In-vitro comparison of different slice thicknesses and kernel settings for measurement of urinary stone size by computed tomography Abstract Non-contrast enhanced computed tomography (NCCT) is widely used measuring stone size in patients with urolithiasis. We performed an evaluation of the accuracy of stone size measuring via NCCT. In an in-vitro study, we analyzed a total of 38 uric acid and 38 phantom stones. Within NCCT, we used different slice thicknesses (1.5 mm, 2.0 mm, and 3.0 mm) and kernel settings (bone and soft-tissue window). Maximal height, maximal length, and maximal width of each stone were measured on a picture archiving and communication system workstation. Blinded to these results, a second physician measured stone size in the same way using a caliper (real stone size). We used the Bland–Altman method for the analysis of agreement between the two measuring methods. The limit of agreement that was deemed clinical insignificant was ± 1.0 mm. All measurements via NCCT correlated significantly with the real stone size (p < 0.001). This was more pronounced for bone window and smaller slice thickness. Bland–Altman plots showed limits of agreement that exceeded the a priori defined level for all types of measurement with bone window and small slice thickness (1.5 mm) being better than soft-tissue window and large slice thickness (3.0 mm). We conclude that stone size measurement by NCCT with established settings is not exact. Stone size can easily be over- or underestimated by several millimeters. Using bone window and small slice thickness leads to more accurate results.

Protective effect of salvianolic acid B against oxidative injury associated with cystine stone formation Abstract The aim of this study was to investigate the role of oxidative stress in cystine crystal formation and whether salvianolic acid B, a natural antioxidant, could prevent cystine-mediated oxidative injury in vivo and in vitro. The levels of oxidative stress and antioxidase activity in cystine stone patients were assessed. Then, the oxidative stress exerted by cystine on human kidney-2 (HK-2) cell viability and biochemical parameters including antioxidase activity and antioxidant protein expression were evaluated, and the protective action of salvianolic acid B was also examined. Finally, salvianolic acid B was tested to determine whether it could prevent or reduce renal crystal formation in Slc7a9 knockout mice. The activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were decreased, and the amount of malondialdehyde (MDA) was increased in patients with cystine stones compared with people without cystine stones (p < 0.05). Significant reductions in cell viability, antioxidase activity and antioxidant protein expression levels were found in the cystine group compared with controls. However, such oxidative injuries were prevented by salvianolic acid B. In the animal study, loose crystals with white spots were seen in the renal parenchyma, bilateral renal pelvis and bladders in the Slc7a9 knockout group. In contrast, no renal crystals were seen in the control group, and markedly fewer crystals with significantly higher antioxidase activity and diminished oxidative stress were detected in the salvianolic acid B group. Cystine cytotoxicity in vitro and cystine stone formation in vivo were associated with oxidative stress, and salvianolic acid B could protect against cystine stone-induced injury.

Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments Abstract Kidney stone formation is governed by thermodynamic (supersaturation) and kinetic (crystal nucleation, growth, aggregation) mechanisms. We adopted a dual theoretical and experimental approach to investigate the potential role of urinary phytate in this regard. Thermodynamic constants for eight protonated phytate species and seven calcium–phytate complexes were determined by potentiometry and incorporated into the speciation program JESS. Urine was collected from 16 heathy males and their urine compositions were used as input for JESS. Phytate concentration was varied during modelling. No statistically significant decreases in Ca2+ concentrations or in supersaturation values were predicted by JESS. Crystallization experiments were then performed in pooled urine. Endogenous phytate concentration was determined using a metal–dye assay. The pool was dosed with various concentrations of phytate to achieve final concentrations equivalent to those used for modelling. Experiments showed that phytate had no effects on Ca2+ concentrations (as predicted by our theoretical modelling), metastable limits or crystal nucleation and growth kinetics. However, crystal aggregation kinetics was inhibited. We speculate that HPhy−11, small amounts of which were revealed by modelling, may bind to crystal surfaces and inhibit aggregation. We conclude that phytate exerts a kinetic, but not a thermodynamic inhibitory effect on crystallization in urine.

The significance of intraoperative renal pelvic urine and stone cultures for patients at a high risk of post-ureteroscopy systemic inflammatory response syndrome Abstract We examined the renal pelvic urine culture (RPUC) and stone culture (SC) during ureteroscopy and evaluated their associations with postoperative systemic inflammatory response syndrome (SIRS). We prospectively collected data of 224 patients who underwent ureteroscopic laser lithotripsy from March 2015 to December 2017. We examined the bladder urine culture pre-operatively. If the patients had positive culture results, we treated them with antibiotics for 5–7 days before surgery based on the sensitivity profile. We collected RPUC and SC samples during surgery. After ureteroscopy, patients were closely monitored for any signs of SIRS. Using a logistic regression model, we analyzed how the clinical factors affected the incidence of SIRS. Pre-operative bladder urine culture (PBUC) was positive in 111 patients (49.6%). Intraoperative RPUC was positive in 43 patients (19.2%), and SC was positive in 34 patients (15.2%). Postoperatively, 23 patients (10.3%) were diagnosed with SIRS. A multivariate analysis revealed that female gender, struvite calculi and positive intraoperative RPUC results were significantly associated with postoperative SIRS. Among the 31 patients who were positive for both PBUC and intraoperative RPUC, the pathogens were not consistent in 11 patients (35.5%). Among the 25 patients who were positive for both PBUC and intraoperative SC, the pathogens were not consistent in 13 patients (52.0%). We recommend collecting RPUC and SC samples during ureteroscopy, especially for patients with high risk factors, including female gender, expected struvite calculi and positive PBUC results.

Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis? Abstract Urine proteins are thought to control calcium oxalate stone formation, but over 1000 proteins have been reported in stone matrix obscuring their relative importance. Proteins critical to stone formation should be present at increased relative abundance in stone matrix compared to urine, so quantitative protein distribution data were obtained for stone matrix compared to prior urine proteome data. Matrix proteins were isolated from eight stones (> 90% calcium oxalate content) by crystal dissolution and further purified by ultradiafiltration (> 10 kDa membrane). Proteomic analyses were performed using label-free spectral counting tandem mass spectrometry, followed by stringent filtering. The average matrix proteome was compared to the average urine proteome observed in random urine samples from 25 calcium oxalate stone formers reported previously. Five proteins were prominently enriched in matrix, accounting for a mass fraction of > 30% of matrix protein, but only 3% of urine protein. Many highly abundant urinary proteins, like albumin and uromodulin, were present in matrix at reduced relative abundance compared to urine, likely indicating non-selective inclusion in matrix. Furthermore, grouping proteins by isoelectric point demonstrated that the stone matrix proteome was highly enriched in both strongly anionic (i.e., osteopontin) and strongly cationic (i.e., histone) proteins, most of which are normally found in intracellular or nuclear compartments. The fact that highly anionic and highly cationic proteins aggregate at low concentrations and these aggregates can induce crystal aggregation suggests that protein aggregation may facilitate calcium oxalate stone formation, while cell injury processes are implicated by the presence of many intracellular proteins.

Do 3D-calculated volume distribution of a stone in pelvicalyceal system affect complications of percutaneous nephrolithotomy? Abstract In our study, we examined the effect of the three-dimensional (3D) stone segmentation volume and its ratio to the renal collecting system on complication rates. Data from141 patients who underwent PCNL surgery were analyzed retrospectively. Volume segmentation of both the renal collecting system and stones was obtained from 3D segmentation software with the images on CT data. After creation of a 3D surface volume rendering of renal stones and the collecting system, segmentation of the renal collecting system volume (RCSV) and analyzed stone volume (ASV) was analyzed and the ASV-to-RCSV ratio was calculated. Univariate analysis and multivariate logistic regression model were used to determine factors that affected complication status. Diagnostic value for the prediction of complication rates was analyzed using receiver operating characteristic (ROC) incline. Overall, there were 141 (92 male and 49 female) eligible patients included in the current study. The overall complication rate for PCNL monotherapy was 31.9%. Multivariate regression analysis (forward stepwise) revealed that the ASV-to-RCSV ratio and number of tracts were independent risk factors for developing complications (OR 1.17, p < 0.001; OR 7.87, p = 0.002; respectively). The ROC analysis revealed a cut-off value of 16.23% (AUC 0.869, p < 0.001, sensitivity 93.3%, specificity 78.1%) for the ASV-to-RCSV ratio. The distribution of stone burden volume in the pelvicalyceal system, which is calculated as a numerical value using the 3D volume segmentation method, is an important predictor of the complication rate before PCNL. The ASV-to-RCSV ratio as a quantitative value may be an instrument for urologists before surgery to help preoperative planning.

Does extracorporeal shock wave lithotripsy-related pain get affected by menstrual cycle and menopause? Abstract The objective of the study was to investigate the effect of the menstrual cycle and menopause on extracorporeal shock wave lithotripsy (ESWL)-related pain outcome. Since March 2017, we evaluated a total of 145 women who underwent the first session of ESWL for renal or ureteral stones. Patients were divided into two groups, as menstruating and menopaused women. For menstruating women, the number of days between the last day of mens and ESWL was noted and women were separated as in the follicular phase (1–14 days) or in the luteal phase (15–30 days) of menstruation. To control these two female groups, 149 men of similar age were included in the study. After the procedure, the experienced pain was recorded on a ten-point visual analog scale (VAS) by the patient and they also rated the severity of pain as no, mild, tolerable, and intolerable on the pain questionnaire. The mean age of the patients was 43 ± 15 years for the female group and 42 ± 13 years for the male group. While stone burden was not different between the female and male groups (p = 0.459), VAS score was not statistically different between genders (p = 0.293). However, men reported a higher rate of mild pain, while women reported a higher rate of tolerable pain (p = 0.008) in the pain questionnaire. Mean VAS score was significantly lower for the menopaused women group than menstruating women, young and old men (p = 0.001). In a subgroup analysis, menopaused women group reported lower VAS score and better pain questionnaire result than menstruating women (p < 0.001). There was no statistically significant difference between the follicular and luteal phase of the menstrual cycle in terms of mean VAS score and pain questionnaire results (p = 0.891 and 0.441, respectively). When compared with the young men group, the only significant difference was pain questionnaire results between women in the luteal phase (p = 0.014). Multiple regression analysis showed that only menstruation (β = 0.639, p < 0.001) was an independent factor for VAS score. Menstrual cycle phase had no effect on pain perception during the ESWL session and menopaused women felt less pain than menstruating women during this procedure. The control male group showed that the reduction of ESWL-related pain in menopause was not related to aging.

