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.

OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall's plaque formation.

BACKGROUND: Randall's plaques (RP) are identified as anchored sites for kidney calcium oxalate stones, but the mechanism remains unclear. Given the importance of osteogenic-like cells in RP formation and OCT4 in reprogramming differentiated cells to osteoblasts, the current study explored the potential role of OCT4 in RP formation. METHODS: OCT4 and biomineralization were evaluated in RP, and immunofluorescence co-staining was performed to identify these cells with alteration of OCT4 and osteogenic markers. Based on the analysis of tissue, we further investigated the mechanism of OCT4 in regulating osteogenic-like differentiation of primary human renal interstitial fibroblasts (hRIFs) in vitro and vivo. RESULTS: We identified the upregulated OCT4 in RP, with a positive correlation to osteogenic markers. Interestingly, fibroblast marker Vimentin was partially co-localized with upregulated OCT4 and osteogenic markers in RP. Further investigations revealed that OCT4 significantly enhanced the osteogenic-like phenotype of hRIFs in vitro and in vivo. Mechanically, OCT4 directly bound to BMP2 promoter and facilitated its CpG island demethylation to transcriptionally promote BMP2 expression. Furthermore, combination of RIP and RNA profiling uncovered that lncRNA OLMALINC physically interacted with OCT4 to promote its stabilization via disrupting the ubiquitination. Additionally, OLMALINC was upregulated in fibroblasts in RP visualized by FISH, and a positive correlation was revealed between OLMALINC and OCT4 in RP. CONCLUSIONS: The upregulation of OCT4 in hRIFs was a pathological feature of RP formation, and OLMALINC/OCT4/BMP2 axis facilitated hRIFs to acquire osteogenic-like phenotype under osteogenic conditions, through which the pathway might participate in RP formation. Our findings opened up a new avenue to better understand RP formation in which osteogenic-like process was partially triggered by lncRNAs and pluripotency maintenance related genes.

The value of procalcitonin for predicting urosepsis after mini-percutaneous nephrolithotomy or flexible ureteroscopy based on different organisms.

PURPOSE: To assess the value of procalcitonin (PCT) as an early biomarker for predicting urosepsis caused by Gram-negative (GN) bacteria, Gram-positive (GP) bacteria and fungi following mini-percutaneous nephrolithotomy (mPCNL) and flexible ureteroscopy (FURS). METHODS: A total number of 356 patients with positive preoperative UC (urine cultures) who underwent mPCNL and FURS between June 2017 and January 2021 were retrospectively analyzed. Univariable analysis and multivariable logistic regression analysis were conducted to compare the predictors for urosepsis caused by different organisms. Furthermore, the nomogram was established as a predicted model for urosepsis. RESULTS: Among 356 positive UC, 265 (74.4%) were positive for GN bacteria, 77 (21.4%) for GP bacteria and 14 (3.9%) for fungal pathogens. Escherichia coli (48.9%) were the predominant pathogens and Enterococcus (54/77) were the most common GP bacteria. Multivariate logistic regression analysis showed that positive nitrite (OR 3.31, 95% CI 1.20-9.14; P = 0.021), operative time > 90 min (OR 3.10, 95% CI 1.10-8.75, P = 0.033) and postoperative PCT > 0.1 ng/mL (OR 56.18, 95% CI 15.20-207.64, P < 0.001) were associated with postoperative urosepsis originated in GN infections, while urosepsis caused by GP bacteria and fungi was not associated with PCT > 0.1 ng/mL (P = 0.198), only stone burden > 800 mm2 (OR 3.69, 95% CI 1.01-13.53, P = 0.049) was an independent risk factor. CONCLUSIONS: For patients with positive preoperative UC, postoperative PCT > 0.1 ng/mL was an independent risk factor of post-PCNL and post-FURS urosepsis caused by GN bacteria rather than GP bacteria and fungi.

α-Klotho released from HK-2 cells inhibits osteogenic differentiation of renal interstitial fibroblasts by inactivating the Wnt-ß-catenin pathway.

