BMC Nephrology

Physical inactivity is common in chronic kidney disease (CKD) and is associated with poor neuromuscular and functional outcomes. Whether habitual physical activity (PA) influences adaptations to structured exercise in CKD remains unclear. This study examined if adaptations to combined flywheel resistance and aerobic exercise (FRE+AE) differed based on self-reported PA in Veterans with CKD stages 3 and 4. Twenty older male Veterans with CKD stages 3-4 (mean eGFR 37.9 +/- 10.2 mL/min/1.73 m2) were randomized to six weeks of FRE+AE (n=11) or health education (EDU; n=9). Participants were classified as meeting (Meets PA) or below (Low PA) weekly moderate intensity PA recommendations using the 7-day Physical Activity Recall. Outcomes included vastus lateralis muscle thickness (VL MT), knee extensor power output (60/s and 180/s), gait speed (GS), and five-repetition sit-to-stand (STS). FRE+AE increased VL MT (p=0.030), power output at 180/s (p=0.021), GS (p=0.001), and reduced STS time (p=0.012), with significant between-group differences versus EDU for VL MT (p=0.009) and GS (p=0.028). Low PA experienced greater increases in power output at 60/s (Hedges g; Low PA=0.44, Meets PA=0.25) and 180/s (Hedges g; Low PA=1.38, Meets PA=0.38) compared to Meets PA after FRE+AE. Conversely, Meets PA had greater improvements in GS (Hedges g; Low PA=0.93, Meets PA=1.29) and STS (Hedges g; Low PA=-0.72, Meets PA=-2.20) compared to Low PA. Six weeks of FRE+AE produced clinically meaningful neuromuscular and functional improvements in Veterans with CKD stages 3 and 4 irrespective of PA level, supporting FRE+AE as a feasible intervention in this population.

BackgroundLife-sustaining hemodialysis (HD) is onerous for patients, especially those with multiple co-morbidities and advanced age. A standard HD prescription is 720 minutes per week. Alternative HD regiments have been proposed in attempt to maintain quality of life (QOL). Studies are needed to investigate the efficacy and safety of less frequent HD prescriptions in this population. This is an institution-wide observational study in New Brunswick, Canada to compare HD prescriptions and the impact on QOL and mortality. ObjectiveThe purpose of this study is to assess the current HD prescribing practices at a provincial healthcare institution in relation to patient QOL. DesignProspective Observational Study. SettingSingle centre hospital and satellite hemodialysis units. PatientsVoluntarily consented patients undergoing in-centre hemodialysis treatment. MeasurementsObservational clinical data was collected for each study participant from their hospital and dialysis electronic medical records. The KDQOL-36TM questionnaire was used to assess patient-reported quality of life at the time of consent. MethodsAdults undergoing in-centre or satellite site HD for at least 3 months were eligible to participate. Consenting patient participants were grouped by HD prescription whether they were prescribed 720 minutes or more per week or less than 720 minutes per week. All participants completed the KDQOL-36 TM questionnaire to estimate QOL and groups were compared using the Mann-Whitney U statistical test. Emergency department visits, hospitalizations, and mortality were analyzed using a negative binomial regression or a logistic regression. ResultsWe enrolled 140 patient participants; 41 were undergoing less than 720 minutes per week of HD and 99 were undergoing 720 minutes or more of HD per week. Patients who were undergoing less than 720 minutes per week of HD were older [Median (IQR): 76 (72- 81) yrs. vs. 64 (55 - 75) yrs.; p < 0.001], had higher median (IQR) QOL scores on the Symptoms/ Problems List scale on the KDQOL-36 TM questionnaire [79.2 (70.8 - 88.5 vs. 70.8 (62.5 - 81.3); p = 0.0022], and were less likely to present to the emergency department (incident rate ratio 0.52, 95% confidence interval [CI] 0.33-0.81). Mortality was similar between groups, even when adjusted for age and comorbidity score (odds ratio 1.62, 95% CI 0.59-4.49). LimitationsPatient participant enrollment was limited by the single centre nature of this study. As this was an observational study, we did not account for how long the patients had been prescribed less than 720 minutes of hemodialysis. We did not include a frailty assessment of the study participants. A higher number of study participants may have identified significant trends in mortality. ConclusionsThe results of this study show that patients undergoing less than 720 minutes of weekly HD had a higher QOL score for the KDQOL-36 TM Symptoms/ Problems List scale, were less frequently in the emergency department and were not more likely to die than patients undergoing 720 minutes or more of weekly HD. Further studies are required to assess the feasibility and safety of a conservative model of HD prescribing to improve QOL of patients with palliative care treatment goals.

