Separate core-shell analysis of urinary stones may influence specific metaphylaxis

Separate core-shell analysis of urinary stones may influence specific metaphylaxis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Separate core-shell analysis of urinary stones may influence specific metaphylaxis F. I. Winterhagen, S. Latz, C. Jacobs, P. Lossin, J. Stein This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7468825/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jan, 2026 Read the published version in World Journal of Urology → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose The recommendation for urinary stone metaphylaxis is based on urinary stone analysis. It is not known to what extent the separate analysis of the core and shell differ and can therefore possibly influence the metaphylaxis. Methods Included were 19,973 stone analyses from 2021 and 2022 using infrared spectroscopy. For mixed stones, the individual components were specified semi-quantitatively in 5% increments. While 62% of the stones were analyzed using a representative sample of the whole stone, a separate core-shell analysis was performed in 38%. Analysis focused on evaluating the distribution of the most common urinary stone minerals. Results In 22.9% of cases, difference in analysis between core and shell could be measured, in 13.6%, analyses differed by at least 10%. Here, a clear shift in the distribution of stone types compared to the distribution using a single representative probe could be demonstrated: Calcium oxalate occurred significantly less frequently in this group (50.2% vs. 73.3%), while struvite (5.9% vs. 2.7%) and carbonate apatite (25,2% vs. 12.1%) occurred significantly more frequently. The number of components detected in the stones increased in separate analysis and were even more when core and shell differ. In 4.3%, the main component between core and shell changed. Discussion In 13.6% of stones, there were clinically significant differences between core and shell. The change in the main component between core and shell may indicate the stone genesis. Separate core-shell analysis can influence and possibly optimize the metaphylaxis. Especially in the high-risk situation and recurrent stones, a separate core-shell analysis may be beneficial. Urolithiasis Metaphylaxis Stone analysis core-shell analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction The prevalence of urinary stones in countries with a high standard of living is constantly increasing with some regions reporting an increase of over 37% in the last two decades [ 1 – 4 ]. Within five years stones recur in up 26%, recurrence can be reduced to 10% under metaphylaxis [ 5 ]. Patients are classified as high-risk stone formers if they have early-onset or recurrent urolithiasis, certain types of stones (e.g., brushite, uric acid, infection stones), associated medical conditions (e.g., CKD, hyperparathyroidism, metabolic disorders), genetic causes, or anatomical abnormalities. Urinary stones contribute potential complications such as acute renal failure or urosepsis as well as chronic kidney disease possible leading to an end stage kidney disease due to the primary conditions causing stone formation or the intervention for stone removal [ 6 , 7 ]. In high-risk patients, multiple guidelines recommend specific stone metaphylaxis, which can reduce the recurrence risk from 50–80% to 10–15% [ 6 , 8 , 9 ]. Strategies of metaphylaxis are based on stone analysis and stone analysis itself can identify a high-risk patient (e.g. struvite, cystine). Therefore, stone analysis is recommended for every first stone event and in case of recurrence under stone metaphylaxis, rapid stone recurrence or stone recurrence after a long stone-free period. Urinary stones can significantly vary in composition, with calcium oxalate stones representing the predominant form with a frequency of 67–80% [ 10 , 11 ]. Recent data published in 2022 showed, that in Germany the most common stone component calcium oxalate account for 71.4% of all stones [ 12 ]. They are followed by those consisting mostly of carbonate apatite with 10.2% (5–16%), and struvite stones, also known as magnesium ammonium phosphate "infection stones" with 2.1% (3–5%). Uric acid stones account for 8.3% (8–13%) and brushite stones for 1.3% while cystine (0.4%) and ammonium urate are rare, each comprising less than 1% of cases. It is known that stones often are composed of different minerals, and the exact analysis can provide essential information about factors affecting stone formation. When analyzing stones macroscopically, some show a different composition of the core of stones than in the shell, which might provide more information about the history of the stone formation. Only one study was found which included separate core and shell analysis on 10,000 urinary stones. It was shown that 29.5% of these stones showed differences between core and shell. Only weddellite and uric acid stones showed a clear preference of the shell [ 13 ]. However, recently there has been no data available which analyzed the difference between core and shell. Stone metaphylaxis and stone analysis are pivotal aspects in nephrology and urology to prevent urinary stone recurrence and avoid severe complications. Given the rising prevalence of urinary stones and their diverse compositions, an individualized approach of metaphylaxis is imperative. Here, further analysis of the core and shell can provide an important approach to establish precise metaphylaxis and thus further reduce the risk of recurrent stone formation. Therefore, the aim was to analyze the differences in composition between the core and the shell of a stone, to better understand stone formation, improve metaphylaxis, and possibly achieve a reduction in recurrence rates. Methods The study underwent review by the Ethics Committee of the University of Bonn, which concluded that ethical vote is not required (2024-248-BO). A total of 20,158 urinary stone samples were collected and analyzed at the Urinary Stone Analysis Center in Bonn during the years 2021 and 2022 using Fourier-transform infrared spectroscopy in ATR technique. In the case of mixed stones, the individual components were semiquantitatively indicated in 5% increments. This allowed for a detailed assessment of the varying composition within mixed stones and was personally conducted by the laboratory management after IT-assisted pre-evaluation. This ensured a standardized approach to the analysis of each urinary stone sample. For explicit requests from the referrer, separate core-shell analyses of the sample were performed. Otherwise, a representative sample of the entire urinary stone was measured. Our statistical analysis focused on the prevalence and distribution of the most common urinary stone minerals. These included whewellite, weddellite, uric acid/uric acid dihydrate, carbonate apatite, brushite, struvite, cystine, and protein. To account for clinical relevance, whewellite and weddellite stones were grouped together as a calcium oxalate. The main component was defined as the constituent that comprises the largest proportion of the stone and defines the type of the stone. In mixed stones, this does not necessarily need to account for 50% of the total mass and may instead be represented by two components of equal prominence. Pure stones are defined as those composed of at least 95% of a single component. Data analysis was performed using IBM SPSS Statistics v26. Descriptive statistics were calculated for categorical variables, including frequencies and proportions, while continuously coded variables were described with means and standard deviations. Differences were analyzed using chi-square paired tests. An unpaired, two-tailed t-test was used to test statistical significance (p < 0.05). Graphics were created with the help of ChatGPT. Results 19,972 of 20,158 stone analyses were used for further statistical analysis, 186 must be excluded. Reasons were that the sum of the stone composition was either greater or less than 100%, components other than whewellite, weddellite, uric acid/uric acid dihydrate, carbonate apatite, brushite, struvite, cystine, and protein were present, or minerals appeared twice in the given results. A separate analysis of core and shell was conducted on 7,658 stones (38.3%, Group B), while a conventional urinary stone analysis (single analysis) was performed on 12,314 stones (61.7%, group A, Fig. 1 , 2 ). Single Analysis For stones where a single analysis was performed (12,314, group A), 64.3% (7,916) were pure when separated according to calcium oxalate, carbonate apatite, uric acid, struvite, cystine, urate and brushite, while 35.7% (4,398) were mixed stones. 73.3% (9,021) of all stones were composed of calcium oxalate as main component, 12.1% (1,485) of carbonate apatite and 7.4% (953) of uric acid. 2.7% (334) were struvite, 1.4% (172) brushite, 0.6% (73) were cystine and each 0.3% protein or urate stones. 0.9% (110) of all stones consisted equally of calcium oxalate and carbonate apatite, while other mixed main components were in total 2.4% (Table 1 , Fig. 3 ). Table 1 Main component of stones after single analysis (A) : A main component is the one that constitutes the largest percentage of the stone; in mixed stones, it does not necessarily have to be 50% of the total mass and can also be determined by two equally frequent components. Stone Type (main component of stone) Number % Uric Acid 953 7.4 Calcium Oxalate 9,021 73.3 Carbonate Apatite 1,485 12.1 Struvite 334 2.7 Cystine 73 0.6 Protein 41 0.3 Urate 39 0.3 Brushite 172 1.4 Calcium Oxalate and Carbonate Apatite 110 0.9 Others > 1 main component 86 0.7 Core and shell analysis For stones where a separate analysis of core and shell was performed (7,658, Group B), 61.9% (4,743) stones were pure, while 38,1% (2,915) were mixed stones consisting of more than one component. In total, 65.3% (5,683) of all measurements of core and shell were equal. Varied findings in the separate analysis accounted for 34.7% (2,657) with 25.8% (1,975) of them differing by at least 10% (Fig. 4 ). When whewellite and weddellite were combined as calcium oxalate, 77,1% (5,903) analysis were equal, diverse results were observed in 22.9% (1,761) of cases, with 13.6% (1,041) showing a difference of at least 10%, this group is from now on called group B2. In total 86.4% of stones where whewellite and weddellite are combined as calcium oxalate were equal or differ at maximum 5% between core and shell, this group is from now on called group B1. Further subgroup analysis showed 3.3% (256) differing more than 20% (Table 2 ). Table 2 Core and shell were analyzed to determine if they differ in their composition. 