Clinical Journal of the American Society of Nephrology

Introduction Acute interstitial nephritis is an important differential diagnosis in patients with deteriorating kidney function. Diagnosis currently requires kidney biopsy, an invasive procedure associated with risks. We hypothesized that urinary T cells may serve as a non-invasive biomarker for acute interstitial nephritis. Methods A total of 320 patients undergoing clinically indicated kidney biopsy were enrolled in a discovery cohort at Charite Berlin (n = 80), an internal validation cohort at Charite (n = 100), and an external validation cohort at The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (n = 140). Urinary immune cells were assessed by flow cytometry. Renal T cell infiltration was evaluated by immunofluorescence in kidney biopsy specimens from the discovery and internal validation cohorts, including 16 patients with acute interstitial nephritis and 9 patients without acute interstitial nephritis. Additionally, CXCL9 was measured by ELISA in 102 urine samples from these cohorts. Results Across all cohorts, 27 patients (8.4%) were diagnosed with acute interstitial nephritis. In the discovery cohort, multiple urinary T cell subsets were increased in acute interstitial nephritis, with activated CD4+ effector memory T cells expressing CD38 and HLA-DR showing the strongest diagnostic performance. This marker outperformed urinary monocytes, eosinophils, and CXCL9 and was validated in both independent cohorts. Across all cohorts, the area under the receiver operating characteristic curve was 0.84 and increased to 0.91 after exclusion of 8 patients receiving corticosteroids. A cutoff of 211 activated CD4+ effector memory T cells per 100 mL urine yielded a sensitivity of 78% and a specificity of 81%. Urinary activated CD4+ effector memory T cell counts correlated with renal CD4+ and CD4+ CD38+ T cell infiltration in acute interstitial nephritis. Conclusions Urinary activated CD4+ effector memory T cells expressing CD38 and HLA-DR represent a promising non-invasive biomarker for the diagnosis of acute interstitial nephritis.

Introduction The hemoglobin, albumin, lymphocytes and platelets (HALP) score, a novel nutritional and inflammatory biomarker, has been used in various chronic disease studies. However, the relationship between the HALP score and chronic kidney disease (CKD) remains poorly elucidated. This study aimed to explore the possible association between the HALP score and CKD. Methods Our analysis encompassed 25,160 adult participants drawn from NHANES cycles spanning 2009 through 2018. Weighted multivariable logistic regression and generalized additive models (GAMs) were employed to evaluate the independent associations between the HALP score and CKD, albuminuria, and low-estimated glomerular filtration rate (eGFR). Threshold effects were examined using two-piecewise linear regression. Subgroup and sensitivity analyses were performed to assess robustness. Receiver operating characteristic (ROC) curve analyses were applied to compare the discriminative capacity of the HALP score with the prognostic nutritional index (PNI), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). The clinical findings were further validated in a 5/6 nephrectomy rat model. Results After adjustment for multiple confounders, higher HALP scores were inversely associated with the risk of CKD (OR = 0.97, 95% CI: 0.94-0.99) and albuminuria (OR = 0.97, 95% CI: 0.93-0.99). However, after full adjustment for demographic characteristics, physical examination indices and laboratory parameters (Model 3), the correlation between the HALP score and low-eGFR was no longer statistically significant. Non-linear analyses revealed a threshold effect, with CKD risk declining as the HALP score increased up to an inflection point of 52.43 (OR = 0.97, 95% CI: 0.95-0.99), beyond which no further protective effect was observed. A similar threshold effect was identified for albuminuria. Subgroup and interaction analyses indicated no meaningful effect modification by age, sex, BMI, hypertension, or diabetes. Sensitivity analyses confirmed the robustness of the results. ROC analysis demonstrated that the HALP score showed superior discriminative ability for CKD and albuminuria compared with PNI, SII, LMR, and PLR. In the animal experiment, CKD model rats exhibited significantly lower HALP scores than controls. Inverse correlations were observed between the HALP score and serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin-to-creatinine ratio (UACR), with UACR showing the strongest correlation, which was consistent with the clinical findings. Conclusion Lower HALP scores are independently associated with increased prevalence of CKD and albuminuria. As an affordable and readily measurable biomarker, the HALP score may facilitate CKD risk assessment.