IntroductionCatastrophic bleeding can be fatal in patients on hemodialysis using Arteriovenous (AV) fistulas or grafts. Campaigns, such as the UK "Put a Lid On It" and the Australia "Stop the Bleed" have recommended use of bleeding cessation devices, but evidence for their use remains limited. Recent creation of the bleeding cessation device "Kidney-CAP" mandated further study. The objective of this study was to determine how the Kidney-CAP modified decisions related to vascular access, dialysis modality, and kidney transplantation. MethodsCross-sectional surveys were administered at a Canadian academic nephrology program, to health care providers (HCP) managing patients with chronic kidney disease (CKD), to patients on hemodialysis (CKD-HD), and to patients with CKD but not on dialysis (CKD-Clinic). Two tailed, one sample sign test was used to determine if the median response to Likert scale questions differed from "no effect" response, to a p-value of < 0.05. ResultsSurvey respondents included 18 HCP, 23 CKD-HD and 30 CKD-Clinic patients. Having a Kidney-CAP increased CKD-Clinic patients desire to undergo AVF or AVG creation (p=0.020). Having a Kidney-CAP had no impact on CKD-HD patients deside to undergo AVF creation, or to pursue hemodialysis at home, but increased desire to undergo kidney transplantation (p=0.031). Availability of the Kidney-CAP had no impact on HCP recommendations related to AVF creation or kidney transplantation, but increased HCP recommendations for home hemodialysis in ESKD patients (p=0.039 for each). ConclusionThis is the first study to assess the perceived benefit of a bleeding cessation device, with a focus on clinical decision making related to vascular access, kidney transplantation, and dialysis modality. The Kidney-CAP is associated with increased patient uptake of kidney transplantation and creation of AVF. Further study is required to delineate patient decisions within demographic subgroups such as previous kidney transplant, or anticoagulation status.

Background: The association between physical activity (PA) and chronic kidney disease (CKD) was initially explored; however, it remained unknown whether PA affected the incidence of CKD through the inflammation pathway. Moreover, objective PA measured by accelerometers was rarely considered for this association. Methods: This study was performed in a large-scale prospective cohort with two different sub-cohorts: the International Physical Activity Questionnaire (IPAQ)-measured cohort (N=314,694); and the device-measured cohort (N=79,454). Cox models were conducted to assess the association of PA with incident CKD. The mediating role of inflammation in such association was investigated by four inflammation metrics [C-reactive protein (CRP), white blood cell (WBC), a low-grade inflammation (INFLA) score, and monocyte to high-density lipoprotein cholesterol ratio (MHR)]. Results: In the questionnaire-measured cohort, compared to low PA, moderate and high PA reduced the risk of CKD by approximately 28.0% (95% CI 24.4[~]31.5%) or 37.6% (34.4[~]40.7%), respectively. Inflammation significantly mediated this association, with the mediation proportion was 4.1% (3.0[~]5.1%), 1.4% (1.1[~]1.7%), 9.8% (7.7[~]11.9%), and 1.4% (1.1[~]1.7%) for CRP, WBC, INFLA score, and MHR, respectively. Evidence from the device-measured cohort further strengthened the robustness of our findings, but the effects were somewhat attenuated, with the mediation proportion being 2.2% (1.2[~]3.2%), 0.8% (0.2[~]1.3%), 4.3% (2.5[~]6.0%), and 1.3% (0.6[~]2.1%) for CRP, WBC, INFLA score, and MHR, respectively. Conclusions: Our study reveals suggestive evidence for the association of active PA with reduced CKD risk and further demonstrates the mediating role of inflammation in such association, providing a novel perspective for the early prevention of CKD.

Background. Hyperkalemia is common in chronic kidney disease (CKD) and chronic heart failure (CHF), often leading to treatment dilemmas regarding renin-angiotensin-aldosterone system (RAAS) inhibitors. Although potassium binders and dietary restrictions are central to chronic management, their quality-of-life (QOL) impact remains insufficiently described. This study aimed to characterize real-world treatment patterns and evaluate treatment impact on QOL. Methods. We analyzed baseline data from a prospective cohort in Japanese nephrology and cardiology outpatient clinics. Participants were adults with CKD ([&ge;] stage G3) or CHF (New York Heart Association class II-IV) who initiated potassium binders within 6 months. Clinical data, serum potassium values, and patient-reported outcomes (generic QOL, disease/treatment-specific QOL, and adherence measures) were obtained at enrollment. Results. Among 347 patients, the median age was 75 years, and 74% were male; 93% had CKD. At enrollment, 300 patients were receiving potassium binders, and 59% were prescribed a RAAS inhibitor. Dietary therapy was implemented in 29%. Physical scores of generic QOL were lower than population norms, whereas mental scores were comparable. Treatment-specific QOL scores indicated that potassium binders had a smaller impact on QOL than dietary therapy. Adherence to potassium binders was high. Conclusions. Concurrent use of RAAS inhibitors and potassium binders was common, suggesting that binders may support RAAS inhibitor continuation. Potassium binders showed less perceived impact than dietary restrictions, indicating that pharmacologic potassium control may be acceptable to patients managing multiple lifestyle limitations. These findings highlight the role of potassium binders in maintaining both RAAS inhibitor therapy and QOL.

