participants and their legal guardians gave informed consent for participation in the procedures, and the study was approved by the ethical committee of the Medical University of Bialystok.

      Statistical analyses

      The statistical analysis was performed by Statistica, version 10.0 PL (StatSoft Inc., Tulsa, OK, USA). Kruskal–Wallis testing was performed to evaluate differences among the predominantly CaOx, CaP and MgNH4P stone groups for a given urinary parameter, and Mann–Whitney test was used for comparisons of two groups. Differences were considered statistically significant if p < 0.05. Correlations between proportional stone constituents and a given urinary parameter were made using the Spearman test. The r values of correlation coefficients ≤0.35 were considered to represent weak a relationship, 0.36–0.67 moderate association and 0.68–1.0 strong correlation [
      • Taylor R.
      Interpretation of the correlation coefficient: a basic review.
      ].

      Results

      Kidney stone analyses revealed that the vast majority of stones presented mixed composition. The most common chemical combinations were CaOx and CaP admixed with small amount of uric acid (38%) followed by biminerals formed of CaOx and CaP (30%). All infection stones revealed some admixture of metabolic components. Qualitative compositions of 135 stones reported by laboratory are given in Table 1.
      Table 1Reported different combinations of analyzed stone components.
      Number of patientsStone composition
      51CaOx – CaP – UA
      40CaOx – CaP
      13CaOx – MgNH4P – UA
      10CaOx – MgNH4P – CaP
      10CaOx
      6CaOx – MgNH4P
      3CaOx – MgNH4P – CaP – UA
      1CaP – MgNH4P
      1Cystine – CaOx
      Calcium oxalate was the most prevalent component included in all but one calculi. We found 10 homogenous and 89 made principally of CaOx stones. Calcium phosphate was the second more abundant chemical admixture found in 105 excrements followed by struvite determined in 33 patients. Crystalline material of 67 patients contained rudimentary amounts of UA. Only one stone consisted of cystine and was not included in further analyses. In four stones containing three or more components, none reached 50% of total composition. Chemical stone components with respect to number of patients and range of content are presented in Table 2.
      Table 2Chemical stone components with respect to frequency of occurrence and range of content.
      Stone componentNumber of stones – totalNumber of stones – main componentRange of contentMedian
      CaOx134 (99%)99 (73%)5–100%75%
      CaP105 (77%)13 (9%)2–84%15%
      MgNH4P33 (24%)18 (13%)8–83%46%
      UA67 (49%)02–20%6%
      Cystine1 (0.7%)1 (0.7%)95%95%
      The majority of our patients presented with urinary metabolic disturbances according to reference values for children [
      • Milliner D.S.
      Urolithiasis.
      ]. Hypercalciuria (>4 mg/kg/24 h) was found in 90 patients (66%), hypocitraturia (<400 mg/g creatinine) in 85 (63%), hyperoxaluria (>0.5 mmol/1.73 m2/24 h) in 65 (48%) and cystinuria (>75 mg/1.73 m2/24 h) in one. None of the participants presented with hyperuricosuria (>815 mg/1.73 m2/24 h).
      Comparison of urine volumes, pH and daily urinary excretions of calcium, oxalate, citrate, uric acid, magnesium and phosphate presented by subgroups forming predominantly CaOx, CaP and MgNH4P stones are presented in Fig. 1.
      Figure thumbnail gr1
      Figure 1Comparison of subgroups forming predominantly calcium oxalate, calcium phosphate and struvite stones. The Kruskal–Wallis analysis of variance was performed among the predominantly CaOx, CaP and MgNH4P stone groups for a given urinary parameter. Differences were statistically significant (p < 0.05; indicated by *) for pH of urine, calciuria, oxaluria and magnesuria. The Mann–Whitney U test was used for comparing two subgroups. Significant differences are marked with letters: aCaOx ≥ 50% vs. CaP ≥ 50%; bCaOx ≥ 50% vs. MgNH4P ≥ 50%; cCaP ≥ 50% vs. MgNH4P ≥ 50%.
      Urinary pH was most acid in the subgroup of patients forming predominantly CaOx stones and was significantly lower than that of CaP and MgNH4P stone formers (median pH 6.11 vs. 6.79 and 6.74, respectively). Additionally, patients with major CaOx stone fractions demonstrated significantly higher calciuria, oxaluria and magnesuria rates when compared with stones mainly composed of CaP and MgNH4P. Patients with predominant CaP stone fraction presented higher uricosuria when compared with CaOx stones and phosphaturia when compared with both CaOx and MgNH4P stones.
      The calculi content of CaOx showed strong correlation with calciuria (r = 0.735) and moderate with oxaluria, magnesuria and acidification of urine (r = 0.516, r = 0.436 and r = −0.388, respectively). The percent content of MgNH4P revealed distinctly reverse and weaker relationships with regard to above urinary parameters. The CaP stone proportion presented low correlations: positive with alkaline urine and phosphaturia rate and negative with calciuria and oxaluria. The urinary citrate, uric acid and phosphate excretions did not significantly correlate with any proportional stone fractions (Table 3).
      Table 3The correlations between the percentage of stone components and evaluated urinary parameter.
      CaOx (%)CaP (%)MgNH4P (%)
      Calciuria0.735*−0.188*−0.503*
      Citraturia0.0220.064−0.108
      Oxaluria0.516*−0.147−0.466*
      Uricosuria−0.0570.0500.048
      Magnesuria0.436*−0.107−0.242*
      Phosphaturia−0.0310.111−0.062
      pH of urine−0.388*0.1050.271*
      Spearman's rank correlation coefficients were calculated for each pair of chemical stone component and urinary parameter, *p < 0.05.

