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INTRODUCTION: Nephrolithiasis is a major source of morbidity in the United States. In recent decades, there has been a notable increase in stone incidence in the pediatric population. We investigate whether recurrent stone formers who had their initial stone episode earlier in life are at risk for more frequent stone recurrences, compared to those with initial episodes later in life. We also examine possible risk factors that might change our approach to treatment of these patients. METHODS: A review of prospectively collected data from the Registry for Stones of the Kidney and Ureter (ReSKU) from September 2015 to July 2018 was conducted to compare stone recurrence and other patient factors in patients who reported an initial stone episode prior to 20 years of age versus patients who reported an initial stone episode after age 20. Data on patient age, gender, BMI, family history, race, income, infectious symptoms, and number of prior stone episodes was analyzed. We excluded patients with a history of cystinuria stones. Univariate analysis was performed using Fishers exact test and students T test. Multivariate analysis was performed using logistic regression. RESULTS: Of the 1140 patients enrolled during this study period, 472 patients were recurrent stone formers, and of these, 66 had their first stone episode prior to the age of 20. On univariate analysis, early stone formers were more likely to be female, present at a younger age, and have more prior stone episodes on enrollment. Using multivariate modelling to control for age, gender, race, BMI, family history, and number of stone episodes, early stone formers were more likely to be female (CI 1.17 - 3.54) and have more than one prior stone episode (CI 1.13 - 3.78). Late stone formers were more likely to have BMI > 30 (CI 0.26 - 0.94). CONCLUSION: Recurrent stone formers who have their first episodes prior to age 20 are more likely to present to stone clinics with multiple prior recurrences and hence more aggressive stone disease. Female gender seems to be a risk factor. Earlier stone formers should be encouraged to have close follow up and surveillance due to the increased rate of recurrence. Adult stone databases focusing on early presentations can improve understanding of pediatric stone disease.

IntroductionNephrolithiasis is a major source of morbidity in the United States. In recent decades, there has been a notable increase in stone incidence in the pediatric population. We investigate whether recurrent stone formers who had their initial stone episode earlier in life are at risk for more frequent stone recurrences, compared to those with initial episodes later in life. We also examine possible risk factors that might change our approach to treatment of these patients.MethodsA review of prospectively collected data from the Registry for Stones of the Kidney and Ureter (ReSKU) from September 2015 to July 2018 was conducted to compare stone recurrence and other patient factors in patients who reported an initial stone episode prior to 20 years of age versus patients who reported an initial stone episode after age 20. Data on patient age, gender, BMI, family history, race, income, infectious symptoms, and number of prior stone episodes was analyzed. We excluded patients with a history of cystinuria stones. Univariate analysis was performed using Fisher's exact test and student's T test. Multivariate analysis was performed using logistic regression.ResultsOf the 1140 patients enrolled during this study period, 472 patients were recurrent stone formers, and of these, 66 had their first stone episode prior to the age of 20. On univariate analysis, early stone formers were more likely to be female, present at a younger age, and have more prior stone episodes on enrollment. Using multivariate modelling to control for age, gender, race, BMI, family history, and number of stone episodes, early stone formers were more likely to be female (CI 1.17 - 3.54) and have more than one prior stone episode (CI 1.13 - 3.78). Late stone formers were more likely to have BMI > 30 (CI 0.26 - 0.94).ConclusionRecurrent stone formers who have their first episodes prior to age 20 are more likely to present to stone clinics with multiple prior recurrences and hence more aggressive stone disease. Female gender seems to be a risk factor. Earlier stone formers should be encouraged to have close follow up and surveillance due to the increased rate of recurrence. Adult stone databases focusing on early presentations can improve understanding of pediatric stone disease.

