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Previous clinical studies have shown that Escherichia coli (E. coli) predominated in urine and stone culture from calcium oxalate (CaOx) stone disease. The characteristic and relationship between E. coli isolated from urine cultures (EUC) and stone cultures (ESC) are compared. 83 E. coli (33 EUC and 50 ESC, respectively) from 66 CaOx stone patients were recruited in the study. E. coli in urine and stones from those patients were assessed by antimicrobial susceptibility test, genotyping and phylogenetic grouping. Furthermore, whole genome sequencing and comparative genomic analysis in paired ESC and EUC isolated strains from eight patients were carried out. The E. coli strains from ESC and EUC were not only multidrug resistant (MDR), but also had the similar pattern of resistant genes. The dominant phylogenetic group was B2, which was found in 54.0% of the ESC samples and 69.7% of the EUC samples, respectively. The virulence genes of E. coli, which isolated from stones and urine in the same patients, were highly homologous and largely consistent. Meanwhile, these E. coli strains were located in the same clade originated from a common ancestor. ESC and EUC isolated from patients with CaOx stones had a high prevalence of phylogenetic groups B2. Bacterial strains isolated from urine and stones in the same patient had consistent antimicrobial susceptibility profiles, genotyping, phylogenetic groups, virulence and resistance genes, also with high sequence co-linearity and close relationships., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

An abnormal urine composition is a key reason for kidney stone formation, but little is known about the roles of small metabolites in the urine during kidney stone formation. Here, we found urine glycine in patients with kidney calcium oxalate (CaOx) stone was significantly lower than that in healthy people via 1 H NMR spectra detection, and investigated the role and underlying mechanism of glycine in the regulation of CaOx stone formation. Our results showed that glycine could significantly attenuate ethylene glycol-induced CaOx crystal depositions in rat kidney via decreasing urine oxalate and increasing urine citrate. Mechanism studies revealed that glycine could decrease urine oxalate through downregulating Slc26a6 expression, whereas increase urine citrate via inhibiting Nadc1 expression. Moreover, glycine decreased the protein expression of both Slc26a6 and Nadc1 via increasing the expression of miRNA-411-3p, which directly bound to the 3'-untranslated regions of Slc26a6 and Nadc1 messenger RNAs, in vitro and in vivo. Together, our results revealed a novel role of glycine in the regulation of kidney CaOx crystal formation and provided a potential target for the treatment of kidney CaOx stone., (© 2021 Wiley Periodicals LLC.)

Escherichia coli ( E. coli ) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone formers. The ability of calcium oxalate monohydrate (COM) aggregation was detected to evaluate the influence of uropathogenic E. coli , then gel electrophoresis and nanoLC-MS/MS to detect the crystal-adhered protein. Flagellin (Flic) and polyphosphate kinase 1 (PPK1) were screened out following detection of their role on crystal aggregation, oxidative injury, and inflammation of HK-2 cell in vitro . By transurethral injection of wild-type, Ppk1 mutant and Flic mutant strains of E. coli and intraperitoneally injected with glyoxylate in C57BL/6J female mice to establish an animal model. We found that E. coli was the most common bacterial species in patients with CaOx stone. It could enhance CaOx crystal aggregation both in vitro and in vivo. Flagellin was identified as the key molecules regulated by PPK1, and both of them could facilitate the crystal aggregation and mediated HK-2 cell oxidative injury and activated the inflammation-related NF- κ B/P38 signaling pathway. Wild-type strain of E. coli injection significantly increased CaOx deposition and enhanced oxidative injury and inflammation-related protein expression, and this effect could be reversed by Ppk1 or Flic mutation. In conclusion, E. coli promotes CaOx stone formation via enhancing oxidative injury and inflammation regulated by the PPK1/flagellin, which activated NF- κ B/P38 pathways, providing new potential drug targets for the renal CaOx calculus precaution and treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Lingyue An et al.)

