The G1 and G2 variants of the APOL1 gene represent significant genetic risk factors for APOL1 kidney disease and contribute substantially to the excess burden of renal disease observed in individuals of African ancestry. Importantly, both variants exhibit incomplete penetrance, with only approximately 15–20
This study aimed to explore the association between obesity and renal parenchymal heterogeneity on T1 map in the general population. This population-based study included participants who underwent renal T1 mapping in UK Biobank imaging cohort. Obesity indices were body roundness index (BRI) and body mass index (BMI). The primary renal imaging parameter was corticomedullary T1 differentiation (ΔT1), quantified by manual region-of-interest placement in bilateral kidneys. Multivariable linear regression sequentially adjusted for sociodemographic, metabolic, and renal covariates. A total of 4214 participants (1812 men, 2402 women; 53.9 ± 7.6 years) were included. Both BRI and BMI were significantly and negatively associated with ΔT1 in fully adjusted models (BRI: β = − 8.507, 95
Though insomnia is highly prevalent in patients undergoing maintenance hemodialysis (HD), it is often underdiagnosed. Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in sleep regulation and neuropsychiatric function, has emerged as a potential biomarker for insomnia. However, BDNF levels may be influenced by confounding factors, such as hypnotic medications and dialysis-related clearance. This study aimed to evaluate the relationship between BDNF, sleep quality, medication use, and dialysis in HD patients. We conducted a single-center cross-sectional study involving 73 maintenance HD patients. Insomnia was diagnosed according to International Classification of Sleep Disorders-3 (ICSD-3) criteria, and sleep quality was assessed using the PSQI. Pre-dialysis and post-dialysis blood samples were collected to measure plasma BDNF concentrations by enzyme-linked immunosorbent assay. Standardized BDNF levels were used in logistic regression analyses. Compared with patients without insomnia, those with insomnia had higher pre-dialysis BDNF levels (6892 ± 2778 vs. 5561 ± 2552 pg/mL, p = 0.04). Post-dialysis BDNF levels remained higher in the insomnia group although the difference was not statistically significant. Spearman’s correlation analysis revealed that BDNF levels before and after dialysis were positively correlated with hypnotic medication use (rs = 0.31 and 0.33, p = 0.01 and 0.01, respectively), but were not significantly associated with total PSQI scores. Stratified analyses further revealed that among participants not using hypnotic medications, higher BDNF levels (both pre- and post-dialysis) were independently associated with a lower risk of poor sleep quality (pre-dialysis: OR = 0.43, 95
To evaluate the burden and temporal trends of chronic kidney disease (CKD) attributable to hypertension in China, Japan, and the Republic of Korea from 1990 to 2023 using Global Burden of Disease (GBD) 2023 data. Age-standardized incidence, mortality, and DALYs rates (ASIR, ASMR, and ASDR [age-standardized DALYs rate], respectively) and estimated annual percentage change (EAPC) were calculated for the three countries and globally. Segmented regression identified phase-specific inflections in incidence trends, decomposition analysis partitioned absolute changes into population growth, aging, and epidemiological contributions, and age-period-cohort (APC) analysis characterized drivers of ASDR. Attributable fractions ranked modifiable risk factors for cause-specific mortality. In 2023, Japan had the highest ASIR (37.43 per 100,000) while China had the lowest (17.50 per 100,000); all three countries fell below the global ASMR and ASDR. China and the Republic of Korea achieved significant declines across all standardized rates, whereas Japan’s near-null overall incidence trend concealed a marked late-period acceleration (2017–2023 APC = 0.86
Three phase 3 trials (CREST, POTOMAC, ALBAN) adding an immune checkpoint inhibitor (ICI) to Bacillus Calmette–Guérin (BCG) in BCG-naive high-risk non-muscle-invasive bladder cancer (NMIBC) reported different results. We used reconstructed individual patient-level data (rIPD) to examine the overall event-free survival (EFS) effect and its change over time. This post hoc analysis used data reconstructed from published Kaplan–Meier curves rather than original trial datasets, harmonized as EFS. A trial-stratified Cox model estimated the pooled hazard ratio (HR). Two-parameter Weibull models described the timing of events (scale, β) and the temporal pattern of risk (shape, α), with proportional hazards assessed by Schoenfeld residuals and log–log plots. The trials differed in agent, endpoint definition, and BCG schedule. Reconstructed event counts and HRs closely matched reported values. The pooled EFS HR was 0.76 (95