Objective: To determine the absolute risk of starting dialysis versus mortality among adults with chronic kidney disease (CKD) treated at EsSalud from 2013 to 2022, utilizing data from the Renal Health Surveillance system (VISARE). Methods: This retrospective cohort study analyzed clinical records from the VISARE system (EsSalud). We estimated rates of dialysis initiation and death using Fine & Gray competitive risk models. Additionally, we calculated Restricted Mean Survival Time (RMST), adjusting for age, sex, clinical stage, and geographic region. Results: Among 142,770 adults with confirmed CKD and available glomerular filtration rate data, only 15.2% had albumin-to-creatinine ratio measurements, allowing KDIGO staging of 40,404 patients (28.3%). Mortality without having previously started dialysis exceeded the probability of starting renal replacement therapy (RRT) from G1, becoming more marked in G3 of chronic kidney disease (CKD); the possibility of dialysis is only greater, as expected, in G5. This outcome was most prevalent in regions with limited healthcare coverage. The combination of diabetes, hypertension, and age over 55 (the triad) was associated with reduced restricted mean survival time at both 5- and 10-year horizons across all enrollment cohorts. While Lima saw the highest rates of renal replacement therapy initiation, the Andean and Amazonian regions reported the lowest indicators. Conclusions Death without prior dialysis was the dominant outcome from G1 to G3 in this Peruvian cohort with national insurance, with direct implications for prognostic counseling, recalibration of renal failure risk equations, and equitable expansion of nephrology services in underserved regions. Keywords: Renal Insufficiency, Chronic; Competitive Risk; Diabetes Mellitus; Hypertension; Mortality; Mass Screening.

Background: Initiation of emergency dialysis, often requiring temporary catheter owing to unprepared definitive vascular access, is associated with infectious and vascular complications and suggests advanced chronic kidney disease (CKD) care gaps. Previous studies focused on kidney failure or dialysis timing. This study aimed to predict initiation of emergency dialysis using machine learning and baseline data. Methods: This retrospective cohort study used the Japan Medical Data Center claims data (2014-2022). Adults with an estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 were included. The primary outcome was initiation of emergency dialysis (temporary catheter code without evidence of previous access preparation). Participants were randomly divided into derivation (80%) and validation (20%) cohorts. Logistic regression, support vector machine, XGBoost, LightGBM, and random forest models were evaluated using internal cross-validation, post-hoc calibration of the selected model, and bootstrap confidence intervals. Results: The cohort included 3,062 individuals (derivation; n=2,449, validation; n=613). Emergency dialysis was initiated in 237 participants (7.7%); 185 (7.6%) and 52 (8.5%) in the derivation and validation cohorts, respectively. Validation area under the receiver operating characteristic curve ranged from 0.781-0.799, with the highest value observed for random forest (0.799, 95% confidence interval; 0.740-0.850). Risk stratification showed clear event enrichment in higher predicted risk categories. SHAP analyses identified hemoglobin, proteinuria, baseline eGFR, diabetes history, and diuretic use as key predictors. Decision curve analysis showed greater net benefit than eGFR alone at lower threshold probabilities. Conclusions: Baseline machine learning models showed moderate discrimination for initiation of emergency dialysis and identified clinically plausible predictors. These findings support potential use for risk stratification, although external validation and evaluation within pre-specified care pathways are needed before implementation.

