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Effects of Progressive Inspiratory Muscle Training on Lung Volume and Respiratory Strength in Patients With Pre-Dialysis Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease can present changes in thoracic cavity volume and respiratory muscle weakness, even in the pre-dialysis stage. However, there is little evidence on the effects of inspiratory muscle training in these patients. METHODS: This was a randomized clinical trial which comprised patients with Chronic Kidney Disease in stages 3, 4, and 5 undergoing conservative treatment, allocated experimental group (EG) with progressive loading (up to 50% of maximal inspiratory pressure [MIP]) and control group (CG) with a fixed load (5 cmH2O) and no load progression performed daily for 8&#xa0;weeks. The outcomes assessed were thoracic cavity volumes, as measured by optoelectronic plethysmography, and inspiratory and expiratory respiratory muscle strength. RESULTS: A total of 30 patients completed the study. All volumes significantly increased at the end of the protocol with a large effect size, but only the pulmonary thoracic cavity volume showed a significant interaction (F&#xa0;=&#xa0;3.698; p&#xa0;=&#xa0;0.042). There was an increase in inspiratory muscle strength in the EG (73.88-90.35&#xa0;cmH2O; p&#xa0;<&#xa0;0.001) and in the CG (70.85-86.92&#xa0;cmH2O; p&#xa0;=&#xa0;0.001), as well as in expiratory muscle strength in the EG (97.71-108.53&#xa0;cmH2O; p&#xa0;=&#xa0;0.001) and in the CG (80.69-94.77&#xa0;cmH2O; p&#xa0;=&#xa0;0.004). CONCLUSION: Daily IMT increased thoracoabdominal volumes, particularly pulmonary rib cage volume in the progressive-load group, as well as respiratory muscle strength in patients with pre-dialysis CKD. However, progressive-load IMT was not superior to minimal-load training.

Humans

Normoalbuminuric and albuminuric diabetic kidney disease exhibit divergent renal proteomic characteristics: implications for management.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. METHODS: Clinicopathological data from 295 biopsy-proven DKD patients were collected and classified into normoalbuminuric (UACR&#xa0;<&#xa0;30&#xa0;mg/g, n&#xa0;=&#xa0;25), microalbuminuric (UACR 30-300&#xa0;mg/g, n&#xa0;=&#xa0;26), and macroalbuminuric (UACR&#xa0;>&#xa0;300&#xa0;mg/g, n&#xa0;=&#xa0;244) groups. Laser microdissection combined with mass spectrometry (LMD/MS) was used to analyze glomerular and proximal tubule proteomics in 5 patients per DKD subgroup and 5 control subjects. Associations with clinical features were examined. RESULTS: Glomerular proteomic analysis revealed that oxidative stress and metabolic pathways (UQCRC1) were upregulated in NADKD group, whereas the complement and coagulation cascades (C3, C5, C6, C9, CFH, CFHR1) were significantly upregulated in the microalbuminuric and macroalbuminuric DKD groups. The proximal tubule proteomics analysis showed that oxidative phosphorylation-related proteins (SDHA, CYCS, UQCRQ) were upregulated in NADKD, and collagen I related proteins (COL1A1, COL1A2) were significantly upregulated. CONCLUSION: Oxidative stress and mitochondrial dysfunction are involved in the progression of NADKD, lesions predominantly located in the tubulointerstitium. The complement pathway participates in the pathogenesis and progression of albuminuric DKD (ADKD). These divergent molecular profiles suggest that NADKD and ADKD may reflect different pathophysiological mechanisms and have important implications for therapeutic strategies in diabetes management.

Humans

A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans

Haemodialysis Nurses' Self-Reported Cultural Competence and Responsiveness: A Cross-Sectional Survey.

