Engineered microorganisms: A new direction in kidney stone prevention and treatment.

Numerous studies have shown that intestinal and urinary tract flora are closely related to the formation of kidney stones. The removal of probiotics represented by lactic acid bacteria and the colonization of pathogenic bacteria can directly or indirectly promote the occurrence of kidney stones. However, currently existing natural probiotics have limitations. Synthetic biology is an emerging discipline in which cells or living organisms are genetically designed and modified to have biological functions that meet human needs, or even create new biological systems, and has now become a research hotspot in various fields. Using synthetic biology approaches of microbial engineering and biological redesign to enable probiotic bacteria to acquire new phenotypes or heterologous protein expression capabilities is an important part of synthetic biology research. Synthetic biology modification of microorganisms in the gut and urinary tract can effectively inhibit the development of kidney stones by a range of means, including direct degradation of metabolites that promote stone production or indirect regulation of flora homeostasis. This article reviews the research status of engineered microorganisms in the prevention and treatment of kidney stones, to provide a new and effective idea for the prevention and treatment of kidney stones.

Ferroptosis and its emerging role in kidney stone formation.

Kidney stone is a common and highly recurrent disease in urology, and its pathogenesis is associated with various factors. However, its precise pathogenesis is still unknown. Ferroptosis describes a form of regulated cell death that is driven by unrestricted lipid peroxidation, which does not require the activation of caspase and can be suppressed by iron chelators, lipophilic antioxidants, inhibitors of lipid peroxidation, and depletion of polyunsaturated fatty acids. Recent studies have shown that ferroptosis plays a crucial role in kidney stone formation. An increasing number of studies have shown that calcium oxalate, urate, phosphate, and selenium deficiency induce ferroptosis and promote kidney stone formation through mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagy. We also offered a new direction for the downstream mechanism of ferroptosis in kidney stone formation based on the "death wave" phenomenon. We reviewed the emerging role of ferroptosis in kidney stone formation and provided new ideas for the future treatment and prevention of kidney stones.

A Novel Hydrodynamic Design Greatly Improves the Debris Clearance Rate of Flexible Ureteroscopy.

Objectives: To introduce a novel hydrodynamic design for a flexible ureteroscope that can increase stone debris clearance. Methods: Based on hydrodynamics, the new design allowed the ureteroscope to have six water jets. Fluid gushed from the six jets and would ultimately converge into an eddy. The safety and stone debris clearance efficiency were tested in a 3D-printed kidney model. Stone fragments between 0.5 and 1 mm were used to mimic the debris. A ureteroscope already approved for marketing was used as a control. Results: The new design did not change the local renal pressure and did not raise the whole renal pressure under irrigation at 80 or 100 mL/min but slightly raised it under irrigation at 120 mL/min. The pressures in the 2 g stone clearance procedures were 26.0, 33.1, and 37.5 cmH2O for the new design and 25.1, 30.2, and 39.3 cmH2O for the current design; in the 4 g stone clearance procedures, the pressures were 30.1, 37.2, and 40.0 cmH2O for the new design and 26.9, 30.8, and 39.8 cmH2O for the current design, all under conditions of 80, 100, and 120 mL/min irrigation, respectively. The new design significantly improved the stone clearance rate by ∼10-fold. It effectively cleared 2 and 4 g stones within 900 seconds under the three irrigation rates. In contrast, the current design cleared <10% of the stone debris in all tests. Conclusion: The new hydrodynamic design significantly improved the stone debris clearance rate without causing obviously increased renal pressure, and the improvement was maintained under different irrigation pressures and stone burdens.

Causal relationship of genetically predicted circulating micronutrients levels with the risk of kidney stone disease: a Mendelian randomization study.

Background: Current studies have reported conflicting associations between circulating micronutrient levels and kidney stone disease (KSD). We aimed to elucidate the causal relationship between circulating micronutrient levels and KSD by a two-sample Mendelian randomization (MR) analysis. Methods: Total of 36 single nucleotide polymorphisms (SNPs) from published genome-wide association studies (GWAS) significantly associated with eight micronutrients (vitamin B12, folic acid, magnesium, iron, phosphorus, copper, zinc, and selenium) were used as instrumental variables. The GWAS summary data associated with KSD (8,060 cases and 301,094 controls) were obtained from the FinnGen consortium. Inverse variance weighted was the main MR analysis method. MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), weighted median and MR-Egger were used to assess pleiotropy and heterogeneity. Results: Genetically predicted circulating vitamin B12 and zinc levels were causally associated with the risk of KSD (vitamin B12: OR: 1.17, 95% CI: 1.04-1.32, p = 0.008; zinc: OR: 1.15, 95% CI: 1.03-1.28, p = 0.015). We found no evidence that other circulating micronutrients were associated with risk of KSD. p-value for Cochrane Q test, MR Egger intercept test, and MR-PRESSO were >0.05, indicating no significant heterogeneity or horizontal pleiotropy in this MR analysis. Conclusion: Increasing circulating zinc levels may increase the risk of KSD. More studies are needed to provide evidence on whether genetically predicted circulating vitamin B12 and zinc levels are a risk factor for KSD.