Objective: To assess the relevance of urine test (UT), urine culture (UC) and stone culture (SC) for postoperative infections and to investigate the optimal perioperative antibiotic treatment strategy in association with percutaneous nephrolithotomy (PCNL) in patients with renal calculi., Materials and Methods: Between September 2016 and September 2018 1,060 patients treated with PCNL were included in the study. The results of UT, UC and SC were reviewed. The details of perioperatively administered antibiotics and postoperative infections were recorded., Results: A positive UT was associated with an increased incidence of infection; this was also the case in patients with negative UC (p < 0.05). There was no significant difference in incidence of infection between patients who were given a single dose of antibiotics compared with those given multiple doses when UC was negative, whether UT was positive or negative (all p > 0.05). The incidence of infection was decreased when pre-operative antibiotics were administered according to the sensitivity pattern based on UC (p < 0.05). This outcome was particularly evident when the treatment duration exceeded 7 days (p < 0.05). A positive SC was associated with increased incidence of infection, even if the patient had a negative UC and UT (p < 0.05). The incidence of infection was significantly decreased when antibiotic treatment was administered based on the results of SC (p < 0.05)., Conclusion: Pre-operative prophylaxis with a single-dose antibiotic was sufficient in patients with negative UC, whether UT was positive or negative. Pre-operative treatment with antibiotics according to the bacterial sensitivity pattern should be administered for ≥7 days in patients with positive UC. The postoperative antibiotic treatment strategy should be tailored according to the SC results., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Upper urinary tract stones is the most common diseases in urology. Percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (fURL) are common treatment, but both their efficacy and safety are controversial. Thus we aim to evaluate the efficacy and safety of PCNL and fURL in the treatment of upper urinary tract stones, providing a reference for clinical work., Methods: PubMed, Web of Science, Embase and CNKI were searched through Apr. 1, 2019 to identify eligible studies. Data were analyzed by using RevMan 5.3 and Stata 12.0 software. Pooled relative risks (RRs) or weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using fixed or random effects methods. Publication bias and sensitivity analysis were performed., Results: Four randomized controlled trials (RCTs), fifteen cohort studies involving 1822 patients were included. Stone-free rate of PCNL was significantly high than that of fURL (RR: 1.07; 95% CI: 1.03, 1.12; P = 0.0004). The decline of hemoglobin in PCNL was significantly high than that of fURL (WMD: 1.07; 95% CI: 0.54, 1.61; P < 0.0001). The number of blood transfusion was significantly greater in the PCNL compared to the fURL (RR: 5.04; 95% CI: 1.78, 14.24; P = 0.002). The incidence of postoperative bleeding or hematuria showed greater significantly difference in the PCNL compared to the fURL (RR: 2.72; 95% CI: 1.55, 4.75; P = 0.0005). Operation time, fever, infection, perforation, requiring drug analgesia was not significantly different between two surgical procedures., Conclusions: In the treatment of upper urinary tract stones, the stones clearance rate of PCNL is higher than fURL, and the safety of fURL is higher than PCNL.

Kidney stone is a chronic metabolic disease that caused by many factors, especially by the metabolic disturbances of urine compositions, but the metabolic profiling of the urine from kidney stone patients remains poorly explored. In the present study, 1 H NMR spectroscopy and multivariate pattern recognition analytical techniques were combined to explore the metabolic profiling of the urine from kidney stone patients. A total of 216 urine samples obtained from kidney stone patients (n = 110) and healthy controls (n = 106) were investigated. The results indicated that principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) models were capable of distinguishing kidney stone patients from healthy controls. In addition, a total of 15 metabolites was obviously different in concentration between the two groups. Furthermore, four metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and citrate cycle (TCA cycle), were closely associated with kidney stone. Together, our results established a preliminary metabolic profiling of the urine from kidney stone patients via using 1 H NMR-based analytical techniques for the first time and provided a novel method for recognizing and observing the kidney stone disease.