Decision-making for complex pediatric urinary system stone disease is still a challenge for pediatric urologists. The interest in supine percutaneous nephrolithotomy (PCNL) is increasing among centers to achieve high surgical success rates with less morbidity. Despite advanced retrograde intrarenal surgery armamentarium, percutaneous approaches remain the first-line surgical treatment modality for >2 cm and complex renal stones. There are no comparative studies yet in the literature for pediatric endoscopic combined intrarenal surgery (ECIRS) In this study, we aimed to contribute to the literature by evaluating the safety and efficacy of ECIRS by comparing it with PCNL. Patients under 18 years of age who underwent PCNL and ECIRS for urinary tract stone disease at our Pediatric Urology department between 2012 and 2024 were included. Preoperative (demographic characteristics, stone characteristics, biochemical parameters), perioperative (duration of surgery, number of accesses, lasing and fluoroscopy times, endoscopic and fluoroscopic stone-free rates) and postoperative (hospital stay, urinary tract infection, complication and radiological stone-free rates) parameters were retrospectively evaluated. A total of 68 children [28 (41%) girls and 40 (59%) boys] aged 5 (0–17) years were included in the study. ECIRS was performed in 19 (28%), supine in 28 (41%) and prone PCNL in 21 (30%) patients. Age (p = 0.029), Guy's stone score (p < 0.001), S.T.O.N.E. (p < 0.001), and Seoul National University Renal Stone Complexity (S-ReSC) scores (p = 0.001) for preoperative parameters were found to be higher in ECIRS group over both PCNL methods (Summary Table). However, Clinical Research Office of the Endourological Society (CROES) score was seen lower for ECIRS group patients compared to other groups (p = 0.028). Surgery time (in favor of supine over prone PCNL), fluoroscopy time (in favor of ECIRS and Supine PCNL over Prone PCNL), preferred laser type (prone PCNL group was mostly performed with holmium laser, whereas other groups were balanced between Holmium and Thulium Fiber Laser) and exit strategy (the preferred exit strategy was DJ Stent in most of the ECIRS patients, whereas nephrostomy tube was used in some of the PCNL group) showed significant difference among the groups as perioperative parameters (p = 0.042, <0.001, <0.001, <0.001, respectively). Surgery time was lower for supine PCNL compared to prone PCNL. For postoperative parameters, stone-free rates, complication rates and urinary tract infections were similar between the 3 groups, while a difference was detected in terms of length of hospital stay in favor of ECIRS over both supine and prone PCNL (p = 0.006). The current trial suggests that stone-free and complication rates of ECIRS and supine PCNL were similar in the pediatric complex stone patients. Although, the stones in the ECIRS group we found to be more complex. Also, ECIRS was superior to PCNL in terms of fluoroscopy exposure and hospital stay. With the widespread use of new generation ureteral access sheaths and flexible ureterorenoscopes, ECIRS may have an important role in treatment of complex pediatric kidney stones. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of various minimally invasive procedures for 10–20 mm pediatric renal stones by Bayesian network meta-analysis (NWA). We searched clinical comparative trials published in Pubmed, Embase, Cochrane Library from inception to 12 April 2020. Two researchers evaluated the quality and extracted data individually. Data was analyzed using STATA and GEMYC R package. The overall network meta-analytic outcome of stone free rate (SFR) in a single session revealed that Retrograde Intrarenal Stone Surgery (RIRS), miniaturized percutaneous nephrolithotomy (mPCNL) and PCNL showed superiority to extracorporeal shockwave lithotripsy (ESWL). Statistical significance was not detected between any intervention from our pooled network analysis of complication rate. SMP was the most likely to ranking in first place to render stone free status, and it also showed the lowest risk possibility of complications. Mini-PCNL had longer operation time and hospitalization than ESWL. The global and loop inconsistency evaluation demonstrated a rather acceptable outcome apart from the comparisons of complication rate