BackgroundCatheter-related bloodstream infection (CRBSI) is a major cause of morbidity and mortality among patients undergoing hemodialysis (HD), particularly in low- and middle-income settings where non-tunneled hemodialysis catheters (NTHC) are widely used. Local epidemiological data are essential to guide preventive and therapeutic strategies. ObjectivesTo determine the prevalence, microbiological profile, antimicrobial resistance patterns, and clinical outcomes of CRBSI in patients undergoing HD via internal jugular NTHC at a tertiary care center in South India. MethodsThis retrospective observational study included adults initiated on HD using internal jugular NTHC between January 2017 and December 2023. Patients with pre-existing infections or catheters inserted elsewhere were excluded. CRBSI was defined using KDOQI criteria. Demographic, clinical, laboratory, microbiological, and outcome data were analyzed. Logistic regression identified risk factors, and receiver operating characteristic (ROC) analysis evaluated predictors of adverse outcomes. ResultsAmong 396 patients (mean age 56.3 {+/-} 14 years; 70.4% male), 65 (16.4%) developed CRBSI, with an incidence of 4.7 per 1000 catheter days. Emergency HD initiation (OR 14.86, p < 0.001) and access failure (OR 2.71, p = 0.004) significantly increased CRBSI risk, while planned initiation for uremic symptoms was protective. Patients with CRBSI had lower serum albumin and higher leukocyte counts. Gram-negative organisms predominated (53.8%), with Klebsiella pneumoniae being the most common isolate. High resistance was observed to {beta}-lactam/{beta}-lactamase inhibitor combinations and carbapenems. Gram-negative CRBSI was associated with significantly higher odds of hospitalization, ICU admission, inotropic support, and mortality. ROC analysis showed good predictive ability for adverse outcomes (AUC 0.73-0.77). ConclusionsCRBSI remains a significant complication of NTHC-based HD. Predominant Gram-negative infections with high antimicrobial resistance are associated with worse clinical outcomes, underscoring the need for early permanent access creation, strict catheter care, and robust antibiotic stewardship.

Background: Chronic kidney disease (CKD) affects approximately 850 million individuals worldwide and remains a leading cause of morbidity, premature mortality, and escalating healthcare costs. Despite the availability of clinical biomarkers, CKD progression to end stage renal disease (ESRD) is frequently identified late, limiting opportunities for preventive intervention. Conventional predictive models have relied predominantly on static cross sectional laboratory values, failing to capture the temporal dynamics of disease trajectory that longitudinal claims data can provide. Objective: This study proposes a novel hybrid machine learning framework: XGBoost LSTM Attention (XLA), that integrates gradient boosted feature selection with long short-term memory (LSTM) networks and a temporal attention mechanism to improve early prediction of CKD progression from Stage 3 to Stages 4/5 or ESRD using longitudinal claims based features. Methods: We conducted two complementary analyses. Primary analysis: a cross sectional validation using real NHANES 2015 to 2018 data (n=701 CKD Stage 3 adults) predicting significant proteinuria (UACR greater than or equal to 30 mg/g) from clinical features excluding UACR. Supplementary analysis: an NHANES-calibrated longitudinal cohort (n=8,412) with simulated quarterly measurements demonstrated XLA performance under real world longitudinal data conditions. All models were evaluated using 5-fold stratified cross-validation. Results: In the primary NHANES cross sectional analysis, the XLA framework achieved AUC ROC of 0.684 (95% CI: 0.641 to 0.727), with all models performing comparably (AUC 0.684 to 0.710), confirming that cross sectional clinical features alone provide limited signal for proteinuria prediction and underscoring the necessity of UACR measurement. In the longitudinal supplementary analysis, XLA achieved AUC ROC of 0.994 versus 0.939 for the best cross-sectional baseline (+5.5%), demonstrating that temporal trajectory features particularly eGFR slope and RAAS adherence trends: confer substantial incremental predictive value when longitudinal data are available. Conclusion: The XLA framework demonstrates meaningful advantages over traditional approaches when applied to longitudinal claims data. Cross sectional findings highlight the irreplaceable role of direct UACR measurement in CKD risk stratification. Together, these results provide actionable evidence for both the limitations of static prediction and the promise of trajectory based approaches in value based care programs managing large CKD populations. Keywords: chronic kidney disease, CKD progression, machine learning, XGBoost, LSTM, temporal attention, claims data, NHANES, proteinuria, healthcare informatics, value based care.

