The immune factors have complex causal regulation effects on kidney stone disease: a mendelian randomization study.

PURPOSE: Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis. METHODS: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. RESULTS: After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93-0.98, p-value = 7.20 × 10- 4, q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger's intercept test, and MR-PRESSO, which were all > 0.05. CONCLUSIONS: Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies.

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.

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.

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.

Inflammatory cytokines and their potential role in kidney stone disease: a Mendelian randomization study.

PURPOSE: Previous studies have reported a complex relationship between inflammatory cytokines and kidney stone disease (KSD). The purpose of this paper is to investigate the potential causal impact of inflammatory cytokines on KSD by Mendelian randomization (MR) analysis. METHODS: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between inflammatory cytokines and kidney stone disease. Utilizing GWAS summary data of inflammatory cytokines and KSD, we performed the first two-sample MR analysis. Genetic variants in GWASs related to inflammatory cytokines were employed as instrumental variables (IVs). The data on cytokines were derived from 14,824 participants and analyzed by utilizing the Olink Target-96 Inflammation Panel. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Reverse MR analysis, Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. RESULTS: 91 cytokines were enrolled in the MR analysis after strict quality control of IV. The IVW analysis revealed 2 cytokines as risk factors for KSD: Cystatin D (OR 1.06, 95% CI 1.01-1.11), Fibroblast growth factor 5 (OR 1.06, 95% CI 1.00-1.12), suggesting they are positively associated with the occurrence of kidney stones. We also found 3 protective associations between cytokines and KSD: Artemin (OR 0.86, 95% CI 0.78-0.96), T-cell surface glycoprotein CD6 isoform (OR 0.92, 95% CI 0.88-0.98), STAM-binding protein (OR 0.83, 95% CI 0.69-0.99). There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our MR Egger's intercept test, Cochrane Q-test, and MR-PRESSO, which were all > 0.05. CONCLUSIONS: Our study explored a variety of inflammatory cytokines related to KSD through MR analysis, which validated several previous findings and provided some new potential biomarkers for KSD. However, the findings require further investigation to validate their exact functions in the pathogenesis and evolution of KSD.