BMC Nephrology

Background: Renal effects of statins in type 2 diabetes mellitus (T2DM) remain uncertain. We evaluated whether statin exposure is associated with time to dialysis initiation. Methods: We conducted a retrospective cohort study of adults with T2DM, indexing follow-up at diagnosis during first hospital admission (day 0) between january 2017 and march 2025. Statin use was modeled as time-varying from statin days; (classified in 3 categories: baseline users, new users, and never users). The primary outcome was dialysis. Analysis estimated cause-specific hazards, censoring deaths; proportional hazards were checked with prespecified windows of statin exposure (0?1, 1?3, > 3 years). Competing-risk analyses (Fine?Gray) assessed the sub-distribution hazard of dialysis with death as a competing event in two models: (i) prevalent users at baseline and (ii) new-users with post-initiation intervals of 30 and 90 days. An Observational Medical Outcomes Partnership Common Data Model standardized dataset of a Brazilian quaternary hospital, and the Real-World Data tool MD Clone were used in the study. Results: Of 36,246 adults identified, 32,125 entered the time-varying cohort (39,943 risk intervals; 656 dialysis events); median follow-up among censored patients was 753 days. At baseline, 70.3% never used statins, 5.5% were users (? 0 days), and 24.2% initiated after diagnosis. Crude dialysis incidence was 4.51 vs. 12.31 per 1,000 patient-years during unexposed vs. exposed time. In the adjusted time-varying Cox model, current statin exposure was associated with a modestly higher hazard of dialysis (HR = 1.043, 95% CI 1.011?1.077). In the new-users analysis, HRs were 0.83 (95% CI 0.66?1.05), and 0.73 (95% CI 0.57?0.92) with a 30-day and 90-day intervals, respectively. Conclusions: In this retrospective cohort of hospitalized diabetic patients at baseline, statin initiation at least 90-days in advance is associated with reduced indication of renal replacement therapy.

Introduction: To investigate the epidemiological characteristics of chronic kidney diseases (CKD) in China in 2021 and its trends between 1990 and 2021, in the context of significant population growth and lifestyle changes over the past 30 years that have likely influenced the CKD spectrum. Methods: Data on CKD prevalence, mortality, disability-adjusted life-years (DALY), and risk factors were obtained from the Global Burden of Disease Study 2021. The estimated decadal percentage changes were calculated to evaluate changes in trends in prevalence, mortality and disease burden. Results: In 2021, an estimated 118.4 (95% UI 109.4 to 127.5) million people in China were affected by CKD, contributing to 204 230 (95% UI 164 736 to 246 372) deaths and 6.13 (95% UI 5.18 to 7.21) million DALY. Although CKD due to diabetes mellitus and hypertension accounted for less than a quarter of all cases, they were responsible for over 90% of CKD-related deaths. Over the past three decades, CKD mortality and DALY rates have steadily increased, although the prevalence has stabilized in the last decade. Diabetes mellitus type 2 and hypertension have emerged as key drivers of CKD burden in China. Conclusions: The CKD burden in China shows a dual pattern of rising incidence and high mortality from diabetes and hypertension-related chronic kidney disease, alongside persistently high years lived with disability from glomerulonephritis and other causes.

Background: Clinical LLM benchmarks rarely test whether algorithmic rankings agree with expert clinical judgment. We developed a trap-embedded peritoneal dialysis (PD) benchmark comparing multiple scoring constructs with blinded nephrologist ratings. Methods: We generated 125 synthetic PD cases containing 13 ISPD-aligned trap types. Five LLMs (Claude Sonnet 4.5, GPT-5.4, Gemini 3.1 Pro, DeepSeek-R1, Grok 4.1 Fast) evaluated each case three times at temperature 0 (1,875 calls). Primary outcome was must-identify TDR_must, analyzed with GEE and case-clustered bootstrap. Secondary analyses included a verbosity-sensitive alarm-burden proxy, WCS, relaxed-match scoring, WCS sensitivity analyses, and a 25-output blinded expert adequacy substudy. Must-identify kappa was 0.89 in Stage 1 and 0.92 in Stage 2. Results: Rankings were discordant. Recall ranked Claude (0.977) and GPT-5.4 (0.955) above the other models (0.86-0.90, p<0.0001). The alarm-burden proxy favored concise models (Grok 0.689; 21.6 vs 2.4 issues/case), while WCS produced a third ordering. In the expert substudy, inter-rater concordance was strong (rho 0.977), but WCS did not show a positive association with expert adequacy (rho -0.17, p=0.41). Conclusion: Clinical LLM rankings in PD prescription review depend strongly on scoring construct. Algorithmic metrics should be reported alongside blinded expert adequacy ratings and should not alone determine deployment.

