Family Matters: Dissecting the Impact of Family Medical History, APOL1 Genotype, and Sociodemographic Factors on CKD Progression in the Chronic Renal Insufficiency Cohort (CRIC) Study

American Journal of Kidney Diseases · 2026-02-25

Preserving Kidney Function in Children with Chronic Kidney Disease (PRESERVE)

2026-01-06

WCN26-5469 GLOMERULAR TRANSCRIPTOME ANALYSIS REVEALS ENDOTHELIAL DISTURBANCES IN PATIENTS WITH IDIOPATHIC NEPHROTIC SYNDROME

Kidney International Reports · 2026-03-25

Blood Pressure Control in Adolescents With CKD and Risk of Kidney Failure in Young Adulthood

Kidney Medicine · 2026-05-06

<h2>Abstract</h2><h3>Rationale & Objective</h3> Understanding risk factors for chronic kidney disease (CKD) progression during adolescence is essential to improve outcomes for these individuals as adults. The objective of the current study was to retrospectively analyze electronic health records (EHR) of children with CKD to understand the effect of cumulative systolic blood pressure (SBP) load during adolescence on time to kidney replacement therapy or death during young adulthood. <h3>Study Design</h3> Retrospective cohort study <h3>Setting & Participants</h3> Adolescents with chronic kidney disease were enrolled from 14 academic medical centers in the Preserving Kidney Function in Children with Chronic Kidney Disease (PRESERVE) study. Individuals between the ages of 1 and <18 years with ≥2 eGFRs between 30 and <90 mL/min/1.73m² separated by ≥90 days without an intervening eGFR value ≥90 mL/min/1.73m² were included. <h3>Exposure</h3> Cumulative systolic blood pressure (SBP) load was defined using area under and above the SBP curve (i.e., time and magnitude), and time-only approaches using the 50th, 75th, and 90th SBP percentiles. <h3>Outcomes</h3> Time to kidney replacement therapy (KRT, chronic dialysis initiation or kidney transplantation) or death were ascertained via linkage with the United States Renal Data System. <h3>Analytical Approach</h3> Cox proportional hazards models were used to investigate the relationship between BP control and the composite of KRT or death. <h3>Results</h3> The cohort included 2,585 individuals with a median follow-up of 7.45 years (IQR: 6.05-9.20), among whom 4.6% (n=118) met the KRT or death outcome between ages 18-30 years. In an adjusted Cox model, each unit increase (pp*time) in cumulative SBP load above the 90th percentile was associated with 1.36 (95% CI: 1.17, 1.58) times higher hazards of KRT or death between ages 18-19 years. SBP control to <90th percentile for 25%, 50%, and 100% of time between ages 14 to 18 years was associated with a 47%, 72%, and 92% risk reduction of KRT or death between ages 18 to 19 years compared to no SBP control. <h3>Limitations</h3> Misclassification of BP control related to white coat or masked hypertension. Adherence to prescribed anti-hypertensive medications was not assessed. <h3>Conclusions</h3> Worse SBP control during adolescence was associated with a markedly increased risk of kidney failure in young adulthood. Cumulative SBP load derived from EHR data can inform risk of adverse long-term kidney outcomes. <h3>Plain-Language Summary</h3> Chronic kidney disease is commonly accompanied by elevated blood pressure. Understanding risk factors for chronic kidney disease progression during adolescence is essential to improve outcomes for these individuals as adults. We used electronic health records to study the effect of systolic blood pressure load in adolescents with chronic kidney disease on risk of kidney failure in young adulthood. We found that worse systolic blood pressure control during adolescence is associated with a markedly increased risk of kidney failure in young adulthood. The study demonstrates that blood pressure readings from electronic health record data can be used to estimate the risk of adverse long-term kidney outcomes.

