Kidney360

Rationale & ObjectiveCompetency-based medical education emphasizes observable skills rather than time-based training. Entrustable Professional Activities (EPA) transform competencies into distinct, assessable clinical tasks but have not yet been systematically developed for U.S nephrology fellowships. We aimed to create and achieve consensus on a set of nephrology-specific EPAs and align them with Accreditation Council for Graduate Medical Education (ACGME) competency standards. Study DesignA consensus framework was developed using an online 3-round modified Delphi method. Settings & ParticipantsStudy was conducted within the University of New Mexico nephrology fellowship program. Participants included eight faculty nephrologists and one nephrology fellow. Analytical ApproachAn initial EPA list was generated by the study team using program objectives, literature review, and clinician insight. Participants rated each EPA using a 5-point Likert scale with consensus requiring strict criteria. Final EPAs were independently mapped to ACGME nephrology program requirements to ensure alignment with national competency. ResultsNine study participants (100% response rate) completed all survey rounds. Through iterative consensus, utilizing strict criteria, a final list of 22 distinct EPAs were achieved covering core domains of practice including dialysis management, acute kidney injury, chronic kidney disease, electrolyte abnormalities, hypertension, kidney stones, glomerular disease, pregnancy, transplant care, and education. Mapping demonstrated that the EPAs sufficiently corresponded to the breadth of ACGME-required sub competencies, offering a practical framework for translating broad milestones into observable clinical tasks. LimitationsThe study was conducted at a single fellowship program with a small number of participants which may limit generalizability. Implementation feasibility, resource implications, and potential unintended consequences such as checklist mentality and documentation burden were evaluated during a subsequent phase of the study. ConclusionsWe developed the first consensus-consensus based set of EPAs geared for U.S based nephrology fellowship programs while being systematically aligned with ACGME program requirements. This framework provides a foundation for standardized assessment and curriculum development in nephrology and may inform broader efforts to implement EPA-based evaluation across fellowship programs nationally.

IntroductionGenomic testing is reshaping nephrology practice, yet the structure, outcomes, and implementation of kidney genetics services remain poorly characterized. MethodsWe conducted a two-part scoping study comprising (i) a literature review (JBI methodology, PRISMA-ScR compliant; OSF registration doi.org/10.17605/OSF.IO/N32VA) of English-language publications (2000-2025) describing kidney genetics services and outcomes, and (ii) an international stakeholder consultation of clinic leads to capture real-world service and implementation experiences. ResultsSixty studies were included, predominantly from North America (n=23), followed by United Kingdom/Ireland (n=5), Europe (n=17), Australia/New Zealand (n=10), and Asia (n=5). Among the 25 studies describing clinic models, four types were identified: multidisciplinary integrated (n=12), nephrologist-led (n=9), mainstreaming (n=2), and traditional genetics referral (n=2). Clinic structure varied by region. Outcome reporting focused on diagnostic yield (92%), with limited data on timeliness (16%), patient-reported outcomes (12%), or implementation outcomes (4%). Test penetration was high across regions and models, while diagnostic yield varied. Nephrologist-led clinics demonstrated comparable performance to multidisciplinary models when adequately supported. International stakeholder consultation data (n=48) revealed diversification of clinic models across regions. In Australia/New Zealand, multidisciplinary clinics predominated, supported by public funding and in-house or hybrid laboratory. United Kingdom/Ireland clinics used public funding and a national laboratory. North American clinics show greater heterogeneity, with higher prevalence of nephrologist-led models, reliance on commercial laboratories, and mixed or private funding. Asian clinics reported nephrologist-led models, with resource constraints, and hybrid testing and funding arrangements. Comprehensive sequencing with virtual panels predominated in Australia/New Zealand, United Kingdom, and Europe; phenotype-driven panels {+/-} reflex testing were more common in North America. ConclusionsKidney genetics care is expanding but remains unevenly implemented. Nephrologist-led and multidisciplinary models can be effective with appropriate support. Patient selection may influence diagnostic yield more than testing modality. Standardized outcome reporting and theory-driven implementation evaluation are essential for delivering equitable, sustainable genomic services. Lay SummaryThis study examined how kidney genetics services are delivered across the globe. We reviewed 60 studies (2000-2025) and consulted 48 clinic leaders globally. Four service models were identified--multidisciplinary integrated, nephrologist-led, mainstreaming, and traditional genetics referral--and mapped variation in care teams, test strategies, test laboratories, and funding. Most studies reported diagnostic yield, but few assessed patient experience or how well services were implemented. European programs showed the highest performance, attributed to clear referral criteria, deep phenotyping, detailed family histories, multidisciplinary review, and strong public funding. Clinics led by nephrologists performed comparably to multidisciplinary teams when adequately supported. Across all settings, patient selection was more important than the specific type of genetic test used in determining diagnostic success. Kidney genetics services are expanding but remain uneven. This study highlights the need for context-specific, theory-informed, and determinants-targeted strategies to support scalable, equitable, and sustainable genomic care worldwide.