Background.Renoprotective therapies - SGLT2 inhibitors, finerenone, and renin-angiotensin system inhibitors (RASi) - remain underutilisedin chronic kidney disease (CKD). Large language models (LLMs) may detect therapy omissions, but their performance acrossCKD severity strata and at clinical decision boundaries has not been evaluated.Methods.We constructed 100 synthetic CKD vignettes (G3a-G5D; 75 with prespecified omissions, 25 decoys) and queried four LLMsthree times each at temperature 0 (1,200 calls). Omission criteria were adapted from KDIGO 2024, including an investigator-defined gray-zone RASi initiation criterion at eGFR<15. Two nephrologists independently classified a stratified 20-casesubset.Results.For SGLT2 inhibitor and finerenone omissions, all models achieved near-ceiling sensitivity (97-100%). For RASi, performancediverged at the eGFR<15 boundary: Grok 4.1 Fast 85% versus GPT-5.4 55%, Gemini 10%, DeepSeek 10%. Gap-detectioninter-rater agreement was perfect (kappa = 1.000). Clinically incorrect reasoning rates ranged from 0% (GPT-5.4) to 27%(DeepSeek R1); of 52 instances, 31 were factual pharmacology errors and 21 reflected conservative boundary-discordantreasoning. Reproducibility (Jaccard) ranged from 0.74 to 0.93.Conclusions.This boundary-aware synthetic benchmark showed that aggregate sensitivity can conceal clinically important operational-rulediscordance. Rule-based SGLT2 inhibitor and finerenone omissions were detected with near-ceiling sensitivity, whereas aninvestigator-defined gray-zone RASi criterion at eGFR<15 exposed model-specific boundary behaviour. Evaluation of LLM-based CKD decision support should report boundary-specific performance, reproducibility, and clinically incorrect reasoningalongside aggregate metrics.

Background and hypothesis: Sodium-glucose cotransporter-2 inhibitors (SGLT2-inhibitors) slow chronic kidney disease progression, but evidence in non-diabetic kidney transplant recipients is limited. We evaluated associations between SGLT2-inhibitor use and major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), and all-cause mortality. Methods: In this retrospective cohort study using the TriNetX federated research network, adult non-diabetic kidney transplant recipients transplanted between January 2015 and January 2022 were identified. SGLT2-inhibitor users initiating therapy [&ge;]1000 days post-transplant were compared with non-users after 1:1 propensity score matching. The primary outcome was MAKE, defined as dialysis initiation or death. Secondary outcomes included all-cause mortality and MACE. Results: Propensity score matching yielded 867 pairs of SGLT2-inhibitor users and non-users. SGLT2-inhibitor use was associated with lower risks of MAKE (adjusted hazard ratio [aHR] 0.64, 95% CI 0.45-0.91) and all-cause mortality (aHR 0.55, 95% CI 0.36-0.85). No significant association was observed for MACE (aHR 0.86, 95% CI 0.64-1.17). No increased risk of urinary tract infections was observed among SGLT2-inhibitor users. Conclusion: SGLT2-inhibitor use was associated with lower risks of MAKE and all-cause mortality in non-diabetic kidney transplant recipients.