22.9% of B showed differences in composition between the core and shell, with a difference of at minimum 10% (B2) in 13.6% of cases. A difference of 10% could be measured in 6.8% of cases, 15–20% difference in 3.4%, and over 20% difference in 3.3%. Equal measurements in core and shell or a difference of 5% (B1) represented 86.4% of all stones. Core and Shell analysis Number Percent Equal 5903 77,1 Unequal 1755 22.9 - Difference < 10% 714 9.3 - Difference ≥ 10% 1047 13.6 Equal = Difference 20% 250 3.3 - Difference 100% 6 0.1 In 3.9% (300) of all core-shell analyses, new components in the core not being presented in the shell or vice versa with at least 10% of the stone mass could be measured. This accounts for 28.8% of all cases where the core and shell differ. Stone composition For analysis and comparison of B the mean value of core and shell was calculated. For comparability, in B2 the mean value of the percentage given for the prevalence in the core and shell is calculated, e.g. brushite represents 2.3% of all core analyses and 2.5% of all shells, here it is said that brushite represents 2.4% of all core-shell analysis (B). However, the overall content of whole stone is influenced by the different core-shell ratios (meaning e.g. thick shell and very small core or vice versa). For the sake of comparability, the mean value is mentioned below. Stones are distributed into groups according to their main component, meaning a stone which consists mainly out of calcium oxalate is said to be a calcium oxalate stone. When analyzing the cases where stone and shell are measured separately (B), calcium oxalate was found in the core in 75.1% (5752) of cases and in the shell in 74.8% (5726) of cases (Table 3 ). In subgroup analysis in those stones where core and shell had the same composition (B1), it represented 78.9% (5520) of the cases. In those stones showing different composition (B2) calcium oxalate represented 50.9% (532) of the core and 49.9% (512) of the shell. Calcium oxalate occurred significantly more frequently in single analysis (A) than to B (p = 0,01). In B it is more frequent than in B1 (p < 0.00) or B2 (p 0.382). In B, carbonate apatite was found in the core in 10% (764) and in the shell in 9.8% (752). In B1 it was found in 7.5% (494) of the cases. In B2 carbonate apatite represented 25.8% (270) of the core and 24.5% (256) of the shell. It was significantly more often present in A compared to single analysis (p < 0.00). Differences could also be seen between B and B1 (B < B1) as well as B and B2 (B < B2) and between B1 and B2 (p < 0.00). It was most often in B2 (B1 < B2, p < 0.00). It is most often present in B2. There is no significant difference in appearance in core or shell (p = 0.59). Table 3 Stone type of core and shell . First, percentage of all core-shell analysis (B) which is represented by the mentioned type of stone (7,658). In sub analysis, listed are those cases where core and shell differ in their composition at a minimum of 10% (unequal, 1,045) and differ not (equal, 6,613). *Analysis differs significantly from single analysis (A), # to B, + to B1, ’ to B2, ^ between core and shell. In no case could a significant change in the frequency of occurrence between core and shell be measured. Stone type Core (%) Shell (%) Single analysis Literature Uric acid (all core and shell (B, 7658)) 8.5 #+ 8.7 #+ 7.4 8 - Equal (B1 6613) 8.3’ # 8.3’ # - Unequal min. 10% (B2 1045) 9.7 +# 11.1 +# Calcium oxalate (all core and shell) B 75.1* + ’ 74.8* + ’ 73.3 67–80 - equal 78.9’ # 78.9’ # - unequal min. 10% 50.9 +# 49.9 +# Carbonate apatite (all core and shell) 10.0* + ’ 9.8* + ’ 12.1 5–16 - equal 7.5’ # 7.5’ # - unequal min. 10% 25.8’ #+ 24.5’ #+ Struvite (all core and shell) 2.2* + ’ 2.3* + ’ 2.7 3–5 - equal 1.7’ # 1.7’ # - unequal min. 10% 5.4 + 6.3 + Cystine (all core and shell) 0.5 0.5 0.6 0.4 - equal 0.5 0.5 - unequal min. 10% 0.1 0.1 Brushite (all core and shell) 1.6 1.7 1.4 0.9 - equal 1.5 1.5 - unequal min. 10% 2.3 2.5 Calcium oxalate + Carbonate apatite 0.9* + 1.1* + 0.9 - equal 1.5 *# ’ 1.5 *# ’ - unequal min. 10% 3.4 + 4.8 + Uric acid was found in the core in 8.5% (652) and in the shell in 8.7% (667) of cases. In subgroup analysis of B1, it was seen in 8.3% (551) of the cases. In B2 uric acid represented 9.7% (101) of the cores and 11.1% (116) of the shells. Uric acid occurs not significantly more frequently in all core-shell analyses (B) compared to single analysis (p = 0.051), but is more frequent in B1 than in B (p = 0.02), and less frequent than in B2 (p = 0.04). There is no significant difference between the core and shell in B (p = 0.52) and between B1 and B2 (p = 0.65). For those stones where a difference between core and shell could be measured (B2), struvite represented 5.4% (57) of cases in the core and in 6.3% (66) of cases in the shell, while in total (B) struvite represented 2.2% (168) of all cores and 2.3% (177) of all stone analysis. In B1 struvite represented 1.7% (111) of the subgroup. In comparison to single analysis, struvite occurs significantly less frequently in B (p = 0.049). In the group of identical analyses (B1), it occurs significantly less frequently (p = 0,02) compared to B, and in the group of different analyses (B2), it is significantly more frequently (p 0.457). Cystine was found in B (35) and B1 (34) in 0.5% of all cases. In those stones showing different composition cystine was represented in both core and shell with 0.1% (1). Cystine differed not significantly in any analysis (p > 0.029). In B2, brushite represents 2.3% (24) of all cores and 2.5% (26) of all shells, while in B brushite represented 1.6% (126) of all cores and 1.7% (128) of all shells. In the group with the same composition (B1) brushite represented 1.5% (102). In the single analysis, brushite does not occur significantly different compared to all core-shell analyses (B) or in B1 and B2, neither between B1 and B2. There is no difference between core and shell (p > 0.886). Stones where calcium oxalate and calcium phosphate were identified as equivalent main components, representing 0.9% (68) of all cores in B, while in the shell, it was 1.1% (86). In B1, it was seen in 1.5% (32) of the cases, in B2 they represented 3.4% (36) of the core and 4.8% (50) of the shell. They appear significantly more often in single analysis than in B (p < 0.00) and more often in B than in B1 (p < 0.00) but more in B2 than in B1 (p < 0.00). Statistically there is no difference between core and shell (p = 0.152). In 95.7% (7,329) of cases, the main component (largest stone proportion) remained the same in the core and shell, while in 329 cases (4.3%), there was a shift (Fig. 5 ). In 103 cases (1.3%), there was a shift from calcium oxalate in the core in favor of carbonate apatite in the shell, and vice versa in 64 cases (0.8%). 39 shells shifted to uric acid (0.5%). However, in total 23 cores shifted to struvite as main component (2.3%). Stone components The number of components was examined in more detail. Here, the 5% value was included. In the single analysis group (A), 64.3% (7,916) consisted of one component, 35.3% (4224) of two components, and 1.4% (175) of three components. In B, 14,1% (1,081) of the stones consisted of one component, 31.1% (4682) of two components, 24,1% (1843) of three components, and 0.7% (52) of four components. In B1, 16% (1,080) of the stones consisted of one component, 65% (4,297) of two components, 18.6% (1,230) of three components, and 0.1% (6) of four components. For B2 18.4% (385) of the stones consisted of two components, 22.3% (613) of the stones consisted of three components, and 1.1% (46) of the stones consisted of a total of four components. In B2, 21.4% (224) of the samples had different components in the core or shell. There is a significant difference in the number of components in all groups (for all A to B, A to B1, B1 to B2 p < 0.00) (Fig. 6 ). When comparing the normalized prevalence per component of stone constituents between A, B, B1, and B2, several clear patterns emerged (Table 4 ). After normalization for the number of components per stone, uric acid prevalence was comparable across all groups (4.6–5.6%), indicating that previously observed differences were largely attributable to variations in stone complexity. Differences were mostly absent or moderate; B2 exhibited a slightly higher prevalence than B, while B1 and A showed similarly high values (Table 5 ). Calcium oxalate remained the most frequent component overall but was markedly lower in B2 (22.15%) compared with A (53.1%), B1 (47.3%), and B (40.9%). It showed extremely significant differences in almost all pairwise comparisons, with B1 and A consistently higher than B, and especially higher than B2, which had the lowest prevalence. In contrast, calcium phosphate was proportionally higher in B2 (11.16%) and A (8.74%) than in B (5.40%) and B1 (4.23%). It was significantly more frequent in B2 in many comparisons, particularly against B1 and B. Struvite was most frequent in B2 (2.61%), followed by A (1.97%), B (1.23%), and B1 (0.95%) with B2 showing consistently and often highly significant higher prevalence compared with all other groups. Brushite proportions were similar across groups (0.87–1.06%), with a slight peak in B2. Most differences were not significant, except for a slightly higher prevalence in B2 compared with A. Cystine was rare in all groups (< 0.5%), with the lowest proportion in B2 (0.04%) with no significant differences observed. Table 4 Normalized Prevalence per Component (%) of Stone Constituents by Group . Normalized prevalence is calculated as the proportion of stones containing the respective component, adjusted for the number of components per stone, allowing for direct comparison between groups with different stone complexities. Stone A B B1 B2 Uric acid 5,61 4,65 5,62 4,62 Calcium oxalate 53,1 40,89 47,27 22,15 Carbonate apatite 8,74 5,4 4,23 11,16 Struvite 1,97 1,23 0,95 2,61 Brushite 1,01 0,9 0,87 1,06 Cystine 0,43 0,25 0,29 0,04 Discussion Prevalence of stone comparing single analysis and core-shell analysis in general According to current data, calcium oxalate stones are the most common stones, followed by carbonate apatite, uric acid stones, struvite, and brushite. Cystine stones are known to be rare. Among the stones for which a single conventional analysis was performed, the frequency of occurrence corresponds to the literature with calcium oxalate representing 73.3% off all stones, carbonate apatite 12.1%, uric acid 7.4%, struvite 2.7 and brushite with 1.4%. The mixed stones containing calcium oxalate and carbonate apatite equally represent 0.9% of all stones. This ranking regarding the prevalence of stones is similar when core and shell are separately analyzed (B). In this group calcium oxalate represents 75% of all stones, carbonate apatite 10%, uric acid 8.6%, struvite 2.3 and brushite 1.7%. The mixed stones containing calcium oxalate and carbonate apatite equally represent 1% of all stones. But significant differences in the prevalence of stones in those being analyzed in one analysis using a representative probe (A) compared to separate analysis of core and shell (B) become apparent. Calcium phosphate is most present in single analysis and does appear even less in those stones showing differences in core and shell. Here, no benefit can be seen when performing different analysis of core and shell. Carbonate apatite and struvite are significantly more present in B2. Uric acid occurs equally in single analysis and B but is significantly most often represented in B1. This shows that single analysis detects uric acid