Background Anticoagulants are high-risk medications that require careful consideration of the risks and benefits. In the setting of advanced kidney disease decisions around prescribing anticoagulants is problematic. This relates to a lack of good-quality evidence and the altered renal clearance and protein binding in kidney disease. This leads to prescribing variation and results in patients experiencing different standards of care. The aim of this study was to explore the factors influencing anticoagulant prescribing decisions among nephrology and haematology healthcare professionals in commonly encountered scenarios, in order to better understand variation in prescribing practice. Methods Three case-vignettes were presented to 15 haematology and nephrology professionals as part of a semi-structured interview. Participants were purposively selected based on variable responses to a UK anticoagulant prescribing practice survey. An inductive thematic analysis was undertaken as described by Braun and Clark with an iterative review process to identify final themes. Results There were five main themes that arose from the analysis; evidence, patient factors, knowledge and experience, team influence and systems and they were present across all the three vignettes. The prescribing of anticoagulation in advanced kidney disease is strongly influenced by the knowledge and expertise gleaned by prescribers previous experiences and the incorporation of patient factors. Prescribers commonly seek opinion from senior staff and other members of the multiprofessional team to support their decision making. Decisions are also influenced by organisational factors that are beyond their individual control. Conclusion Development of guidelines, delivery of education and good-quality evidence is needed to improve prescribing variation and ultimately the quality of care provided to patients with advanced kidney disease.

Background: Early renal function decline is often accompanied by bothersome urological symptoms, yet effective early-stage nutritional interventions remain limited. L-Ergothioneine (EGT), a diet-derived antioxidant concentrated in renal tissue via the OCTN1 transporter, has shown renoprotective potential preclinically, but human interventional data are sparse. Methods: In this single-center, open-label, self-controlled trial, 31 adults (aged 45-70 years) with early renal function decline and persistent urological symptoms ([&ge;]3 months) received oral EGT (120 mg/day) for 90 days; 27 completed the study. Participants served as their own controls. The primary outcome was the within-subject change in eGFR (CKD-EPI 2021 creatinine); secondary outcomes included cystatin C-based eGFR, serum creatinine, UACR, a 10-item voiding diary, and a low-back-pain visual analogue scale (VAS). Within-subject changes were assessed by paired t-test or Wilcoxon signed-rank test. Results: Creatinine-based eGFR increased from 86.04 {+/-} 17.89 to 93.25 {+/-} 19.00 mL/min/1.73 m2 (+8.4%; p = 0.0016) and serum creatinine fell by 7.0% (p = 0.015). However, cystatin C-based eGFR and serum cystatin C were unchanged (p = 0.31 and p = 0.99), so the filtration signal was not corroborated by an independent, muscle-mass-independent marker. UACR showed a non-significant downward trend. Patient-reported outcomes improved most robustly: the total voiding diary score decreased by 57.2% (p < 0.0001) and low-back-pain VAS by 67.2% (p = 0.0002), with significant relief of urgency, frequency, and voiding difficulty. No product-related adverse events occurred. Conclusions: In this uncontrolled study, 90-day EGT supplementation was associated with marked improvement in urological symptoms and in creatinine-based eGFR, although the latter was not confirmed by cystatin C. These changes cannot be attributed to EGT alone and may substantially reflect placebo and natural-history effects. The findings are hypothesis-generating and warrant confirmation in a randomized, placebo-controlled trial using validated symptom instruments. Trial Registration: ChiCTR2500108897; Prospectively registered on 2025-09-08.

Recent initiatives by the U.S. Food and Drug Administration and the National Institutes of Health to reduce animal testing in drug development have highlighted the need for in vitro platforms that better recapitulate human biology for preclinical safety assessment. Drug-induced nephrotoxicity remains a major cause of drug attrition, underscoring the need for human-relevant kidney models. To address this, a pump-free human patient-derived proximal tubule microphysiological system was developed by integrating human renal proximal tubular epithelial cells (hRPTECs), isolated from non-tumorous nephrectomy cortex, with a porous membrane-based microfluidic device. Expanded hRPTECs were cultured for 10 days under static conditions or rocker-driven shear stress approximating physiological proximal tubular flow. Shear stress increased epithelial density, enhanced proximal tubule marker expression (Na+/K+-ATPase and aquaporin-1), and improved Zonula occludens-1 and occludin localization. Bulk RNA sequencing demonstrated transcriptomic changes associated with enhanced apical maturation and epithelial signature. In cisplatin-induced injury assays, shear-conditioned epithelia exhibited reduced cell density and increased {gamma}H2AX staining, indicating greater sensitivity to nephrotoxicity. These findings demonstrate that rocker-driven shear stress promotes epithelial maturation in patient-derived hRPTECs. The pump-free human patient-derived proximal tubule microphysiological system offers a practical, scalable, and physiologically relevant platform for modeling flow-dependent proximal tubule biology and assessing human-relevant nephrotoxicity.