Importance: Recently, proteinuria has been accepted as a surrogate end point for clinical trials in focal segmental glomerulosclerosis (FSGS) ang IgA nephropathy. However, proteinuria has not been evaluated in Apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD). Methods: Real world data (RWD) analysis of 128 patients of African ancestry with APOL1 high risk genotypes, without diabetes, enrolled in the Million Veteran Program (MVP; n=109) or the biorepository at Vanderbilt University (BioVU; n=19), who had urine albumin-creatinine ratio (UACR) >= 420 mg/g (PCR~0.9 g/g) with a concurrent GFR value. The main predictor was change in the log-UACR at 12 months. The primary outcome was annual GFR slope over 24 months. Secondary outcomes included a kidney composite of a sustained 30% GFR decline, end stage kidney disease (ESKD) or death and ESKD as a single outcome. Linear regression and Cox proportional hazards models were used to assess the effect of changes in UACR and the outcomes. Results: In the pooled analysis the mean age was 56.8 (SD 15.5) y, 116 were male (90.6%) and three patients had diagnosis of FSGS at baseline. Mean baseline eGFR was 46.8 (SD 16.1) mL/min/1.73m2, mean baseline UACR was 1240.8 (1107.7) mg/g, mean eGFR slope was -4.67[-6.00, -3.33] mL/min/1.73m2/year and the geometric mean percentage changes in the UACR at 12 months were -57.5% [-65.0%, -48.4%]. For every 1 unit of log (UACR) increment at 12 months, the annual eGFR slope decreased by -1.80 [-2.56, -1.03] mL/min/1.73m2 in the pooled analysis. For every 1 unit of log (UACR) increment at 12 months, the Cox regression showed a 61% increase in the risk of a kidney composite (p=0.002) and a 98% increase in the risk of ESKD (p<0.001). It was estimated that a 50% reduction of UACR at 12 months was associated with a 28% reduction in the kidney composite endpoint (adjusted hazard ratio [aHR]=0.72; 95% confidence interval [CI]:0.59-0.88; p=0.002), and a 38% reduction in the risk of ESKD (aHR=0.62; 95% CI:0.49-0.80; p<0.001). Conclusions and relevance: Changes in UACR at 12 months significantly modify the rate of decline of GFR over 24 months and clinically meaningful endpoints, supporting the use of UACR changes as surrogate endpoint in AMKD.

Background: Psychological distress is common in chronic kidney disease (CKD) and is associated with reduced quality of life, treatment non-adherence, and worse clinical outcomes. Distress in CKD is also linked to difficulties adjusting to the demands of illness management. Despite this, psychological support remains inconsistently integrated within kidney care pathways, and existing interventions often lack clear theoretical specification and explicit targeting of mechanisms underpinning adjustment to CKD. Objectives: To describe the systematic development of iADJUST, a theory-informed patient co-designed digital psychological intervention targeting key cognitive and behavioural mechanisms involved in adjustment to CKD. Methods: Intervention development was guided by the Medical Research Council framework for complex interventions. A structured, iterative process integrated empirical evidence, psychological theory, and patient and public involvement and engagement. The Common-Sense Model of Self-Regulation and cognitive behavioural theories informed the identification of modifiable maintaining mechanisms associated with adjustment to CKD. Intervention components were mapped onto these mechanisms and refined through co-design with people living with CKD. Results: iADJUST is a six-session self-guided digital psychological intervention delivered over 12 weeks and supplemented by therapist contact. The intervention targets illness-related uncertainty, fatigue-related activity dysregulation, catastrophic what-if thinking, self-critical evaluation, and behavioural withdrawal. It integrates psychoeducation, cognitive and behavioural strategies, maintenance planning, and elements from acceptance and commitment therapy and compassion-focused approaches. Content is delivered through video, audio, and guided tasks and activities. Conclusion: iADJUST provides a theory-informed, evidence-based psychological intervention for CKD explicitly mapping intervention components to maintaining cognitive and behavioural mechanisms implicated in adjustment. Feasibility evaluation is underway.