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.

BackgroundProgression into more severe stages of chronic kidney disease (CKD) based on estimated glomerular filtration rate (eGFR) and albuminuria are associated with increased risk of end-stage renal failure, cardiovascular diseases, and mortality. Vesicles in the urine are cell-derived particles containing constituents of the cells of origin. Little is known about the prognostic capacity of urinary vesicles for CKD progression. PurposeTo evaluate the association between components of urinary vesicles and incident CKD. MethodsIn the AugUR study, a prospective population-based cohort study in individuals aged 70-95 years at baseline, we isolated and characterized urinary vesicles from 580 participants at two timepoints. In cross-sectional data, influences of age, sex and established kidney biomarkers on vesicular albumin and podocalyxin were characterised. Longitudinal data were used to test associations of vesicular albumin and podocalyxin with incident eGFR-based CKD and albuminuria. ResultsCross-sectionally, urinary vesicle albumin and urinary vesicle-bound podocalyxin were moderately correlated with each other and with urinary albumin and alpha1-microglobulin, but not with eGFR. Vesicular albumin concentrations were influenced by sex, whereas age showed an effect on podocalyxin. After adjusting for age and sex, higher vesicular albumin was associated with higher urinary albumin and lower eGFR. Higher vesicular podocalyxin concentrations were associated with higher urinary albumin but not with eGFR. Both markers showed identical associations with urinary alpha1-microglobulin. In longitudinal analyses, baseline vesicular albumin showed association with incident CKD based on eGFR. This association was no longer present after adjustment for baseline eGFR. In contrast, higher baseline podocalyxin concentrations were predictive for decreased risk of incident albuminuria after adjustment for baseline free urinary albumin. Baseline-adjusted change in urinary vesicle albumin and urinary vesicle-bound podocalyxin were both associated with incident albuminuria, independent of free urinary albumin and other kidney biomarkers. Here, increase in follow-up versus baseline values were associated with higher risk for incident albuminuria, with higher effect sizes for vesicular albumin. ConclusionThis study indicates that higher vesicular podocalyxin at baseline might be a potential predictor for lower risk for albuminuria over three years in an old-aged cohort. In contrast, longitudinal increase in urinary vesicle biomarkers, especially vesicular albumin, might be diagnostic markers for incident albuminuria in the elderly. KEY MessagesWhat is known O_LIAccording to a previous study in animals, accumulation of albumin in the subpodocyte space leads to subsequent endocytosis by the podocytes. C_LIO_LIPodocyte-produced vesicles contain potential biomarkers of the deterioration of kidney function in humans. C_LI What is new O_LIBiomarkers from urinary vesicles can be quantified from biobanked human samples. C_LIO_LIHigher vesicular podocalyxin at baseline might be a potential predictor for lower risk for albuminuria over three years in an old-aged cohort. C_LIO_LIChanges in urinary vesicle biomarkers over time, especially vesicular albumin, are associated with incident albuminuria independent of eGFR and free urinary albumin. C_LI