between two randomized control studies. Herein, the authors reviewed and explored the optimal management pattern for pediatric 10–20 mm renal stones. This NWA revealed RIRS and mPCNL could render higher SFR without increasing risk of complications compared with ESWL. Although SMP was deemed to be the best choice in our study, the limited source of study and sample size implied the results required to be further validated. In addition, there were still some problems requiring to be underlined for various surgical options. ESWL was inferior to RIRS, mPCNL and PCNL for 10–20 mm pediatric renal stones, among which SMP might be the most ideal option associated with the least possibility of complications and the highest probability of stone clearance. [ABSTRACT FROM AUTHOR]

Summary Objective Kidney stone disease has become more common among children and young adults. Despite its well-documented success in adults, published success rates of medical expulsive therapy (MET) for pediatric urolithiasis vary widely. Our objective was to determine whether the aggregated evidence supports the use of MET in children. Methods We searched the Cochrane Controlled Trials Register, clinicaltrials.gov , MEDLINE, and EMBASE databases, and recently presented meeting abstracts for reports in any language. In addition, the bibliographies of included studies were then hand-searched. The protocol was prospectively registered at PROSPERO (CRD42013005960). Inclusion criteria were children (aged ≤ 18 years) with urolithiasis treated with medications with the specific goal of increasing spontaneous stone passage rate, including but not limited to alpha-adrenergic blockers (e.g., tamsulosin or doxazosin), calcium channel blockers (e.g., nifedipine), or other adjuvant medications (e.g., steroids or tolterodine). Manuscripts were then assessed and data abstracted in duplicate, with differences resolved by the senior author. Risk of bias was assessed using standardized instruments. Descriptive statistical analyses were performed as appropriate. Results We identified 11,197 studies, five of which (3 randomized controlled trials, 2 retrospective cohorts) were included in the pooled meta-analysis. Although we found little evidence of significant publication bias, we were unable to assess the likelihood of other forms of bias (allocation, selection) for most included studies due to reporting limitations. The pooled results demonstrate that MET significantly increased the odds of spontaneous stone passage (OR 2.21, 95% CI 1.40–3.49). Between-study heterogeneity was not statistically significant ( I 2 = 14%, p = 0.36). Bivariate meta-regression models revealed no significant association between the likelihood of stone passage and study COI ( p = 0.9), study country ( p = 0.7), patient age ( p = 0.4), patient gender ( p = 0.4), duration of follow-up ( p = 0.3), or stone size ( p = 0.7). Side effects of MET were reported to be minimal. Relatively few patients reported any adverse effects at all; the most commonly reported issue was somnolence. Concerns about biases affecting the published outcomes of the included studies exist due to the low quality of the randomized controlled trials reviewed for analysis. However, there was little visual evidence of publication bias noted on the funnel plot, as confirmed by the Begg test ( p = 0.5). Conclusions Consistent with the adult literature, pediatric studies demonstrate that treatment with MET results in increased odds of spontaneous ureteral stone passage and a low rate of adverse events. Although the accumulated literature is limited by inconsistent and/or incomplete reporting, there is nonetheless a clear, cumulative positive effect of MET on stone passage among children. The available evidence thus supports a prominent role for MET in treatment algorithms for pediatric urolithiasis. [ABSTRACT FROM AUTHOR]