BACKGROUND: People receiving in-centre haemodialysis have distinct cultural care needs and preferences, and nurses are expected to respond to these. However, haemodialysis nurses' cultural competence and responsiveness are unknown. OBJECTIVES: To examine nurses' cultural competence and responsiveness when caring for people with diverse cultural characteristics. DESIGN: An online cross-sectional survey. PARTICIPANTS: Haemodialysis nurses from Australia and New Zealand (n&#x2009;=&#x2009;123), recruited through the Renal Society of Australasia and professional networks. MEASUREMENTS: The 25-item Cultural Competence Assessment instrument measured cultural awareness and sensitivity, and culturally responsive behaviours. Demographic characteristics were also collected. RESULTS: Of 123 complete responses, overall cultural competence was high (M&#x2009;=&#x2009;5.09, SD&#x2009;=&#x2009;0.76), particularly awareness and sensitivity (M&#x2009;=&#x2009;5.76, SD&#x2009;=&#x2009;0.53), with significantly higher scores among those who had completed cultural awareness training (p&#x2009;=&#x2009;0.009). In contrast, culturally responsive behaviours were moderate (M&#x2009;=&#x2009;4.53, SD&#x2009;=&#x2009;1.23), highlighting the gap between cultural competence and responsiveness. The lowest scoring areas were documentation of patients' cultural needs (M&#x2009;=&#x2009;3.88, SD&#x2009;=&#x2009;2.02) and access to cultural learning resources (M&#x2009;=&#x2009;3.02, SD&#x2009;=&#x2009;1.75), indicating limited supports. Qualitative findings reflected practices of culture care preservation and accommodation, with themes of cultural awareness and language differences highlighting barriers related to language and resources. CONCLUSIONS: High cultural competence does not necessarily translate into culturally responsive behaviour. Organisational supports, including guidance for documenting cultural needs, cultural assessment tools and accessible learning resources, may help strengthen culturally responsive haemodialysis care.

Humans

Vesicoureteral reflux and anorectal malformations.

BACKGROUND: Renal and urinary tract anomalies are frequently associated with anorectal malformations (ARMs) and may adversely affect long-term renal outcomes, if not detected early. However, reliable clinical predictors for significant urologic abnormalities across different ARM phenotypes remain poorly defined. OBJECTIVE: To determine the prevalence and grade distribution of vesicoureteric reflux (VUR) in neonates with ARMs, and to explore its association with renal and urinary tract anomalies, the complexity of the ARM phenotype, and other factors are associated with high-grade VUR. METHODS: In this retrospective cross-sectional study, medical records of 64 neonates diagnosed with ARMs and managed at a tertiary children's hospital between 2018 and 2025 were reviewed. All patients underwent renal and urinary tract ultrasonography. Voiding cystourethrography (VCUG) was performed for all neonates according to our institutional protocol, regardless of ultrasound findings or ARM phenotype. Demographic characteristics, ARM phenotype (less-complex vs. complex), urologic findings, urinary tract infection (UTI) history, and associated anomalies were analyzed. Multivariable logistic regression models were used to identify independent predictors of complex ARM phenotype and high-grade VUR. RESULTS: The cohort consisted of 64 neonates (75% male) with a mean gestational age of 37.36 &#xb1; 1.83 weeks and a mean birth weight of 2940 &#xb1; 601 g. Renal and urinary tract anomalies were common, with hydronephrosis observed in 48.4%, VUR of any grade in 39.1% and hydroureter in 35.9%,of patients. High-grade VUR was identified in 21.9% of patients, and a documented history of UTI was present in 18.8% of the entire cohort. In multivariable analyses, birth weight, presence of VUR, and UTI history were not independently associated with complex ARM phenotype. Additionally, no demographic or clinical variables reliably predicted high-grade VUR. The predictive performance of the regression model for high-grade VUR was limited (AUC = 0.60). CONCLUSION: Renal and urinary tract anomalies are highly prevalent among neonates with ARMs, with VUR representing a prominent finding. The lack of robust clinical predictors for complex ARM phenotype or high-grade VUR underscores the limitations of selective screening strategies and supports the role of comprehensive urologic evaluation in neonates with ARM, regardless of anatomic subtype.

Humans

Genetic Diversity of BK Polyomavirus Among Renal Transplant Recipients in Yunnan, China.