Abstract Background Alport Syndrome (AS), caused by pathogenic variants in type IV collagen genes COL4A3/4/5, is a leading monogenic cause of Kidney Failure (KF). Clinical course varies widely, and disease specific predictors of progression relevant to clinical care and trial design remain incompletely defined. Methods In this retrospective cohort study of individuals with AS in the UK National Registry of Rare Kidney Diseases, patients were classified as having AS or heterozygous genotypes and followed to assess proteinuria progression, eGFR slope and kidney survival. Proteinuria and eGFR trajectories were analysed using mixed effects regression models; kidney survival using Kaplan Meier analysis. Results Among 1032 participants (median follow up 11.6 years; 47% female), 475 (46%) had AS genotypes (Male XLAS or autosomal recessive AS). eGFR decline accelerated with advancing CKD stage across all genotypes (p<0.001). Proteinuria increased as eGFR declined and occurred earlier in AS genotypes. After reaching proteinuria thresholds of more than 1.0 and 3.0g/g, kidney survival over the subsequent 5 years did not differ significantly between genotypes (logrank p=0.14, p=0.17, respectively), although modest differences emerged over longer follow-up. Across eGFR thresholds (90, 60, and 45mL/min/1.73m2), higher proteinuria was associated with shorter time to KF; for example, at eGFR 45mL/min/1.73m2, median time to KF was 3.0 years (IQR, 1.6-5.4) for above-median vs 6.5 years (5.1-not estimable) for below-median proteinuria (p<0.0001). Almost all patients who reached KF had developed proteinuria of more than 0.3g/g. Conclusion In this national cohort, eGFR decline accelerated with CKD stage and proteinuria was strongly associated with progression to KF across genotypes. The non linearity of eGFR decline may inform its interpretation in clinical practice and use as a trial endpoint. Once comparable proteinuria levels were reached, differences in outcomes by genotype were attenuated, supporting proteinuria as a key prognostic marker and strengthening rationale for its use as a surrogate endpoint in AS clinical trials

Background: ADTKD-MUC1 is one of the major entities of ADTKD caused by frameshift variants in the MUC1 VNTR that standard short-read sequencing fails to detect. Existing 59dupC-targeted probe-extension assays do not allow for broad screening and cannot detect atypical non-dupC variants. Recently, VNtyper, a Kestrel-based genotyping pipeline with optional code-adVNTR cross-validation for MUC1 VNTR genotyping from short-read sequencing data allowed to circumvent this diagnostic limitation, but needed further development for easy access and rapid sample processing. Methods: We developed VNtyper 2, by refactoring VNtyper into a modular, production-grade tool with a companion web platform, VNtyper-Online (https://vntyper.org), for freely available browser-based analysis with short turnaround time and without local bioinformatics infrastructure. We validated VNtyper 2 on 400 simulated samples generated with MucOneUp and 142 clinical exomes with independently confirmed genotypes. Results: In simulation, VNtyper 2 detected the canonical 59dupC variant with 96% sensitivity and 100% specificity. Reference-standard validation on 142 samples yielded 90.6% sensitivity and 98.2% specificity overall, with cohort-dependent performance across the Twist Exome v2 French-German cohort (98% sensitivity, 87.5% specificity) and the KAPA HyperExome V2 (Roche) Czech-US cohort (79.4% sensitivity, 100% specificity). Screening of 3582 exomes and targeted panels from international CKD referral programmes identified 51 positive individuals, including 9 with atypical non-dupC frameshift variants that would have been missed by 59dupC-targeted probe-extension assays. In unselected CKD cohorts, a descriptive random-effects summary estimated a detection rate of 1.4% (95% CI 0.6 to 3.1%). Conclusions: VNtyper 2 and VNtyper-Online are open-source tools for MUC1 VNTR genotyping from short-read data and can support locally validated workflows when VNTR coverage is adequate. By improving accessibility and turnaround time, these tools democratize MUC1 diagnostics at global scale. For its integration into routine diagnostics, we propose an expert-informed two-pathway workflow developed through European ADTKD-Net consortium consensus.

Background: Patients with CKD and polypharmacy face high rates of drug-related problems, yet comprehensive medication review remains time-intensive and inconsistently performed. Large language models (LLMs) may augment this process, but existing benchmarks use multiple-choice formats that do not reflect open-ended, nephrology-specific review. We developed a trap-embedded synthetic CKD benchmark and evaluated five current-generation LLMs (GPT-5.4, Claude Sonnet 4.6, Gemini 3.1 Pro, Grok 4.1 Fast, DeepSeek R1; tested April-May 2026) for open-ended medication review. Methods: Fifty synthetic CKD cases across three complexity groups (G3a-G3b [n=20], G4 [n=15], G5/G5D/transplant [n=15]) with 8-12 medications and [&ge;]2 embedded clinical traps each were scored against nephrologist-adjudicated gold standards. Each model produced three independent responses per case (temperature 0; 750 total outputs). Primary endpoint was per-case macro F1; secondary endpoints were safety-critical omission rate, PI-adjudicated hallucination rate, and intra-model consistency. Blinded inter-rater reliability for gold-standard item detection was assessed on a 30% sample. Results: Consensus-level macro F1 ranged from 0.41 (Claude Sonnet 4.6) to 0.49 (Grok 4.1 Fast) (Friedman P < 0.001). Phosphate binder timing (11%) and hyperkalemia combinations (33%) were poorly detected across all models. Safety-critical omission rate ranged from 22% to 48% (P < 0.001); PI-adjudicated hallucination ranged from 0% (GPT-5.4) to 54% (DeepSeek R1), including fabricated dose caps and non-existent guideline citations. Blinded reliability for gold-standard item detection was high (kappa = 0.934, n = 92). Conclusions: This nephrology-specific benchmark exposes clinically important LLM blind spots that generic multiple-choice evaluations would not detect. Heterogeneous hallucination and omission rates indicate that model selection and domain-specific guardrails should precede any clinical deployment of LLM-assisted CKD medication review. Prospective validation with real patient data and human comparators is required before deployment recommendations can be made.