Randall's plaques (RP) are well established as precursor lesions of idiopathic calcium oxalate (CaOx) stones, and the process of biomineralization driven by osteogenic-like cells has been highlighted in RP formation, but the mechanism is poorly understood. Given the inhibitory role of α-Klotho (KL), an aging suppressor protein with high expression in kidneys, in ectopic calcification and the close association between KL gene polymorphisms and urolithiasis susceptibility, we determined the potential role of KL in RP formation. This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL) or HK-2 cells suppressed osteogenic differentiation of hRIFs, and this effect was abolished by coculture with KL-silenced HK-2 cells or the ß-catenin agonist SKL2001. Mechanistically, s-KL inactivated the Wnt-ß-catenin pathway by directly binding to Wnt2 and upregulating SFRP1. Further investigations identified activation of the Wnt-ß-catenin pathway and downregulation of SFRP1 and DKK1 in RP tissues. In summary, this study identified s-KL deficiency as a pathological feature of RP and revealed that s-KL released from HK-2 cells inhibited osteogenic differentiation of hRIFs by inactivating the Wnt-ß-catenin pathway, not only providing in-depth insight into the role of s-KL in renal interstitial biomineralization but also shedding new light on the interaction of renal tubular epithelial cells with interstitial cells to clarify RP formation.

Incidence and risk factors of venous thromboembolism after percutaneous nephrolithotomy: a single-center experience.

PURPOSE: To determine the incidence and risk factors of the venous thromboembolism (VTE) in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively reviewed the records of 896 consecutive cases receiving PCNL between July 2018 and August 2020 in our institution. Univariate analysis was performed to identify the risk factors of VTE, and multivariate logistic regression analysis was further performed to determine the independent risk factors. Furthermore, the corresponding nomogram was conducted to establish a predicted model for VTE. RESULTS: The overall incidence of VTE was 2.8%. The multivariate logistic regression analysis showed that discontinued anticoagulant or antiplatelet therapies (OR 4.505, 95% CI 1.410-14.401), increased postoperative 12-h D-dimer (OR 11.162, 95% CI 2.370-52.574), hydronephrosis (OR 3.303, 95% CI 1.303-8.375), higher Caprini risk assessment model (RAM) score (OR 3.233, 95% CI 1.207-8.659) and postoperative sepsis or septic shock (OR 3.784, 95% CI 1.163-12.306) were independent risk factors of VTE following PCNL. Moreover, the area under the curve of postoperative 12-h D-dimer, hydronephrosis and Caprini RAM score was 0.826, 0.621 and 0.660, respectively. Based on the identified independent risk factors, the well-calibrated nomogram showed a moderate discriminative ability with concordance index 0.731. CONCLUSIONS: 2.8% of patients developed VTE following PCNL. Regarding those patients who have independent risk factors in this study, due attention should be paid to the effective thromboprophylaxis and the early detection of VTE.

Correction to: Long non-coding RNA H19 promotes osteogenic differentiation of renal interstitial fibroblasts through Wnt-ß-catenin pathway.

In the original article, Fig. 2c was published incorrectly. The correct version of Fig. 2c is provided in this correction.

Long non-coding RNA H19 promotes osteogenic differentiation of renal interstitial fibroblasts through Wnt-ß-catenin pathway.

Randall's plaque (RP) serves as a nidus on which idiopathic calcium oxalate stones form. Renal interstitial mineralization may be the cause underlying RP, and recent studies demonstrated the similarities between the interstitial mineralization and ectopic calcification. The present study aimed to investigate whether human renal interstitial fibroblasts (hRIFs) could form calcification under osteogenic conditions, and whether long non-coding RNA H19 participated in regulating osteogenic differentiation of hRIFs through Wnt-ß-catenin pathway. HRIFs were isolated and induced for osteogenic differentiation under osteogenic conditions. Runx2, OCN, alkaline phosphatase (ALP) activity, and the mineralized nodule formation were used to assess the osteogenic phenotype. Molecule expressions were determined by qRT-PCR, immunofluorescence staining, and western blot. The mineralized nodules were assessed by Alizarin red staining. Compared to the normal renal papillary tissue, Runx2, OCN, and H19 were significantly upregulated in RP. After hRIFs were induced with osteogenic medium, osteogenic markers (Runx2, OCN and ALP), ß-catenin and H19 were significantly upregulated, and the mineralized nodules are formed. Additionally, overexpression of H19 promoted the osteogenic phenotype of hRIFs and increased the expression of ß-catenin, whereas knock-down of H19 or XAV939 (inhibitor of Wnt-ß-catenin signaling pathway) significantly repressed the osteogenic phenotype of hRIFs and decreased the ß-catenin. Moreover, XAV939 was shown to abolish the osteogenic differentiation of hRIFs promoted by H19. The study demonstrated that ectopic calcification partly participated in the formation of RP, and H19 promoted osteogenic differentiation of hRIFs by activating Wnt-ß-catenin pathway, which shed new light on the molecular mechanism of the RP formation.