more often and might be missed during single analysis. Struvite is slightly more often present in single analysis but it is highly significant more often present in B2. Struvite stones tend to be formed in presence of urinary tract infection, which can be caused by and induce further stone formation. It might be important to further analyze stones containing struvite to get knowledge of the real stone composition. Cystine did not appear significantly different in any since cystine stone is known to be particularly pure. Reason for this might be the well known genetic origin of stone formation, those patients usually have regular follow up visits. Prevalence of stone composition comparing core-shell analysis for B1 and B2 In B2 there was a significant shift in prevalence of the stone composition. Carbonate apatite and struvite occur significantly more frequently in B2 than in B1, brushite and uric acid occur more frequently in B2, but not on significant level. Calcium oxalate is presented significantly more frequently in B1, Cystine is more prevalent in B1, however it is not statistically relevant. This can be in part be explained by the stone characteristics and the genesis of the stone development. Cystine stone is known to be mostly pure, however the development of a different shell can be potentially caused by specific stone metaphylaxis. A urinary tract infection can be caused by the presence of a stone, in this case, struvite and carbonate apatite as so called “infectious stones” may crystallize what makes it more likely to be part of a mixed stone. Overall, B2 exhibited the lowest normalized calcium oxalate proportion but the highest relative prevalence of carbonate apatite, struvite, and brushite, suggesting a more heterogeneous and potentially infection-related stone composition. For carbonate apatite and struvite a separate analysis of core and shell seems to have a clear benefit, for uric acid and brushite it should be considered. Concerning the number of stone components more components could be detected when separate analysis was performed (B), interestingly, those stones showing difference in core and shell (B2) are built up of more components. Table 5 Summary of statistically significant comparisons (Chi² test) for each substance across A, B, B1, and B2, with the group showing higher normalized prevalence per component indicated in parentheses. Whenever single analysis is relevant it is in bolt letters. Substance Significant comparisons Uric acid A vs B1 ( B1 ); A vs B2 ( B2 ); B vs B1 (B1); B vs B2 ( B2 ); B1 vs B2 (B1) relevance and recommendation for separate analysis: should be considered Calcium oxalate A vs B ( B ); A vs B1 (B1); A vs B2 (A); B vs B1 (B1); B vs B2 (B); B1 vs B2 (B1) relevance and recommendation for separate analysis: no Carbonate apatite A vs B (A); A vs B1 (A); A vs B2 ( B2 ); B vs B1 (B); B vs B2 ( B2 ); B1 vs B2 ( B2 ) relevance and recommendation for separate analysis: yes Struvite A vs B (A); A vs B1 (A); A vs B2 ( B2 ); B vs B1 (B); B vs B2 ( B2 ); B1 vs B2 ( B2 ) relevance and recommendation for separate analysis: yes Brushite A vs B2 ( B2 ) relevance and recommendation for separate analysis: should be considered Cystine None relevance and recommendation for separate analysis: no Overall discussion These data show that with single analyses, there is a risk of underdiagnosing specific stone components, which could lead to misguided specific metaphylaxis. Therefore, if results of single analysis identify additional urinary stone components that contradict the basic principles of metaphylaxis, special care should be taken. In conclusion, it can be said, that for carbonate apatite and struvite stones, separate core-shell analysis should be recommended, as well as for uric acid and brushite. However, for those patients suffering from stone recurrence although they have metaphylaxis separate analysis also in other stones might be helpful to adjust metaphylaxis. For example: A stone containing calcium oxalate, carbonate apatite and struvite. The specific metaphylaxis for calcium oxalate stones is based on alkali citrates. However, these are potentially lithogenic for carbonate apatite and struvite due to their urinary alkalinizing effect. In this case, citrate substitution should be considered cautiously and depending on the urine collection analysis (e.g. in the case of hypocitraturia). On the contrary, one might consider lowering urine pH with methionine and deliberately forgoing citrate substitution. Since bacteria-associated stones and components are prone to rapid recurrences, antibiotic prophylaxis may also be necessary even with smaller amounts of struvite or carbonate apatite. Moreover, the finding of such a stone composition should warrant increased awareness regarding phosphate lithogenesis. Regular urine culture checks are advisable, and it would also be advisable to look more closely for predisposing factors for urinary tract infections, such as bladder emptying disorders, urinary reflux or urinary tract obstructions. However, to perform a core-shell analysis, both the core and the shell must be present in the sample sent in. This means that a representative piece of material containing both components must be available or clearly labeled parts of the stone must be saved. The size of the collected stone samples is primarily determined by the surgical procedure. In case of percutaneous nephrolitholapaxy larger fragments are typically retrieved, allowing for a core-shell analysis. However, with retrograde intrarenal surgery (RIRS), especially in the era of dusting, sufficiently large fragments that include both the core and shell are usually not obtained. Often only small samples are extracted, usually the core, as these are the fragments that remain at the end of the dusting procedure. A core shell analysis is feasible with samples that are at least 4–5 mm in size. It must be possible to split the stone to identify and separately analyze samples from the core and the shell. Conclusion To conclude one should consider a separate core-shell analysis for stones containing carbonate apatite and struvite in the first place. It might not be necessary in the first place for calcium oxalate and cystine. With single analyses, there is a risk of misinterpreting important components of the stone and thus the genesis of the stones. Therefore, a potentially effect of core-shell analysis on metaphylaxis strategies is assumed. At least in high-risk stone formers and especially in patients with stone recurrence despite medication-based metaphylaxis, core-shell analysis can potentially enhance diagnostic value and help to optimize and individualize specific and stone metaphylaxis. Abbreviations PNL percutane nephrolitholapaxie URS ureterorenoscopy Declarations Funding Declaration The authors declare that they have no financial or non-financial interests that are directly or indirectly related to the research described in this paper. Author Contribution F. I. Winterhagen and S. Latz contributed equally to the study and wrote the main text of the manuscript, the laboratory work was carried out by S. Latz, P. Lossin and C. Jacobs. The statistical analysis was performed by I. Winterhagen, the scientific analysis and classification into the current state of the art was performed by I. Winterhagen, S. Latz and J. Stein. All authors have reviewed the manuscript. References Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63(5):1817–1823. 10.1046/j.1523-1755.2003.00917.x Hesse A, Brändle E, Wilbert D, Köhrmann K-U, Alken P (2003) : Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. In: European urology . 10.1016/S0302-2838(03)00415-9 Sánchez-Martín FM, Millán Rodríguez F, Esquena Fernández S, Segarra Tomás J, Rousaud Barón F, Martínez-Rodríguez R, Villavicencio Mavrich H (2007) Incidencia y prevalencia de la urolitiasis en España: Revisión de los datos originales disponibles hasta la actualidad. Actas Urol Esp 31(5):511–520. 10.1016/s0210-4806(07)73675-6 Scales CD, Smith AC, Hanley JM, Saigal CS (2012) Prevalence of kidney stones in the United States. Eur Urol 62(1):160–165. 10.1016/j.eururo.2012.03.052 Ferraro PM, Curhan GC, D'Addessi A, Gambaro G (2017) Risk of recurrence of idiopathic calcium kidney stones: analysis of data from the literature. J Nephrol. ;30(2):227–233. 10.1007/s40620-016-0283-8 . Epub 2016 Mar 11. PMID: 26969574 Siener R (2006) Impact of dietary habits on stone incidence. Urol Res 34(2):131–133. 10.1007/s00240-005-0025-1 Keddis MT, Rule AD (2013) Nephrolithiasis and loss of kidney function. Curr Opin Nephrol Hypertens 22(4):390–396. 10.1097/MNH.0b013e32836214b9 EAU Guidelines Edn. presented at the EAU Annual Congress Paris 2024. ISBN 978-94-92671-23-3 S2k-Leitlinie Diagnostik Therapie und Metaphylaxe der Urolithiasis, Version 4.0) Schubert G (2006) Stone analysis. Urol Res 34(2):146–150. 10.1007/s00240-005-0028-y Lieske JC, Rule AD, Krambeck AE, Williams JC, Bergstralh EJ, Mehta RA, Moyer TP (2014) Stone composition as a function of age and sex. Clin J Am Soc Nephrology: CJASN 9(12):2141–2146. 10.2215/CJN.05660614 Siener R, Herwig H, Rüdy J, Schaefer RM, Lossin P, Hesse A (2022) Urinary stone composition in Germany: results from 45,783 stone analyses. World J Urol 40(7):1813–1820. 10.1007/s00345-022-04060-w Schubert G, Brien G, Bick C (1983) Separate examinations on core and shell of urinary calculi. Urol Int 38(2):65–69. 10.1159/000280865 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 31 Jan, 2026 Read the published version in World Journal of Urology → Version 1 posted Editorial decision: Revision requested 29 Oct, 2025 Reviews received at journal 24 Oct, 2025 Reviews received at journal 20 Oct, 2025 Reviewers agreed at journal 15 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers invited by journal 13 Oct, 2025 Editor assigned by journal 02 Sep, 2025 Submission checks completed at journal 02 Sep, 2025 First submitted to journal 27 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7468825","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":534433024,"identity":"a2492fe8-08a3-4786-91e7-18db75f00f11","order_by":0,"name":"F. I. Winterhagen","email":"data:image/png;base64,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","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":true,"prefix":"","firstName":"F.","middleName":"I.","lastName":"Winterhagen","suffix":""},{"id":534433025,"identity":"769d2cfd-2343-4f48-a5d8-2e2ea06cb91f","order_by":1,"name":"S. Latz","email":"","orcid":"","institution":"Urologie Bonn-Rhein-Sieg","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Latz","suffix":""},{"id":534433026,"identity":"949d3b27-f11d-49ab-b423-58fcccbe1c21","order_by":2,"name":"C. Jacobs","email":"","orcid":"","institution":"Urologie Bonn-Rhein-Sieg","correspondingAuthor":false,"prefix":"","firstName":"C.","middleName":"","lastName":"Jacobs","suffix":""},{"id":534433027,"identity":"3952970b-d4b9-442e-b860-fa64b482905d","order_by":3,"name":"P. Lossin","email":"","orcid":"","institution":"Urologie