Background: Exercise-based cardiac rehabilitation (CR) improves peak oxygen uptake ([V]O2peak) in patients with coronary heart disease (CHD); however, whether women and men exhibit similar adaptations across the steps of O2 transport remains unknown. We aimed to compare the ventilatory and circulatory determinants of [V]O2peak changes between women and men with CHD following a structured exercise training program. Methods: A total of 28 women (27%) and 75 men (73%) with CHD, matched for age, body mass index, and [V]O2peak (% predicted), underwent maximal cardiopulmonary exercise testing (CPET) before and after 12 weeks of CR. [V]O2peak and minute ventilation ([V]E) were measured breath by breath. Heart rate and cardiac output ([Q]c)were assessed non-invasively using impedance cardiography. Exercise efficiency ({Delta}[V]O2/{Delta}W), alveolar ventilation ([V]A), ventilatory efficiency (OUES), O2 pulse, arteriovenous oxygen content difference (C(a-[v])O2) and gross muscular efficiency (W) were calculated using standard equations. Mixed model analyses (sex x time) were used to compare training-induced changes between sexes. Results: At baseline, values of [V]O2peak (absolute and normalized by fat free mass), [V]E, [V]A, O2 pulse, C(a-[v])O2, {Delta}[V]O2/{Delta}W, W were significantly lower in women than in men with CHD (group effect, p<0.01). [V]O2peak normalized by fat-free mass improved similarly in both sexes after CR (p<0.0001, no significant sex x time interaction). Pulmonary convection ([V]E, [V]A), ventilatory efficiency (OUES), circulatory convection ([Q]c, cardiac index, O2 pulse), and peripheral gross muscular efficiency (W) all improved similarly after CR in women and men (effect sizeXtime effect, p<0.05, no significant group x time interaction). The prevalence of responder categories did not differ between sexes (p=0.826). Conclusion: Women and men with CHD demonstrated equivalent O2 transport phenotype adaptations after CR, with comparable improvements across the O2 transport chain (pulmonary, circulatory, and peripheral determinants of [V]O2peak).

Background: Generative AI tools can support data-intensive research by writing code, drafting prose, searching analytical possibilities, and stress-testing claims. They can also produce false citations, drift between statistical specifications, and lose continuity across long investigations. This paper describes a practical workflow for using AI systems in empirical research while keeping discovery, verification, and accountability inspectable. Methods: We developed and applied a three-phase human-AI workflow to a case study of 14 elite Ethiopian distance runners. The dataset contained 22,605 GPS-segments collected across 97 consecutive days in late 2025, supplemented by venue and athlete metadata collected in the field. Phase 1 used an autonomous data-exploration tool to pre-filter the hypothesis space across five seeded research questions. Phase 2 used an AI system under direct human guidance to construct candidate findings into numerical claims, verification scripts, and draft text. Phase 3 used an independent AI system in an adversarial role to stress-test methods, statistics, prose, figures, and citations. The workflow was informed by Pearl's distinction between association, intervention, and counterfactual reasoning, with human judgement retained for research direction, interpretation, and final claims. Results: The workflow produced three empirical analyses and a documented correction process. The analyses estimated an altitude-to-sea-level pace correction of +0.10 min/km per 1,000 m at matched heart rate, showed why pooled altitude-surface regression was not identifiable within this venue system, documented method-dependence in heart-rate-based intensity classification, characterised within-venue route variation as a 64/36 path-fixed-to-trail-variable split with the Sululta label resolving into two functionally distinct sub-venues, and reframed the cohort's training through a 3x3x3 prescription lattice grounded in Ethiopian coaching practice. The adversarial phase identified several hallucinated citations, a terminology error between HC1 and cluster-robust standard errors, and several inconsistencies between prose, figures, and computed results. Verification scripts re-derived nearly all numerical claims from the cleaned lap-level data. Conclusions: The case study shows how researchers can organise AI-assisted empirical work so that candidate discovery, claim construction, independent stress-testing, and final accountability remain separated. The workflow did not remove the need for domain expertise or human judgement. Its value was in making the route from candidate finding to manuscript claim explicit, reproducible, and open to challenge. Trial registration: Not applicable.