      Discussion

      Although many papers have considered urinary stone composition and concomitant urinary metabolic disturbances in adults, only few studies have focused exclusively on a pediatric population [
      • DeFoor W.
      • Asplin J.
      • Jackson E.
      • Jackson C.
      • Reddy P.
      • Sheldon C.
      • et al.
      Urinary metabolic evaluations in normal and stone forming children.
      ,
      • VanDervoort K.
      • Wiesen J.
      • Frank R.
      • Vento S.
      • Crosby V.
      • Chandra M.
      • et al.
      Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome.
      ].
      Our study revealed that the vast majority of kidney stones in children represent mixed calculi, evidenced by major and minor stone components. We found that 54% of stones consisted of three components, 35% were composed of two minerals, 8% were monominerals, and 3% were formed of four constituents.
      By comparison, a study in Germany based on over 70 000 adult urinary stones showed that 44% consisted of two minerals, 34% were monominerals, 22% of stones were made of three constituents, and 0.7% excrements consisted of four or more components [
      • Schubert G.
      Urinary stone analysis.
      ]. Our study confirms that pediatric kidney stones are made of a larger number of constituents when compared with published data on adulthood calculi.

      Calcium oxalate

      There was a definite predominance of CaOx in upper urinary tract stones. It was present in all except one stone, and was a predominant fraction of 73% calculi. The percent of CaOx in stones rose in parallel, as could be expected from physical chemistry, with increasing calciuria, oxaluria, and acidification of urine. We also revealed modest positive correlation with urinary magnesium excretion (Table 3). So far, the role of magnesium in CaOx crystallization has not been fully elucidated. Although magnesium salts are commonly regarded important inhibitors of crystallization, under certain conditions of supersaturation they may presumably operate as promoters of the process [
      • Bibilash B.S.
      • Vijay A.
      • Fazil Marickar Y.M.
      Stone composition and metabolic status.
      ]. Thus, the role of magnesium in calcium oxalate stone formation deserves further research.

