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.

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.

A simple predictive model with internal validation for assessment of stone-left after ureteroscopic lithotripsy in upper ureteral stones.

Background: Stone free rate in upper ureteral stones is not as high. We sought to identify easily accessible risk factors attributing to stones left in the ureteroscopy in the treatment of upper ureteral calculi, and to build a simple and reliable predictive model. Methods: Patients treating only for upper ureteral stones in 2018 were retrospectively analyzed. Correlations between factors and the stone free rate were analyzed using bidirectional stepwise regression, curve fitting and binary logistic regression. Stone shape was judged by the gap between length and width in the two-dimensional section. A predictive nomogram model was built based on those selected variables (P<0.05). The area under the receiver operator characteristic curve (AUC) and calibration curve were used to access its discrimination and calibration. Decision curve analysis (DCA) was conducted to test the clinical usefulness. Results: Totally, 275 patients with 284 stones were enrolled in this research. Bidirectional stepwise regression showed that stone length had a significant effect on stone free, instead of width or burden. Stone shapes were also found playing a big role. Curve fitting showed that quasi-circular stones had a high risk of retropulsion, and eventually led to stone left. Finally, stone length, shape, modality, and the distance of stones to the ureteropelvic junction were enrolled in the model. Among them, the distance of the stone to the ureteropelvic junction showed a noticeable impact on stone left. AUC was 0.803 (95% CI: 0.730-0.876), and the calibration curve showed good calibration of the model (concordance index, 0.792). DCA indicated the model added net benefit to patients. Conclusions: The present predictive model based on those factors, stones length, shape, modality, and distance of the stone to the ureteropelvic junction was easy, reliable and useful.

Cost-effectiveness of anti-retropulsive devices varies according to the locations of proximal ureteral stones: a retrospective cohort study.

BACKGROUND: Anti-retropulsive devices are often used to prevent stone migration in the treatment of proximal ureteral calculi. They are helpful. However, in the meantime, they also add extra expenses. This study was carried out to investigate the best criteria for treating proximal ureteral stones with anti-retropulsive devices. METHODS: Data from all patients who underwent ureteroscopic holmium: YAG laser lithotripsy for solitary upper ureteral stones in 2018 were collected. Patients who encountered stone retropulsion during the process of inserting the ureteroscope were excluded. Patients were divided into either group URS or group URS + ARD depending on whether the anti-retropulsive device was used. Then, the stone-free rate, expenses and other criteria were compared between groups according to stone location. Stone-free was defined as no stones present. RESULTS: For stones located ≤ 30 mm from the ureteropelvic junction (UPJ), the stone-free rates for the URS group were 80% and 80% at one day and one month after the operation, respectively. Those for the URS + ARD group were 71.4% and 78.6% at one day and one month, respectively. For stones located 31-90 mm from the UPJ, the stone-free rates were 84.7% and 84.7% for the URS group and 89.6% and 95.5% for the URS + ARD group at one day and one month, respectively. A statistically significant difference occurred at one month. For stones located > 90 mm from the UPJ, the two groups were both stone free. In the URS + ARD group, expenses were higher. In addition, the mean diameter of residual stones derived from stones located at 31-90 mm from the UPJ was statistically smaller, and 4 of 7 residual stones passed spontaneously within one month, which was obviously more than that in other locations and the URS group. Other outcomes, including operation time and postoperative stay, showed no significant difference between the groups. CONCLUSION: Anti-retropulsive devices are indeed helpful, but they might be cost-effective for stones located solely in the middle part of the upper ureter, not for those too close to or far from the ureteropelvic junction.