Bonn-Rhein-Sieg","correspondingAuthor":false,"prefix":"","firstName":"P.","middleName":"","lastName":"Lossin","suffix":""},{"id":534433028,"identity":"3cac34ce-d249-456a-b4c0-ed1cf4ce7ed2","order_by":4,"name":"J. Stein","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"J.","middleName":"","lastName":"Stein","suffix":""}],"badges":[],"createdAt":"2025-08-27 07:23:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7468825/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7468825/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00345-025-06162-7","type":"published","date":"2026-01-31T15:59:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":94546579,"identity":"4144a1af-cb30-46f2-bb48-5033ddb1f7b7","added_by":"auto","created_at":"2025-10-28 17:39:49","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":738646,"visible":true,"origin":"","legend":"","description":"","filename":"250829coreshell.technicalcheck.docx","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/2286e54960a9f041ee3cbcf2.docx"},{"id":94546577,"identity":"7527b7f5-2e7a-4182-a058-c1158972221c","added_by":"auto","created_at":"2025-10-28 17:39:48","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6771,"visible":true,"origin":"","legend":"","description":"","filename":"1bbd494d27a948adbe3da5c18e6ca830.json","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/77cea599bf672a49e67ecaaf.json"},{"id":94597946,"identity":"6cd5ef99-0f3f-4e52-b284-128ad77486e7","added_by":"auto","created_at":"2025-10-28 18:50:22","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":80180,"visible":true,"origin":"","legend":"","description":"","filename":"1bbd494d27a948adbe3da5c18e6ca8301enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/9ff0ecb8f88df5aa7252934e.xml"},{"id":94546853,"identity":"81285ff9-ab1b-4fe5-b9aa-ff1c24c2d9ea","added_by":"auto","created_at":"2025-10-28 17:41:12","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6534,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/f839e7b2345ae23643d74e6b.png"},{"id":94546856,"identity":"39420b7c-f43f-476a-92ef-6ce5038c7447","added_by":"auto","created_at":"2025-10-28 17:41:12","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17179,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/804d92ef3fd3aa303c57d7b3.png"},{"id":94546705,"identity":"9d8038e1-fa36-4ee7-bfcd-30e6b25ab896","added_by":"auto","created_at":"2025-10-28 17:40:23","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":9706,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/46ed0f08a758e1cae842b360.png"},{"id":94547179,"identity":"1cdf9964-79ce-468d-8288-6f1aeba16e67","added_by":"auto","created_at":"2025-10-28 17:42:16","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":9625,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/e3ca94e0e44308b1b3435756.png"},{"id":94546614,"identity":"98908323-41a7-4fa2-9c8c-1322eae29c69","added_by":"auto","created_at":"2025-10-28 17:39:55","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":16738,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/84fecc30eeb2b87b79622b36.png"},{"id":94546973,"identity":"043ea771-1095-449e-bc01-0c7fb0df5b6a","added_by":"auto","created_at":"2025-10-28 17:41:39","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":26186,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/d852bb2e4f9ff968713aa111.png"},{"id":94546928,"identity":"3670e6b1-63b9-4a6a-8799-5165336ca676","added_by":"auto","created_at":"2025-10-28 17:41:28","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81690,"visible":true,"origin":"","legend":"","description":"","filename":"1bbd494d27a948adbe3da5c18e6ca8301structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/92c023d115c8266ea29029c8.xml"},{"id":94546858,"identity":"484fda63-a023-42ef-a4af-32dfad5989da","added_by":"auto","created_at":"2025-10-28 17:41:13","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":85987,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/4de90d00a43bf2a5f3740624.html"},{"id":94546701,"identity":"82a23d2c-0a7a-41ae-8f37-9f27a16550db","added_by":"auto","created_at":"2025-10-28 17:40:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22318,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMethod of Analysis\u003c/strong\u003e: A conventional single analysis was performed in 61.7% of all stones, in 38,3% core and shell were measured separately.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/e0d94a108e7da047e87d9a27.png"},{"id":94546886,"identity":"34f00263-00b3-4fa7-bdd4-01160655e954","added_by":"auto","created_at":"2025-10-28 17:41:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":379719,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution and naming of groups\u003c/strong\u003e: In total, 19,972 stone measurements were analyzed, 12,314 were analyzed with single conventional stone analysis (group A), 7,658 were analyzed separately in core and shell (group B). 6,613 of all stones of group B are said to be equal with a difference in both core and shell \u0026lt;10% (group B1). 1,045 of all stones differ in their analysis between core and shell with at minimum 10% (group B2).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/fed3b878c42e546ca3b59475.png"},{"id":94546927,"identity":"ee98936c-e7b5-4b10-8c73-6f2e0b74bd3f","added_by":"auto","created_at":"2025-10-28 17:41:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29193,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStone distribution\u003c/strong\u003e: In single analysis 73.3% of all stones were calcium oxalate, 12.1% carbonate apatite, 7.4% uric acid, 2.7% struvite, 0.6% cystine, 0.3% urate, 1.4% brushite.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/1fe6223e2f5f7d057a4bcbc8.png"},{"id":94546877,"identity":"735142b1-20c6-4d77-bdca-8751f12c1e89","added_by":"auto","created_at":"2025-10-28 17:41:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":29465,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDifference between core and shell\u003c/strong\u003e: In 77.1% of all core and shell analysis results were same, in 22.9% of cases they differ. 9.3% of all stones differ less than 10%, 6.8% differ 10% and 6.8% differ more than 10%. Those stones differing less than 10% are said to be group B1 and those differing at least 10% are said to be group B2.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/b9dad28786161cc6da671e3f.png"},{"id":94546873,"identity":"dfc325ab-414d-40cc-95bd-4f056772bca4","added_by":"auto","created_at":"2025-10-28 17:41:19","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":65907,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of stone types in Core (a) and Shell (b)\u003c/strong\u003e: (a) In separate analysis 75.1% of all were Calcium oxalate, 10.0% Carbonate apatite, 8.5% Uric acid, 2.2% Struvite, 0.5% Cystine, 0.3% Urate, 1.6% Brushite. (b) In separate analysis 74.8% of all stones were Calcium oxalate, 9.8% Carbonate apatite, 8.7% Uric acid, 2.3% Struvite, 0.5% Cystine, 0.2% Urate, 21.7% Brushite.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/eb9f6613084a6c35a61d0ec9.png"},{"id":94546578,"identity":"30d5f6a6-3839-4ece-a925-d31c742d462c","added_by":"auto","created_at":"2025-10-28 17:39:49","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":125550,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of component counts across groups [%]\u003c/strong\u003e. In A, 64.3% show one, 34.3% show two and 1.4% show 3 components. In B, 14.1% show 1, 61.1% show 2 and 24.1% show 3 and 0.7 show 4 components. In B1, 16,8% show one, 67% show two, 16.1% show 3 and 0.1 show 4 compomnents. In B2 36.8% show two, 58.7% show three and 4.4% show 4 components. 5% counts were not excluded.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/5fe742b06ffa65483c421a73.png"},{"id":101690585,"identity":"1c41faeb-c1b0-4558-ad90-3725487c7762","added_by":"auto","created_at":"2026-02-02 16:06:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1503102,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7468825/v1/1164bc99-0cf0-486b-8adb-26cfd68fd44d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Separate core-shell analysis of urinary stones may influence specific metaphylaxis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe prevalence of urinary stones in countries with a high standard of living is constantly increasing with some regions reporting an increase of over 37% in the last two decades [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Within five years stones recur in up 26%, recurrence can be reduced to 10% under metaphylaxis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Patients are classified as high-risk stone formers if they have early-onset or recurrent urolithiasis, certain types of stones (e.g., brushite, uric acid, infection stones), associated medical conditions (e.g., CKD, hyperparathyroidism, metabolic disorders), genetic causes, or anatomical abnormalities. Urinary stones contribute potential complications such as acute renal failure or urosepsis as well as chronic kidney disease possible leading to an end stage kidney disease due to the primary conditions causing stone formation or the intervention for stone removal [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn high-risk patients, multiple guidelines recommend specific stone metaphylaxis, which can reduce the recurrence risk from 50\u0026ndash;80% to 10\u0026ndash;15% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Strategies of metaphylaxis are based on stone analysis and stone analysis itself can identify a high-risk patient (e.g. struvite, cystine). Therefore, stone analysis is recommended for every first stone event and in case of recurrence under stone metaphylaxis, rapid stone recurrence or stone recurrence after a long stone-free period.\u003c/p\u003e\u003cp\u003eUrinary stones can significantly vary in composition, with calcium oxalate stones representing the predominant form with a frequency of 67\u0026ndash;80% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Recent data published in 2022 showed, that in Germany the most common stone component calcium oxalate account for 71.4% of all stones [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. They are followed by those consisting mostly of carbonate apatite with 10.2% (5\u0026ndash;16%), and struvite stones, also known as magnesium ammonium phosphate \"infection stones\" with 2.1% (3\u0026ndash;5%). Uric acid stones account for 8.3% (8\u0026ndash;13%) and brushite stones for 1.3% while cystine (0.4%) and ammonium urate are rare, each comprising less than 1% of cases.\u003c/p\u003e\u003cp\u003eIt is known that stones often are composed of different minerals, and the exact analysis can provide essential information about factors affecting stone formation. When analyzing stones macroscopically, some show a different composition of the core of stones than in the shell, which might provide more information about the history of the stone formation. Only one study was found which included separate core and shell analysis on 10,000 urinary stones. It was shown that 29.5% of these stones showed differences between core and shell. Only weddellite and uric acid stones showed a clear preference of the shell [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, recently there has been no data available which analyzed the difference between core and shell.