Background: Deceased-donor kidney transplantation is a component of the Brazilian transplant system and takes place within a deceased-donation environment that in-cludes donor identification, notification, family approach and authorization, organ allocation, and logistics. This study described temporal, macroregional, and federative unit-level variation in deceased-donor kidney transplantation in Brazil from 2014 to 2024, together with hospitalization-based indicators and contextual indicators of the deceased-donation environment. Methods: This nationwide descriptive time-series study used publicly available secondary data from the Hospital Information System of the Unified Health System (SIH/SUS), the Brazilian Transplant Registry (RBT/ABTO), and the Brazilian National Transplant System (SNT). Indicators includ-ed the number of transplants, transplant rates per million population, kidney transplant waiting list stock, mean length of hospital stay, in-hospital mortality, potential donor notifications, and family interview and refusal proportions. The three databases were analyzed separately and in parallel, without linkage. Results: The annual number of deceased-donor kidney transplants increased over the study period. The kidney trans-plant waiting list stock also increased. Mean length of hospital stay decreased, and in-hospital mortality decreased over time. Marked macroregional and federative unit-level heterogeneity was observed in transplant activity, hospitalization-based indica-tors, and contextual indicators of the deceased-donation environment. Conclusions: Deceased-donor kidney transplantation increased in Brazil between 2014 and 2024, although regional disparities persisted. These findings support monitoring strategies that incorporate contextual indicators alongside measures of transplant activity. Be-cause this was a descriptive study based on secondary data from distinct sources, the findings should not be interpreted as evidence of causal relationships.

Background: Uremic pruritus affects up to 90% of individuals and substantially impairs quality of life, in the group of patients undergoing chronic dialysis. Despite multiple therapeutic options, an optimal and well tolerated treatment remains elusive. Ketotifen, a mast cell stabilizer with antihistaminic properties prevent itch by inhibition of mast cell derived tryptase, which modulates protease-activated receptor-2 (PAR-2) in the cowhage itch pathway. Materials and Methods: In this prospective observational study, 230 chronic dialysis patients were screened, of whom 48 (20.9%) had clinically significant pruritus identified using a structured questionnaire. Twenty-four patients with moderate-to-severe symptoms who were prescribed ketotifen as part of routine clinical care consented to prospective follow-up. Ketotifen was initiated at 1 mg twice daily, with dose escalation to 2 mg twice daily in patients with persistent symptoms according to routine clinical practice. Pruritus severity was assessed using visual (VAS), verbal (VRS), and numerical (NRS) rating scales before and after treatment. Results: After two weeks of initial 1mg therapy, 19 showed significant clinical improvement. Mean scores reduced 77.5 [-&gt;] 27.1 (VAS), 87.5 [-&gt;] 20.8 (VRS), and 74.2 [-&gt;] 25 (NRS) (around 65% reduction with p < 0.001 across all scales). Clinical relief was achieved in 83.3% overall and mild tolerable drowsiness occurred only at the 2mg dose. Conclusion: Ketotifen is a safe, effective and well tolerated option for moderate to severe uremic pruritus in dialysis patients. Larger multicenter studies are warranted to confirm efficacy and optimize dosing.