Objective To analyze the success and complication rates of percutaneous nephrolithotomy (PCNL) performed in pediatric patients and to compare outcomes of the patients undergoing primary PCNL with those of patients who had undergone previous open nephrolithotomy. Materials and methods Between 2000 and 2011, PNL procedures were performed in 123 renal units (RU) of 111 children. We compared RU on which previous open surgery had been performed (group 1 RU = 26) on the same kidney with RU that had not been involved in previous surgery (group 2 RU = 97). Patient characteristics, pre- and postoperative hematocrit and creatinin levels, operative time, fluoroscopic screening time, stone free rate, complications and hospitalization time were documented and compared. Results There were no significant differences between the groups in sex, stone burden, pre- and postoperative hematocrit levels. Mean age and pre- and postoperative creatinin levels were significantly higher in group 1 ( p < 0.05). Mean operative time, fluoroscopic screening time and hospitalization times were similar in each group ( p > 0.05). The stone free rates after PCNL were 65.4% in group 1 and 81.4% in group 2 ( p > 0.05). Multiple access rate was higher in group 1; however, this was not statistically significant (27% vs. 15%, p > 0.05). Conclusion PCNL can be performed in pediatric patients who have previously undergone open nephrolithotomy but the success rates may be lower and risk of bowel injury higher. NCCT should be considered preoperatively for patients who have previously undergone open renal surgeries to investigate the presence of retrorenal colons. Our study includes relatively few patients with a history of open surgery and we believe that additional clinical studies with larger numbers of patients are needed to confirm our initial findings. [ABSTRACT FROM AUTHOR]

Nephrolithiasis is detected on ultrasound by the presence of an echogenic focus, posterior acoustic shadowing and/or twinkle artifact (TA). TA has been shown to be highly predictive of nephrolithiasis in adults with renal colic and ureteral stones. We sought to evaluate if TA is reliable for diagnosing nephrolithiasis in the pediatric population. We reviewed renal ultrasound reports indicating presence or absence of TA associated with a single echogenic focus in the kidney or ureter. Exclusion criteria were age >18, multiple echogenic foci or medullary calcinosis, no follow-up, or TA located outside the kidney or ureter. Stone was confirmed either by CT within 3 months of color Doppler ultrasound, visualization on ureteroscopy, or patient report of passing the stone. Five hundred and ninety-nine ultrasound reports were reviewed and 293 met inclusion criteria. Sixty-nine had diffuse twinkle without echogenic focus and 224 showed TA with single echogenic focus. 135 patients had confirmatory information available (Summary Table). Nephrolithiasis was diagnosed using TA and confirmed on confirmatory studies for 49 ultrasounds. The majority of confirmed stones were in the kidney (n = 40; 82%) and mean size of confirmed stones on ultrasound was 5 mm (range 1.5–10). Sensitivity, specificity, positive predictive value and negative predictive value of TA for detecting nephrolithiasis were 83%, 78%, 74% and 86% respectively. Compared to the adult literature, TA in children has lower sensitivity, specificity and positive predictive value, but similar negative predictive value for diagnosing nephrolithiasis. This may be related to renal location and smaller stone size. The presence of TA should be weighed in the setting of other clinical and radiographic evidence of nephrolithiasis. [ABSTRACT FROM AUTHOR]

To compare the effects of micropercutaneous nephrolithotomy (micro-PCNL) and retrograde intrarenal surgery (RIRS) in treating 1–2 cm solitary renal stones in pediatric patients aged less than 3 years. A retrospective analysis was performed on data from 57 children younger than 3 years who received micro-PCNL and RIRS surgery in the authors hospital from October 2016 to August 2018. The patients were divided into group 1, the micro-PCNL group, and group 2, the RIRS group. Peri-operative data including surgical time, number of anesthesia sessions, stone-free rate (SFR), and complications were analyzed. There were 27 patients in group 1 and 30 patients in group 2, and the patients' mean ages were 19 ± 9.9 months and 21 ± 7.8 months, respectively (P = 0.462). The stone size was 1.6 ± 0.3 cm in group 1 and 1.7 ± 0.2 cm in group 2 (P = 0.217); the mean surgical time was 52 ± 7 min in group 1 and 48 ± 9 min in group 2 (P = 0.163), and the mean lithotripsy time was 21 ± 4 min in group 1 and 23 ± 5 min in group 2 (P = 0.148); and the SFR at 1 month after surgery was 88.9% in group 1 and 86.7% in