Unilateral congenital kidney anomalies (renal agenesis, hypoplasia, ectopia, MCDK) may affect kidney growth, blood pressure, and function over time. Comparative compensatory responses among different anomalies remain poorly defined. This longitudinal multicenter study included 130 children (71 patients, 59 controls) aged 0–19 years. Kidney volumes were measured by ultrasound at two visits (median interval two years). Age- and Body Surface Area (BSA)-adjusted Z scores for total kidney volume (TKV) were calculated using LMS reference data. Office blood pressure, eGFR, and urinary albumin-to-creatinine ratio (UACR) were assessed at both visits. Right-sided pathology predominated ( 60
Rituximab (RTX) is the first-line treatment for primary membranous nephropathy (MN), but 30–40
End-stage kidney disease (ESKD) remains a major global health burden. Although advances in surgery, immunosuppression, and dialysis have improved short-term graft survival after kidney transplantation, long-term outcomes remain unsatisfactory. The atherogenic index of plasma (AIP), a marker of insulin resistance and atherosclerotic risk, has been widely studied in the general population and dialysis patients, but its prognostic value in kidney transplant recipients is unclear. This study evaluated the association between AIP and post-transplant outcomes. In this retrospective cohort study, kidney transplant recipients treated at Shulan (Hangzhou) Hospital in 2019 were included. The primary outcome was a composite endpoint assessed within 12 months after kidney transplantation, including a ≥50
Childhood nephrotic syndrome (NS), is a glomerular disease, characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema. The pathophysiology of primary NS suggests a strong connection between genetic susceptibilities and inflammatory processes. This study investigated the association between TNF-α (G238A, G308A), IL-2 (T330G), and IL-10 (A592C) gene polymorphisms and susceptibility to steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS). A total of 300 samples from 100 SSNS and 100 SRNS patients, as well as 100 healthy controls aged between 1 and 18 years, were genotyped using the restriction fragment length polymorphism (RFLP) method. Genotype frequencies were analyzed and compared using odds ratios (ORs) and confidence intervals (CIs) to assess disease association. In SSNS, TNF-α G238A (AA), TNF-α G308A (GA and AA), and IL-2 T330G (TG) were associated with increased disease risk, whereas IL-10 A592C (CC) showed a protective effect. In SRNS, TNF-α G238A and G308A (AA and GA), IL-2 T330G(TG) and IL-10 A592C (AC and CC) were significantly associated with increased risk, with the strongest effect observed for the GA genotype of TNF-α G308A. Comparative analysis between SSNS and SRNS indicated stronger associations of TNF-α G308A and IL-10 A592C with SRNS. After Bonferroni correction, only these polymorphisms remained significantly associated. Genetic polymorphisms in TNF-α G308A and IL-10 A592C may contribute to susceptibility to SRNS, highlighting the role of inflammatory pathways in disease pathogenesis. These findings may support the identification of potential biomarkers for disease susceptibility and immune dysregulation in pediatric NS.
This study aimed to investigate the imaging characteristics and molecular mechanisms by which pelvic floor electrical stimulation (PFES) improves pelvic floor muscle injury in a rat model of stress urinary incontinence (SUI). An SUI model was established in female Sprague‑Dawley rats via vaginal distension combined with bilateral ovariectomy. One week post‑modeling, the stimulation group received intravaginal PFES for 2 weeks. Evaluations included 9.4 T MRI, urodynamic tests, histopathological staining, qPCR, Western blotting, and RNA‑seq. PFES significantly elevated ALPP compared with controls, indicating improved urinary continence. MRI demonstrated that PFES attenuated focal hyperintensity, muscle edema, and fiber disorganization in the pubococcygeus muscle. Histological analyses confirmed that PFES restored dense muscle fiber arrangement and collagen distribution, and immunohistochemistry showed upregulated expression of COL1A1, COL3A1, and CD34. RNA‑seq revealed that differentially expressed genes were prominently enriched in ECM organization, focal adhesion, ECM–receptor interaction, and the PI3K–Akt pathway. Western blotting verified that PFES increased COL1A1, COL3A1, and VEGFA, while suppressing the atrophy‑related ubiquitin ligase FBXO32. PFES effectively repairs pelvic floor muscle structure and function by reducing muscle edema and fiber disruption. This effect may be associated with up‑regulation of type I and III collagens to facilitate ECM remodeling, induction of VEGF mediated angiogenesis, and down‑regulation of FBXO32 to counteract muscle atrophy. These findings elucidate PFES mechanisms and support its clinical application.