Microarray expression profiles analysis revealed lncRNA OXCT1-AS1 promoted bladder cancer cell aggressiveness via miR-455-5p/JAK1 signaling.

Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3'-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.

Tamsulosin as a Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Tamsulosin is widely administered as a medical expulsive therapy to facilitate stone passage in patients with ureteral calculi. Recently several large, multicenter, randomized controlled trials revealed conflicting results, which led to considerable uncertainty about the efficacy of tamsulosin in the management of ureteral stones. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of tamsulosin in the management of ureteral stones. MATERIALS AND METHODS: We searched MEDLINE®, Embase®, Web of Knowledge, Google Scholar™ and the Cochrane Central Search Library databases up to June 2018. Two reviewers independently evaluated eligible randomized controlled trials of the efficacy of tamsulosin to treat ureteral stones. Study quality was assessed with the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Subgroup analyses were performed to explore heterogeneity. RESULTS: Included in study were 56 randomized controlled trials in a total of 9,395 patients. The observed treatment effect indicated that tamsulosin was associated with a higher stone expulsion rate (RR 1.44, 95% CI 1.35-1.55, p <0.01), a shorter stone expulsion time (weighted mean difference -0.73, 95% CI -1.00--0.45, p <0.01), a lesser incidence of ureteral colic (weighted mean difference -0.81, 95% CI -1.24--0.39, p <0.01) and fewer incidences of requiring subsequent intervention (RR 0.68, 95% CI 0.50-0.93, p = 0.017). Treatment with tamsulosin did not differ from a control group in the overall incidence of side effects (RR 1.14, 95% CI 0.86-1.51, p = 0.36). On subgroup analysis we observed a significant benefit in the stone expulsion rate for tamsulosin among patients with stones greater than 5 mm (RR 1.44, 95% CI 1.22-1.68, p <0.01) but no effect for stones 5 mm or less (RR 1.08, 95% CI 0.99-1.68, p <0.01). CONCLUSIONS: Our current meta-analysis results indicate that tamsulosin is effective and relatively safe in patients with ureteral stone as a medical expulsive therapy to facilitate stone passage. It is suggested to administer it selectively in patients with 5 to 10 mm ureteral stones.

miR-10b suppresses cell invasion and metastasis through targeting HOXA3 regulated by FAK/YAP signaling pathway in clear-cell renal cell carcinoma.

BACKGROUND: MicroRNAs have been related to tumor progression in diverse human cancers including clear-cell renal cell carcinoma (ccRCC). Previous study has suggested the important regulation function of miR-10b in ccRCC. However, the direct target of miR-10b in ccRCC and the related molecular mechanisms has not yet been revealed. METHODS: miR-10b and HOXA3 was detected by qRT-PCR. MTT, colony formation assay, wound-healing and transwell assays were performed to detect cell proliferation, colony formation, migration, and invasion abilities in ccRCC. Western blot analyses were performed to evaluate the protein expression of HOXA3, YAP, FAK and MMP-9. Dual luciferase reporter assay was employed to measure potential molecular mechanism of miR-10b in ccRCC. RESULTS: miR-10b was down-regulated in 786-O and A498 cells as compared to renal tubular HK-2 cells. By contrast, HOXA3 and YAP was up-regulated in ccRCC cells and tissues. Functionally, knockdown of YAP inhibited cell proliferation, migration and invasion. Knockdown of FAK downregulated YAP, in turn, resulted in a decrease of HOXA3 expression. Mechanically, miR-10b targets HOXA3 to exert its tumor-suppressive effect on ccRCC in vitro. CONCLUSIONS: These novel data suggest that miR-10b suppresses cell invasion and metastasis through targeting HOXA3, which partially passed through the FAK/YAP signaling pathway.

Comparison of retrograde flexible ureteroscopy and percutaneous nephrolithotomy in treating intermediatesize renal stones (2-3cm): a meta-analysis and systematic review.

