The impact of anxiety on the risk of kidney stone disease: Insights into eGFR-mediated effects.

BACKGROUND: Previous studies have linked kidney stone disease (KSD) with depression, but there are no reports on the relationship between anxiety and KSD, and the mechanism underlying the potential relationship remains unclear. METHODS: Associations of anxiety and incident KSD were assessed in the National Health and Nutrition Examination Survey (NHENES) using multivariate logistic regression. Two-sample bidirectional Mendelian randomization studies and a two-step two-sample MR was used to estimate the mediating factors that influence KSD risk. RESULTS: Examinations of NHANES data revealed that a rise in the frequency and intensity of anxiety were independently associated with incident KSD. In MR analysis, anxiety (uk-a-51 and uk-b-6519) were from the UK Biobank, with sample sizes of 328,717 and 450,765 respectively. KSD data were from the FinnGen, including 8597 cases and 333,128 controls. In the IVW analysis, genetically predicted anxieties (ukb-a-51 and ukb-b-6519) were found to be causally associated with a higher risk of KSD, with odds ratios of 6.18 (95 % CI 2.54-15.04) and 3.44 (95 % CI 1.67-7.08), respectively. There were no reverse causal effects. Further mediation analysis indicated that anxiety increases the risk of KSD by raising eGFR, through which 11.8 % of the effect of anxiety on KSD risk was mediated. LIMITATIONS: The research was confined to individuals of European heritage, and there could be specific genetic variances among diverse ethnicities. CONCLUSION: The current study suggests anxiety as an independent causal risk factor for KSD and unveils a new pathogenic mechanism, showing that anxiety raises eGFR, thereby increasing the risk of KSD.

Both enantiomers of ß-aminoisobutyric acid BAIBA regulate Fgf23 via MRGPRD receptor by activating distinct signaling pathways in osteocytes.

With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-ß-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes. The D enantiomer, described to be elevated with exercise in humans, can also induce Fgf23 but through a delayed, indirect process via sclerostin. The two enantiomers both signal through the same receptor, Mas-related G-protein-coupled receptor type D, but activate distinct signaling pathways; L-BAIBA increases Fgf23 through Gαs/cAMP/PKA/CBP/ß-catenin and Gαq/PKC/CREB, whereas D-BAIBA increases Fgf23 indirectly through sclerostin via Gαi/NF-κB. In vivo, both enantiomers increased Fgf23 in bone in parallel with elevated urinary phosphate excretion. Thus, exercise-induced increases in BAIBA and FGF23 work together to maintain phosphate homeostasis.

Metabolic Syndrome and the Risk of Kidney Stones: a Large-scale Cohort Study from 487,860 UK Biobank participants.

OBJECTIVE: While some studies have suggested an association between metabolic syndrome and kidney stones, the quality and level of evidence in these studies vary. Whether some individual characteristics and clustering of metabolic syndrome traits increase the risk of kidney stones has not been examined in a large-scale prospective cohort. MATERIALS: We conducted a retrospective analysis of data from a prospective cohort of 487,860 UK Biobank participants who were free from kidney stones at baseline. The presence of metabolic syndrome was based on five criteria: abdominal obesity, high triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, high blood pressure (HBP), and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to evaluate the association between metabolic syndrome and risk of kidney stones. RESULTS: After an average follow-up period of 12.6 years, a total of 5,213 of the 487,860 participants included in the UK Biobank study developed kidney stones. The partial traits of metabolic syndrome, including waist circumference (HR: 1.15, 95% CI: 1.10-1.20), HDL cholesterol (0.66, 0.55-0.79), HBP (1.11, 1.03-1.19) and T2DM (1.14, 1.04-1.21), were independently associated with the occurrence of kidney stones. The clustering of metabolic syndrome is significantly associated with kidney stone formation, and as the number of metabolic syndrome traits increases, the risk of kidney stones gradually increases. CONCLUSION: Metabolic syndrome is a significant and independent risk factor for the development of kidney stones. This association suggests that kidney stones may represent a systemic disorder influenced by the interplay of various metabolic risk factors.

Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007-2018.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones. METHODS: We performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders. RESULTS: The multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10-1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15-1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09-1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13-1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06-1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02-1.54, P = 0.033) in Model 3. CONCLUSIONS: Our study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.

Exposure to per- and polyfluoroalkyl substance and metabolic syndrome: A nationally representative cross-sectional study from NHANES, 2003-2018.

