Interconnections between urolithiasis and oral health: a cross-sectional and bidirectional Mendelian randomization study.

Introduction: Urolithiasis is one of the most common diseases for urologists and it is a heavy burden for stone formers and society. The theory of the oral-genitourinary axis casts novel light on the pathological process of genitourinary system diseases. Hence, we performed this study to characterize the crosstalk between oral health conditions and urolithiasis to provide evidence for prevention measures and mechanisms of stone formation. Materials and methods: This population-based cross-sectional study included 86,548 Chinese individuals who had undergone a comprehensive examination in 2017. Urolithiasis was diagnosed depending on the results of ultrasonographic imaging. Logistic models were utilized to characterize the association between oral health conditions and urolithiasis. We further applied bidirectional Mendelian randomization to explore the causality between oral health conditions and urolithiasis. Results: We observed that presenting caries indicated a negative correlation with the risk for urolithiasis while presenting gingivitis [OR (95% CI), 2.021 (1.866-2.187)] and impacted tooth [OR (95% CI), 1.312 (1.219-1.411)] shown to be positively associated with urolithiasis. Furthermore, we discovered that genetically predicted gingivitis was associated with a higher risk of urolithiasis [OR (95% CI), 1.174 (1.009-1.366)] and causality from urolithiasis to impacted teeth [OR(95% CI), 1.207 (1.027-1.418)] through bidirectional Mendelian randomization. Conclusion: The results cast new light on the risk factor and pathogenesis of kidney stone formation and could provide novel evidence for the oral-genitourinary axis and the systematic inflammatory network. Our findings could also offer suggestions for tailored clinical prevention strategies against stone diseases.

Ten-year Time-trend Analysis of Dyslipidemia Among Adults in Wuhan.

OBJECTIVE: Dyslipidemia is associated with an increased risk of cardiovascular disease, the major cause of death in an aging population. This study aimed to estimate the prevalence of dyslipidemia for the past decade among adults in Wuhan, China. METHODS: We performed a serial cross-sectional study that recruited 705 219 adults from the Health Management Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2010 to 2019. The diagnosis of dyslipidemia was based on the 2016 Chinese Guidelines for the Management of Dyslipidemia in Adults. Fixed effects and random effects models were applied to adjust the confounding variables (gender and age). RESULTS: The overall prevalence of dyslipidemia was 33.1% (46.2% in men and 14.7% in women) in 2019. The prevalence of dyslipidemia was significantly increased over 10 years [from 28.6% (95% CI: 28.2%-29.1%) in 2010 to 32.8 % (95% CI:32.6%-33.1%) in 2019;. P-0.001], especially for hypo-high-density lipoprotein cholesterolemia [from 18.4% (95% CI: 18.0%-18.8%) in 2010 to 24.5% (95% CI: 24.3%-24.7%) in 2019; P-0.001]. In 2019, the prevalence of dyslipidemia was higher in participants with comorbidities, including overweight/obesity, hypertension, diabetes, hyperuricemia, or chronic kidney disease, and dyslipidemia was the most significant among participants aged 30-39 years. CONCLUSION: This study demonstrated that dyslipidemia is on the rise in men, and more emphasis should be provided for the screening of dyslipidemia in young males for the primary prevention of cardiovascular and renal diseases.

Sex disparities and the risk of urolithiasis: a large cross-sectional study.

BACKGROUND: Urolithiasis is one of the most common diseases in urology, with a lifetime prevalence of 14% and is more prevalent in males compared to females. We designed to explore sex disparities in the Chinese population to provide evidence for prevention measures and mechanisms of stone formation. MATERIALS AND METHODS: A total of 98232 Chinese individuals who had undergone a comprehensive examination in 2017 were included. Fully adjusted odds ratios for kidney stones were measured using restricted cubic splines. Multiple imputations was applied for missing values. Propensity score matching was utilised for sensitivity analysis. RESULTS: Among the 98232 included participants, 42762 participants (43.53%) were females and 55470 participants (56.47%) were males. Patients' factors might cast an influence on the development of kidney stone disease distinctly between the two genders. A risk factor for one gender might have no effect on the other gender. The risk for urolithiasis in females continuously rises as ageing, while for males the risk presents a trend to ascend until the age of around 53 and then descend. CONCLUSIONS: Patients' factors might influence the development of kidney stones distinctly between the two genders. As age grew, the risk to develop kidney stones in females continuously ascended, while the risk in males presented a trend to ascend and then descend, which was presumably related to the weakening of the androgen signals.Key messagesWe found that patients' factors might cast an influence on the development of kidney stone disease distinctly between the two sexes.The association between age and urolithiasis presents distinct trends in the two sexesThe results will provide evidence to explore the mechanisms underlying such differences can cast light on potential therapeutic targets and promote the development of tailored therapy strategies in prospect.

Sex Disparities in the Association of Serum Uric Acid With Kidney Stone: A Cross-Sectional Study in China.