Novel R Shiny Tool for Survival Analysis With Time-Varying Covariate in Oncology Studies: Overcoming Biases and Enhancing Collaboration

JCO Clinical Cancer Informatics · 2026-01-01

PURPOSE: Our study is motivated by evaluating the role of hematopoietic cell transplantation (HCT) after chimeric antigen receptor T-cell (CAR-T) therapy for ALL, a debated topic. Because patients may receive HCT at different times after CAR-T infusion or never, HCT post-CAR-T should be considered as a time-varying covariate (TVC). METHODS: Standard Cox models and Kaplan-Meier (KM) curves (naïve method) assume that TVC status is known and fixed at baseline, which can yield biased estimates. Landmark analysis is a popular alternative but depends on a chosen landmark time. Time-dependent (TD) Cox model is better suited for TVC although visualizing survival curves is complex. The newly proposed Smith-Zee method generates appropriate survival curves from TD Cox models. RESULTS: To address these challenges, we developed an open-source R Shiny tool integrating multiple models (naïve Cox, landmark Cox, and TD Cox) and curves (naïve KM, landmark KM, Smith-Zee, and Extended KM) to facilitate TVC analysis. Reanalysis of post-CAR-T HCT's effect on leukemia-free survival (LFS) showed consistent results between naïve and TD Cox models, whereas landmark analyses varied by landmark time. A separate data analysis of chronic graft-versus-host disease and survival showed that substantial differences emerged across statistical methods. Simulations revealed increased bias in naïve methods when TVC changed late and minimal bias when TVC changes occurred early relative to time to events. CONCLUSION: We recommend TD Cox models and Smith-Zee curves for robust TVC analysis. Our R Shiny tool supports standardized analyses without requiring data sharing, thereby promoting collaboration across different institutions and providing a practical tool to advance survival analysis in oncology research.

Comparative Effectiveness of Antihypertensive Medications in Children With Chronic Kidney Disease

JAMA Pediatrics · 2026-03-16 · 1 citations

Importance: Hypertension is a major modifiable factor for kidney function decline in chronic kidney disease (CKD). Comparative trials of antihypertensive medications in pediatric CKD are lacking. Objective: To evaluate the comparative effectiveness of renin-angiotensin-aldosterone system inhibition (RAASi) vs calcium channel blockade (CCB), the most widely used first-line antihypertensive treatment approaches in pediatric CKD, on preservation of kidney function. Design, Setting, and Participants: Using target trial emulation methods, this comparative-effectiveness study emulated a pragmatic, open-label clinical trial using electronic health record data from the Preserving Kidney Function in Children with CKD (PRESERVE) study from January 2009 through December 2020. Thirteen health care institutions from 5 PCORnet Clinical Research Networks were represented. Children and adolescents aged 2 to 20.9 years with CKD stage 2-4 and systolic blood pressure higher than the 90th percentile or with a hypertension diagnosis who initiated treatment with RAASi or CCB were included. Exclusion criteria included kidney replacement therapy, renal artery stenosis, malignancy, and pregnancy. Data analysis was completed in July 2025. Exposures: Incident RAASi or CCB treatment. Randomization was emulated by propensity score weighting to balance groups on sociodemographic factors, institution, year, CKD etiology, proteinuria, CKD stage, obesity, health care use, medications, comorbidities, and blood pressure control (percentage of time at greater than the 90th percentile). Main Outcomes and Measures: The primary outcome was progression to kidney replacement therapy within 2 years of follow-up, ascertained through linkage with the United States Renal Data System. The secondary outcome was a composite of kidney replacement therapy, 50% decline in estimated glomerular filtration rate, or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. Cox proportional hazards regression with propensity score stratification was used to estimate adjusted hazard ratios (aHRs) in the intention-to-treat analysis. Adjusted analyses also compared systolic blood pressure control within 2 years of follow-up. Results: Of 2762 children and adolescents, 1757 initiated RAASi (median [IQR] age, 13.1 [9.2-15.5] years; 897 [51.1%] male) and 1005 initiated CCB (median [IQR] age, 12.6 [8.4-15.3] years; 500 [49.8%] male). In adjusted analyses, RAASi was associated with reduced risk of both kidney replacement therapy (aHR, 0.58; 95% CI, 0.40-0.84, P = .004) and the secondary composite outcome (aHR, 0.67; 95% CI, 0.53-0.83). Systolic blood pressure control was better with RAASi than CCB (29% vs 39% of time >90th percentile). Conclusions and Relevance: In this comparative-effectiveness study, RAASi was associated with lower risk of CKD progression and better blood pressure control compared to CCB. Findings support first-line use of RAASi for antihypertensive treatment in pediatric CKD.