Introduction People with kidney failure receiving haemodialysis experience significantly high rates of depression. However, there is a lack of evidence on how to treat depression in this population. A significant barrier to effective treatment is the high treatment burden of haemodialysis, which makes additional appointments prohibitive. Behavioural activation (BA) is an evidence-based brief therapy for depression that has been delivered in a variety of different clinical settings. However, it has not previously been evaluated in the haemodialysis setting. Methods This study aims to evaluate the feasibility and acceptability of a cluster randomised controlled trial (cRCT) of intradialytic BA for people with kidney failure. The study consists of three main components: A pilot cRCT, where we will recruit 52 people who are receiving haemodialysis and experiencing symptoms of depression across two sites. Patients will be cluster-randomised to either BA or usual care and will be followed up for three months; a qualitative process evaluation using semi-structured interviews to explore the experiences of patients, healthcare professionals and carers; and a feasibility economic evaluation exploring the feasibility of collecting healthcare resource use data. Results Key findings will include the feasibility of screening and recruiting participants, participant retention, completion of clinical outcome measures, and the acceptability of the intervention. Conclusion If feasible, the next step will be to conduct a definitive, adequately powered cRCT to determine the effectiveness of the intervention in this population, so that we can improve the identification and management of depression for people with kidney failure.

Monoallelic pathogenic or likely pathogenic variants in COL4A3 and COL4A4 occur in approximately 1 in 106 individuals, yet whether these paralogous genes confer equivalent pathogenicity for the same variant classes has not been tested at population scale. Using whole-genome sequencing data from the UK Biobank (UKB; n = 500,000), with replication in the All of Us Research Program (n = 414,000), we performed per-variant association testing, gene-based collapsing analyses and phenome-wide association studies (PheWAS) across haematuria, proteinuria and chronic kidney disease. We identified 64 COL4A3 and 92 COL4A4 rare variants significantly associated with haematuria or proteinuria, generating a quantitative allelic series for clinical variant interpretation. Glycine substitutions within collagenous domains conferred similar risks in both genes. In contrast, truncating and non-collagenous domain (NC1) missense variants were strongly associated with haematuria and proteinuria in COL4A4 carriers but showed substantially attenuated or absent associations in COL4A3 carriers despite comparable carrier frequencies and predicted pathogenicity scores. These findings were independently replicated in All of Us. Genome-wide association analysis identified the COL4A3/COL4A4 locus as the dominant genetic determinant of haematuria, with the signal attributable to the aggregate effects of rare coding variants and no evidence of independent common variant or trans-acting modifier effects. These findings demonstrate substantial gene-specific differences in tolerance to truncating and NC1 variants between COL4A3 and COL4A4, challenging assumptions of equivalent pathogenicity across paralogous collagen IV genes. Gene identity and not variant class alone, should inform risk stratification, variant interpretation and genetic counselling in individuals carrying collagen IV risk genotypes.

Chronic kidney disease (CKD) is accompanied by systemic inflammation, but whether inflammatory proteins improve risk stratification beyond kidney function and albuminuria remains unclear. We profiled baseline serum samples from 683 children with CKD in the prospective European 4C study using the Olink Target 96 Inflammation panel and related protein levels to kidney outcomes over 8 years. eGFR and albuminuria were the dominant determinants of the inflammation-related serum proteome. Nonetheless, a four-protein inflammation score (iScore; CD40, CD137, PD-L1 and CX3CL1), defined from protein residuals independent of eGFR and albuminuria, stratified kidney survival and predicted CKD progression beyond established clinical risk factors (adjusted hazard ratio per elevated protein, 1.11; 95% CI, 1.01-1.22). The score showed concordant associations in 2,770 UK Biobank participants with reduced eGFR (adjusted hazard ratio, 1.08; 95% CI, 1.02-1.14). Kidney single-cell transcriptomic analysis mapped these axes to immune-parenchymal communication programs in CKD, supporting inflammation-based risk stratification across the life course.