BackgroundKidney cell lines are widely used to model kidney physiology and disease; however, their gene expression profiles may differ from primary cells due to immortalization, culture conditions, or experimental treatments. Determining whether a cell line resembles its native cell type is critical for interpreting in vitro findings. We developed a transcriptome-based approach that matches bulk RNA-seq data from kidney cell lines, primary cells, or tissues to reference cell types derived from single-cell RNA-seq (scRNA-seq) datasets. MethodsReference transcriptomic profiles were generated from two human and two murine kidney scRNA-seq datasets by pseudobulk aggregation. Bulk RNA-seq data from microdissected kidney tissue, non-kidney negative controls, and kidney cell lines were matched to these references using three statistical similarity measures (Spearman correlation, Euclidean distance, Poisson distance) and three machine learning classifiers (Random Forest, XGBoost, TabPFN). Each was assessed with global gene expression, curated kidney marker gene lists, and the most variable genes. Matching accuracy was evaluated through a three-step validation strategy: within-dataset matching, cross-reference comparison, and validation against primary kidney tissue and negative controls. ResultsGene expression rank-based Spearman correlation and TabPFN, a foundation model for tabular data, emerged as the most accurate and specific approaches, particularly with curated kidney marker gene lists. Both methods correctly identified microdissected kidney tubule segments and were robust against non-kidney negative controls. Applied to commonly used kidney cell lines, OK cells retained proximal tubule identity, particularly under shear stress, while other proximal tubule lines (HK-2, HKC-8, HKC-11) showed inconsistent matching. Collecting duct-derived mIMCD-3 maintained stable similarity across passages, culture conditions, and genetic modifications. ConclusionWe provide two complementary implementations: CellMatchR, an accessible web-based tool using Spearman correlation for routine use, and comprehensive scripts for TabPFN-based matching (link will be added after peer reviewed publication). Together, these resources enable researchers to make informed decisions about kidney cell culture model selection, interpretation, and stability. Translational StatementKidney cell lines are fundamental tools in nephrology research, yet their transcriptomic similarity to native cell types is rarely validated systematically. We demonstrate that combining bulk RNA-seq data with single-cell reference datasets enables robust assessment of cell line identity using gene expression-rank-based correlation and machine learning approaches. By providing a comprehensive evaluation of matching methods, curated kidney marker gene lists, and reference datasets, our study serves as both a practical resource and a methodological framework for the kidney research community, facilitating informed selection of cell culture models, quality control of experimental conditions, developing new experimental cell culture models, and more reliable translation of in vitro findings to kidney physiology and disease.

IntroductionGenome-wide association studies (GWAS) for kidney function have mainly focused on creatinine-based glomerular filtration rate (eGFRcrea), which is affected by variation in muscle mass. Moreover, the genetic basis of the sexual dimorphism of chronic kidney disease is underexplored. MethodsWe performed a GWA meta-analysis for creatinine clearance (CrCl), a muscle mass-independent kidney function phenotype, in 58,976 individuals of European descent from the Lifelines Cohort Study. ResultsWe identified 16 independent loci with 21 genome-wide significant lead single nucleotide polymorphisms (SNPs) associated with CrCl, two of which had not been reported previously in kidney function GWASs: rs146465192, located near the RP1-249F5.3 gene (effect allele frequency (EAF) = 0.01, P = 3.38 x 10-9) and rs117014836, located near the AGPAT4 gene (EAF = 0.02, P = 5.42 x 10-9). Both SNPs were also associated with eGFRcrea in Lifelines (rs146465192: P = 1.34 x 10-8; rs117014836: P = 3.64 x 10-7), but not in previously published eGFR GWASs. In silico follow-up analyses revealed that rs146465192 was associated with plasma IGF2R ({beta} = -0.519, P = 1.40 x 10-6), while rs117014836 was associated with blood expression levels of AGPAT4 (eQTL P = 6.54 x 10-6). Furthermore, we identified two female-specific CrCl loci (t-statistic P < 0.004): rs8002366 (GPC6) and rs12908437 (IGF1R), associated with GPC6 expression in kidney (eQTL P = 8.38 x 10-10) and IGF1R expression in blood (eQTL P = 2.62 x 10-6), respectively. ConclusionThis first large-scale GWAS of CrCl revealed two new genetic variants among both sexes and two female-specific variants influencing kidney function. Lay summaryKidney function is a complex phenotype influenced by many different factors, including genetics. Earlier genetic studies often used the creatinine-based estimated glomerular filtration rate (eGFRcrea) as the measure of kidney function. However, eGFRcrea is influenced not just by kidney function but also by an individuals muscle mass, which may distort the results. Therefore, in this study we used creatinine clearance (CrCl), a measure of kidney function independent of muscle mass, to look for genes in a European-ancestry population. We identified 16 genetic regions; two of which had not been found before. We also found two additional regions that were only related to CrCl in females. This shows the added value of investigating CrCl and suggests sex-based differences in how genetics affect kidney function.

Background: Patients with kidney failure undergoing maintenance hemodialysis suffer high rates of major adverse cardiovascular events(MACE) that are not accurately predicted by traditional cardiovascular risk models. There is an urgent need to identify novel, modifiable cardiovascular risk factors for these patients. Methods: We analyzed associations of 6287 circulating proteins with MACE among 1048 participants undergoing hemodialysis in the Chronic Renal Insufficiency Cohort(CRIC) (14-year follow-up) with validation in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study(PACE) (7-year follow-up). In both cohorts, proteins were measured shortly after dialysis initiation and one year later. We compared protein-based risk models derived by elastic net regression to the Pooled Cohort Equations(PCE) optimized for these cohorts(Refit PCE), and to an Expanded Refit PCE that included Troponin T and N-terminal pro-B-type natriuretic peptide. Results: In CRIC, 149 proteins were associated with MACE at false discovery rate<0.05. Among 22 proteins significant at Bonferroni p<8x10-6, proteins that validated in PACE included Sushi von Willebrand factor type A EGF and pentraxin domain-containing protein 1(SVEP1), Complement component C7, R-spondin 4, Tenascin, Fibulin-3 and Fibulin-5. Complement pathways were prominent in network analyses. SVEP1 surpassed other markers by statistical significance, with CRIC HR per log2 1.8 (p=2.1x10-12) and HR per annual doubling 1.6 (p=6.8x10-6). For 2-year MACE, AUC(95%CI) for SVEP1 alone was 0.72(0.59, 0.84) in CRIC, and 0.73(0.63, 0.81) in PACE. SVEP1 surpassed the Expanded Refit PCE in CRIC (0.61 (0.48, 0.73)) (p=0.038). In the pooled CRIC + PACE cohort, SVEP1 AUC(95%CI) (0.79(0.70, 0.88)) surpassed Refit PCE (0.61(0.51, 0.72)) (p=0.004). Conclusions: SVEP1, a 390 kDa protein unlikely to be renally cleared, surpassed over 6000 other proteins and by itself outperformed traditional clinical risk models in predicting MACE in two populations of patients undergoing maintenance hemodialysis. Future studies should provide mechanistic insights behind these findings.