Objectives To examine the acute effects of a single bout of high-intensity interval training (HIIT) on fetal blood flow distribution during the third trimester of pregnancy. Methods Thirty-four healthy pregnant participants (mean age 31.6 years, standard deviation (SD) 4.1; gestational week 33.8 (SD 0.4) completed eight 30-second high-intensity cycling work-bouts interspersed with 2-minute rest periods. Fetal heart rate (FHR), maternal blood pressure, and Doppler-derived blood flow indices in the middle cerebral artery, umbilical artery and vein, and ductus venosus were assessed before and after exercise. We estimated fetal liver blood flow and the ratio of umbilical vein flow to ductus venosus. Maternal heart rate (HR) and FHR were recorded throughout exercise. Paired t-tests compared pre- and post-exercise values. Results No significant changes were observed in fetal blood flow indices or distribution following exercise. Average maternal HR and FHR during the work-bouts were 158 bpm (SD 16) and 152 bpm (SD 12), respectively. Following HIIT, maternal systolic blood pressure increased by 5 mmHg (95% CI 1 to 8, p=.014), maternal HR by 22 bpm (95% CI 15 to 28, p<.001), and FHR by 13 bpm (95% CI 10 to 17, p<.001). We recorded 16 instances of FHR above normal range during HIIT. Conclusion A single HIIT session in late pregnancy increased maternal blood pressure and HR and transiently elevated FHR but did not affect fetal blood flow indices or distribution. Brief episodes of fetal tachycardia were observed but appeared to be clinically insignificant. Future research should investigate the effects of repeated HIIT exposure during pregnancy.

1. Background: With the rising prevalence of hypertension, especially among younger populations, there is a critical need to better assess health status and predict associated complications. This study developed a biological age model ("hypertension age") for hypertensive patients to predict the risk and timing of major complications. 2. Methods: Using South Korea's NHIS-NHID data, researchers analyzed 4,535,041 hypertensive patients who underwent health examinations between 2009 and 2010. Patients were followed for an average of 12.40 years (until 2022). Principal Component Analysis (PCA) was used to develop the biological age (cBA) model. The risk and onset timing of complications were analyzed using Cox proportional hazards and multiple regression models, adjusting for variables like medication use and baseline diseases. 3. Results: A 1-standard deviation (SD) increase in the age gap?where biological age exceeds chronological age (cBA - CA)?was significantly associated with an elevated risk for all major complications in both sexes (p < 0.001). Furthermore, a 1-SD increase in this gap significantly accelerated the time to complication onset for nearly all conditions (p < 0.001), with the exception of dementia in women. The impacts of medication use, hypertension duration, and baseline comorbidities varied by specific complication. 4. Conclusions: Lowering "hypertension age" relative to chronological age can significantly reduce the risk and delay the onset of major cardiovascular and related complications. Quantifying this biological age gap serves as a powerful motivational tool for personalized health management and complication prevention in hypertensive patients.