Chronic kidney disease is a major global health burden, and its early detection is critical for delaying progression to kidney failure using recently developed targeted therapies. However, current diagnostic screening relies heavily on blood markers that are confounded by muscle mass, and on urine tests that frequently miss structural damage occurring without protein leakage. This creates a critical diagnostic blind spot that hinders timely intervention. Here we show a non-invasive liquid biopsy platform that quantifies a specific protein marker, MUC1, on urinary extracellular vesicles to accurately assess renal parenchymal integrity. By bypassing the systemic metabolic noise of traditional blood tests, our assay provides a remarkably stable, person-specific functional signature. Following extensive validation across diverse cohorts, our longitudinal analysis demonstrated that the discrepancy between this novel urine-based readout and standard blood tests unmasks hidden renal vulnerability, successfully predicting rapid functional decline. By comprehensively evaluating both tubular and glomerular integrity from a single spot urine sample, these findings establish a completely non-invasive, highly scalable prescreening tool that resolves the diagnostic blind spot, enabling broader early detection strategies and ushering in a new era of proactive risk management.

Rationale & Objective: People who live in rural areas with advanced chronic kidney disease (CKD) face well-documented structural barriers to receiving care, yet little is known about how they experience their illness or perceive interactions with their healthcare teams. We aimed to characterize the lived experiences and care perceptions of adults living in rural areas with advanced, pre-dialysis CKD. Study Design: We conducted semi-structured qualitative interviews with patients and care partners. Setting & Participants: We recruited patients with advanced CKD (stages 4-5, not on dialysis) and their care partners from a single hospital-based nephrology clinic in northern New England serving a predominantly rural population. Analytical Approach: We analyzed interview transcripts using participatory Practical Thematic Analysis (PTA), an inductive, stakeholder-engaged approach to qualitative analysis. Results: We interviewed 12 patients and 4 care partners. Four themes were identified: (1) logistical challenges of rural CKD care were pervasive but frequently normalized as an expected feature of rural life; (2) disease progression and future treatments were sources of uncertainty and concern, with expectations about dialysis often shaped by peer accounts rather than clinical discussion; (3) clinical conversations centered on laboratory results and medications, leaving emotional concerns and psychologic challenges unaddressed; and (4) physical symptoms and lifestyle changes were common but frequently attributed to comorbid conditions rather than to CKD. Limitations: Recruitment from a single clinic with a small, racially homogeneous sample limits transferability. While in-person recruitment may have excluded patients with greater transportation barriers, those who attended represent a population navigating substantial access challenges to receive care. Conclusions: Adults living in rural areas with advanced CKD experience logistical, emotional, and informational challenges broadly consistent with those reported in non-rural CKD populations. Patients normalized geographic barriers and did not consistently identify rurality as a source of disadvantage, even as structural barriers persisted. These findings support the development of structured communication approaches in nephrology care that invite discussion of disease trajectory, daily life impacts, and emotional concerns.