      Calcium phosphate

      Calcium phosphate was a frequent admixture detected in 77% of stones, but was the major fraction in only 9% of calculi. Calcium phosphate stones are formed when urinary CaP saturation is elevated, mainly because of the alkaline milieu of urine (pH > 6.3) [
      • Pak C.Y.
      • Poindexter J.R.
      • Adams-Huet B.
      • Pearle M.S.
      Predictive value of kidney stone composition in the detection of metabolic abnormalities.
      ,
      • Worcester E.M.
      • Coe F.L.
      Nephrolithiasis.
      ]. Some reports suggest that calcium phosphate supersaturation is higher in children when compared with adults because of higher pH of urine [
      • Battino B.
      • DeFoor W.
      • Coe F.
      • Tackett L.
      • Erhard L.
      • Wacksman J.
      • et al.
      Metabolic evaluation of children with urolithiasis: are adult references for supersaturation appropriate?.
      ,
      • DeFoor W.
      • Asplin J.
      • Jackson E.
      • Jackson C.
      • Reddy P.
      • Sheldon C.
      • et al.
      Results of a prospective trial to compare normal urine supersaturation in children and adults.
      ].
      In our study, the children with predominant CaP stones also presented with significantly higher pH when compared with CaOx stone formers. They presented higher uricosuria when compared with CaOx stones and phosphaturia when compared with both CaOx and MgNH4P stones (Fig. 1).
      However, the correlation coefficients of CaP stone content with pH of urine and urinary risk factors were very low and thus of unclear clinical significance.

      Struvite

      Struvite stones, a mixture of magnesium ammonium phosphate, are formed when the urinary tract is infected with bacteria that produce a specific enzyme, urease [
      • Rodman J.S.
      Struvite stones.
      ]. We found that 24% of stones contained variable amounts of MgNH4P, whereas in 13% it was the major phase. Thirteen children suffering from MgNH4P stones presented with urinary tract infection at hospital admission, and the other 17 had positive history of recurrent infections of the urinary system. Ten children whose stones were made principally of MgNH4P have had neurogenic bladder. Subjects with struvite stones tended to be younger in relation to other subgroups. It may be explained by more common infections of the urinary tract in younger children. We did not observe female preponderance in this subgroup of stones, as has been reported elsewhere [
      • Sarica K.
      Pediatric urolithiasis: etiology, specific pathogenesis and medical treatment.
      ,
      • Rodman J.S.
      Struvite stones.
      ]. We revealed moderate inverse relationships of MgNH4P stone content with calciuria and oxaluria rates, and weak positive correlation with urine pH (Table 3). Interestingly, the urinary magnesium was the lowest among all subgroups. Presumably, MgNH4P precipitation in vivo could have lowered post-renal concentration of urinary magnesium in these individuals [
      • Laube N.
      • Pullmann M.
      • Hergarten S.
      • Hesse A.
      Influence of urinary stones on the composition of a 24-hour urine sample.
      ]. These pre-analytical factors are unavoidable and might lead to changes in excreted element concentration.
      Despite relatively low urinary calcium, oxalate and UA in this subgroup of patients, all stones made of MgNH4P also had a variable component of CaOx, CaP or UA (Table 1). Admixture of CaP could be explained by increased urine pH enabling its precipitation, whereas admixture of the latter is difficult to clarify. We are not able to adjudicate whether other types of stones became secondarily infected with urea-splitting micro-organisms, ensuing secondary struvite stone formation, or, primarily, infection stones were encrusted with metabolic minerals. Children with struvite stones presented with low citrate excretion, have been reported elsewhere, probably because of degradation of urinary citrate by bacterial enzymes [
      • Edin-Liljegren A.
      • Hedelin H.H.
      • Grenabo L.
      • Pettersson S.
      Impact of Escherichia coli on urine citrate and urease-induced crystallization.
      ].