BackgroundAmerican Indian/Alaska Native individuals are disproportionately affected by end-stage kidney disease. Once diagnosed, treatment options include receiving a kidney transplant or starting dialysis. Disparities in treatment options are linked to social determinants of health, and in rural areas, dialysis is often the preferred treatment due to limited access to transplant. A recent nationwide analysis of survival differences showed a survival advantage after starting dialysis but also found that patients in these populations are less likely to receive hospice care before death. They face early diagnosis, leading to more years on dialysis and reduced quality of life. Using a predictive model can help identify factors that affect hospice use among patients. This study proposes a predictive model to estimate the likelihood of hospice use before death among patients who received a kidney transplant. MethodsUsing the 2022 USRDS Standard Analysis Files, adults who fit inclusion criteria were retrospectively identified. Area Deprivation Index (ADI) data, used for this analysis, includes 17 variables from US Census data, such as income, education, housing security, employment, and healthcare access, to generate the standardized ranking. This study employed regression tree, random forest, boosting, and support vector machine techniques to predict hospice use among participants. The covariates used in this study are race, IHS region, age, sex, mean ADI, comorbidities, and transplant status. Models are assessed based on their predictive performance using accuracy, sensitivity, and specificity. ResultsThe random forest model outperforms others in accuracy, boosting offers the best sensitivity, and support vector machine and random forest excel in specificity. Overall, random forest and boosting are top models, with logistic regression as second-best. Logistic regression provides more interpretable results. The results, however, suggest a nonlinear relationship between covariates and the response that logistic regression might not capture. Based on both metrics, IHS region, age, and ADI are the most important features. ConclusionsIncluding measures like the ADI in predictive models highlights geographic disparities that are often overlooked and can guide interventions toward communities that have been historically underserved. Researchers and healthcare systems should improve access to hospice and palliative care for those who face these disparities.

Background: Microvascular dysfunction contributes to chronic kidney disease (CKD), but reproducible clinical measures are limited. Laser Doppler flowmetry (LDF) provides a noninvasive assessment of cutaneous microvascular blood flow and may reflect systemic microvascular health. Its relationship with kidney function and histopathology in CKD remains unclear. Methods: We assessed cutaneous microvascular function in 150 participants with CKD (eGFR <90 mL/min/1.73 m2) using a standardized forearm LDF protocol. Baseline perfusion was recorded at ~30{degrees}C, followed by local heating to 44{degrees}C to induce hyperemia. Percent change in perfusion units (PU) defined microvascular functional reserve. Associations of LDF measures with eGFR and urine protein-to-creatinine ratio (uPCR) were evaluated using multivariable linear regression. K-means clustering identified microvascular phenotypes. In a subset (n=20), associations with glomerulosclerosis (GS) and interstitial fibrosis/tubular atrophy (IFTA) were examined. Results: The mean (SD) age was 64 (14) years, 46% were female. The mean eGFR was 42 (21) mL/min/1.73m2 and median uPCR was 0.21 (interquartile range (IQR) 0.11 to 1.20) mg/mg. Higher baseline PU ({beta} = -12; 95% CI, -24 to -1) and reduced percentage change in PU ({beta} = 7; 95% CI, 2 to 13) were associated with lower eGFR, independent of covariates. Neither measure was associated with uPCR. Clustering identified four phenotypes with graded differences in perfusion and reserve. In biopsy participants, higher baseline PU and lower percent change were associated with greater GS and IFTA severity. Conclusion: CKD is characterized by elevated resting perfusion and impaired microvascular reserve, which are associated with lower eGFR and histopathologic injury.