BK polyomavirus (BKV) infection, a common complication following kidney transplantation, can lead to BKV-associated nephropathy (BKVN). Molecular genetic studies have classified BKV into four genotypes (I-IV); however, comprehensive molecular characterization of BKV strains circulating in China remains limited. This study aimed to elucidate the predominant subtypes and clinical infection characteristics of BKV strains among kidney transplant recipients in Yunnan, a province in southwestern China. PCR-amplified BKV DNA sequences from kidney transplant recipients were aligned with reference strains and subjected to phylogenetic analysis. The viral VP1 gene was successfully amplified from 180 participants, spanning 16 ethnic groups. Genotype I was the predominant viral strain (56.66%, 102/180), followed by genotype IV (43.33%, 78/180), while genotypes II and III were not detected. Among genotypic subtypes, IVc-1 was most prevalent (40.0%, 72/180), followed by Ic (38.3%, 69/180) and Ib-1 (18.3%, 33/180). IVa-1 and IVa-2 were rare, identified in only 0.6% (n&#x2009;=&#x2009;1) and 2.2% (n&#x2009;=&#x2009;4) of cases, respectively. No significant differences in sex, age, BKVN incidence, BK viremia, or viruria were observed between patients with BKV-I and BKV-IV infections. Among the five confirmed BKVN cases, two were genotyped as subtype Ic, one as Ib-1, and two as IVc-1. Clinical phenotypes were also comparable between patients with BKV-I and BKV-IV infections. This study represents the largest single-center sequencing analysis of BKV in kidney transplant recipients in China, offering a valuable genomic resource for future research.

Humans

Acute Haemodynamic and Perceptual Responses to Graded Intradialytic Exercise in Patients on Maintenance Haemodialysis: A Randomised Crossover Trial.

BACKGROUND: Acute responses to graded intradialytic exercise in people receiving haemodialysis remain incompletely characterised. OBJECTIVES: To examine acute haemodynamic and perceptual responses to graded intradialytic resistance exercise compared with a non-exercise control condition. DESIGN: Randomised crossover trial. PARTICIPANTS: Forty-eight clinically stable adults receiving maintenance haemodialysis. MEASUREMENTS: Participants completed seated control and graded lower-limb resistance exercise targeting Borg category-ratio 10 ratings of 3, 5 and 7. Systolic and diastolic blood pressure, mean arterial pressure, heart rate, peripheral oxygen saturation, rating of perceived exertion and acute fatigue were measured before, immediately after and 30&#x2009;min after each condition. RESULTS: Responses increased progressively with perceived intensity. Compared with control, higher perceived intensity increased systolic blood pressure by 14.9&#x2009;mmHg (95% confidence interval&#x2009;=&#x2009;12.7-17.0), diastolic blood pressure by 8.4&#x2009;mmHg (6.8-10.0), mean arterial pressure by 10.6&#x2009;mmHg (9.2-12.0) and heart rate by 15.5 beats per minute (12.9-18.1). Rating of perceived exertion increased by 6.7 points (95% confidence interval&#x2009;=&#x2009;6.3-7.1). Mean peripheral oxygen saturation remained between 95.1% and 97.5%, with no value below 90%. Recorded symptoms occurred in 13 out of 48 higher perceived-intensity sessions; no serious adverse events occurred. CONCLUSIONS: Graded, rating-guided intradialytic resistance exercise produced clear acute dose-response haemodynamic and perceptual changes. These findings support supervised individualisation of acute exercise dose but do not establish long-term safety or superiority of higher perceived-intensity training. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR202606476360900.

Humans

Nephropathies Associated with Sickle Cell Trait and How to Study Them.