To develop and externally validate a simplified apparent diffusion coefficient (ADC)-based MRI radiomics model for differentiating benign and malignant Prostate Imaging Reporting and Data System (PI-RADS) 3–5 lesions and assess its incremental value beyond clinical predictors. This retrospective multicenter study included 340 patients assigned to training (n = 182), internal test (n = 71), and external validation (n = 87) cohorts. Radiomics features were extracted from ADC maps and underwent reproducibility filtering and training-only feature selection. Four machine-learning classifiers were compared using nested cross-validation. Prostate-specific antigen (PSA), PSA density (PSAD), and PI-RADS were evaluated individually, and clinical and combined clinical-radiomics models were constructed. Logistic regression was selected as the final radiomics classifier. The radiomics model achieved area under the receiver operating characteristic curve (AUC) values of 0.712 and 0.679 in the internal test and external validation cohorts, respectively. Corresponding AUCs were 0.775 and 0.777 for the clinical model and 0.829 and 0.808 for the combined model. The combined model did not significantly outperform the clinical model (Holm-adjusted P = 0.123 and 0.392, respectively) and showed an external specificity of 0.538. ADC radiomics provided complementary information for differentiating benign and malignant PI-RADS 3–5 prostate lesions, but its incremental value beyond the clinical model was limited. Further prospective multicenter validation is warranted before clinical implementation.
Cognitive impairment is common in patients with advanced kidney disease and may persist after kidney transplantation (KT). This systematic review synthesized evidence on posttransplant cognitive trajectories, associated factors, and clinical outcomes. PubMed, Embase, and Web of Science were searched from inception through July 21, 2026. After screening and citation searching, 22 reports were included. Eligible studies included longitudinal studies assessing cognitive trajectories or studies evaluating associations between cognitive function and posttransplant clinical outcomes among adult kidney transplant recipients. Due to heterogeneity in cognitive measures and follow-up intervals, findings were synthesized narratively rather than conducting meta-analysis. Certainty of evidence for the trajectory of cognitive domains was assessed using GRADE. Global cognition showed no consistent improvement after KT, whereas more favorable changes were observed in selected measures of processing and psychomotor speed, verbal learning and immediate memory, and delayed verbal memory and recall. Findings for attention, executive function, verbal fluency, visuospatial and constructional function, and working memory were mixed or limited. Certainty of evidence was low for delayed verbal memory and recall, and very low for all other cognitive domains. Studies examined a range of factors associated with cognitive function after KT, including demographic, kidney disease-related, transplantation-related, comorbidity, physical function, and neuroimaging-derived brain-related factors. But the evidence was sparse and inconsistent. Three reports suggested potential associations between cognitive impairment and mortality or allograft loss. Cognitive change after KT may be domain-specific. Current evidence remains uncertain due to heterogeneous follow-up period, incomplete adjustment for confounding, lack of a comparison group, and other methodological limitations.
To evaluate the risk factors associated with mortality and recurrence following nephroureterectomy for upper tract urothelial carcinoma (UTUC) in a large Brazilian cohort. This retrospective study analyzed 126 patients who underwent nephroureterectomy for UTUC between 2009 and 2023 at a single institution in Brazil. Cox regression and Kaplan–Meier analyses were performed to identify factors associated with mortality and recurrence. The median follow-up duration was 38 months. In multivariate analysis, positive surgical margins (HR 3.45, 95
The posterior reconstruction (PR) during robot-assisted radical prostatectomy (RARP)—as originally described by Rocco F and coworkers—has been introduced in 2006 aiming to restore anatomical disruption occurring after radical prostatectomy and to improve continence recovery. The original open technique has been adapted to laparoscopy and to robotics thereafter. The approximation achieved after PR may also reduce the anastomotic tension—while tying the suture – and thus enhance the anatomical alignment. The Rocco’s stitch was introduced by October 2024 at a tertiary robotic center previously unfamiliar to the technique; therefore, a comparative study to assess the impact of PR on the self-perceived quality and easiness of VUA of robotic surgeons was performed. This is a retrospective, single-center comparative study performed at Fondazione Policlinico Gemelli IRCCS, Rome, Italy. The Rocco Stitch was introduced in October 2024 using the standardized two-layer technique. Cases before and after the introduction of PR were retrieved from a prospectively maintained database (Protocol ID 7314) and 271 patients undergoing RARP between November 2023 and February 2025 were evaluated. Post-operative cystogram was performed when deemed necessary (7–9 PO day), based on the surgeon’s ease of anastomosis execution and final perceived quality. The primary outcome of the study is the rate of cystogram use; the overall rate of urinary leakage and the need for additional imaging due to suspect urine extravasation are secondary endpoint. Multivariable logistic regression was performed to identify independent predictors of leakage. Overall, 87 patients received PR, 184 did not; PR group had significantly lower cystogram use (34.5