      Uric acid

      Uric acid stones are uncommon in childhood, and their prevalence continuously increases with age [
      • Worcester E.M.
      • Coe F.L.
      Nephrolithiasis.
      ,
      • Daudon M.
      • Dore J.C.
      • Jungers P.
      • Lacour B.
      Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach.
      ]. In our study, neither the 24-hour urinary uric acid excretion was elevated nor pure uric acid stones identified. However, small fractions of UA, mostly not exceeding 10% of total stone composition, were noted in almost half of the stones. This phenomenon is likely to be primarily related to circadian fluctuations in uric acid excretion and, more importantly, in acidification of urine, because precipitation of UA results mainly from low urine pH (pK = 5.5) [
      • Pak C.Y.
      • Sakhaee K.
      • Peterson R.D.
      • Poindexter J.R.
      • Frawley W.H.
      Biochemical profile of idiopathic uric acid nephrolithiasis.
      ,
      • Sakhaee K.
      • Adans-Huet B.
      • Moe O.W.
      • Pak C.Y.
      Pathophysiologic basis for normouricosuric uric acid nephrolithiasis.
      ].
      Uric acid crystals may facilitate development of urinary calcareous stones by forming a nidus for their heterogeneous crystallization [
      • Pak C.Y.
      • Waters O.
      • Arnold L.
      • Holt K.
      • Cox C.
      • Barilla D.
      Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate.
      ]. Nevertheless, our study did not include the microscopic assessment of the fine inner structure of calculi, therefore, limiting the possibility to determine the role of UA in calcium stone development. The correlations between percentage of a stone's UA with studied urinary risk factors were not presented as they appear sparsely reliable, mainly because of both extremely small amounts found in the stones and a narrow range of UA content.
      The study is limited ultimately by the single method used in the assessment of stone composition. The chemical method has no capacity to differentiate crystalline forms of stone components that could provide an additional insight into structure and potential relationships [
      • Schubert G.
      Urinary stone analysis.
      ,
      • Krambeck A.E.
      • Khan N.F.
      • Jackson M.E.
      • Lingeman J.E.
      • McAteer J.A.
      • Williams Jr., J.C.
      Inaccurate reporting of mineral composition by commercial stone analysis laboratories: implications for infection and metabolic stones.
      ]. The other point is the small population studied especially with regard to calcium phosphate and struvite stones. Finally, considering geographical and ethnicity-related differences reported in the topic, we are aware that our data might be affected by region-specific nutritional and lifestyle habits.
      In summary, in children, the vast majority of kidney stones are complex: 54% consisted of three components, 35% were composed of two minerals, 8% were monominerals, and 3% were formed of four constituents. Calcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. All struvite stones had also a variable metabolic component. The calculi content of CaOx showed positive correlations with calciuria, oxaluria and magnesuria, and negative correlation with urine pH. The percent content of MgNH4P revealed distinctly reverse and weaker relationships with regard to the above urinary parameters. The CaP stone proportion presented low correlations with urinary risk factors. The urinary citrate, uric acid and phosphate excretions did not significantly correlate with any proportional stone fractions.

      Conclusions

      Calciuria, oxaluria, magnesuria, and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. The relationships of urinary risk factors with calculi calcium phosphate content were of unclear clinical significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.

      Conflict of interest

      None.

      Funding

      None.