Background Donation after circulatory death (DCD) is an increasingly accepted strategy to expand the adult heart donor pool, but its use in children remains limited and incompletely characterized. We compared national characteristics and post-transplant outcomes of pediatric DCD versus donation after brain death (DBD) heart transplantation. Methods We performed a retrospective cohort study of the Organ Procurement and Transplantation Network (OPTN) registry, including patients younger than 18 years who underwent primary isolated heart transplantation between January 1993 and March 2025. Recipients were stratified by donor type (DCD vs DBD). Continuous variables were compared with the Mann Whitney U test and categorical variables with the Fisher exact test. Survival was estimated by the Kaplan Meier method and compared using the log-rank test and Cox proportional hazards regression. Results Of 10,671 pediatric heart transplant recipients, 33 (approximately 0.3%) received DCD allografts. The first DCD transplant was recorded in 2004, with a marked increase in 2023 to 2024. Compared with DBD recipients, DCD recipients were more frequently infants (<1 year, 51.5% vs 28.4%) and more often had congenital heart disease (69.7% vs 47.6%; P=0.033); DCD donors were younger (median 0 vs 6 years; P=0.038) and more frequently died of anoxia (72.7% vs 37.0%; P<0.001). Donor and recipient left ventricular mass were lower in the DCD group (P<0.05), but predicted left ventricular mass matching was similar. DCD recipients had longer hospital stays (median 31.5 vs 19 days; P=0.023); rates of treated rejection, dialysis, stroke, and pacemaker implantation were comparable. Early survival did not differ (30-day, 90-day, and 1-year), and Kaplan Meier survival through 5 years was not significantly different (hazard ratio 1.17; 95% CI 0.49 to 2.81; log-rank P=0.73). More than 90% of DCD transplants were performed in four UNOS regions (11, 4, 5, and 8). Conclusions In this national analysis, pediatric DCD heart transplantation was uncommon but expanding rapidly, concentrated in a few regions, and used preferentially in infants and children with congenital heart disease. Early post-transplant outcomes were not significantly different from DBD, supporting cautious expansion of DCD as a means of enlarging the pediatric donor pool. The small number of DCD recipients and limited followup warrant confirmation in larger, longer-term studies. Keywords: pediatric heart transplantation; donation after circulatory death; donor pool; congenital heart disease; OPTN registry; organ allocation.

Abstract Familial kidney disease is common in Cyprus. Patients with a glomerular phenotype are most likely to have an autosomal dominant variant in collagen type IV alpha 3 chain (COL4A3) or collagen type IV alpha 4 chain (COL4A4) genes but pathogenic variants are not found in the majority of families. We compare the clinical phenotype between two groups of 10 Turkish Cypriot families who lack a pathogenic variant of COL4A3 or COL4A4 but have either the COL4A4 variant p.G545A or p.G999E. Both groups had identical clinical phenotypes with microscopic haematuria detected at least once in 76% of affected family members; urine protein was less than 1 g/day until glomerular filtration rate (GFR) was <30 ml/min. End-stage kidney disease (ESKD) occurred in 24.1% of those over 50 at a median age of 62.8 (36-86) years. Although the genetic cause of renal injury in this large group is still unknown, these families present with a clinical phenotype best characterised as familial hypertensive nephropathy. We propose that this condition accounts for the great excess of renal failure in the Eastern Mediterranean in those over 65 years of age.

Unplanned readmissions after liver transplantation occur in over 30% of recipients, yet no validated prediction models exist, and prior observational studies suffer from immortal time bias. The optimal readmission window for outcome prediction and the feasibility of early risk stratification remain undefined. This study is a retrospective analysis of 922 adult liver transplant recipients (August 2018-August 2025) at a single center. Time-varying Cox regression evaluated 14-, 30-, and 90-day readmission windows as predictors of 1-year mortality, correcting for immortal time bias. Gradient-boosted machine learning models leveraging 528,400 laboratory measurements (28 analytes) predicted 90-day readmission using either complete hospitalization data or data restricted to postoperative day 7. Feature importance was quantified by gain, and clinical utility was assessed through risk stratification. Among 902 hospital survivors, 342 (37.9%) experienced an unplanned readmission within 90 days of initial discharge. Only the 90-day readmission window predicted 1-year mortality in time-varying analysis (HR 1.73, 95% CI 1.17-2.57, p=0.006). The model for readmission using complete data achieved AUC 0.614 (95% CI 0.576-0.652); the postoperative day 7 restricted model achieved AUC 0.615 (95% CI 0.577-0.652), with no meaningful performance difference. The tacrolimus coefficient of variation x peak creatinine interaction was the dominant predictor in both the complete model (17.3% importance, rank 1) and the day 7 restricted model (20.4% importance, rank 2). This interaction stratified patients into high-risk (tacrolimus CV >0.3 and creatinine >2.0 mg/dL; 49.8% readmission) versus low-risk (24.8% readmission) groups (risk ratio 2.01, p<0.001). These results identify a modifiable biological determinant of readmission and establish a framework for targeted interventions to reduce unplanned readmission and improve post-transplant outcomes.