Sickle cell trait (SCT), which carries a single point mutation in the hemoglobin-&#x3b2; (HBB) gene, has long been considered a benign condition. However, epidemiological evidence challenges this assumption, revealing that individuals with SCT face an elevated risk of renal dysfunction. However, this field of study remains ill-defined as it has focused on sickle cell disease (SCD), where renal complications are severe. As SCT is more prevalent than SCD, consequences of nephropathies in this group translate into a substantial and largely unaddressed public health burden. Clinical data, primarily observational, implicate age and sex in the development of SCT-associated nephropathies. These manifestations span glomerular hyperfiltration, tubular damage, hematuria, renal papillary necrosis, renal medullary carcinoma, and progression to chronic kidney disease, all complications that cluster disproportionately in older male individuals. Despite this, the mechanistic basis of SCT nephropathy, the thresholds at which renal injury becomes clinically significant, and the optimal strategies for early identification and prevention remain inadequately defined. In vitro studies have primarily focused on SCD blood cell biology, with SCT receiving comparatively little attention. Humanized murine models (i.e., Berkeley and Townes) have recapitulated some SCT-associated renal phenotypes but need to be more fully characterized. This review aims to provide an overview of the biology of sickle cell trait nephropathies, the gaps in our knowledge, and the model systems we can use to fill those gaps.

Journal Article

Analysis of end-stage renal disease mediated by cuproptosis-related genes.

OBJECTIVE: The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. MATERIALS AND METHODS: The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3&#xa0;:&#xa0;1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. RESULTS: The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC >&#xa0;0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. CONCLUSION: This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.

Humans

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12&#x2009;weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32&#x2009;mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n&#x2009;=&#x2009;119) or the sevelamer carbonate group (n&#x2009;=&#x2009;120). The mean change in serum phosphorus levels was -0.70&#x2009;&#xb1;&#x2009;0.50&#x2009;mmol/L in the ferric citrate group and -0.61&#x2009;&#xb1;&#x2009;0.59&#x2009;mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09&#x2009;mmol/L; 95% CI, -0.24 to 0.05&#x2009;mmol/L; non-inferiority margin, 0.32&#x2009;mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p&#x2009;=&#x2009;0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P&#x2009;=&#x2009;0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent

Effects of intradialytic nutrition on dialysis adequacy and fatigue in hemodialysis patients: a randomized crossover study.

OBJECTIVE: To assess intradialytic nutrition's effects on dialysis adequacy and fatigue in maintenance hemodialysis patients. METHODS: A randomized, two-period, two-sequence, self-controlled crossover trial was conducted in two outpatient hemodialysis centers in T&#xfc;rkiye. Thirty-six patients were randomized; 32 completed both periods. The participants received standardized intradialytic nutrition in one period and no food intake during the control period. Dialysis adequacy was evaluated using the urea reduction ratio and single-pool Kt/V. Intradialytic blood pressure was recorded during dialysis sessions, and fatigue severity was measured using the Piper Fatigue Scale at the end of each period. RESULTS: No significant differences were observed in dialysis adequacy or fatigue scores between the two periods. Intradialytic nutrition was associated with greater reductions in systolic and diastolic blood pressure, particularly during the second hour of dialysis. No clinically relevant adverse events occurred. CONCLUSION: Intradialytic nutrition did not compromise dialysis adequacy or worsen fatigue severity but was associated with increased intradialytic blood pressure reductions. Individualized clinical decisions and careful hemodynamic monitoring are warranted when implementing intradialytic nutritional interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07687498.

Humans

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 &#xb1; 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans

Effect of levothyroxine therapy on albuminuria and glomerular function in patients with type 2 diabetes and subclinical Hypothyroidism: a randomized controlled pilot trial.