Background: Epidemiological evidence of over 9000 people suggests that daily intake of vinegar whose principal bioactive component is acetic acid is associated with a reduced risk of nephrolithiasis. The underlying mechanism, however, remains largely unknown., Methods: We examined the in vitro and in vivo anti-nephrolithiasis effects of vinegar and acetate. A randomized study was performed to confirm the effects of vinegar in humans., Findings: We found individuals with daily consumption of vinegar compared to those without have a higher citrate and a lower calcium excretion in urine, two critical molecules for calcium oxalate (CaOx) kidney stone in humans. We observed that oral administration of vinegar or 5% acetate increased citrate and reduced calcium in urinary excretion, and finally suppressed renal CaOx crystal formation in a rat model. Mechanism dissection suggested that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of microRNAs-130a-3p, -148b-3p and -374b-5p by increasing H3K9, H3K27 acetylation at their promoter regions. These miRNAs can suppress the expression of Nadc1 and Cldn14, thus enhancing urinary citrate excretion and reducing urinary calcium excretion. Significantly these mechanistic findings were confirmed in human kidney tissues, suggesting similar mechanistic relationships exist in humans. Results from a pilot clinical study indicated that daily intake of vinegar reduced stone recurrence, increased citrate and reduced calcium in urinary excretion in CaOx stone formers without adverse side effects., Interpretation: Vinegar prevents renal CaOx crystal formation through influencing urinary citrate and calcium excretion via epigenetic regulations. Vinegar consumption is a promising strategy to prevent CaOx nephrolithiasis occurrence and recurrence. FUND: National Natural Science Foundations of China and National Natural Science Foundation of Guangdong Province., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To obtain more accurate and rapid predictors of postoperative infections following percutaneous nephrolithotomy (PCNL) in patients with complex kidney stones, and provide evidence for early prevention and treatment of postoperative infections., Patients and Methods: A total of 802 patients with complex kidney stones who underwent PCNL, from September 2016 to September 2017, were recruited. Urine tests, urine cultures (UCs) and stone cultures (SCs) were performed, and the perioperative data were prospectively recorded., Results: In all, 19 (2.4%) patients developed postoperative urosepsis. A multivariate logistic regression analysis revealed that an operating time of ≥100 min, urine test results with both positive urine white blood cells (WBC+) and positive urine nitrite (WBC+NIT+), positive UCs (UC+), and positive SCs (SC+) were independent risk factors of urosepsis. The incidence of postoperative urosepsis was higher in patients with WBC+NIT+ (10%) or patients with both UC+ and SC+ (UC+SC+; 8.3%) than in patients with negative urine test results or negative cultures (P < 0.01). Preoperative WBC+NIT+ was predictive of UC+SC+, with an accuracy of >90%. The main pathogens found in kidney stones were Escherichia coli (44%), Proteus mirabilis (14%) and Staphylococcus (7.4%); whilst the main pathogens found in urine were E. coli (54%), Enterococcus (9.4%) and P. mirabilis (7.6%). The incidence of E. coli was more frequent in the group with urosepsis than in the group without urosepsis (P < 0.05)., Conclusions: WBC+NIT+ in preoperative urine tests could be considered as an early and rapid predictor of UC+SC+ and postoperative urosepsis. Urosepsis following PCNL was strongly associated with E. coli infections in patients with complex kidney stones., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

The differentiated phenotype of renal tubular epithelial cell exerts significant effect on crystal adherence. Peroxisome proliferator-activated receptor γ (PPARγ) has been shown to be critical for the regulation of cell transdifferentiation in many physiological and pathological conditions; however, little is known about its role in kidney stone formation. In the current study, we found that temporarily high oxalate concentration significantly decreased PPARγ expression, induced Madin Darby Canine Kidney cell dedifferentiation, and prompted subsequent calcium oxalate (CaOx) crystal adhesion in vitro. Furthermore, cell redifferentiation after the removal of the high oxalate concentration, along with a decreasing affinity to crystals, was an endogenic PPARγ-dependent process. In addition, the PPARγ antagonist GW9662, which can depress total-PPARγ expression and activity, enhanced cell dedifferentiation induced by high oxalate concentration and inhibited cell redifferentiation after removal of the high oxalate concentration. These effects were partially reversed by the PPARγ agonist 15d-PGJ2. Similar results were observed in animals that suffered from temporary hyperoxaluria followed by a recovery period. The active crystal-clearing process occurs through the transphenotypical morphology of renal tubular epithelial cells, reflecting cell transdifferentiation during the recovery period. However, GW9662 delayed cell redifferentiation and increased the secondary temporary crystalluria-induced crystal retention. This detrimental effect was partially reversed by 15d-PGJ2. Taken together, our results revealed that endogenic PPARγ activity plays a vital regulatory role in crystal clearance, subsequent crystal adherence, and CaOx stone formation via manipulating the transdifferentiation of renal tubular epithelial cells., (© 2018 Wiley Periodicals, Inc.)