Circulating biomarkers are increasingly used for patient risk stratification in chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF). However, clinically relevant circulating biomarkers remain insufficiently characterized in rodent models recapitulating diabetic cardiorenal disease with HFpEF. To address this gap, we evaluated 20 translationally relevant inflammation-associated biomarkers in the diabetic db/db uninephrectomized (UNx)-ReninAAV mouse model of CKD and HFpEF. db/db UNx-ReninAAV mice exhibited marked increases in circulating soluble urokinase-type plasminogen activator receptor (suPAR) and monocyte chemoattractant protein-1 (MCP-1), and in interleukin 10 (IL-10) at late stages of disease. Histological analyses confirmed increased tissue expression of suPAR in the heart and kidney and of MCP-1 in the heart. Notably, circulating suPAR levels correlated with disease severity, including systolic and diastolic cardiac dysfunction and albuminuria. Together, these results provide a systematic analysis of biomarkers in a rodent model of diabetes, CKD and HFpEF and identify suPAR as the biomarker most closely associated with disease severity.

Objectives: To estimate hyperlipidemia medication order prevalence and associated variables in U.S. skilled nursing facility (SNF) residents. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 447,080 SNF residents with a hyperlipidemia diagnosis identified in PointClickCare's Life Sciences clinical database (January-April 2025) were reviewed. Methods: The presence and absence of medication orders for hyperlipidemia treatments recommended by the American Heart Association were assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 83.3% of residents diagnosed with hyperlipidemia had at least one hyperlipidemia medication order. Statins were ordered by 96.2% of active order residents, while other medication classes i.e., omega-3 fatty acids, cholesterol absorption inhibitors, fibrates were less common (<8%). Risk ratios (RRs) for medication orders ranged from 0.87-1.16. Factors most strongly associated with having an order included hypertension medication orders (RR=1.16), unspecified hyperlipidemia diagnosis (RR=1.10), and active diabetes medication orders (RR=1.09); female sex (RR=0.95) and private (0.94) or other (0.87) payer types were associated with a lower likelihood of having an order. Conclusions and Implications: Most residents with a hyperlipidemia diagnosis had an active relevant medication order, but use of non-statin therapies was rare. Differences in treatment patterns by sex and payer type, along with limited uptake of newer agents, warrant further investigation into prescribing practices and access within SNFs.

Introduction Patients with nephrolithiasis face challenges in making a high-quality, preference sensitive decision. Our prior work established feasibility and patient acceptance of a software-based decision aid (DA). The objectives for this study were to identify implementation strategies for the DA in routine care and determine whether DA implementation enhances decisional quality for patients. Methods New nephrolithiasis patients were recruited from the institution Medical Center from June 2018 to April 2024 to receive a software-based pre-visit DA that measured care preferences and used decision analysis to rank treatments. The RE-AIM framework and Plan-Do-Study-Act (PDSA) cycles were used to improve implementation outcomes. Patients completed survey instruments evaluating decisional conflict, shared decision-making, care satisfaction, and treatment choice following their provider visit. These metrics were compared in the DA cohort (n=81) to those in a usual care cohort (n=78) with Wilcoxon rank-sum and Chi-square (or Fishers exact) tests. Results Implementation data revealed sustained reach and progressive improvement in fidelity. The DA cohort reported higher decisional quality relative to controls (p=0.003) and reported greater support/advice to make a choice (p=0.005). The DA cohort more often discussed options with their doctor (87.5% vs 69.2%, p=0.005) and were more likely to be promoters of their provider (p<0.001) and health system (p=0.029). The DA cohort was less likely to have switched their treatment preference post-consultation (32.1% vs 71.8%, p<0.001) suggesting greater consistency in decision-making. Conclusions Software-based DAs in nephrolithiasis can mitigate decisional conflict, improve SDM, and improve patient satisfaction. Further work should explore broader implementation and long-term clinical outcomes.