Background: An increasing demand for organic food has risen due to perceived health benefits. Current evidence for the health effects of organic food is limited. Objective: To evaluate the association between organic food purchase as a proxy for organic food consumption and hypertension in a nationally representative population of the US. Methods: This was a cross-sectional study that included 9173 participants aged >= 18 and had available data of both organic food purchase and hypertension from the National Health and Nutrition Examination Survey 2007-2010. Organic food purchase and frequency were obtained from survey questionnaires. Hypertension was defined as having either a systolic BP >= 130 mm Hg/ diastolic BP >= 80 mm Hg, currently taking antihypertensive medication, or self-reported diagnosis of hypertension. We used multivariable logistic regression with sample weights and adjustment of potential confounders to assess associations (adjusted odds ratio [aOR] and 95% confidence intervals [CI]) between organic food purchase and hypertension status. Results: Findings suggest an 11% decrease in odds of hypertension (aOR = 0.89, 95% CI: 0.75-1.06) among organic food purchasers compared to non-purchasers. Lower odds of hypertension were observed across all categories of organic food purchasing frequency, with 13% lower among rarely purchasing organic food (aOR = 0.87, 95% CI: 0.67-1.14), 9% lower (aOR = 0.91, 95% CI: 0.71-1.16) among sometimes purchasing organic food, and 17% lower (aOR = 0.83, 95% CI: 0.55-1.27) among always or mostly purchasing organic food, as compared to those who never purchased organic food. Conclusion: Our findings suggest that organic food purchase, a proxy for organic food consumption, may be associated with lower odds of hypertension. These findings may reflect either the true benefits of organic food consumption, including lower pesticide amounts and higher nutrient content, or the health-seeking behaviors among health-conscious, healthy, and highly educated individuals.

Secondary hyperparathyroidism persists in the majority of kidney transplant recipients and is associated with adverse graft and cardiovascular outcomes. The immunosuppressive drug class used post-transplant may modulate parathyroid hormone (PTH) levels through distinct mechanisms: calcineurin inhibitors (CNI) stabilize PTH mRNA, while mTOR inhibitors (mTORi) suppress parathyroid cell proliferation in experimental models. We report supporting evidence from two independent analyses. In a multinational real-world database analysis (TriNetX Global Collaborative Network), kidney transplant recipients with documented mTORi use and eGFR in the target range had lower PTH than those on CNI across eGFR strata examined (15-30, 30-45, 45-60, 60-75, >75 mL/min/1.73 m2), with risk ratios for PTH >130 pg/mL ranging from 0.47 to 0.67 in propensity-matched analyses (all p < 0.05). The known confounders - calcium (higher in CNI) and phosphate (higher in mTORi) - both act to oppose this pattern, strengthening the possibility of a drug effect. In a longitudinal single-center cohort (n = 118; 796 PTH measurements), a linear mixed-effects model with time-varying mTORi exposure confirmed a 42% lower PTH during on-mTORi periods after adjustment for eGFR, transplant vintage, diabetes, age, and sex (fold-change 0.58 [95% CI 0.50-0.68]; p < 0.0001). These findings suggest a direct PTH-lowering effect of mTORi. Immunosuppression choice may be considered in the management of post-transplant hyperparathyroidism in selected patients.

This study analyzes 794,811 digitized medical examina- tions from Indian life-insurance applicants, a working-age, urban-skewed demographic often undersampled by national surveys. The cohort exhibits a pronounced South-Asian car- diometabolic risk profile: among valid adult records, 41.9% met the criteria for dyslipidemia (driven heavily by low HDL and elevated triglycerides), and 61.4% met AHA 2017 crite- ria for stage 1 hypertension. However, canonicalizing this dataset across 33,244 diagnostic centers revealed significant heterogeneity in laboratory reference ranges. At the clinical prediabetes threshold of 110 mg/dL for fasting blood sugar, the record-pair disagreement rate across laboratories was 49.7%, with similar variance across other common tests. This structural inconsistency materially affects patient classi- fication and the tracking of disease prevalence, underscoring a critical need for the national standardization of laboratory reporting in India