AIMS: To evaluate the effect of levothyroxine therapy on renal outcomes in patients with type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) with background SGLT2 inhibitor therapy. METHODS: In this hypothesis generating open-label, randomized controlled pilot trial, adults with T2DM and SCH were assigned (1:1) to levothyroxine or no levothyroxine therapy and followed for 6&#xa0;months. Primary outcomes were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: Sixty participants were randomized (30 per group); 24 and 27 completed follow-up in the treatment and control groups respectively. UACR decreased with levothyroxine (-13.09&#xa0;mg/g) and increased in controls (31.84&#xa0;mg/g). The difference was significant in per-protocol (PP)(-44.93&#xa0;mg/g; 95% CI -77.6 to -12.26; p&#xa0;=&#xa0;0.008) but insignificant in intention to treat (ITT)(-35.61&#xa0;mg/g; 95% CI -77.31 to 6.08; p&#xa0;=&#xa0;0.092). eGFR changes were statistically insignificant in both ITT(4.65&#xa0;mL/min/1.73&#xa0;m2; 95% CI -8.3 to 17.6; p&#xa0;=&#xa0;0.472) and PP(7.35&#xa0;mL/min/1.73&#xa0;m2; 95% CI -1.68 to 16.37; p&#xa0;=&#xa0;0.108). Thyroid-stimulating hormone decreased significantly in treatment arm in comparison to control arm (p&#xa0;<&#xa0;0.001) in ITT and PP. No adverse event was reported. CONCLUSIONS: Levothyroxine treatment showed trend toward improving albuminuria and eGFR without reaching statistical significance, suggesting possible renoprotective effect warranting further studies. CLINICAL TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of India (CTRI/2025/06/089606).

Humans

Emerging hantavirus risks in mass gatherings: epidemiology, diagnostic challenges, and outbreak preparedness.

Hantaviruses are emerging rodent borne zoonotic pathogens of increasing global public health concern because of their high mortality, expanding ecological distribution, and potential for international dissemination. Although traditionally associated with sporadic rural outbreaks, recent ecological disruption, climate variability, urbanization, and increased global mobility have heightened concerns regarding hantavirus risks in mass gathering settings. This review critically examines the epidemiology, transmission uncertainty, diagnostic and surveillance challenges, and preparedness strategies related to hantavirus infections in the context of mass gatherings, including religious events, refugee settlements, cruise tourism, sporting events, and temporary accommodations. Particular emphasis is placed on the 2026 multinational cruise ship associated outbreak linked to the MV Hondius, which highlighted vulnerabilities related to delayed diagnosis, international passenger dispersal, and uncertainties surrounding possible human to human transmission of Andes virus. Current evidence indicates that hantavirus transmission occurs primarily through inhalation of aerosolized rodent excreta; however, controversies regarding limited interpersonal transmission, environmental persistence, and asymptomatic infections continue to complicate risk assessment and outbreak preparedness. Diagnostic limitations, underreporting, insufficient environmental surveillance, and lack of mass gathering specific preparedness frameworks remain major public health challenges, especially in resource limited settings. Strengthening proactive preparedness through integrated One Health approaches, ecological surveillance, genomic monitoring, AI driven epidemic intelligence, and coordinated international response systems is essential for mitigating future risks. The review emphasizes the urgent need for multidisciplinary research and evidence based policy development to improve global preparedness against emerging hantavirus associated threats in increasingly interconnected mass gathering environments.

Humans

Assay-dependent variability in peptide biomarker quantification: experimental evidence from renalase in chronic kidney disease.

BACKGROUND: Renalase is a promising biomarker for kidney disease, but published levels vary widely between studies. We hypothesised that variability in commercial enzyme-linked immunosorbent assays (ELISAs) kits and matrix effects (serum vs plasma) drive these inconsistencies. METHODS: Paired serum and plasma samples from 56 participants (28 chronic kidney disease (CKD) stages 2-5, 28 healthy controls) were tested using three commercial renalase ELISAs (BTLAB, Cloud-Clone, EIAab). We assessed intra-assay precision, inter-assay agreement (Spearman's rank correlation and Bland-Altman analysis on log10-transformed values), matrix effects, and associations with estimated glomerular filtration rate (eGFR). Diagnostic performance was evaluated by Receiver operating characteristic (ROC) analysis. RESULTS: Inter-assay renalase concentrations differed markedly (up to orders of magnitude), with weak inter-assay correlations (r&#x2009;&#x2264;&#x2009;0.25). Bland-Altman analyses revealed large, systematic biases between kits. Only the BTLAB assay showed consistent serum/plasma agreement, a significant correlation with eGFR (&#x3c1;&#x2009;&#x2248;&#x2009;0.32-0.42, p&#x2009;<&#x2009;0.05), and moderate discriminatory performance for CKD in serum (AUC = 0.70) and plasma (AUC = 0.68). Cloud-Clone and EIAab produced divergent results and strong matrix-dependent biases. CONCLUSIONS: Observed variability among commercial ELISA platforms may compromise comparability between studies. Harmonisation, standardised reference materials, and cross-validation are necessary before renalase assays can be used reliably in clinical practice.