BackgroundRising kidney discard rates and uncertainty around accepting higher risk donor kidneys highlight the need for decision support tools that integrate donor and recipient factors and communicate risk in ways that are understandable and usable at the time of offer. Conventional indices (e.g., KDPI/KDRI) provide population level signals but do not deliver individualized, cognitively accessible information aligned with real time clinical workflows. ObjectiveTo describe how key transplant stakeholders (patients, coordinators, and providers) interpret and evaluate a prototype Kidney Risk Calculator app that generates donor-recipient specific survival projections and to identify the content, format and features, and functionality needed for clinically meaningful, patient-centered decision support. DesignQualitative study using focus groups and individual interviews. SettingUniversity of New Mexico Hospital (UNMH) Kidney Transplant Center. ParticipantsFive patients (four transplant candidates and one patient advocate), three transplant coordinators, and five transplant providers (3 attending physicians and 2 advanced practice practitioners). MethodsSemi-structured sessions (45 to 60 minutes) with 13 stakeholders (patients, coordinators, and providers) included a live app demonstration and explored usability, interpretability, contextual information needs, perceived clinical utility, and anticipated barriers/facilitators. Data were collected via one coordinator focus group, one patient focus group, and five provider interviews; sessions were recorded, transcribed, de-identified, and analyzed using inductive reflexive thematic analysis. ResultsStakeholders affirmed the value of personalized projections as an adjunct to clinical judgment, particularly for higher risk offers. Participants prioritized: 1) Content: clear education on hepatitis C virus (HCV) positive donors and Public Health Service (PHS) risk criteria; plain explanations of Calculated Panel Reactive Antibody (CPRA); and framing that makes time on dialysis and tradeoffs salient; 2) Format & Features: plain language narratives, percentages rather than decimals, simple visuals, minimized acronyms, U.S. customary units, and a stepwise (TurboTax-like) input flow preferred by patients; and 3) Functionality: attention to cognitive load and workflow alignment, given phone based time pressure and digital access constraints. Stakeholders emphasized that the value of the tool hinges on clarity, context, and workflow fit, not predictive accuracy alone. LimitationsSingle center, formative prototype study with a modest sample; findings are illustrative and may have limited transferability. Participants reacted to a demonstration rather than using the app during real time offer calls; convenience/email recruitment and Zoom only English sessions may introduce selection bias; team involvement in app development may contribute residual confirmation bias despite mitigation. ConclusionsEarly stakeholder input suggests that a kidney offer decision support tool should integrate individualized predictions with plain language explanations, contextual information that addresses common misconceptions, workflow aligned functionality, and accessible outputs. Tools designed and implemented with these features may support acceptance of medically complex kidneys and may help reduce offer bypass and organ discard. These inferences reflect stakeholder perceptions in a formative qualitative study and warrant prospective evaluation.

Background and objectivesDiagnostic disclosure practices for autosomal dominant polycystic kidney disease (ADPKD) vary and may influence patient experience and linkage to nephrology care. We characterized patient-reported diagnostic pathways, perceived timing, and disclosure experiences in the PK-DIAG survey. Design, setting, participants, and measurementsCross-sectional web-based survey in France (February 2019-August 2024) among adults with self-reported ADPKD, disseminated via patient organizations. Primary outcomes were poor tact (tact score 0-1 on a 0-5 scale) and very negative diagnostic disclosure experience (overall score 0-1 on a 0-5 scale). Multivariable logistic regression used complete-case analyses. ResultsAmong 1,021 respondents, diagnosis was commonly disclosed outside nephrology care; 49% reported disclosure by a radiologist. Poor tact was reported by 25% and was associated with radiologist (vs nephrologist) disclosure (adjusted odds ratio 2.50; 95% confidence interval 1.57-3.98). Very negative experience was reported by 29% and was associated with poor tact (adjusted odds ratio 4.55; 95% confidence interval 2.90-7.12) and information perceived as insufficient/unclear/inaccurate (adjusted odds ratio 2.52; 95% confidence interval 1.53-4.15). Most participants perceived diagnosis as timely (67%), while 18% perceived it as too early and 15% as too late. Distress (36%) or unmet psychological needs (40%) in the immediate post-disclosure period was common. ConclusionsADPKD diagnostic disclosure often occurred outside dedicated nephrology consultations and was frequently associated with poor tact and inadequate information. These findings support structured, guideline-aligned disclosure pathways incorporating timely counseling, psychosocial support, and rapid linkage to nephrology care. Key PointsO_LIIn PK-DIAG, initial disclosure of ADPKD frequently occurred outside nephrology care, most often by radiologists in radiology settings. C_LIO_LIAbout one quarter of respondents reported poor tact and 29% reported a very negative overall diagnostic disclosure experience. C_LIO_LIPoor tact and information perceived as insufficient/unclear/inaccurate were strongly associated with a very negative diagnostic experience. C_LI

BackgroundRenal biopsy provides important prognostic information for patients with chronic kidney disease (CKD), primarily through evaluation of cortical histopathological lesions, including interstitial fibrosis and tubular atrophy (IFTA). However, the prognostic significance of renal medullary lesions remains poorly understood. We investigated whether medullary pathological findings are independently associated with renal outcomes and whether they improve prognostic discrimination beyond conventional cortical assessments. MethodsThis single-center retrospective cohort study screened 1,136 adult patients who underwent native kidney biopsy between 2011 and 2023. After applying predefined inclusion and exclusion criteria, 488 patients with adequate medullary tissue were included in the final analysis. Medullary fibrosis, inflammatory cell infiltration, and cast formation were semi-quantitatively graded and evaluated as predictors of renal outcomes. The primary outcome was a composite of [&ge;]40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Associations were assessed using Cox proportional hazards models with sequential adjustment for demographic factors, baseline eGFR, proteinuria, and cortical IFTA. Model discrimination was evaluated using Harrells concordance-index (C-index). ResultsDuring a median follow-up of 2.3 years, 112 patients (23.0%) reached the composite renal outcome. In multivariable analysis adjusted for age, sex, baseline eGFR, and proteinuria, medullary cast formation was significantly associated with adverse renal outcomes (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.28-2.24). This association remained significant after additional adjustment for IFTA (HR 1.64, 95% CI 1.21-2.21), whereas medullary fibrosis lost significance after IFTA adjustment. Addition of medullary cast formation improved C-index by 0.016, indicating incremental prognostic value beyond conventional predictors. ConclusionMedullary cast formation is independently associated with renal outcomes and improves prognostic discrimination beyond established cortical parameters. Systematic evaluation of medullary lesions during routine kidney biopsy may enhance risk stratification in CKD. Prospective studies are warranted to clarify the causal role of medullary pathology in CKD progression.