\u003c/p\u003e\u003cp\u003eStone metaphylaxis and stone analysis are pivotal aspects in nephrology and urology to prevent urinary stone recurrence and avoid severe complications. Given the rising prevalence of urinary stones and their diverse compositions, an individualized approach of metaphylaxis is imperative. Here, further analysis of the core and shell can provide an important approach to establish precise metaphylaxis and thus further reduce the risk of recurrent stone formation. Therefore, the aim was to analyze the differences in composition between the core and the shell of a stone, to better understand stone formation, improve metaphylaxis, and possibly achieve a reduction in recurrence rates.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study underwent review by the Ethics Committee of the University of Bonn, which concluded that ethical vote is not required (2024-248-BO).\u003c/p\u003e\u003cp\u003eA total of 20,158 urinary stone samples were collected and analyzed at the Urinary Stone Analysis Center in Bonn during the years 2021 and 2022 using Fourier-transform infrared spectroscopy in ATR technique. In the case of mixed stones, the individual components were semiquantitatively indicated in 5% increments. This allowed for a detailed assessment of the varying composition within mixed stones and was personally conducted by the laboratory management after IT-assisted pre-evaluation. This ensured a standardized approach to the analysis of each urinary stone sample.\u003c/p\u003e\u003cp\u003eFor explicit requests from the referrer, separate core-shell analyses of the sample were performed. Otherwise, a representative sample of the entire urinary stone was measured. Our statistical analysis focused on the prevalence and distribution of the most common urinary stone minerals. These included whewellite, weddellite, uric acid/uric acid dihydrate, carbonate apatite, brushite, struvite, cystine, and protein. To account for clinical relevance, whewellite and weddellite stones were grouped together as a calcium oxalate. The main component was defined as the constituent that comprises the largest proportion of the stone and defines the type of the stone. In mixed stones, this does not necessarily need to account for 50% of the total mass and may instead be represented by two components of equal prominence. Pure stones are defined as those composed of at least 95% of a single component.\u003c/p\u003e\u003cp\u003eData analysis was performed using IBM SPSS Statistics v26. Descriptive statistics were calculated for categorical variables, including frequencies and proportions, while continuously coded variables were described with means and standard deviations. Differences were analyzed using chi-square paired tests. An unpaired, two-tailed t-test was used to test statistical significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Graphics were created with the help of ChatGPT.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e19,972 of 20,158 stone analyses were used for further statistical analysis, 186 must be excluded. Reasons were that the sum of the stone composition was either greater or less than 100%, components other than whewellite, weddellite, uric acid/uric acid dihydrate, carbonate apatite, brushite, struvite, cystine, and protein were present, or minerals appeared twice in the given results. A separate analysis of core and shell was conducted on 7,658 stones (38.3%, Group B), while a conventional urinary stone analysis (single analysis) was performed on 12,314 stones (61.7%, group A, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSingle Analysis\u003c/p\u003e\u003cp\u003eFor stones where a single analysis was performed (12,314, group A), 64.3% (7,916) were pure when separated according to calcium oxalate, carbonate apatite, uric acid, struvite, cystine, urate and brushite, while 35.7% (4,398) were mixed stones. 73.3% (9,021) of all stones were composed of calcium oxalate as main component, 12.1% (1,485) of carbonate apatite and 7.4% (953) of uric acid. 2.7% (334) were struvite, 1.4% (172) brushite, 0.6% (73) were cystine and each 0.3% protein or urate stones. 0.9% (110) of all stones consisted equally of calcium oxalate and carbonate apatite, while other mixed main components were in total 2.4% (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eMain component of stones after single analysis (A)\u003c/b\u003e: A main component is the one that constitutes the largest percentage of the stone; in mixed stones, it does not necessarily have to be 50% of the total mass and can also be determined by two equally frequent components.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStone Type (main component of stone)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUric Acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e953\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium Oxalate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9,021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e73.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarbonate Apatite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1,485\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStruvite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e334\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCystine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProtein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrushite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e172\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium Oxalate and Carbonate Apatite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u0026thinsp;\u0026gt;\u0026thinsp;1 main component\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eCore and shell analysis\u003c/h3\u003e\n\u003cp\u003eFor stones where a separate analysis of core and shell was performed (7,658, Group B), 61.9% (4,743) stones were pure, while 38,1% (2,915) were mixed stones consisting of more than one component.\u003c/p\u003e\u003cp\u003eIn total, 65.3% (5,683) of all measurements of core and shell were equal. Varied findings in the separate analysis accounted for 34.7% (2,657) with 25.8% (1,975) of them differing by at least 10% (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). When whewellite and weddellite were combined as calcium oxalate, 77,1% (5,903) analysis were equal, diverse results were observed in 22.9% (1,761) of cases, with 13.6% (1,041) showing a difference of at least 10%, this group is from now on called group B2. In total 86.4% of stones where whewellite and weddellite are combined as calcium oxalate were equal or differ at maximum 5% between core and shell, this group is from now on called group B1. Further subgroup analysis showed 3.3% (256) differing more than 20% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eCore and shell were analyzed to determine if they differ in their composition.\u003c/b\u003e 22.9% of B showed differences in composition between the core and shell, with a difference of at minimum 10% (B2) in 13.6% of cases. A difference of 10% could be measured in 6.8% of cases, 15\u0026ndash;20% difference in 3.4%, and over 20% difference in 3.3%. Equal measurements in core and shell or a difference of 5% (B1) represented 86.4% of all stones.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCore and Shell analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercent\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEqual\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5903\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77,1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnequal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1755\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Difference\u0026thinsp;\u0026lt;\u0026thinsp;10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e714\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Difference\u0026thinsp;\u0026ge;\u0026thinsp;10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1047\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEqual\u0026thinsp;=\u0026thinsp;Difference\u0026thinsp;\u0026lt;\u0026thinsp;10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6617\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnequal\u0026thinsp;\u0026ge;\u0026thinsp;10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Difference 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e504\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Difference 15\u0026ndash;20%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e264\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Difference\u0026thinsp;\u0026gt;\u0026thinsp;20%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Difference 100%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn 3.9% (300) of all core-shell analyses, new components in the core not being presented in the shell or vice versa with at least 10% of the stone mass could be measured. This accounts for 28.8% of all cases where the core and shell differ.\u003c/p\u003e\n\u003ch3\u003eStone composition\u003c/h3\u003e\n\u003cp\u003eFor analysis and comparison of B the mean value of core and shell was calculated. For comparability, in B2 the mean value of the percentage given for the prevalence in the core and shell is calculated, e.g. brushite represents 2.3% of all core analyses and 2.5% of all shells, here it is said that brushite represents 2.4% of all core-shell analysis (B). However, the overall content of whole stone is influenced by the different core-shell ratios (meaning e.g. thick shell and very small core or vice versa). For the sake of comparability, the mean value is mentioned below.\u003c/p\u003e\u003cp\u003eStones are distributed into groups according to their main component, meaning a stone which consists mainly out of calcium oxalate is said to be a calcium oxalate stone.\u003c/p\u003e\u003cp\u003eWhen analyzing the cases where stone and shell are measured separately (B), calcium oxalate was found in the core in 75.1% (5752) of cases and in the shell in 74.8% (5726) of cases (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In subgroup analysis in those stones where core and shell had the same composition (B1), it represented 78.9% (5520) of the cases. In those stones showing different composition (B2) calcium oxalate represented 50.9% (532) of the core and 49.9% (512) of the shell. Calcium oxalate occurred significantly more frequently in single analysis (A) than to B (p\u0026thinsp;=\u0026thinsp;0,01). In B it is more frequent than in B1 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00) or B2 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant difference in the appearance between core and shell (p\u0026thinsp;\u0026gt;\u0026thinsp;0.382).