BACKGROUND AND AIMS: Urolithiasis is characterized by high rates of prevalence and recurrence. Hyperuricemia is related to various diseases. We hope to determine the association between serum uric acid (UA) level and kidney stone (KS). METHODS: In this population-based cross-sectional study, a total of 82,017 Chinese individuals who underwent a comprehensive examination in 2017 were included. The KS was diagnosed based on ultrasonography examination outcomes. Fully adjusted odds ratio (OR) for KS, and mean difference between the two groups were applied to determine the association of UA level with KS. RESULTS: Among the 82,017 participants included in this study (aged 18~99 years), 9,435 participants (11.5%) are diagnosed with KS. A proportion of 56.3% of individuals is male. The mean UA level of overall participants is 341.77 µmol/L. The participants with KS report higher UA level than the participants without KS [mean UA level 369.91 vs. 338.11 µmol/L; mean difference (MD), 31.96 (95% CI, 29.61~34.28) µmol/L]. In men, the OR for KS significantly increases from 330 µmol/L UA level. Every 50 µmol/L elevation of UA level increases the risk of KS formation by about 10.7% above the UA level of 330 µmol/L in men. The subgroup analysis for male is consistent with the overall result except for the participants presenting underweight [adjusted OR, 1.035 (0.875~1.217); MD, -5.57 (-16.45~11.37)], low cholesterol [adjusted OR, 1.088 (0.938~1.261); MD, 8.18 (-7.93~24.68)] or high estimated glomerular filtration rate (eGFR) [adjusted OR, 1.044 (0.983~1.108); MD, 5.61 (-1.84~13.36)]. However, no significant association is observed in women between UA and KS either in all female participants or in female subgroups. CONCLUSION: Among Chinese adults, UA level is associated with KS in a dose-response manner in men but not in women. However, the association becomes considerably weak in male participants with malnutrition status.

Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats.

We used high-throughput RNA sequencing to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord during ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in rats. We observed that of 32662 mRNAs, 4296 out were differentially expressed in the T8-12 segments of the spinal cord upon I/R-induced AKI. Among these, 62 were upregulated and 34 were downregulated in response to I/R (FDR < 0.05, |log2FC| > 1). Further, 52 differentially expressed lncRNAs (35 upregulated and 17 downregulated) were identified among 3849 lncRNA transcripts. The differentially expressed mRNAs were annotated as "biological process," "cellular components" and "molecular functions" through gene ontology enrichment analysis. KEGG pathway enrichment analysis showed that cell cycle and renin-angiotensin pathways were upregulated in response to I/R, while protein digestion and absorption, hedgehog, neurotrophin, MAPK, and PI3K-Akt signaling were downregulated. The RNA-seq data was validated by qRT-PCR and western blot analyses of select mRNAs and lncRNAs. We observed that Bax, Caspase-3 and phospho-AKT were upregulated and Bcl-2 was downregulated in the spinal cord in response to renal injury. We also found negative correlations between three lncRNAs (TCONS_00042175, TCONS_00058568 and TCONS_00047728) and the degree of renal injury. These findings provide evidence for differential expression of lncRNAs and mRNAs in the lower thoracic spinal cord following I/R-induced AKI in rats and suggest potential clinical applicability.

Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity.

Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients. We found that DACH1 expression was decreased in the nephropathy group relative to healthy controls. DACH1 staining in the glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively with serum creatinine (r = -0.37, p < 0.01). In vitro, DACH1 overexpression in human podocytes or HK2 cells decreased expression of cyclin D1, but increased expression of p21 and p53, which suggested that DACH1 overexpression in human podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together, These findings indicate that DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. These data suggest that DACH1 is a potential a marker of disease progression and severity for glomerular diseases.

Effect of uric-acid-lowering therapy on progression of chronic kidney disease: a meta-analysis.

The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=-62.55 µmol/L, 95% CI: -98.10 to -26.99) and blood urea nitrogen (MD= -6.15 mmol/L, 95% CI: -8.17 to -4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min·1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= -6.08 mmHg, 95% CI: -11.67 to -0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression.

Prevention of infection in immunosuppressive patients with autoimmune nephrosis by using an immunostimulating bacterial lysate Broncho-vaxom.

UNLABELLED: The utilization of immunosuppressive agents presents patients with autoimmune nephrosis at a high risk of infection. The present trial was to investigate the efficacy and safety of Broncho-Vaxom on preventing infection in immunosuppressive patients with autoimmune nephrosis. METHODS: 40 patients with autoimmune nephrosis were randomly divided into two groups. The control group (20 cases) routinely received corticosteroid and (or) immunosuppressive therapy, while the treatment group (20 cases) received a capsule containing 7 mg Broncho-Vaxom daily for the first 10 d of each month for 3 consecutive months on the basis of conventional corticosteroid and (or) immunosuppressive therapy. The condition of infection and blood lymphocyte were assessed. RESULTS: 4 patients in the treatment group and 5 patients in the control group were lost during the follow-up period. 25% of patients in the treatment group and 40% of patients in the control group suffered infection. There was no difference in the incidence of infection between the two groups (p > 0.05), while Broncho-Vaxom treated patients suffered a shorter infection period and of which fewer patients need to receive antibiotics therapy (p < 0.05). After the treatment with Broncho-Vaxom, the total number of blood T lymphocyte, proportion of CD4 (+) T lymphocyte, CD4 (+) /CD8 (+) reduced less and the serum IgG rose more obviously (p < 0.05), but the blood lymphocyte, B lymphocyte, CD8 (+) T lymphocyte, IgA and IgM have no differences between the two groups (p > 0.05). CONCLUSION: Broncho-Vaxom might be a good choice for preventing the respiratory infection in nephrosis, especially in the patients under the therapy of immunosuppressive agents.