group 2 (P = 0.799). The number of anesthesia sessions for patients was 1.4 ± 0.5 in group 1 and 2.7 ± 0.5 in group 2 (P < 0.001). The complication rate was 14.8% and 16.7% in group 1 and group 2, respectively (P = 0.714). None of the patients needed conversion to the 12–14 F mini-PCNL. The results of this study showed that the surgical effects and complications from micro-PCNL and RIRS in treating young children with 1–2 cm solitary renal stones were similar. However, micro-PCNL reduced the need to prestent before surgery and allowed lower anesthesia sessions. Therefore, micro-PCNL is an effective alternative method for 1–2 cm solitary renal stones in patients below 3 years of age. Summary Fig. Image 1 [ABSTRACT FROM AUTHOR]

Summary Background We investigated the clinical value of treating pediatric multiple kidney stones with extensive distribution using flexible ureteroscopic lithotripsy (FUL) combined with micro-percutaneous nephrolithotomy (micro-PNL). Patients and methods In total, 21 pediatric patients with multiple renal calculi between May 2016 and June 2017 received FUL combined with micro-PNL. The group included 13 boys and eight girls; the patients' mean age was 3.8 years (range 1–8 years). The maximum stone diameter ranged from 1.0 to 1.5 cm. FUL was first performed in the lithotomy position to fragment stones that were located in the renal pelvis, and upper and mid-renal calyx. Patients were then moved to a prone position, and micro-PNL was performed to treat lower pole stones that could not be reached by the flexible ureteroscope during FUL. Percutaneous renal access to the lower calyx was achieved using a 4.8F “all-seeing needle” with ultrasound guidance, and stone fragmentation was performed with a 200-μm holmium laser at different settings to disintegrate 1- to 2-mm fragments. Results All 21 pediatric patients with multiple kidney stones underwent combined FUL and micro-PNL. The stone free rate (SFR) was 85.7% (18/21). The mean surgical time was 45 min (range 30–70 min). The mean volume of irrigation fluid used was 480 mL (range 300–1200 mL). The mean surgical time for FUL and micro-PNL was 31 min and 14 min, respectively, and the mean volume of fluid used for FUL and micro-PNL was 360 mL and 120 mL, respectively. According to the modified Clavien classification, grade 1 and 2 postoperative complications occurred in five and one patients, respectively. The mean decrease in the level of hemoglobin was 0.4 g/dL (0–0.7 g/dL), and no patients required a transfusion. The average hospital stay was 3 days (range 2–5 days). Conclusion Combined FUL and micro-PNL is a safe, effective, and minimally invasive operation to remove multiple renal calculi with extensive distribution in children in selected cases. [ABSTRACT FROM AUTHOR]

Summary Introduction Upper pole access in percutaneous nephrolithotomy (PCNL) provides a straight tract to the ureter, resulting in easier placement of a guidewire to the ureter, good exposure of the pelvis, calices, and upper ureter, and comfortable manipulations. However, despite these benefits, upper pole access is usually avoided because of the risk of chest complications in both pediatric and adult patients. Objective We aimed to evaluate the safety and morbidity of single upper pole access in pediatric patients undergoing PCNL. Study design We retrospectively reviewed patients aged ≤17 years with renal stones who underwent PCNL with a single access between August 2004 and February 2016. The patients were separated into two groups: the single upper pole access group (SUPAG) and the single other pole access group (SOPAG). We compared the SUPAG and SOPAG in terms of the demographic features of the patients, stone burden and location, operative data, and postoperative outcomes. Complications were classified according to the modified Clavien system. Results During the study period, 101 PCNL procedures were performed, 77 of which were managed with only one access. The median age of the 77 patients managed with a single access was 12 years (range 3–17 years). The number of cases in the SUPAG and SOPAG was 10 and 67, respectively. There were no statistically significant differences between the SUPAG and SOPAG in terms of age, sex, stone location, hydronephrosis status, stone area, side of kidney, and previous stone treatment