      References

        • Parks J.H.
        • Coward M.
        • Coe F.L.
        Correspondence between stone composition and urine supersaturation in nephrolithiasis.
        Kidney Int. 1997; 51: 894-900
        • Asplin J.
        • Parks J.
        • Lingeman J.
        • Kahnoski R.
        • Mardis H.
        • Lacey S.
        • et al.
        Supersaturation and stone composition in a network of dispersed treatment sites.
        J Urol. 1998; 159: 1821-1825
        • Kourambas J.
        • Aslan P.
        • Teh C.L.
        • Mathias B.J.
        • Preminger G.M.
        Role of stone analysis in metabolic evaluation and medical treatment of nephrolithiasis.
        J Endourol. 2001; 5: 181-186
        • Pak C.Y.
        • Poindexter J.R.
        • Adams-Huet B.
        • Pearle M.S.
        Predictive value of kidney stone composition in the detection of metabolic abnormalities.
        Am J Med. 2003; 115: 26-32
        • Worcester E.M.
        • Coe F.L.
        Nephrolithiasis.
        Prim Care. 2008; 35: 369-391
        • Daudon M.
        • Dore J.C.
        • Jungers P.
        • Lacour B.
        Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach.
        Urol Res. 2004; 32: 241-247
        • Battino B.
        • DeFoor W.
        • Coe F.
        • Tackett L.
        • Erhard L.
        • Wacksman J.
        • et al.
        Metabolic evaluation of children with urolithiasis: are adult references for supersaturation appropriate?.
        J Urol. 2002; 168: 2568-2571
        • Cameron M.A.
        • Sakhaee K.
        • Moe O.W.
        Nephrolithiasis in children.
        Pediatr Nephrol. 2005; 20: 1587-1592
        • DeFoor W.
        • Asplin J.
        • Jackson E.
        • Jackson C.
        • Reddy P.
        • Sheldon C.
        • et al.
        Results of a prospective trial to compare normal urine supersaturation in children and adults.
        J Urol. 2005; 174: 1708-1710
        • DeFoor W.
        • Asplin J.
        • Jackson E.
        • Jackson C.
        • Reddy P.
        • Sheldon C.
        • et al.
        Urinary metabolic evaluations in normal and stone forming children.
        J Urol. 2006; 176: 1793-1796
        • VanDervoort K.
        • Wiesen J.
        • Frank R.
        • Vento S.
        • Crosby V.
        • Chandra M.
        • et al.
        Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome.
        J Urol. 2007; 177: 2300-2305
        • Sarica K.
        Pediatric urolithiasis: etiology, specific pathogenesis and medical treatment.
        Urol Res. 2006; 34: 96-101
        • Porowski T.
        • Zoch-Zwierz W.
        • Konstantynowicz J.
        • Taranta-Janusz K.
        A new approach to the diagnosis of children's urolithiasis based on the Bonn Risk Index.
        Pediatr Nephrol. 2008; 23: 1123-1128
        • Taylor R.
        Interpretation of the correlation coefficient: a basic review.
        JDMS. 1990; 1: 35-39
        • Milliner D.S.
        Urolithiasis.
        in: Avner E.D. Harmon W.E. Niaudet P. Yoshikava N. Pediatric nephrology. Springer-Verlag, Berlin, Heidelberg2009: 1408-1430
        • Schubert G.
        Urinary stone analysis.
        in: Rao N.P. Preminger G.M. Kavanagh J.P. Urinary tract stone disease. Springer-Verlag London Limited, 2011: 341-353
        • Bibilash B.S.
        • Vijay A.
        • Fazil Marickar Y.M.
        Stone composition and metabolic status.
        Urol Res. 2010; 38: 211-213
        • Rodman J.S.
        Struvite stones.
        Nephron. 1999; 81: 50-59
        • Laube N.
        • Pullmann M.
        • Hergarten S.
        • Hesse A.
        Influence of urinary stones on the composition of a 24-hour urine sample.
        Clin Chem. 2003; 49: 281-285
        • Edin-Liljegren A.
        • Hedelin H.H.
        • Grenabo L.
        • Pettersson S.
        Impact of Escherichia coli on urine citrate and urease-induced crystallization.
        Scanning Microsc. 1995; 9: 901-905
        • Pak C.Y.
        • Sakhaee K.
        • Peterson R.D.
        • Poindexter J.R.
        • Frawley W.H.
        Biochemical profile of idiopathic uric acid nephrolithiasis.
        Kidney Int. 2001; 60: 757-761
        • Sakhaee K.
        • Adans-Huet B.
        • Moe O.W.
        • Pak C.Y.
        Pathophysiologic basis for normouricosuric uric acid nephrolithiasis.
        Kidney Int. 2002; 62: 971-979
        • Pak C.Y.
        • Waters O.
        • Arnold L.
        • Holt K.
        • Cox C.
        • Barilla D.
        Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate.
        J Clin Invest. 1977; 59: 426-431
        • Krambeck A.E.
        • Khan N.F.
        • Jackson M.E.
        • Lingeman J.E.
        • McAteer J.A.
        • Williams Jr., J.C.
        Inaccurate reporting of mineral composition by commercial stone analysis laboratories: implications for infection and metabolic stones.
        J Urol. 2010; 184: 1543-1549