Humans

Efficacy and safety of revascularization in patients with chronic limb-threatening ischemia by kidney function.

BACKGROUND: The optimal revascularization strategy for patients with chronic limb-threatening ischemia (CLTI) with chronic kidney disease (CKD) remains unknown. We evaluated whether the efficacy and safety of surgical vs endovascular revascularization differ by kidney function. METHODS: In this post hoc secondary analysis of BEST-CLI trial (NCT02060630), 1,704 patients with CLTI were stratified by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m&#xb2;): non-CKD (eGFR &#x2265; 90), mild-moderate CKD (eGFR 45-89), advanced CKD (eGFR < 45 or dialysis). The primary outcome was a composite of major adverse limb events (MALE) or death. We estimated the difference in restricted mean time lost (RMTL, in days) adjusted for inverse probability treatment weights. RESULTS: Surgical revascularization was significantly associated with fewer days with MALE or death in non-CKD (RMTL difference: -127.8 days; 95% CI -176.1, -79.6) and mild-moderate CKD (-63.2 days; 95% CI -104.7, -21.8) but not in advanced CKD (-16.4 days; 95% CI -78.8, 46.0; P interaction = .02). This attenuation reflected a diminishing mortality benefit with more severe CKD (P interaction = .01), whereas the association with fewer days with MALE remained consistent across CKD strata (P interaction = .34). Major adverse cardiovascular events and serious adverse events were more common with more severe CKD but did not differ significantly by treatment. CONCLUSIONS: Surgical vs endovascular revascularization was consistently associated with fewer days with MALE across CKD strata. However, its association with mortality varied by kidney function, attenuating the overall benefit for the composite endpoint of MALE or death. These results support individualized revascularization strategies, but require prospective confirmation. TRIAL REGISTRATION: The BEST CLI trial is registered at ClinicalTrials.gov (NCT02060630).

Humans

The effect of nutrition education interventions on dialysis patients' outcomes: a systematic review and meta-analysis.

BACKGROUND: Non-adherence to dietary and fluid restrictions among dialysis patients is associated with adverse clinical outcomes. Quantifying the effectiveness of nutrition education interventions can inform practice and policy. METHODS: We searched MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, Web of Science, and Scopus up to 15 July 2025, supplemented by trial registries and Google Scholar, with an updated search through 8 April 2026. Eligible studies included randomized and non-randomized trials evaluating nutritional education interventions in adult dialysis populations. Risk of bias was assessed using RoB-2 and ROBINS-I, certainty graded using GRADE, and random-effects meta-analyses conducted alongside subgroup, sensitivity, and meta-regression analyses. Publication bias was assessed with Egger and Begg tests and trim-and-fill where applicable. RESULTS: Forty-four studies comprising 4,106 participants were included. Nutrition education significantly improved knowledge (SMD = 1.09; 95% CI: 0.67-1.51) and health-related quality of life (SMD = 1.43; 95% CI: 0.86-2.00; I&#xb2; = 0%), and reduced serum potassium (SMD = -0.52; 95% CI: -0.91 to -0.14; I&#xb2; = 92%) and serum phosphate (SMD = -0.35; 95% CI: -0.56 to -0.15; I&#xb2; = 81%). Results for albumin, creatinine, sodium, calcium, and BUN were inconsistent and non-significant. Most outcomes were rated low or very low certainty by GRADE, reflecting inconsistency, indirectness, and imprecision. Potential publication bias was identified for certain outcomes. CONCLUSIONS: Nutrition education consistently improves knowledge and quality of life and may modestly reduce serum phosphate and potassium in dialysis patients. High-quality registered trials with standardized outcomes and longer follow-up are needed to establish effectiveness and sustainability. PROSPERO REGISTRATION: CRD420251119567.

Humans