or renal surgery. Furthermoret, there were no significant differences between the groups in terms of the operative parameters. Although the difference was insignificant, the median operation times in the SUPAG and SOPAG were 37 and 45 min, respectively. There was no chest complication or bleeding that required transfusion in the SUPAG. Two cases required transfusion, and one case was managed with a double pigtail catheter (double-J) placement because of prolonged extravasation in the SOPAG. The stone-free ratios were 100% and 82.1% in the SUPAG and SOPAG, respectively. Conclusion Upper pole access provides similar outcomes to other (middle and lower) pole accesses, and may be performed without serious complications. These results indicate that this is a safe and effective approach of PCNL, and it presents a good alternative for removal of renal stones in pediatric patients. [ABSTRACT FROM AUTHOR]

Summary Introduction The risk of kidney stone formation increases with urinary stasis, which is associated with decreased peristaltism. The relationship between nonobstructive kidney stone formation and ureteral jet dynamics, which can be measured with Doppler ultrasonography (US) and provide information about ureteral peristaltism, has been demonstrated in adults. Objective To investigate the relationship between ureteral jet dynamics, which provide information about ureteral peristaltism, and stone formation in children. Study design Children admitted to Dokuz Eylul University Hospital with flank pain, and asymptomatic age-matched children for the control group, were prospectively enrolled and underwent Doppler US for diagnostic reasons and bilateral ureteral jet flow measurements. Children diagnosed with unilateral nonobstructive lower pole kidney stones formed Group 1, and the control group, without any evidence of stone disease, formed Group 2. Ureteral jet dynamics were compared between the affected renal units in Group 1, and healthy renal units in Group 1 and Group 2. Results A total of 32 children were included for each group. The mean average jet flow-rate (JETave (cm/second)) in affected renal units in Group 1 was found to be significantly lower than in the healthy renal units in Group 1 and left and right healthy renal units in Group 2 ( P < 0.05). The continuous JETpattern rate in affected renal units in Group 1 was found to be significantly higher compared with healthy renal units in Groups 1 and 2 ( P = 0.012) (Table). The odds ratio for kidney stone formation was 5.6 for renal units with JETave <9.5 cm/s when compared with renal units with JETave ≥9.5 cm/s. Discussion In a recent study, it was demonstrated in adults that low ureteral jet flow-rate and continuous JETpattern were significantly higher in affected renal units. The findings in children were also similar to adults: the mean JETave was significantly lower and determination rate of continuous flow pattern was significantly higher in affected renal units. Conclusions Children with low JETave and continuous JETpattern as a sign of decreased ureteral peristaltism are at an increased risk of kidney stone formation. However, it is vital that further studies are conducted to elaborate on this topic. Summary Table Comparison of JETave and continuous jet flow pattern between affected renal units in Group 1, and healthy renal units in Group 1, healthy left renal units in Group 2 and healthy right renal units in Group 2. Group 1 affected renal units (n = 32) Group 1 healthy renal units (n = 32) P * Group 2 left healthy renal units (n = 32) P † Group 2 right healthy renal units (n = 32) P ° JETave (cm/second) (min–max) 8.6 ± 5.7 (1.5–22.6) 11.6 ± 5.5 (3.0–25.3) 0.038 12.8 ± 6.5 (3.6–28.6) 0.008 13.4 ± 10.2 (3.0–49.3) 0.023 Continuous JETpattern (%) 6 (18.7) 0 (0) 0.012 0 (0) 0.012 0 (0) 0.012 * P -value between affected and healthy renal units in Group 1. † P -value between affected renal units in Group 1 and left healthy renal units in Group 2. ° P -value between affected renal units in Group 1 and right healthy renal units in Group 2. [ABSTRACT FROM AUTHOR]