\u003c/p\u003e\u003cp\u003eIn B, carbonate apatite was found in the core in 10% (764) and in the shell in 9.8% (752). In B1 it was found in 7.5% (494) of the cases. In B2 carbonate apatite represented 25.8% (270) of the core and 24.5% (256) of the shell. It was significantly more often present in A compared to single analysis (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00). Differences could also be seen between B and B1 (B\u0026thinsp;\u0026lt;\u0026thinsp;B1) as well as B and B2 (B\u0026thinsp;\u0026lt;\u0026thinsp;B2) and between B1 and B2 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00). It was most often in B2 (B1\u0026thinsp;\u0026lt;\u0026thinsp;B2, p\u0026thinsp;\u0026lt;\u0026thinsp;0.00). It is most often present in B2. There is no significant difference in appearance in core or shell (p\u0026thinsp;=\u0026thinsp;0.59).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eStone type of core and shell\u003c/b\u003e. First, percentage of all core-shell analysis (B) which is represented by the mentioned type of stone (7,658). In sub analysis, listed are those cases where core and shell differ in their composition at a minimum of 10% (unequal, 1,045) and differ not (equal, 6,613). *Analysis differs significantly from single analysis (A), \u003csup\u003e#\u003c/sup\u003e to B, \u003csup\u003e+\u003c/sup\u003eto B1, \u0026rsquo; to B2, \u003csup\u003e^\u003c/sup\u003ebetween core and shell. In no case could a significant change in the frequency of occurrence between core and shell be measured.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStone type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCore (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eShell (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSingle analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eLiterature\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUric acid (all core and shell (B, 7658))\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.5\u003csup\u003e#+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.7\u003csup\u003e#+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Equal (B1 6613)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.3\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.3\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Unequal min. 10% (B2 1045)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.7\u003csup\u003e+#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.1\u003csup\u003e+#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium oxalate (all core and shell) B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75.1*\u003csup\u003e+\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74.8*\u003csup\u003e+\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e73.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e67\u0026ndash;80\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- equal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.9\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.9\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- unequal min. 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.9\u003csup\u003e+#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49.9\u003csup\u003e+#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarbonate apatite (all core and shell)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.0*\u003csup\u003e+\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.8*\u003csup\u003e+\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5\u0026ndash;16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- equal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.5\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- unequal min. 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25.8\u0026rsquo;\u003csup\u003e#+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.5\u0026rsquo;\u003csup\u003e#+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStruvite (all core and shell)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2*\u003csup\u003e+\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.3*\u003csup\u003e+\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3\u0026ndash;5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- equal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.7\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7\u0026rsquo;\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- unequal min. 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.4\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCystine (all core and shell)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- equal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- unequal min. 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrushite (all core and shell)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- equal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- unequal min. 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium oxalate\u0026thinsp;+\u0026thinsp;Carbonate apatite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.9*\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.1*\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- equal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5\u003csup\u003e*#\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5\u003csup\u003e*#\u003c/sup\u003e\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- unequal min. 10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.4\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eUric acid was found in the core in 8.5% (652) and in the shell in 8.7% (667) of cases. In subgroup analysis of B1, it was seen in 8.3% (551) of the cases. In B2 uric acid represented 9.7% (101) of the cores and 11.1% (116) of the shells. Uric acid occurs not significantly more frequently in all core-shell analyses (B) compared to single analysis (p\u0026thinsp;=\u0026thinsp;0.051), but is more frequent in B1 than in B (p\u0026thinsp;=\u0026thinsp;0.02), and less frequent than in B2 (p\u0026thinsp;=\u0026thinsp;0.04). There is no significant difference between the core and shell in B (p\u0026thinsp;=\u0026thinsp;0.52) and between B1 and B2 (p\u0026thinsp;=\u0026thinsp;0.65).\u003c/p\u003e\u003cp\u003eFor those stones where a difference between core and shell could be measured (B2), struvite represented 5.4% (57) of cases in the core and in 6.3% (66) of cases in the shell, while in total (B) struvite represented 2.2% (168) of all cores and 2.3% (177) of all stone analysis. In B1 struvite represented 1.7% (111) of the subgroup. In comparison to single analysis, struvite occurs significantly less frequently in B (p\u0026thinsp;=\u0026thinsp;0.049). In the group of identical analyses (B1), it occurs significantly less frequently (p\u0026thinsp;=\u0026thinsp;0,02) compared to B, and in the group of different analyses (B2), it is significantly more frequently (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Statistically, there is no difference between core and shell (p\u0026thinsp;\u0026gt;\u0026thinsp;0.457).\u003c/p\u003e\u003cp\u003eCystine was found in B (35) and B1 (34) in 0.5% of all cases. In those stones showing different composition cystine was represented in both core and shell with 0.1% (1). Cystine differed not significantly in any analysis (p\u0026thinsp;\u0026gt;\u0026thinsp;0.029).\u003c/p\u003e\u003cp\u003eIn B2, brushite represents 2.3% (24) of all cores and 2.5% (26) of all shells, while in B brushite represented 1.6% (126) of all cores and 1.7% (128) of all shells. In the group with the same composition (B1) brushite represented 1.5% (102). In the single analysis, brushite does not occur significantly different compared to all core-shell analyses (B) or in B1 and B2, neither between B1 and B2. There is no difference between core and shell (p\u0026thinsp;\u0026gt;\u0026thinsp;0.886).\u003c/p\u003e\u003cp\u003eStones where calcium oxalate and calcium phosphate were identified as equivalent main components, representing 0.9% (68) of all cores in B, while in the shell, it was 1.1% (86). In B1, it was seen in 1.5% (32) of the cases, in B2 they represented 3.4% (36) of the core and 4.8% (50) of the shell. They appear significantly more often in single analysis than in B (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00) and more often in B than in B1 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00) but more in B2 than in B1 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.00). Statistically there is no difference between core and shell (p\u0026thinsp;=\u0026thinsp;0.152).\u003c/p\u003e\u003cp\u003eIn 95.7% (7,329) of cases, the main component (largest stone proportion) remained the same in the core and shell, while in 329 cases (4.3%), there was a shift (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). In 103 cases (1.3%), there was a shift from calcium oxalate in the core in favor of carbonate apatite in the shell, and vice versa in 64 cases (0.8%). 39 shells shifted to uric acid (0.5%). However, in total 23 cores shifted to struvite as main component (2.3%).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eStone components\u003c/h3\u003e\n\u003cp\u003eThe number of components was examined in more detail. Here, the 5% value was included. In the single analysis group (A), 64.3% (7,916) consisted of one component, 35.3% (4224) of two components, and 1.4% (175) of three components. In B, 14,1% (1,081) of the stones consisted of one component, 31.1% (4682) of two components, 24,1% (1843) of three components, and 0.7% (52) of four components. In B1, 16% (1,080) of the stones consisted of one component, 65% (4,297) of two components, 18.6% (1,230) of three components, and 0.1% (6) of four components. For B2 18.4% (385) of the stones consisted of two components, 22.3% (613) of the stones consisted of three components, and 1.1% (46) of the stones consisted of a total of four components. In B2, 21.4% (224) of the samples had different components in the core or shell. There is a significant difference in the number of components in all groups (for all A to B, A to B1, B1 to B2 p\u0026thinsp;\u0026lt;\u0026thinsp;0.00) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWhen comparing the normalized prevalence per component of stone constituents between A, B, B1, and B2, several clear patterns emerged (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). After normalization for the number of components per stone, uric acid prevalence was comparable across all groups (4.6\u0026ndash;5.6%), indicating that previously observed differences were largely attributable to variations in stone complexity. Differences were mostly absent or moderate; B2 exhibited a slightly higher prevalence than B, while B1 and A showed similarly high values (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCalcium oxalate remained the most frequent component overall but was markedly lower in B2 (22.15%) compared with A (53.1%), B1 (47.3%), and B (40.9%). It showed extremely significant differences in almost all pairwise comparisons, with B1 and A consistently higher than B, and especially higher than B2, which had the lowest prevalence.\u003c/p\u003e\u003cp\u003eIn contrast, calcium phosphate was proportionally higher in B2 (11.16%) and A (8.74%) than in B (5.40%) and B1 (4.23%). It was significantly more frequent in B2 in many comparisons, particularly against B1 and B.\u003c/p\u003e\u003cp\u003eStruvite was most frequent in B2 (2.61%), followed by A (1.97%), B (1.23%), and B1 (0.95%) with B2 showing consistently and often highly significant higher prevalence compared with all other groups.