Chronic pelvic pain syndrome (CPPS) is a complex and prevalent condition in men, but with few long-term treatment options. Yoga can reduce pain and pelvic floor dysfunction, but there is no evidence comparing yoga with medical management in men. Effects of yoga Therapy (YT) with medical therapy (MT) in men with CPPS are compared in this study. We performed a prospective randomised crossover study at a tertiary referral centre. We randomised 40 men aged ≥18 years with CPPS (as per European Association of Urology criteria) to either MT followed by YT or YT followed by MT with a 1 week washout period in between. In MT, alfuzosin 10 mg daily and titrated amitriptyline 10–50 mg daily was given for 6 weeks. YT comprised of supervised structured 1 h daily yoga for 6 weeks. Primary outcome was recorded as the change in total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score. The secondary outcomes consisted of pain, urinary, and quality-of-life subdomain scores. This trial has been registered on Clinical Trials Registry of India (CTRI/2022/05/042706). All patients who were randomised completed both phases of treatment. There was a mean improvement in NIH-CPSI total score of −10.8 points with MT and −8.4 with YT. This resulted in a difference of −2.4 points (95
To compare the expression of immune checkpoint molecules in tumor cells and tumor microenvironment and their role on prognosis among surgically treated non-metastatic clear cell renal cell carcinoma (ccRCC), papillary RCC (papRCC), and chromophobe RCC (chRCC). We retrospectively evaluated patients undergoing curative partial or radical nephrectomy for non-metastatic RCC between 2015 and 2023, who had available formalin-fixed paraffin-embedded tumor tissue and postoperative follow-up. Immunohistochemical staining was performed for PD-L1, PD-1, and CTLA-4. PD-L1 expression was evaluated using tumor proportion score, combined positive score, and immune cell score, whereas PD-1 and CTLA-4 expression were evaluated using immune cell score. Immunopositivity was defined as ≥1
Peritoneal dialysis (PD) is a core renal replacement therapy for end-stage renal disease (ESRD), but PD patients face elevated cardiovascular risk, with vascular calcification (VC) severely impairing long-term prognosis. This meta-analysis aimed to synthesize factors associated with VC in PD patients to support early risk stratification and targeted clinical management. We searched the Cochrane Library, Web of Science, PubMed, and Embase up to June 30, 2026, for English studies on factors associated with VC in PD patients. Study quality was assessed via the Newcastle–Ottawa Scale, and pooled odds ratios (ORs) with 95
Radical cystectomy (RC) with orthotopic neobladder (ONB) reconstruction provides oncological control and quality-of-life benefits for selected patients with bladder cancer. However, prognostic factors for recurrence remain to be elucidated. Herein, we evaluated 10-year oncological and renal functional outcomes after ONB reconstruction at a single institution. We retrospectively reviewed 84 patients who underwent RC with ONB reconstruction at our institution between June 2009 and August 2024. We analyzed clinicopathological characteristics, perioperative variables, and postoperative outcomes. All patients were male, the median age was 68 (range, 45–82) years, and the median follow-up was 79 months (range, 4–179). The 5- and 10-year recurrence-free survival (RFS) rates were 76
Conventional prostate cancer screening profiles rely heavily on static serum prostate-specific antigen (PSA) thresholds, consistently overlooking the confounding impacts of the modern metabolic syndrome epidemic. This study aimed to isolate and quantify the long-term longitudinal impact of insulin resistance (HOMA-IR) and Body Mass Index (BMI) on serum PSA levels. We retrospectively evaluated 9095 routine annual screening records from 5,846 asymptomatic male subjects (2016–2026) with concurrent clinical data for PSA, HOMA-IR, BMI, and total testosterone. Linear Mixed-Effects Models with subject-specific random intercepts were constructed to rigorously account for intra-subject correlations across consecutive annual follow-up visits. Multi-variable longitudinal analysis demonstrated that while BMI exhibited a strong downward trend on baseline biomarkers (per-unit decrease of 0.018 ng/mL (p = 0.057), elevated HOMA-IR served as a statistically significant, independent biochemical marker inversely associated with serum PSA (p = 0.042). Crucially, categorical stratification revealed a highly significant, non-linear biomarker collapse: subjects in the highest cumulative metabolic burden quadrant (concurrent BMI ≽35 kg/m2 and HOMA-IR > 3.0) exhibited a profound 34.8