IntroductionThere remains considerable debate as to the cause of the epidemic of Mesoamerican Nephropathy (MeN). We have previously reported early loss of estimated glomerular filtration rate (eGFR) as a surrogate for disease onset in a population-representative cohort study of young-adults at risk of disease from Northwest Nicaragua. Using a nested case-control approach we analysed urine and serum proteins surrounding this timepoint with the aim of gaining insight into the primary disease aetiology. MethodsWe conducted label-free ultra high-performance liquid chromatography mass-spectrometry based proteomics using urine samples collected at the study visit before, and at, first observed eGFR loss amongst cases and compared results to matched controls. We then performed direct protein measurements in a discovery cohort followed by quantification of serum total immunoglobulin E (stIgE) at multiple timepoints in a replication cohort. ResultsProteomic analysis demonstrated no differences in the levels of any single protein between cases and controls (n=25 each), at either timepoint, after correction for multiple comparisons. However, functional enrichment analysis demonstrated upregulation of adaptive immune pathways amongst cases. Direct measurements in the discovery cohort using high-sensitivity PCR-based immunoassay (n=21 controls, 19 cases) demonstrated higher stIgE in cases at the study visit immediately prior to first observed eGFR loss (mean difference 810kU/L, 95% confidence interval (CI): 162-1457kU/L). In the replication cohort (n=22 cases, 21 controls) an stIgE level >500kU/L measured by electrochemiluminescence in study samples from any timepoint in the 3 years prior to the first observed loss of eGFR was independently associated with case status when compared to samples from controls at matched visits (adjusted Odds Ratio: 8.1, 95% CI: 1.4-47.8). DiscussionA high level of stIgE precedes loss of eGFR in those at risk of MeN. Understanding what leads to this rise is likely to be key to understanding the cause of the MeN epidemic. Lay SummaryMesoamerican nephropathy describes an epidemic-level chronic kidney disease impacting rural working age adults in Central America. Although a number of exposures, including occupational heat exposure, have been proposed the cause of the epidemic, there remains much debate as to the primary aetiology of the disease. In this study we interrogated urine and blood samples from individuals from affected communities at risk of disease both before and after they develop kidney dysfunction. Using two different approaches, analysis of both urine and blood samples provide evidence of upregulation of immunoglobulin-E (IgE) related pathways in the 2-3 years before individuals develop evidence of kidney disease. Infections (particularly those involving parasites) and allergic reactions, but not heat exposure, have been reported to increase IgE levels. Going forwards, understanding the cause of this increase in IgE in individuals at risk of disease is likely to provide insight into the cause of Mesoamerican Nephropathy epidemics.

IntroductionChronic kidney disease imposes a high clinical and economic burden on the Brazilian Unified Health System, and kidney transplantation offers the best prognosis. ObjectiveTo describe trends in living kidney (LD) donation in Brazil (2010-2023), analyzing the donor-recipient relationship and the operational stock-to-annual production ratio on the waiting list, and to compare hospital indicators and estimated patient and graft survival between LD and deceased-donor (DD) kidney transplants. MethodsDescriptive ecological time-series study using aggregated, publicly available data. ResultsThe waiting list increased by 15% (from 33,253 to 38,258), and the total number of transplants rose by 29% (from 4,656 to 6,047). Data showed an increase in deceased-donor transplants (from 3,001 to 5,189) and a decrease in LD transplants (from 1,655 to 858), with the LD share declining from 35.55% to 14.19% and the per-million-population rate falling from 8.8 to 4.2. Among LD, there was a relative decrease in related donors (from 82.80% to 71.21%), a relative increase in unrelated spouse donors (from 10.57% to 18.65%), and in other unrelated donors (from 6.63% to 10.14%). Comparatively, LD showed better descriptive performance on survival indicators and lower in-hospital mortality, length of stay, and mean Hospital Admission Authorization value. ConclusionThe findings indicate a need for strategies to sustain DD procurement and LD donation.