Per- and polyfluoroalkyl substances(PFAS) are widespread organic pollutants with endocrine-disrupting effects on human health, but the association of PFAS exposure with metabolic syndrome remains conflicting. National Health and Nutrition Examination Survey(NHANES) program was utilized to evaluate the association of individual PFAS exposure and metabolic disorders and further determined the joint effect of PFAS co-exposures. 13921 participants and five PFAS exposures(PFHxS, MPAH, PFDE, PFNA, and PFUA) were included for analysis. The association between individual PFAS and metabolic syndrome varied in the specific PFAS and the specific metabolic disorder examined. PFHxS was negatively associated with obesity(Q4; OR = 0.75; P < 0.001), but positively associated with hyperlipidemia (Q3; OR = 1.2; P = 0.013). PFUA was negatively associated with obesity (Q4; OR = 0.6; P < 0.001), hyperlipidemia (Q3; OR = 0.85; P = 0.03), and non-alcoholic fatty liver disease (NAFLD, Q4; OR = 0.64; P = 0.015), but positively associated with hyperglycemia(Q3; OR = 1.27; P = 0.004). Furthermore, PFAS co-exposures were negatively associated with obesity(OR = 0.63; P < 0.001) and NAFLD(OR = 0.85; P = 0.021), and positively associated with hyperlipidemia(OR = 1.05; P = 0.022), but not significantly associated with hyperglycemia or hypertension. Overall, there was a negative association between PFAS co-exposures and metabolic severity score(ß = -0.15; P < 0.001). Subgroup analysis stratified by gender and obesity consistently showed the negative association of PFAS co-exposures with metabolic severity score, and the positive association with hyperlipidemia. However, subgroup analysis showed a negative association with NAFLD in females but not in males, and a negative association with hyperglycemia in the obesity group, but not in the non-obesity group. Collectively, our study showed a negative association of PFAS co-exposures with metabolic syndrome severity score, but did not support a consistent association between PFAS co-exposures and individual components of metabolic syndrome. Additionally, there were gender-specific as well as BMI-specific differences in these associations. Further studies are needed to rule out the reverse causality and clarify the relationship of PFAS co-exposures with the specific metabolic disorder.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

Association between tea consumption and risk of kidney stones: results from dose-response meta-analysis of prospective studies and Mendelian randomization analysis.

PURPOSE: The association between tea consumption and kidney stones is inconsistent in observational studies. Thus, we performed a dose-response meta-analysis of prospective cohort studies and a two-sample Mendelian randomization (MR) analysis to identify this association. METHODS: The prospective cohort studies reporting the relationship between tea consumption and kidney stones were searched from PubMed, the Cochrane Library, EMBASE, and Web of Science from inception to December 1, 2023. For MR analysis, the summary-level data for tea consumption and kidney stones were extracted from the UK Biobank available data and the 8th release of the FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was the primary analytical method. RESULTS: In our dose-response meta-analysis, four prospective cohort studies involving 1,263,008 participants were included, and tea consumption was found to have significant associations with kidney stones (RR: 0.80, 95% CI: 0.73-0.87). We also observed a substantially linear negative relationship between tea consumption and the risk of kidney stones. In MR analysis, the IVW method indicated that tea consumption was inversely associated with kidney stones (OR: 0.71, 95% CI: 0.53-0.94). CONCLUSION: Our study confirmed a causal relationship between tea consumption and kidney stones, and higher tea consumption may reduce the risk of kidney stones.

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for esophageal neoplasms: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To evaluate the efficacy and safety of neoadjuvant chemotherapy (a CRTS group) plus surgery versus surgery alone (a SA group) in the treatment of resectable esophageal neoplasms. Methods    PubMed, Ovid Technologies, SCI, CBM Database, CNKI Database, VIP Database and Wanfang Database were searched to identify all published or unpublished RCTs those compared neoadjuvant chemotherapy plus surgery with surgery alone for resectable esophageal neoplasms up to August 1, 2015. Meta-analysis was conducted by using Stata12.0 software. Results    Twenty-six RCTs included 3 252 patients (1 606 in the CRTS group, 1 646 in the SA group) were selected. There was a significant difference between the CRTS group and the SA group in 3-year survival rate, 5-year survival rate, R0 resection rate, local recurrence rate, local recurrence and distant metastasis rate with relative risk (RR) value and 95%CI at 1.24 (1.13–1.36, P<0.000 1), 1.29 (1.10–1.50, P=0.001), 1.13 (1.05–1.212, P=0.001), 0.67 (0.52–0.85, P=0.001), 0.60 (0.40–0.90, P=0.013). And there was no significant difference between the CRTS group and the SA group in 1-year survival rate and distant metastasis with RR (95%CI) of 1.05 (0.99–1.12, P=0.103) and 0.84 (0.70–1.00, P=0.053). There was no significant  difference in postoperative complications, 30-days mortality, pulmonary infections, anastomotic leakage, anastomotic stricture, cardiac complications, chylothorax between the two groups with RR (95%CI) at 1.09 (0.96–1.24, P=0.166), 1.32 (0.96–1.83, P=0.485), 1.45 (0.94–2.23, P=0.091), 0.89 (0.63–1.25, P=0.485), 0.93 (0.64–1.35, P=0.731), 1.24(0.84–1.87, P=0.283), and 1.62 (0.85–3.07, P=0.142). Conclusion    CRTS significantly benefits to survival rate, R0 rescetion rate, and local recurrence rate compared to SA. Additionally there is no increased postoperative complication for patients with resectable esophageal neoplasms.