Summary Objective Pediatric stone disease is a significant health issue which has increased in incidence because of lifestyle changes, dietary habits, and obesity. The incidence of urolithiasis among pediatric age groups varies according to region and is high in Turkey. The management of stone disease in children has improved dramatically over the last two decades. The high success rate of percutaneous nephrolithotomy (PNL) have led modern researchers to suggest that it be used as a first-line treatment of kidney stones greater than 2 cm in size. This study compared the outcomes, including morbidity and success rates, of different groups of pediatric patients who underwent PNL via pediatric- and adult-sized instruments. Methods Percutaneous nephrolithotomy was performed in 194 children in a clinical setting between the years 2000 and 2015. Patients were categorized into 2 groups (group 1: pediatric-sized devices used, n = 90 [46.4%]; group 2: adult-sized devices used, n = 104 [53.6%]). The children in group 2 were further divided into subgroups: a 24 F nephroscope was used for group 2a ( n = 84 [43.3%]) and a 26 F nephroscope was used for group 2b ( n = 20 [10.3%]) (Figure). Results For this study, a total of 194 pediatric patients (99 boys and 95 girls ranging from 8 months to 17 years of age, with a mean age of 9.43 years) underwent PNL for the removal of kidney stones in a clinical setting. Between the examined groups, there were no significant differences in patient height or weight, stone site or localization, pre- and post-operative creatinine levels, duration of nephrostomy, or hospitalization time. There was also no significant variation in minor complications such as fever or urinary infection. However, the stone burden was notably smaller in the group wherein pediatric-sized nephroscopes were used. Additionally, the incidence of hemorrhage was markedly lower in groups where a 17 F nephroscope was used than in groups where treatment was administered via 24 and 26 F nephroscopes. Conclusions Stone disease is considered to be relatively rare in childhood, but recent studies have indicated that it presents a considerable health problem. According to some researchers, a decrease in instrument size has not meaningfully reduced complication rates. In contrast, some studies have reported that the use of smaller sized nephroscopes may reduce rates of morbidity and mortality. In this study, success rates of PNL were similar across all groups, regardless of nephroscope size. However, the use of a 17 F nephroscope significantly decreased the rate of hematocrit level reduction ( p < 0.001). While instrument size does not affect the success of PNL, smaller instruments can be used to reduce various complications such as bleeding. Figure Nephroscopes with different diameters. Figure [ABSTRACT FROM AUTHOR]

Summary Introduction Bladder and renal calculi after bladder augmentation are thought to be primarily infectious, yet few studies have reported stone composition. Objective The primary aim was to assess bladder stone composition after augmentation, and renal stone composition in those with subsequent nephrolithiasis. The exploratory secondary aim was to screen for possible risk factors for developing infectious stones. Study design Patients treated for bladder stones after bladder augmentation at the present institution between 1981 and 2012 were retrospectively reviewed. Data were collected on demographics, surgeries and stone composition. Patients without stone analysis were excluded. Stones containing struvite, carbonate apatite or ammonium acid ureate were classified as infectious. The following variables were analyzed for a possible association with infectious bladder stone composition: gender, history of cloacal exstrophy, ambulatory status, nephrolithiasis, recurrent urea-splitting urinary tract infections, first vs recurrent stones, timing of presentation with a calculus, history of bladder neck procedures, catheterizable channel and vesicoureteral reflux. Fisher's exact test was used for analysis. Results Of the 107 patients with bladder stones after bladder augmentation, 85 met inclusion criteria. Median age at augmentation was 8.0 years (follow-up 10.8 years). Forty-four patients (51.8%) recurred (14 multiple recurrences, 143 bladder stones). Renal calculi developed in 19 (22.4%) patients with a bladder stone, and 10 (52.6%) recurred (30 renal stones). Overall, 30.8% of bladder stones were non-infectious (Table). Among patients recurring after an infectious bladder stone, 30.4% recurred with a