The integration of regenerative medicine into dynamic organ preservation may mitigate ischemia-reperfusion injury in kidney transplantation. This systematic review and meta-analysis evaluated the therapeutic potential of stem cell-based interventions during machine perfusion. Following PRISMA guidelines, PubMed, Embase, and Scopus were searched for experimental studies using stem cells or extracellular vesicles (EVs) during hypothermic or normothermic machine perfusion in animal or discarded human kidneys. Outcomes included renal function, injury biomarkers, inflammation, and histology. Nine studies were included, seven in meta-analysis. Despite heterogeneity in models and protocols, several reported reductions in inflammatory cytokines (e.g., IL-6, IL-1{beta}) and biomarkers (e.g., NGAL) following stem cell or EVs administration. However, meta-analysis showed no significant effects on creatinine clearance (Standardized Means (SMD): 0.00; 95% CI: -0.54 to 0.55), urine output (SMD: 0.54; 95% CI: -0.46 to 1.55), or NGAL (SMD: -1.68; 95% CI: -5.60 to 2.25). Histological protection varied, and stem cell retention was limited. Only one study assessed post-transplant function. While stem cell therapies during perfusion may have immunomodulatory and cytoprotective effects, consistent functional benefits were not observed. Further standardized studies, including transplant models and long-term outcomes, are needed to clarify therapeutic potential and optimize delivery strategies.

BackgroundImmune checkpoint inhibitor (ICI)-associated acute interstitial nephritis (ICI-AIN) has emerged as a common cause of acute kidney injury (AKI). However, acute tubular necrosis (ATN) may present with similar clinical features yet requires fundamentally different management. Robust data on the prevalence of ATN among patients with suspected ICI-AIN are limited. The aim of this study was to determine the prevalence of ATN in patients with suspected ICI-AIN and to estimate the risk of diagnostic error associated with empirical corticosteroid therapy in the absence of kidney biopsy. MethodsWe conducted a retrospective multicenter study including ICI-treated patients who developed AKI and underwent kidney biopsy. Patients with glomerular presentations were excluded. Based on histopathological findings, patients were classified into two groups: ICI-AIN and isolated ATN. The primary outcome was the prevalence of ATN among patients with suspected ICI-AIN. Secondary outcomes included the description of clinical characteristics, concomitant medications, and laboratory findings, as well as the identification of factors potentially distinguishing ATN from ICI-AIN. ResultsA total of 132 patients were included. ICI-AIN was diagnosed in 76 patients (58%), while isolated ATN was identified in 56 patients (42%). Among subgroups with known risk factors for ICI-AIN, isolated ATN was observed in 20% (7/35) of patients exposed to proton pump inhibitors (PPIs), 23% (3/13) receiving combination ICI therapy, 31% (5/16) with pre-existing chronic kidney disease (CKD), and 34% (10/34) with concomitant extrarenal immune-related adverse events (irAEs). ATN was also present in 23% (6/26) of patients treated with ICI monotherapy. Patients with AIN had more severe renal impairment, with a higher median serum creatinine level at presentation (200 {micro}mol/L vs. 141 {micro}mol/L, p < 0.001). Leukocyturia and hematuria were significantly more frequent in the AIN group (p = 0.007 and p = 0.009, respectively). PPI use was significantly more common in patients with AIN than in those with ATN (40% vs. 19%, p = 0.027), whereas exposure to platinum-based chemotherapy was more frequent in the ATN group (78% vs. 59%, p = 0.027). ConclusionAlthough certain clinical features are associated with ICI-AIN, they are insufficient to reliably differentiate it from ATN without histological confirmation. An empirical management strategy involving corticosteroid therapy without kidney biopsy carries a diagnostic error risk of approximately 40%, underscoring the importance of kidney biopsy as the diagnostic gold standard.

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.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric kidney failure, but predicting individual progression remains challenging. This multicenter study developed and validated POCC, a machine learning model for predicting kidney failure risk at 1, 3, and 5 years post-diagnosis in CAKUT patients. Two versions were created using data from 2,249 children. The general model achieved internal AUCs of 0.93-0.99 and external AUCs of 0.90-0.98 and 0.81- 0.90 in two independent validations at pediatric and general hospitals, respectively. The specialized model, integrating congenital-hereditary features, achieved internal AUCs of 0.93-0.99 and external AUCs of 0.91-0.96 in pediatric hospitals. Deployed online, POCC demonstrated 90.7% accuracy in real-world validation, with the specialized model reaching 100% sensitivity and specificity for 5-year predictions. As the first tool for multi-timepoint risk prediction across diverse CAKUT subphenotypes per patient, POCC has strong potential to support personalized management.