\u003c/p\u003e\u003cp\u003eBrushite proportions were similar across groups (0.87\u0026ndash;1.06%), with a slight peak in B2. Most differences were not significant, except for a slightly higher prevalence in B2 compared with A.\u003c/p\u003e\u003cp\u003eCystine was rare in all groups (\u0026lt;\u0026thinsp;0.5%), with the lowest proportion in B2 (0.04%) with no significant differences observed.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eNormalized Prevalence per Component (%) of Stone Constituents by Group\u003c/b\u003e. \u003cem\u003eNormalized prevalence is calculated as the proportion of stones containing the respective component, adjusted for the number of components per stone, allowing for direct comparison between groups with different stone complexities.\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStone\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eB1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eB2\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUric acid\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5,61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4,65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5,62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4,62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCalcium oxalate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e53,1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40,89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e47,27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e22,15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCarbonate apatite\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8,74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4,23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11,16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStruvite\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1,97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1,23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0,95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2,61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBrushite\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1,01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0,9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0,87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCystine\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0,43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0,25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0,29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003ePrevalence of stone comparing single analysis and core-shell analysis in general\u003c/h2\u003e\u003cp\u003eAccording to current data, calcium oxalate stones are the most common stones, followed by carbonate apatite, uric acid stones, struvite, and brushite. Cystine stones are known to be rare. Among the stones for which a single conventional analysis was performed, the frequency of occurrence corresponds to the literature with calcium oxalate representing 73.3% off all stones, carbonate apatite 12.1%, uric acid 7.4%, struvite 2.7 and brushite with 1.4%. The mixed stones containing calcium oxalate and carbonate apatite equally represent 0.9% of all stones.\u003c/p\u003e\u003cp\u003eThis ranking regarding the prevalence of stones is similar when core and shell are separately analyzed (B). In this group calcium oxalate represents 75% of all stones, carbonate apatite 10%, uric acid 8.6%, struvite 2.3 and brushite 1.7%. The mixed stones containing calcium oxalate and carbonate apatite equally represent 1% of all stones.\u003c/p\u003e\u003cp\u003eBut significant differences in the prevalence of stones in those being analyzed in one analysis using a representative probe (A) compared to separate analysis of core and shell (B) become apparent. Calcium phosphate is most present in single analysis and does appear even less in those stones showing differences in core and shell. Here, no benefit can be seen when performing different analysis of core and shell.\u003c/p\u003e\u003cp\u003eCarbonate apatite and struvite are significantly more present in B2. Uric acid occurs equally in single analysis and B but is significantly most often represented in B1. This shows that single analysis detects uric acid more often and might be missed during single analysis. Struvite is slightly more often present in single analysis but it is highly significant more often present in B2. Struvite stones tend to be formed in presence of urinary tract infection, which can be caused by and induce further stone formation. It might be important to further analyze stones containing struvite to get knowledge of the real stone composition.\u003c/p\u003e\u003cp\u003eCystine did not appear significantly different in any since cystine stone is known to be particularly pure. Reason for this might be the well known genetic origin of stone formation, those patients usually have regular follow up visits.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePrevalence of stone composition comparing core-shell analysis for B1 and B2\u003c/h3\u003e\n\u003cp\u003eIn B2 there was a significant shift in prevalence of the stone composition. Carbonate apatite and struvite occur significantly more frequently in B2 than in B1, brushite and uric acid occur more frequently in B2, but not on significant level. Calcium oxalate is presented significantly more frequently in B1, Cystine is more prevalent in B1, however it is not statistically relevant. This can be in part be explained by the stone characteristics and the genesis of the stone development. Cystine stone is known to be mostly pure, however the development of a different shell can be potentially caused by specific stone metaphylaxis. A urinary tract infection can be caused by the presence of a stone, in this case, struvite and carbonate apatite as so called \u0026ldquo;infectious stones\u0026rdquo; may crystallize what makes it more likely to be part of a mixed stone.\u003c/p\u003e\u003cp\u003eOverall, B2 exhibited the lowest normalized calcium oxalate proportion but the highest relative prevalence of carbonate apatite, struvite, and brushite, suggesting a more heterogeneous and potentially infection-related stone composition. For carbonate apatite and struvite a separate analysis of core and shell seems to have a clear benefit, for uric acid and brushite it should be considered.\u003c/p\u003e\u003cp\u003eConcerning the number of stone components more components could be detected when separate analysis was performed (B), interestingly, those stones showing difference in core and shell (B2) are built up of more components.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eSummary of statistically significant comparisons\u003c/b\u003e (Chi\u0026sup2; test) for each substance across A, B, B1, and B2, with the group showing higher normalized prevalence per component indicated in parentheses. Whenever single analysis is relevant it is in bolt letters.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubstance\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSignificant comparisons\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUric acid\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA vs B1 (\u003cb\u003eB1\u003c/b\u003e); A vs B2 (\u003cb\u003eB2\u003c/b\u003e); B vs B1 (B1); B vs B2 (\u003cb\u003eB2\u003c/b\u003e); B1 vs B2 (B1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003erelevance and recommendation for separate analysis: should be considered\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCalcium oxalate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA vs B (\u003cb\u003eB\u003c/b\u003e); A vs B1 (B1); A vs B2 (A); B vs B1 (B1); B vs B2 (B); B1 vs B2 (B1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003erelevance and recommendation for separate analysis: no\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCarbonate apatite\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA vs B (A); A vs B1 (A); A vs B2 (\u003cb\u003eB2\u003c/b\u003e); B vs B1 (B); B vs B2 (\u003cb\u003eB2\u003c/b\u003e); B1 vs B2 (\u003cb\u003eB2\u003c/b\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003erelevance and recommendation for separate analysis: yes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStruvite\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA vs B (A); A vs B1 (A); A vs B2 (\u003cb\u003eB2\u003c/b\u003e); B vs B1 (B); B vs B2 (\u003cb\u003eB2\u003c/b\u003e); B1 vs B2 (\u003cb\u003eB2\u003c/b\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003erelevance and recommendation for separate analysis: yes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBrushite\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA vs B2 (\u003cb\u003eB2\u003c/b\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003erelevance and recommendation for separate analysis: should be considered\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCystine\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003erelevance and recommendation for separate analysis: no\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eOverall discussion\u003c/h3\u003e\n\u003cp\u003eThese data show that with single analyses, there is a risk of underdiagnosing specific stone components, which could lead to misguided specific metaphylaxis. Therefore, if results of single analysis identify additional urinary stone components that contradict the basic principles of metaphylaxis, special care should be taken. In conclusion, it can be said, that for carbonate apatite and struvite stones, separate core-shell analysis should be recommended, as well as for uric acid and brushite. However, for those patients suffering from stone recurrence although they have metaphylaxis separate analysis also in other stones might be helpful to adjust metaphylaxis.\u003c/p\u003e\u003cp\u003eFor example: A stone containing calcium oxalate, carbonate apatite and struvite. The specific metaphylaxis for calcium oxalate stones is based on alkali citrates. However, these are potentially lithogenic for carbonate apatite and struvite due to their urinary alkalinizing effect. In this case, citrate substitution should be considered cautiously and depending on the urine collection analysis (e.g. in the case of hypocitraturia). On the contrary, one might consider lowering urine pH with methionine and deliberately forgoing citrate substitution. Since bacteria-associated stones and components are prone to rapid recurrences, antibiotic prophylaxis may also be necessary even with smaller amounts of struvite or carbonate apatite. Moreover, the finding of such a stone composition should warrant increased awareness regarding phosphate lithogenesis. Regular urine culture checks are advisable, and it would also be advisable to look more closely for predisposing factors for urinary tract infections, such as bladder emptying disorders, urinary reflux or urinary tract obstructions.