Analysis of Correlated Image Features Using Scalar‐On‐Matrix Regression

Statistical Analysis and Data Mining The ASA Data Science Journal · 2026-04-01

ABSTRACT Image features from digital kidney biopsies may serve as novel biomarkers of kidney function in glomerular disease. Every subject's biopsy contains a different number of histologic objects, and for every object, a common set of image features is measured across all subjects. These data can be represented by a matrix for each subject with the row dimension representing the objects and the column dimension representing the image features which are computed per object. However, no existing regression method can select informative features of outcomes when feature matrices are unbalanced across subjects and features are correlated. Therefore, we developed the Random CLUstering Structured lasSO (Random CLUSSO), a bootstrap‐based and L1‐penalized scalar‐on‐matrix approach. We demonstrated through simulations that Random CLUSSO has lower bias and a higher true positive rate for identifying informative image features relative to existing approaches when features are correlated. Finally, we applied Random CLUSSO to predict kidney function using image features from kidney biopsies of subjects with glomerular disease from the Nephrotic Syndrome Study Network (NEPTUNE) and Cure Glomerulonephropathy (CureGN) studies.

Erratum: Novel R Shiny Tool for Survival Analysis With Time-Varying Covariate in Oncology Studies: Overcoming Biases and Enhancing Collaboration

JCO Clinical Cancer Informatics · 2026-04-01

Long-Term Comparative Effectiveness of Rituximab vs. Calcineurin Inhibitors for the Treatment of Membranous Nephropathy

Journal of the American Society of Nephrology · 2025-10-01

Improving Frozen Kidney Biopsy Interpretation Using DUET-Generated Virtual PAS Stains

medRxiv · 2025-11-13

Frozen section biopsies stained with Hematoxylin & Eosin (H&E) are standard for assessing donor kidneys but are often interpreted by general pathologists with limited renal expertise, and hindered by freezing artifacts and poor tissue morphology. There is currently no rapid, cost-effective, and easily deployable method for generating virtual special stains and quantifying clinically significant histopathological features on frozen section H&E slides. This study evaluates the utility of DUET-generated virtual Periodic acid-Schiff (vPAS) stains produced from H&E-stained frozen kidney biopsies. DUET produces virtual PAS by combining pixel-registered brightfield and fluorescence images from the frozen section H&E-stained slide, overlaying extracted collagen masks to generate the virtual stain. Renal and general pathologists evaluated interstitial fibrosis/tubular atrophy (IF/TA), inflammation, and arteriosclerosis on 29 kidney biopsies, comparing their assessments using H&E images alone versus using both H&E and virtual PAS images. Among general pathologists' evaluations, ICC scores from the H&E to virtual PAS stain increased for IF/TA percentage, inflammation percentage, and arteriosclerosis number. For renal pathologists' evaluations, ICC scores from the H&E to virtual PAS stain increased for the percentage of sclerotic glomeruli, IF/TA percentage, inflammation percentage, and number of arteriosclerotic lesions. No improvement in ICC score was observed for arteriolar hyalinosis in either pathologist's group. We have demonstrated that the use of frozen virtual PAS stains enables higher consistency among pathologist evaluations when compared to the use of frozen section H&E alone for various metrics used to assess donor kidney viability. This approach has the potential to reduce diagnostic variability, improve transplant decision-making, and optimize donor kidney utilization.