Cancer as a risk factor for urinary tract calculi: a retrospective cohort study using ‘The Health Improvement Network’ Abstract Purpose Urolithiasis is a common condition that poses significant morbidity to patients. There are similarities in the development of certain cancers and urinary tract calculi (UTC), however, little is known about their temporal relationship. This study aims to identify if cancer is a risk factor for the development of UTC. Methods A population-based retrospective cohort study was conducted for the period 1st January 1990 to 1st May 2016. 124,901 exposed patients identified using clinical codes with newly diagnosed cancer were matched to 476,203 unexposed controls by age, gender, BMI, and general practice. The main outcome measure was the risk of developing UTC described by hazard ratios. Results There were 512 incident UTC events in the cancer group compared to 1787 in the unexposed controls. This translated to an adjusted hazard ratio of 1.26 (95% CI 1.14–1.39; p < 0.001). A sub-analysis assessing cancer-specific effects demonstrated increased risks for 10 out of 12 common cancers, most significantly in bladder, colorectal and prostate cancer. Conclusion This study demonstrated a 26% increased risk of UTC in cancer patients suggesting wider recognition of this risk amongst clinicians could improve diagnosis and prevention of UTC, as well as encourage further research exploring this association.

Evaluating pathogenicity of SLC34A3 -Ser192Leu, a frequent European missense variant in disorders of renal phosphate wasting Abstract Loss-of-function mutations of SLC34A3 represent an established cause of a distinct renal phosphate wasting disorder termed hereditary hypophosphatemic rickets with hypercalciuria (HHRH). SLC34A3 encodes the renal phosphate transporter NaPi2c expressed at the apical brush border of proximal renal tubules. Substitution of p.Ser192Leu is one of the most frequent genetic changes among HHRH patients in Europe, but has never been systematically evaluated, clinically or on a cellular level. Identification of a 32-year-old female with a homozgyous c.575C>T, p.Ser192Leu substitution enabled a more comprehensive assessment of the impact of this missense variant. Clinically, the patient showed renal phosphate wasting and nephrocalcinosis without any bone abnormalities. Heterozygous carriers of deleterious SLC34A3 variants were previously described to harbor an increased risk of kidney stone formation and renal calcification. We hence examined the frequency of p.Ser192Leu variants in our adult kidney stone cohort and compared the results to clinical findings of previously published cases of both mono- and biallelic p.Ser192Leu changes. On a cellular level, p.Ser192Leu-mutated transporters localize to the plasma membrane in different cellular systems, but lead to significantly reduced transport activity of inorganic phosphate upon overexpression in Xenopus oocytes. Despite the reduced function in ectopic cellular systems, the clinical consequences of p.Ser192Leu may appear relatively mild, at least in our index patient, and can potentially be missed in clinical practice.

Percutaneous nephrostomy vs ureteral stent for hydronephrosis secondary to ureteric calculi: impact on spontaneous stone passage and health-related quality of life—a prospective study Abstract Ureteral calculi can be associated with urinary drainage blockage, requiring urinary diversion with percutaneous nephrostomy (PCN) or retrograde ureteral stent (RUS). Currently no evidence exists to support the superiority of one method over the other. This study proposes to compare both approaches regarding the probability of spontaneous stone passage (SSP) and its effect on patient’s quality of life (QoL). A prospective trial was carried out from July to October of 2017. 50 patients were selected with hydronephrosis secondary to ureteral stones requiring urgent urinary diversion and divided into two groups according to diversion technique: percutaneous nephrostomy (PCN) or retrograde ureteral stent (RUS). The rate of SSP and QoL were evaluated. A PCN group (18 patients) and a RUS group (32 patients) were set. Stone size was higher in PCN (median 92 mm2) than RUS (median 47 mm2) (p = .012). The rate of SSP was 25% in RUS group and 38.9% in PCN. On the univariable analysis no statistical effect was found; however, when adjusted for stone size, location, previous ureteral manipulation and expulsive therapy, PCN showed a significant higher chance of SSP than RUS (OR = 6667). Besides, it was found that 30.2% (n = 13) of stones had an upward displacement associated with retrograde endoscopy. A significant decrease between pre- and post-intervention QoL was found with RUS (p < .001), but not found with PCN (p = .206). Patients in RUS group experienced more urinary symptoms, mostly haematuria (68.7% vs 16.7% in PCN group < .001) and dysuria (78.3% vs 16.7% in PCN group, p < .001). PCN was associated with a higher rate of spontaneous stone passage when adjusted for stone size and location. Moreover, PCN was better tolerated and associated with fewer urinary symptoms when compared with RUS.