BackgroundThe Kidney Precision Medicine Project (KPMP) consortium aims to redefine chronic kidney disease (CKD) by integrating clinical, pathological, and molecular tissue data from kidney biopsies. Here, we demonstrate how biopsy data in CKD can clarify disease etiology and contribute to understandings of disease pathophysiology and clinical prognosis. MethodsThe KPMP is obtaining research kidney biopsies from individuals with CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 and/or albuminuria [&ge;]30 mg/g creatinine) and diabetes (enrolled as diabetes and CKD or DKD) or hypertension (enrolled as hypertension and CKD or HCKD). A team of kidney pathologists and nephrologists adjudicated the primary clinico-pathological diagnosis for 258 participants with CKD. We compared pathological features and kidney transcriptional signatures between participants with a primary adjudicated diagnosis of diabetic nephropathy and those with other causes of CKD. We developed a model using clinical and biomarker data that predicted the probability of diabetic nephropathy and tested associations of the signature with CKD progression among Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n=229). ResultsAmong 183 participants enrolled as DKD, 102 (56%) had a primary adjudicated clinico-pathologic diagnosis of diabetic nephropathy. Among 75 participants enrolled as HCKD, 42 (56%) had a primary diagnosis of hypertension-associated kidney disease. Those with diabetic nephropathy, compared with other diagnoses, had more severe interstitial fibrosis, tubular atrophy, tubular injury, segmental sclerosis, and severe arteriolar hyalinosis, and single-nucleus and single-cell transcriptional analyses revealed upregulation of immune and inflammatory pathways and downregulation of oxidative phosphorylation. A combination of age, hemoglobin A1c, urine albumin-creatinine ratio, and serum KIM-1 and sTNFR1 predicted a clinico-pathologic diagnosis of diabetic nephropathy in the KPMP (AUC 0.82, 95% CI 0.75-0.89) and was associated with an increased risk of CKD progression among patients with diabetes enrolled in CRIC (HR 1.48 [95% CI 1.27-1.73] per 10% higher predicted probability of diabetic nephropathy). ConclusionIn common presentations of CKD, kidney biopsies may alter a priori impressions, reveal a diversity of diagnosis, structure, and function that is associated with clinical outcomes and can impact therapeutic decisions.

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

Allocation out of sequence (AOOS) allows organ procurement organizations (OPOs) to bypass the standard match-run to expedite kidney placement and prevent nonuse. Inclusion of all AOOS attempts is vital when attempting to assess impact of AOOS on organ utility, including those attempts that do not lead to successful transplant. We assessed the frequency of AOOS documentation in discarded kidneys. Using Scientific Registry of Transplant Recipients (SRTR) Potential Transplant Recipient (PTR) offer data from 2021-2024, we identified match-runs with at least one discarded kidney. AOOS was defined according to Health Resources and Services Administration (HRSA) guidelines and match runs were stratified by kidney recovery and disposition patterns, focusing on 2024 when AOOS was well established. AOOS coding frequency was assessed within each group and across OPOs. In 2024, only 4.3% of all match-runs with at least one discarded kidney contained evidence of AOOS documentation. Across OPOs, AOOS-coded discards ranged from 0.0% to 17.1% (median 3.9%, IQR [2.7-7.6%]). AOOS documentation among discarded kidneys remains rare and inconsistent, suggesting major data-capture deficiencies when attempting to accurately assess AOOS efforts. Improved AOOS reporting is essential before future expedited allocation pathways can be effectively evaluated or implemented.

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.