Background: Single-nephron glomerular filtration rate (GFR) represents a nephron-level functional index that may reveal key pathophysiological mechanisms driving progression in patients with diabetic nephropathy. However, its clinical relevance remains incompletely understood. This cross-sectional study assessed single-nephron estimated GFR (eGFR) across different chronic kidney disease (CKD) stages in patients with advanced diabetic nephropathy. Methods: Nephron number was estimated as the number of nonglobally sclerotic glomeruli per kidney using computed tomography-derived cortical volume combined with biopsy stereology. Single-nephron eGFR was calculated by dividing eGFR by the nephron number of both kidneys. Patients were stratified according to CKD stage at kidney biopsy. Associations between CKD stages and single-nephron eGFR were evaluated using multivariable linear regression models adjusted for age, sex, urinary protein excretion, and eGFR. Results: The study included 105 patients with biopsy-proven diabetic nephropathy and overt proteinuria (median age 59 years, 83% male, HbA1c 6.6%, 57% had nephrotic range proteinuria). The percentage of globally sclerotic glomeruli, mesangial expansion score, and prevalence of nodular lesions increased significantly with advancing CKD stage. Median nephron number declined from 529,178 to 224,458 per kidney, whereas glomerular volume remained constant. Single-nephron eGFR decreased markedly with CKD stage and remained significantly inversely associated with CKD stage after adjustment for clinicopathologic covariates (P for trend <0.001). Conclusion: In overt diabetic nephropathy, single-nephron eGFR decreased with advancing CKD stage, despite relatively preserved glomerular volume. At this stage of disease, structural alterations specific to diabetic nephropathy may impair effective single-nephron filtration capacity.

IntroductionGlomerular filtration rate (GFR) is invasive to measure. Therefore, in clinical care, estimated GFR is derived from serum levels of endogenous filtration markers such as creatinine and cystatin C. Multiple studies from high income countries showed differences between estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr). This study aimed to assess the agreement between eGFRcys and eGFRcr in Ethiopian children and identify factors influencing higher eGFRcys and eGFRcr. MethodWe studied 350 Ethiopian children who were part of the iABC birth cohort study. At the recent follow-up (average age 10 years), serum cystatin C and creatinine were measured. Formulas by Berg (2015) and Hoste (2014) were used to estimate eGFRcys and eGFRcr, respectively, and Bland-Altman plots assessed their agreement. The difference in eGFR (eGFRdiff) was calculated and categorized as less than-15 mL/min/1.73 m{superscript 2} (higher eGFRcr), between-15 and <15 mL/min/1.73 m{superscript 2} (concordant), and greater than or equal to 15 mL/min/1.73 m{superscript 2} (higher eGFRcys). Multinomial logistic regression was used to identify factors associated with higher eGFRcr and higher eGFRcys. ResultEstimated glomerular filtration rate (eGFR) showed significant variation based on the estimation formula used. When using formulas by Berg (2015) and Hoste (2014), the median (IQR) eGFRcys and eGFRcr were 99.4 (90.0; 114.1), and 123.2 (110.3; 143.8) mL/min/1.73 m2, respectively. Overall, we observed a poor agreement between eGFRcys and eGFRcr, with only 94 (27.6%) children having concordant results compared to 220 (64.7%) with higher eGFRcr and 26 (7.6%) with higher eGFRcys. If the eGFRcys results are considered reliable, 27.5% of the children had eGFR below 90 mL/min/1.73 m{superscript 2}. ConclusionThere was very marked variation in the distributions of estimated eGFRs depending on which formulas for children were used. Agreement between eGFR estimated using cystatin C and creatinine was poor among Ethiopian children. Relative to eGFRcys, kidney function may be overestimated by creatinine-based equation as up to 30ml/min in Ethiopia. Ideally, a validation study with GFR measured by gold standard methods (Inlulin clearance) among children is required. However, because of its invasive nature and financial concerns, Iohexol clearance studies are recommended.

IntroductionPatients with type 2 diabetes mellitus (T2DM) are at increased risk of coronary artery disease and frequently undergo coronary angiography or percutaneous coronary intervention. Although risk factors for post-contrast acute kidney injury (PC-AKI) are well defined, effective preventive strategies remain limited. MethodsThis multicenter observational cohort study included 975 patients aged 18-75 years who underwent coronary angiography and/or percutaneous coronary intervention with iodinated contrast between June 2023 and June 2024. All patients received standardized intravenous hydration. Participants were grouped according to chronic sodium-glucose co-transporter-2 (SGLT2) inhibitor use ([&ge;]3 months). PC-AKI was defined as a [&ge;]25% or [&ge;]0.5 mg/dL increase in serum creatinine within 48-72 hours after contrast exposure. ResultsThe mean age was 59.2 {+/-} 11.7 years, and 70.8% were male; 16.9% were using SGLT2 inhibitors. PC-AKI occurred in 7.3% of patients, and 0.7% required renal replacement therapy. In univariate analysis, advanced age, diabetes, hypertension, heart failure, diuretic use, and elevated urea, creatinine, potassium, and uric acid levels were associated with PC-AKI. Higher eGFR, albumin, sodium levels, and SGLT2 inhibitor use were inversely associated. In multivariate analysis, age [&ge;]65.5 years (OR 4.53), diabetes (OR 2.49), and uric acid >6.75 mg/dL (OR 2.34) remained independent risk factors, while eGFR >81.5 mL/min/1.73 m2 (OR 0.38), sodium >137.5 mmol/L (OR 0.36), and SGLT2 inhibitor use (OR 0.09) were independently protective. ConclusionBeyond established cardioprotective and renoprotective effects, SGLT2 inhibitors may reduce the risk of PC-AKI in patients with T2DM, potentially through decreased renal oxygen consumption and attenuation of contrast-induced hypoxic injury.