Objective: To compare the efficacy and safety of micropercutaneous nephrolithotomy (Microperc) and retrograde intrarenal surgery (RIRS) in treating renal stones using published literature., Methods: A systematic literature review was performed on August 21, 2017, using PubMed, Embase, and Cochrane Library databases in accordance with the PRISMA guidelines. Summarized mean differences (MDs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the differences in outcomes between Microperc and RIRS., Results: A total of nine studies (7 in adult patients and 2 in pediatric patients) containing 842 patients (381 Microperc cases and 461 RIRS cases) with renal stones were included in this analysis. Among the adult patients, Microperc was associated with higher stone-free rate(SFR)(OR: 1.6; 95% CI, 1.03 to 2.48), significantly longer hospital stays (MD: 0.66 day; 95% CI, 0.17 to 1.15), longer fluoroscopy time (MD: 78.12 s; 95% CI, 66.08 to 90.15), and larger decreases in hemoglobin (MD: 0.59 g/dl; 95% CI, 0.16 to 1.02) than was RIRS. No significant differences were observed with respect to operative time, stone-free rate, complication rate or auxiliary procedures., Conclusions: Our results demonstrated that Microperc might be more effective in adult patients than RIRS will due to its higher SFR. However, longer hospital stays, longer fluoroscopy time and a larger decrease in hemoglobin should be considered cautiously., Competing Interests: The authors have declared that no competing interests exist.

Hypercalciuria is a main risk factor for kidney stone  formation. TRPV5 is the gatekeeper protein for mediating calcium transport and reabsorption in the kidney. In the present study, we tested the effect of TRPV5 activation with small activating RNA (saRNA), which could induce gene expression by targeting the promoter of the gene, on ethylene glycol (EG)-induced calcium oxalate (CaOx) crystals formation in rat kidney. Five pairs of RNA activation sequences targeting the promoter of rat TRPV5 were designed and synthesized. The synthesized saRNA with the strongest activating effect was selected, and transcellular calcium transportation was tested by Fura-2 analysis. Subsequently, Sprague-Dawley rats were equally divided into three groups and fed with water, 1% EG for 28 days after injecting the negative control saRNA, 1% EG for 28 days after injecting the selected TRPV5-saRNA, respectively. The CaOx crystal formation and the 24-h urine components were assessed. In vitro study, saRNA ds-320 could significantly activate the expression of TRPV5 and transcellular calcium transportation. In vivo study, after 28 days treatment of EG, rats pre-infected with saRNA ds-320 had lower urinary calcium excretion and renal CaOx crystals formation as compared to that pre-infected with negative control saRNA. Activation of TRVP5 with saRNA ds-320 could inhibit EG-induced calcium oxalate crystals formation via promoting urine calcium reabsorption and decreasing urine calcium excretion in rats.

Objectives: To investigate the prevalence and associated factors of kidney stones among adults in China., Subjects and Methods: A nationwide cross-sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre-designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors., Results: A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18-96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age- and sex-adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation., Conclusion: Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Objective: Epidemiological data reveal that the overall risk for kidney stones disease is lower for women compared to age-matched men. However, the beneficial effect for the female sex is lost upon menopause, a time corresponding to the onset of fall in estrogen levels. The aim of this study was to describe the serum estradiol (E2) and testosterone (T) characteristics of naturally postmenopausal women with kidney stones., Methods: 113 naturally postmenopausal women with newly diagnosed kidney stones (aged 57.4±4.98 years) and 84 age frequency matched stone-free controls (56.9±4.56 years) were validly recruited in the case-control study. The odds ratios (ORs) for the associations between sex hormones and kidney stones were estimated with logistic regression models, adjusting for demographic data and medical history. Patients were also stratified analyzed according to stone components (calcium oxalate stones [COS]; non-calcium oxalate stones [NCOS])., Results: Serum E2 (21.1 vs. 31.1 pg/ml) was significantly lower in kidney stones patients compared to controls. Post-hoc analysis demonstrated that this effect was driven by COS patients (p<0.001). According to tertiles of the E2 levels, a significant higher frequency of COS was seen in the lowest E2 group (p <0.001). Multiple logistic regression analysis identified E2 level as a strong factor that was independently associated with the risk for COS (per 1 SD increase, OR=0.951, 95% confidence interval [CI] = 0.919-0.985; highest: lowest tertile, OR=0.214, 95%CI = 0.069-0.665). However, serum T levels did not significantly differ among the groups., Conclusions: Naturally postmenopausal women with higher remaining estradiol levels appear less likely to suffer from kidney calcium oxalate stones. However, no correlation was found between serum T level and kidney stones. These findings support the hypothesis that higher postmenopausal endogenous estrogens may protect against kidney stones with ageing.