PURPOSE: To systematically assess the effectiveness and safety of retrograde flexible ureteroscopy (FURS) versus percutaneous nephrolithotomy (PCNL) in treating intermediate-size renal stones (2-3cm). MATERIALS AND METHODS: PubMed, Ovid MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE were researched to identify relevant studies up to May 2018. Article selection was performed through the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The Newcastle-Ottawa Scale was applied to assess the methodological quality of case-control studies. RESULTS: Six retrospective case-controlled trials were included for meta-analysis. The pooled results showed that PCNL was associated with a higher initial stone-free rate (SFR). After more complementary treatments, FURS provided a final SFR (OR: 1.69; 95% CI, 0.93-3.05; P = 0.08) comparable to that achieved by PCNL. PCNL was associated with a higher rate of overall intraoperative complications (OR: 1.48; 95% CI, 1.01-2.17; P = 0.04) and longer hospital stay (MD: 2.21 days; 95% CI, 1.11 to 3.30; P < 0.001). Subgroup analysis by Clavien-graded complication showed PCNL had significantly higher rates of minor complications (OR: 1.58; 95% CI, 1.04-2.41; P = 0.03). No significant difference was noted in major complications (OR: 1.14; 95% CI, 0.53-2.45; P = 0.73) or operative times (MD: -9.71 min; 95% CI, -22.02 to 2.60; P = 0.12). CONCLUSIONS: Multisession FURS is an effective and safe alternative to PCNL for the management of intermediate-size renal stones (2-3cm). It is advisable to balance the benefits and risks according to the individual characteristics of patients and to decide with patients by discussing the advantages and disadvantages of each procedure.

Comparative study of the treatment of 20-30 mm renal stones with miniaturized percutaneous nephrolithotomy and flexible ureterorenoscopy in obese patients.

PURPOSE: To evaluate and compare flexible ureteroscopy (f-URS) and mini-percutaneous nephrolithotomy (mPNL) for 20-30 mm renal stones in obese patients regarding efficacy and safety. METHODS: Between May 2011 and June 2017, 254 obese patients who had 20-30 mm kidney stone were consecutively included in the study; 106 patients underwent mPNL and 148 underwent f-URS by the same surgeon. The following parameters were retrospectively assessed: patient and stone characteristics, surgical details, perioperative outcomes, and stone-free rates (SFR). RESULTS: F-URS group was similar to mPNL group in terms of the mean duration of surgery (92.8 ± 26.1 vs 87.4 ± 31.5 min, P = 0.137) and the final SFR (89.1 vs 92.5%, P = 0.381). The f-URS group had significantly shorter postoperative stay (1.0 ± 0.8 vs 4.3 ± 1.7 days, P < 0.001) and lower postoperative complications (11.5 vs 26.4%, P = 0.002). However, the f-URS group had a lower SFR after first session (67.2 vs 87.4%, P < 0.001) and needed more number of procedures (1.5 ± 0.4 vs 1.3 ± 0.4, P < 0.001) than the mPNL group. CONCLUSIONS: MPNL has a higher efficacy (higher SFR after first session and lower number of procedures); however, f-URS offers advantages regarding safety (lower complication rate). Therefore, both options can be offered to obese patients with renal stones from 20 to 30 mm in size. Nevertheless, these results must be confirmed by further prospective randomized trials.

[Expression of matrix Gla protein and bone morphogenetic protein 2 in renal papillary tissues in patients with calcium oxalate kidney stones].