Individuals with chronic kidney disease (CKD) have higher rates of hip fracture and post-fracture mortality. Although they may develop age-related osteoporosis similar to those without CKD, they may also exhibit CKD-related metabolic bone disease (MBD), characterized by low, high, or mixed turnover at similar levels of bone mineral density (BMD). Because BMD does not provide information about turnover status, clinical decision-making is challenging. This study evaluated the associations between circulating bone-turnover biomarkers and static histomorphometry in patients undergoing hip-fracture surgery. In this cross-sectional study, we enrolled adults with and without CKD, defined as estimated glomerular filtration rate (eGFR) [&le;]60 ml/min/1.73m{superscript 2} (CKD-EPI 2021), undergoing hip-fracture surgery. Blood samples, bone specimens from the femoral head or greater trochanter, and demographic and clinical data were collected at the time of surgery. Plasma biomarkers included -Klotho, bone alkaline phosphatase (BAP), dickkopf-related protein 1 (DKK-1), fibroblast growth factor 23 (FGF23), tartrate-resistant acid phosphatase 5b (TRAP5b), parathyroid hormone (PTH), and sclerostin. Logistic regression models, adjusted for age, gender, eGFR, and osteoporosis, assessed associations with CKD status. Tertiles of osteoblast surface (Ob.S/BS) and eroded surface (ES/BS) were defined in participants without CKD and applied to the full cohort. Multinomial and multivariable linear regression evaluated associations of biomarkers with these histomorphometry parameters. Among 97 enrolled participants (mean age 80 {+/-} 11 years; 67% female), 68% had CKD. Of 75 with complete biomarker and histomorphometry data, 96% demonstrated low bone turnover. CKD was associated with lower trabecular thickness (Tb.Th) and higher osteoid thickness (O.Th), osteoid volume (OV/BV), and osteoid surface (OS/BS), suggesting thinner, largely unmineralized trabeculae. Higher BAP (222.2% difference per doubling; 95% CI 77.2-485.8) and TRAP5b (319.3%; 95% CI 128.3-669.5) were directly associated with Ob.S/BS and ES/BS, whereas sclerostin was inversely associated with ES/BS (-28.9%; 95% CI -44.8 to -7.1). PTH was not associated with bone-turnover measures. These findings suggest that BAP, TRAP5b, and sclerostin may provide useful adjunct information alongside PTH for assessing bone turnover and guiding therapy in patients with and without CKD.

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.

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.

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.

A substantial proportion of recovered deceased-donor (DD) kidneys go unused. Accumulated refusals by transplant centers during the offer process may signal nonuse risk, and quantifying this phenomenon could inform frameworks for rescue strategies or out-of-sequence (OOS) placement. Using OPTN data on adult DD kidneys offered for transplant in 2024, we empirically estimated the probability of nonuse as a function of accumulated refusal count (ARC). Kidneys transplanted OOS were excluded from analysis. Among recovered adult DD kidneys offered in-sequence, risk of nonuse exceeded 50% after ARC=6 for blood type O kidneys, ARC=4 for type A and type B, and after ARC=1 for type AB. Risk exceeded 80% after ARC=128 (type O), ARC=55 (type A), ARC=50 (type B), and ARC=14 (type AB), and exceeded 90% after 980, 414, 278, and 41 refusals, respectively. The C-statistic of the ARC by blood type ranged from 0.896 to 0.933. ARC thresholds offer a pragmatic trigger for rescue allocation, incorporating center perception of kidney quality not easily captured in standard metrics. A policy allowing OPOs to offer kidneys OOS or deploy alternative rescue strategies once a certain ARC threshold is reached may improve utilization of hard-to-place donor kidneys while keeping easier-to-place kidneys in-sequence.

Background In the United States, streamlining the kidney transplantation (KT) evaluation process may reduce disparities and barriers to KT access. Prior work showed that the Kidney Transplant Fast Track (KTFT) program shortened this process and reduced racial disparities in waitlisting and overall KT. However, within a setting where evaluation-related structural barriers have been addressed, a comprehensive longitudinal evaluation incorporating sociocultural factors (e.g., medical mistrust, healthcare-related discrimination/racism) alongside race/ethnicity as prespecified predictors across multiple KT milestones, including KT type (living [LDKT] and deceased donor KT [DDKT]), has not been performed. MethodsIn this secondary analysis, data came from the KTFT study, a prospective KT candidate cohort. Participants were recruited before KT evaluation start (05/2015-06/2018), coinciding with baseline measure collection, then followed via medical record through 08/2022. We used hierarchically-adjusted Fine-Gray proportional hazards models in this exploratory analysis. ResultsAmong 1108 KT candidates (243 Black, 783 White, 82 Other), medical mistrust was associated with lower cumulative incidence of waitlisting, but no other sociocultural factors were associated with outcomes. Racial and ethnic differences emerged for KT type: Black participants had a greater cumulative incidence of DDKT, and participants categorized as Other race/ethnicity had a lower cumulative incidence of LDKT, relative to White participants. Conclusions Although KTFT reduced racial/ethnic disparities in waitlisting and overall KT receipt, we identified racial/ethnic differences in LDKT and DDKT. Medical mistrust was a significant barrier to waitlisting. Findings suggest that even when the KT evaluation process is streamlined, sociocultural factors and race/ethnicity may influence KT outcomes.