Introduction: APOL1 high-risk variants markedly increase susceptibility to kidney disease among individuals of African ancestry; however, only a subset of carriers develops clinically significant CKD or ESKD. This discrepancy highlights a gap between genetic risk and clinical trajectory. Current prognostic tools rely primarily on eGFR and albuminuria, which incompletely reflect the underlying biological processes driving APOL1-associated kidney injury. We hypothesized that plasma biomarkers reflecting inflammatory and tubular injury pathways could identify biologically active disease states within this genetically high-risk population and improve prognostic stratification. Methods: Participants from the Mount Sinai BioMe Biobank carrying two APOL1 high-risk alleles (G1, G1; G1, G2; or G2 G2) were followed for a median of 6 years. Baseline plasma biomarkers of inflammation and tubular injury (TNFR1, TNFR2, KIM-1, MCP-1, YKL-40, IL-18, suPAR) were measured. The composite outcome was sustained 40% decline in eGFR or ESKD. Multivariable Cox models assessed associations between biomarkers and outcomes. A weighted biomarker risk score was derived from tertile-based hazard ratios and categorized into low-, moderate-, and high-risk groups. Results: Among 498 participants (median eGFR 83 ml/min/1.73 m2), 80 (16.1%) reached the composite outcome. Higher concentrations of TNFR1, TNFR2, suPAR, KIM-1, and IL-18 were independently associated with kidney events after multivariable adjustment. Event rates were 7% in the low-risk group, 16% in the moderate-risk group, and 36% in the high-risk group. Conclusions: Plasma biomarkers reflecting inflammatory and tubular injury pathways reveal marked heterogeneity in kidney outcomes among individuals with high-risk APOL1 genotypes. Integration of these signals into a biology-weighted score identifies distinct prognostic phenotypes beyond genotype and traditional clinical measures, supporting multidomain biomarker frameworks for risk stratification and potential trial enrichment in APOL1-associated kidney disease.

The Na+/K+-ATPase (NKA) regulates ion balance in the kidney and influences cellular processes like proliferation and apoptosis through its signal transduction. The endogenous ligand 20-Hydroxyeicosatetraenoic acid (20-HETE) contributes to inflammation and fibrosis in chronic kidney disease (CKD) and inhibits NKA activity in renal tubules. However, the molecular mechanism of this interaction remains unclear. In this study, we used in-silico approach to investigate the potential interaction between 20-HETE and NKA. Various ligands, including known NKA ligands such as cardiotonic steroids (CTS), 20-HETE, and negative controls, were docked using rigid and Induced Fit Docking to predict the affinity of the ligands toward NKA. Binding free energy calculations with the Prime Molecular mechanics with generalized Born and surface area (Prime MM/GBSA) tools were used to confirm the involvement of key amino acids in ligand-receptor interactions. The docking analyses revealed that 20-HETE exhibited a binding affinity comparable to negative control, with some differences between rigid and induced fit docking. Binding free energy data highlighted key amino acids in the 20-HETE and NKA interaction. Interaction fingerprint and mutations such as Ala330Gly and Val329Ala significantly reduced binding free energy, while Thr804Ala showed a notable decrease, underscoring the potential importance of these amino acids in ligand stabilization. These findings provide computational evidence supporting potential direct interaction between 20-HETE and NKA and identify candidate residues for future experimental validation.

Background: Comprehensive assessment of hypertension-mediated organ damage (HMOD) across multiple organ systems remains limited in sub-Saharan Africa. We aimed to determine the prevalence and predictors of multidomain HMOD in a geographically diverse Ghanaian adult population. Methods: This secondary analysis of the Ghana Heart Study included 1,106 adults from four regions. Multidomain HMOD was defined as a pre-specified 9-domain TOD composite score ?2, based on the ESH/ESC 2018 guidelines framework. Logistic regression and ROC analysis were used to identify predictors and compare discriminative performance. Results: Mean age was 46.9 (17.2) years and 58% were female. Multidomain HMOD prevalence was 21.2% (235/1,106) and increased steeply with age: 8.6% (<45 years), 20.6% (45?59 years), and 44.4% (?60 years). Hypertension prevalence was 73% in the HMOD group versus 28% in those without HMOD (p < 0.001). The strongest independent associations were peripheral artery disease (OR 41.2), valvular burden (OR 14.4), and ECG-LVH (OR 9.0). baPWV showed superior discriminative performance (AUC 0.827, 95% CI 0.794?0.860) compared with the ASCVD Pooled Cohort Equations (AUC 0.466; ?AUC +0.351, DeLong test p < 0.001). Conclusions: One in five Ghanaian adults has hypertension-mediated organ damage in ?2 organ systems. baPWV is the strongest predictor and substantially improves risk stratification beyond conventional scores. These findings support the use of baPWV to guide hypertension management and HMOD assessment in West Africa.