OBJECTIVE: To compare expression levels of matrix Gla protein (MGP) and bone morphogenetic protein 2 (BMP-2) in Randall's plaque of renal papillary tissues in patients with calcium oxalate kidney stones and the underlying mechanism for stone formation.
 Methods: A total of 30 samples of Randall's plaque in renal papillary tissues from patients with calcium oxalate kidney stones were collected from the Department of Urology of Xiangya Hospital of Central South University from April, 2015 to December, 2015 and served as an experimental group. Ten samples of renal papillary tissues in patients undergone renal tumor nephrectomy were collected from the same hospital and served as a control group. The expressions of MGP and BMP-2 mRNA and protein were detected by quantitative real-time PCR and Western blot.Meanwhile, immunohistochemical technique was used to observe the expressions of MGP and BMP-2 in different parts of renal papillary tissues in the 2 groups.
 Results: 1) The mRNA expression levels of MGP in the experimental group and the control group were 0.760±0.804 and 1.365±0.348, respectively, with significant difference between them (P<0.05). Them RNA levels of BMP-2 in the experimental group and the control group were 2.500±0.725 and 1.485±0.870, respectively, with significant difference between them (P<0.05). The expression levels of MGP protein in the experimental group and the control group were 0.130±0.424 and 0.202±0.704, respectively, with no significant difference between them (P>0.05). The expression levels of BMP-2 protein in the experimental group and the control group were 0.885±0.220 and 0.682±0.272, respectively, with significant difference between them (P<0.05). The immunohistochemistry showed that the protein expression of MGP in the experimental group was lower than that in the control group, while the protein expression of BMP-2 in the experimental group was higher than that in the control group (both P<0.05).
 Conclusion: The BMP-2 expression is increased while MGP expression is decreased in renal papillary tissues in patients with calcium oxalate kidney stones, and the formation of calcium oxalate kidney stone might be a kind of osteogenetic reaction or ectopic calcification.

The association of dyslipidemia with kidney stone: result from the NHANES 2007-2020.

OBJECTIVE: To examine the association between dyslipidemia and kidney stone disease (KSD). METHODS: A cross-sectional study data from 2007 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. Multivariate logistic regression was conducted with serum lipid levels as the exposure and presence of KSD as the outcome, and included adjustment for confounders and subgroup analysis. RESULTS: A total of 38,617 participants were enrolled and classified into two groups according to whether they ever had (n = 3689) or did not have (n = 34,928) KSD. After multivariate logistic regression models, compared to quartile 1 (Q1) of lipid profile, the participants in Q3 (OR 0.8380; 95 CI 0.7380, 0.9515, P < 0.01) and Q4 (OR 0.7373; 95 CI 0.6377, 0.8525, P < 0.01) of high-density lipoprotein cholesterol (HDL) had a significantly lower risk of KSD in adjusted model 3. Results remained stable after stratified by age, gender, and body mass index (BMI) in subgroup analysis. No association was observed between low-density lipoprotein cholesterol (LDL), total cholesterol (TC) and triglycerides (TG) levels, and KSD. CONCLUSIONS: Low HDL was associated with a higher risk of kidney stones in the USA adult population.

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.

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.

A high-calcium environment induced ectopic calcification of renal interstitial fibroblasts via TFPI-2-DCHS1-ALP/ENPP1 axis to participate in Randall's plaque formation.

Randall's plaques (RP) serve as anchoring sites for calcium oxalate (CaOx) stones, but the underlying mechanism remains unclear. Renal interstitium with a high-calcium environment is identified as pathogenesis of RP formation where the role of human renal interstitial fibroblasts (hRIFs) was highlighted. Our study aims to elucidate the potential mechanism by which a high-calcium environment drives ectopic calcification of hRIFs to participate in RP formation. Alizarin Red staining demonstrated calcium nodules in hRIFs treated with high-calcium medium. Utilizing transcriptome sequencing, tissue factor pathway inhibitor-2 (TFPI-2) was found to be upregulated in high-calcium-induced hRIFs and RP tissues, and TFPI-2 promoted high-calcium-induced calcification of hRIFs. Subsequently, the downstream regulator of TFPI2 was screened by transcriptome sequencing analysis of hRIFs with TFPI-2 knockdown or overexpressed. Dachsous Cadherin Related 1 (DCHS1) knockdown was identified to suppress the calcification of hRIFs enhanced by TFPI-2. Further investigation revealed that TFPI-2/DCHS1 axis promoted high-calcium-induced calcification of hRIFs via disturbing the balance of ENPP1/ALP activities, but without effect on the canonical osteogenic markers, such as osteopontin (OPN), osteogenic factors runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2). In summary, our study mimicked the high-calcium environment observed in CaOx stone patients with hypercalciuria, and discovered that the high-calcium drove ectopic calcification of hRIFs via a novel TFPI-2-DCHS1-ALP/ENPP1 pathway rather than adaption of osteogenic phenotypes to participate in RP formation.

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.

Electroacupuncture reduces oxidative stress response and improves secondary injury of intracerebral hemorrhage in rats by activating the peroxisome proliferator-activated receptor-γ/nuclear factor erythroid2-related factor 2/γ-glutamylcysteine synthetase pathway.

Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.