non-infectious one. Among patients recurring after a non-infectious stone, 84.6% recurred with a non-infectious one ( P = 0.005). Compared with bladder stones, renal stones were more likely to be non-infectious (60.0%, P = 0.003). Of patients with recurrent renal calculi after an infectious stone, 40.0% recurred with a non-infectious one. No clinical variables were significantly associated with infectious stone composition on univariate (≥0.28) or bivariate analysis (≥0.36). Discussion This study had several limitations: it was not possible to accurately assess adherence with bladder irrigations, and routine metabolic evaluations were not performed. The findings may not apply to patients in all clinical settings. While stone analysis was available for 3/4 of the stones, similar rates of incomplete stone analyses have been reported in other series. Conclusions In patients with bladder augmentation, 1/3 of bladder stones and >1/2 of renal stones were non-infectious. Furthermore, an infectious stone does not imply an infectious recurrent stone and no known clinical variables appear to be associated with stone composition, suggesting that there is a possible metabolic component in stone formation after bladder augmentation. Table Stone composition of bladder and renal stones in patients with augmented bladders. Stone composition Bladder stones (n = 143) (%) Renal stones (n = 30) (%) Infectious stones 99 (69.2%) 12 (40.0%) Struvite 79 (55.2%) 11 (36.7%) Pure carbonate apatite 15 (10.5%) 1 (3.3%) Pure ammonium acid ureate 2 (1.4%) 0 (0.0%) Mixed stones with calcium phosphate 4 (2.8%) 0 (0.0%) Non-infectious stones 44 (30.8%) 18 (60.0%) Calcium phosphate 41 (28.7%) 14 (46.7%) Pure calcium oxalate 0 (0.0%) 4 (13.3%) Uric acid 3 (2.1%) 0 (0.0%) [ABSTRACT FROM AUTHOR]

Summary Introduction The gene mutations responsible for cystinuria do not fully explain kidney stone activity, suggesting that specific proteins may serve as promoters of cystine precipitation, aggregation or epithelial adherence. In this study we assessed (1) the differences in the urinary proteins between children with cystinuria and kidney stones (CYS) and healthy controls (HC), with particular attention to the fibrosis-related proteins, and (2) the presence of diagnostic biomarkers for CYS. Material and methods We conducted a pilot study comparing individual urinary proteomes of 2 newly diagnosed children with CYS and 2 age- and gender-matched HC, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest in both CYS and HC were selected using the following criteria: i) ≥5 spectral counts; ii) ≥2-fold difference in spectral counts; and iii) ≤0.05 p-value for the Fisher’s Exact Test. Discussion This study demonstrates a different urinary polypeptide profile in two children with CYS compared to two HC. Of the 623 proteins identified by proteomic analysis, 180 exhibited at least a 2-fold increased relative abundance in CYS compared to HC. Of these, 39 were involved in response to stress, 26 in response to wounding, 21 in inflammatory response, 18 in immune response, and 4 in cellular response to oxidative stress. 133 proteins were found only in children with CYS, 33 of which met the selection criteria. Of these 33 unique proteins, six are known to be associated with fibrosis pathways (Table). Accession Number a Protein MW (kDa) No. of assigned peptides b No. of unique peptides b Sequence coverage (%) ACTG Actin 42 202/117 52/37 70/51 VIME Vimentin 54 10/9 8/5 21/14 HSP70 Heat shock 70 kDa protein 70 24/18 7/5 14/15 ITIH2 Inter-alpha-trypsin inhibitor 106 33/81 12/11 27/16 MMP9 Matrix metalloproteinase 9 78 26/15 9/7 18/12 PON1 Serum paraoxonase 40 23/74 9/14 48/55 a Human. b Values presented in each patient (Patient 1/Patient 2). The major limitation of this study is the small number of samples that were analyzed. Validation using highly specific methods such as ELISA is needed. Conclusion We provide proteomic evidence of oxidative injury, inflammation, wound healing and fibrosis in two children with CYS. We speculate that oxidative stress and inflammation may cause remodeling via actin and vimentin pathways, leading to fibrosis. Additionally, we identified ITIH and MMP-9 as potential diagnostic biomarkers and novel therapeutic targets in CYS. These proteins merit further investigation. [ABSTRACT FROM AUTHOR]