\u003c/p\u003e\u003cp\u003eHowever, to perform a core-shell analysis, both the core and the shell must be present in the sample sent in. This means that a representative piece of material containing both components must be available or clearly labeled parts of the stone must be saved. The size of the collected stone samples is primarily determined by the surgical procedure. In case of percutaneous nephrolitholapaxy larger fragments are typically retrieved, allowing for a core-shell analysis. However, with retrograde intrarenal surgery (RIRS), especially in the era of dusting, sufficiently large fragments that include both the core and shell are usually not obtained. Often only small samples are extracted, usually the core, as these are the fragments that remain at the end of the dusting procedure. A core shell analysis is feasible with samples that are at least 4\u0026ndash;5 mm in size. It must be possible to split the stone to identify and separately analyze samples from the core and the shell.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo conclude one should consider a separate core-shell analysis for stones containing carbonate apatite and struvite in the first place. It might not be necessary in the first place for calcium oxalate and cystine. With single analyses, there is a risk of misinterpreting important components of the stone and thus the genesis of the stones. Therefore, a potentially effect of core-shell analysis on metaphylaxis strategies is assumed. At least in high-risk stone formers and especially in patients with stone recurrence despite medication-based metaphylaxis, core-shell analysis can potentially enhance diagnostic value and help to optimize and individualize specific and stone metaphylaxis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePNL\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;percutane nephrolitholapaxie\u003c/p\u003e\n\u003cp\u003eURS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; ureterorenoscopy\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding Declaration\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no financial or non-financial interests that are directly or indirectly related to the research described in this paper.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eF. I. Winterhagen and S. Latz contributed equally to the study and wrote the main text of the manuscript, the laboratory work was carried out by S. Latz, P. Lossin and C. Jacobs. The statistical analysis was performed by I. Winterhagen, the scientific analysis and classification into the current state of the art was performed by I. Winterhagen, S. Latz and J. Stein. All authors have reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976\u0026ndash;1994. Kidney Int 63(5):1817\u0026ndash;1823. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1523-1755.2003.00917.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1523-1755.2003.00917.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHesse A, Br\u0026auml;ndle E, Wilbert D, K\u0026ouml;hrmann K-U, Alken P (2003) : Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. In: \u003cem\u003eEuropean urology\u003c/em\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0302-2838(03)00415-9\u003c/span\u003e\u003cspan address=\"10.1016/S0302-2838(03)00415-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eS\u0026aacute;nchez-Mart\u0026iacute;n FM, Mill\u0026aacute;n Rodr\u0026iacute;guez F, Esquena Fern\u0026aacute;ndez S, Segarra Tom\u0026aacute;s J, Rousaud Bar\u0026oacute;n F, Mart\u0026iacute;nez-Rodr\u0026iacute;guez R, Villavicencio Mavrich H (2007) Incidencia y prevalencia de la urolitiasis en Espa\u0026ntilde;a: Revisi\u0026oacute;n de los datos originales disponibles hasta la actualidad. Actas Urol Esp 31(5):511\u0026ndash;520. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0210-4806(07)73675-6\u003c/span\u003e\u003cspan address=\"10.1016/s0210-4806(07)73675-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eScales CD, Smith AC, Hanley JM, Saigal CS (2012) Prevalence of kidney stones in the United States. Eur Urol 62(1):160\u0026ndash;165. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eururo.2012.03.052\u003c/span\u003e\u003cspan address=\"10.1016/j.eururo.2012.03.052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerraro PM, Curhan GC, D'Addessi A, Gambaro G (2017) Risk of recurrence of idiopathic calcium kidney stones: analysis of data from the literature. J Nephrol. ;30(2):227\u0026ndash;233. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40620-016-0283-8\u003c/span\u003e\u003cspan address=\"10.1007/s40620-016-0283-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2016 Mar 11. PMID: 26969574\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSiener R (2006) Impact of dietary habits on stone incidence. Urol Res 34(2):131\u0026ndash;133. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00240-005-0025-1\u003c/span\u003e\u003cspan address=\"10.1007/s00240-005-0025-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKeddis MT, Rule AD (2013) Nephrolithiasis and loss of kidney function. Curr Opin Nephrol Hypertens 22(4):390\u0026ndash;396. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MNH.0b013e32836214b9\u003c/span\u003e\u003cspan address=\"10.1097/MNH.0b013e32836214b9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEAU Guidelines Edn. presented at the EAU Annual Congress Paris 2024. ISBN 978-94-92671-23-3\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eS2k-Leitlinie Diagnostik Therapie und Metaphylaxe der Urolithiasis, Version 4.0)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchubert G (2006) Stone analysis. Urol Res 34(2):146\u0026ndash;150. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00240-005-0028-y\u003c/span\u003e\u003cspan address=\"10.1007/s00240-005-0028-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLieske JC, Rule AD, Krambeck AE, Williams JC, Bergstralh EJ, Mehta RA, Moyer TP (2014) Stone composition as a function of age and sex. Clin J Am Soc Nephrology: CJASN 9(12):2141\u0026ndash;2146. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2215/CJN.05660614\u003c/span\u003e\u003cspan address=\"10.2215/CJN.05660614\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSiener R, Herwig H, R\u0026uuml;dy J, Schaefer RM, Lossin P, Hesse A (2022) Urinary stone composition in Germany: results from 45,783 stone analyses. World J Urol 40(7):1813\u0026ndash;1820. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00345-022-04060-w\u003c/span\u003e\u003cspan address=\"10.1007/s00345-022-04060-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchubert G, Brien G, Bick C (1983) Separate examinations on core and shell of urinary calculi. Urol Int 38(2):65\u0026ndash;69. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000280865\u003c/span\u003e\u003cspan address=\"10.1159/000280865\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjur","sideBox":"Learn more about [World Journal of Urology](https://link.springer.com/journal/345)","snPcode":"345","submissionUrl":"https://submission.nature.com/new-submission/345/3","title":"World Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Urolithiasis, Metaphylaxis, Stone analysis, core-shell analysis","lastPublishedDoi":"10.21203/rs.3.rs-7468825/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7468825/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThe recommendation for urinary stone metaphylaxis is based on urinary stone analysis. It is not known to what extent the separate analysis of the core and shell differ and can therefore possibly influence the metaphylaxis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIncluded were 19,973 stone analyses from 2021 and 2022 using infrared spectroscopy. For mixed stones, the individual components were specified semi-quantitatively in 5% increments. While 62% of the stones were analyzed using a representative sample of the whole stone, a separate core-shell analysis was performed in 38%. Analysis focused on evaluating the distribution of the most common urinary stone minerals.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn 22.9% of cases, difference in analysis between core and shell could be measured, in 13.6%, analyses differed by at least 10%. Here, a clear shift in the distribution of stone types compared to the distribution using a single representative probe could be demonstrated: Calcium oxalate occurred significantly less frequently in this group (50.2% vs. 73.3%), while struvite (5.9% vs. 2.7%) and carbonate apatite (25,2% vs. 12.1%) occurred significantly more frequently. The number of components detected in the stones increased in separate analysis and were even more when core and shell differ. In 4.3%, the main component between core and shell changed.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e\u003cp\u003eIn 13.6% of stones, there were clinically significant differences between core and shell. The change in the main component between core and shell may indicate the stone genesis. Separate core-shell analysis can influence and possibly optimize the metaphylaxis. Especially in the high-risk situation and recurrent stones, a separate core-shell analysis may be beneficial.\u003c/p\u003e","manuscriptTitle":"Separate core-shell analysis of urinary stones may influence specific metaphylaxis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-28 02:11:53","doi":"10.21203/rs.3.rs-7468825/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-29T14:06:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-24T10:04:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-20T19:33:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114778784398744152108410761543265988361","date":"2025-10-15T13:51:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"207347827683254789826171207518830629127","date":"2025-10-13T12:00:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258915556019469977461786891316425450261","date":"2025-10-13T09:00:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-13T08:19:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-03T00:40:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-02T17:35:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Urology","date":"2025-08-27T07:16:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjur","sideBox":"Learn more about [World Journal of Urology](https://link.springer.com/journal/345)","snPcode":"345","submissionUrl":"https://submission.nature.com/new-submission/345/3","title":"World Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4c81d7de-e85d-4041-95ea-e30bde8b0378","owner":[],"postedDate":"October 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:02:36+00:00","versionOfRecord":{"articleIdentity":"rs-7468825","link":"https://doi.org/10.1007/s00345-025-06162-7","journal":{"identity":"world-journal-of-urology","isVorOnly":false,"title":"World Journal of Urology"},"publishedOn":"2026-01-31 15:59:30","publishedOnDateReadable":"January 31st, 2026"},"versionCreatedAt":"2025-10-28 02:11:53","video":"","vorDoi":"10.1007/s00345-025-06162-7","vorDoiUrl":"https://doi.org/10.1007/s00345-025-06162-7","workflowStages":[]},"version":"v1","identity":"rs-7468825","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7468825","identity":"rs-7468825","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}