Efficacy and safety of Water Vapor Thermal Therapy in the treatment of benign prostate hyperplasia: a systematic review and single-arm Meta-analysis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common chronic condition among men aged 50 or older, causing voiding and obstructive lower urinary tract symptoms. Water vapor thermal therapy (WVTT) using the Rezum® system is a new minimally invasive surgical technique that is increasingly reported as a treatment for BPH. METHODS: The protocol was submitted to the PROSPERO registry. We searched PubMed, Web of Science, Embase, Cochrane Library and ClinicalTrials.gov up to July 29, 2022. Quality assessment was carried out by a 20-item checklist form prepared by the Institute of Health Economics (IHE). Double arcsine transformation was performed to stabilize the variance of the original ratio. When I2 > 50%, the random effect model was used to calculate the pooled parameters. Otherwise, the fixed effect model was used. 95% confidence intervals (CIs) were calculated. A leave-one-out sensitivity analysis was performed to evaluate the impact of each study on the pooled outcomes, and finally, Egger's test was used to assess publication bias. RESULTS: A total of seven single-arm observational studies and one random controlled trial, including 1015 patients, were included. One year after WVTT, the International Prostate Symptom Score decreased by 11.37 (95% CI: -12.53, -10.21), the IPSS Quality of Life scale decreased by 2.59 (95% CI: -2.92, -2.26), the maximum urine flow rate increased by 5.26 ml/s (95% CI: 4.53, 5.99), and the postvoid residual decreased by 13.18 ml (95% CI: -24.32, -2.03). The most common complication was dysuria, with a pooled incidence of 21% (95% CI: 14%, 29%), and the second most common complication was hematuria, with a pooled incidence of 14% (95% CI: 10%, 18%). The pooled incidence of retreatment was 3% (95% CI: 2%, 5%). CONCLUSIONS: WVTT is an attractive alternative to medication or more invasive surgical procedures and can serve as first-line therapy for men with BPH.

Analysis of Preoperative Risk Factors for Postoperative Urosepsis After Mini-Percutaneous Nephrolithotomy in Patients with Large Kidney Stones.

Purpose: To assess the preoperative risk factors for postoperative urosepsis after mini-percutaneous nephrolithotomy (mPCNL) in patients with large kidney stones. Methods: Records of 171 patients with large (≥30 mm) kidney stones who underwent mPCNL from December 2013 to October 2019 were reviewed. Demographic data of patients, preoperative urine analysis, urine culture, and routine blood tests and abdominal computerized cosmography data were collected and analyzed. A predictive nomogram model was established based on the results of logistic regression. Results: Twenty-nine patients (17%) developed postoperative urosepsis in this study. Univariate analysis demonstrated that preoperative urine leukocytes (p < 0.001), urine nitrite (p < 0.001), stones in adjacent calices on the coronal plane (p < 0.001), the maximum cross-sectional area of stones (p < 0.001), the diameter of hydronephrosis (p = 0.010), and number of stones (p = 0.044) were associated with postoperative urosepsis after mPCNL in patients with large kidney stones. And preoperative urine leukocytes ≥450/µL (p = 0.002) was the only independent risk factor for postoperative urosepsis in multivariate logistic regression analysis. Based on the results of multivariate regression, a nomogram model was established for the prediction of postoperative urosepsis with ideal discrimination (area under receiver operating characteristic curve was 0.867). Conclusion: Patients with certain preoperative characteristics, including higher urine leukocytes, positive urine nitrite, stones in adjacent calices on the coronal plane, larger maximum cross-sectional area of stones, larger diameter of hydronephrosis, and larger number of stones, who received mPCNL may have a higher risk of postoperative urosepsis. A predictive model can help urologists identify patients who may develop postoperative urosepsis with high probability.