BackgroundKidney disease refers to a broad range of disorders that impair renal structure and function. Among these, chronic kidney disease (CKD) is the most prevalent worldwide, affecting approximately 10% of the global adult population. While large-scale omics studies have identified numerous molecular associations with kidney function and disease, these insights often remain isolated within individual data layers, hindering a systems-level understanding of the functional interplay between genes, proteins, metabolites and clinical phenotypes. MethodsWe developed the Kidney Disease Atlas (KD Atlas) using an extended QTL-based integration strategy combined with a composite network approach. For this purpose, we leveraged results from omics studies in population-based and kidney disease-specific cohorts from the CKDGen Consortium and other large-scale initiatives and integrated them with data from knowledge databases, inferring a comprehensive network of relationships between metabolites, proteins, genes, and kidney disease-related traits. ResultsWe present the KD Atlas, an online resource (https://metabolomics.helmholtz-munich.de/kdatlas) integrating over 25 large studies providing disease-relevant information on 20,456 protein-coding genes, 1,962 proteins, 1,375 metabolites and 40 kidney disease phenotypes connected by more than 1.2 million relationships. Through an interactive web interface, researchers can dynamically construct context-specific molecular subnetworks and perform integrated analyses without requiring specialized bioinformatics expertise. Application showcases demonstrate the resources utility for providing the molecular context of KD-associated genes or metabolites and for generating novel mechanistic hypotheses. ConclusionThe KD Atlas provides a global, multi-omics network view of kidney pathophysiology through an intuitive interface, empowering researchers to formulate mechanistic hypotheses and prioritize candidate targets for subsequent experimental validation.

BackgroundSnakebite is a neglected tropical disease with a high burden in South Asia, particularly India. Acute kidney injury (AKI) is one of the most serious complications of snake envenomation, which has significant morbidity, mortality and risk of chronic kidney disease (CKD). The present study aimed to evaluate the incidence, predictors, and outcomes of snakebite-associated AKI (SBE-AKI) in a tertiary care centre. MethodsWe retrospectively analysed 325 patients with snakebite envenomation, admitted to our institution. Demographic, clinical, laboratory, and treatment variables were compared between patients with and without AKI. AKI was staged according to KDIGO criteria. Renal biopsy was performed in selected patients. Outcomes assessed included recovery, Progression to CKD, and mortality. ResultsOf the 325 patients, 79 (32.1%) developed AKI. Patients with AKI were significantly younger (mean age 34 vs. 45 years, p = 0.001). Delay in anti-snake venom (ASV) administration (18 vs. 6 hrs, p = 0.001), need for inotropes (41.8% vs. 14.2%, p = 0.001), and mechanical ventilation (36.7% vs. 6.9%, p = 0.001) were strong predictors. Proteinuria was more frequent in AKI (80% vs. 32.5%). Among AKI patients, 57% had stage 3 AKI; 39.2% required dialysis. Biopsy (n=8) showed acute tubular necrosis in 37.5% and cortical necrosis in 25%. Outcomes included 77.2% recovery, 6.3% progression to CKD, and 16.5% mortality. ConclusionSBE-AKI is a common and serious complication of snakebite. Delay in ASV administration, hemodynamic instability, proteinuria, advanced AKI stage and cortical necrosis predict poor outcomes. Early ASV, timely dialysis, and long-term nephrology follow-up are essential to improve survival and reduce CKD progression.