Cardiovascular and Thromboembolic Events in Children and Adults With Glomerular Disease: Findings From the Cure GlomeruloNephropathy (CureGN) Network
Bibliographic record
Abstract
Rationale & ObjectiveCardiovascular (CV) and thromboembolic (TE) events are known complications of glomerular disease (GD), but their incidence and risk factors are poorly characterized. This analysis describes CV and TE outcomes in the Cure GlomeruloNephropathy (CureGN) Network.Study DesignProspective cohort study.Setting & ParticipantsCureGN is a prospective cohort study of children and adults with biopsy-proven minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy (IgAN)/vasculitis (IgAV). Data from 2,545 children and adults (23% MCD, 23% MN, 25% FSGS, 29% IgAN/IgAV) was analyzed.ExposureEstimated glomerular filtration rate (eGFR), proteinuria, serum albumin, tobacco use, body mass index, hypertension, renin-angiotensin-aldosterone system.OutcomesCV and TE events.Analytic ApproachKaplan–Meier curves were used to estimate cumulative incidence, and multivariable Cox proportional hazards models were fitted to estimate associations of histologic diagnosis, age, sex, and race. Laboratory and other clinical data were evaluated separately in models adjusted for base model covariates.ResultsMedian follow-up time was 4.6 years (IQR 2.7-6.1). The cumulative incidence of first CV and TE event postbiopsy was 3% and 2% in children and 10% and 5% in adults, respectively. No association between GD subtype and risk of CV or TE event was detected. Older age and Black race were associated with higher risk of first CV and TE event {hazard ratio (HR) (95% confidence interval {CI}) per 5 years, CV = 1.17 (1.12-1.23); TE = 1.11 (1.05-1.18); for Black race, CV = 1.62 (1.03-2.56), TE = 2.25 (1.27-4.01)}. Lower eGFR, higher urinary protein-creatinine ratio (UPCR), and lower serum albumin levels at enrollment were associated with higher risk of first CV and TE event (eGFR per 10 mL/min/1.73 m2, CV = 0.87 [0.81-0.93], TE = 0.80 [0.73-0.88]; UPCR per mg/mg, CV = 1.04 [1.02-1.07], TE = 1.03 [1.00-1.07]; serum albumin per g/dL, CV = 0.75 [0.59-0.95], TE = 0.71 [0.53-0.96]).LimitationsAge of cohort, duration of follow-up.ConclusionsIn CureGN, elevated risk of incident CV and TE events is associated with severity of kidney disease rather than GD subtype.Plain-Language SummaryIndividuals with glomerular disease are at risk for cardiovascular and thromboembolic events. The aim of our study was to determine the frequency and risk factors for such events in adults and children with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy/vasculitis enrolled in the CureGN study. Our ultimate goal is to equip physicians with tools to identify high-risk individuals and help develop mitigative therapies. We found that poor kidney function, low serum albumin level, and high levels of urine protein at the time participants entered the study, along with older age and self-reported Black race were associated with a higher risk of both cardiovascular and thromboembolic events. In addition, these risk factors are more important than the specific type of glomerular disease. Cardiovascular (CV) and thromboembolic (TE) events are known complications of glomerular disease (GD), but their incidence and risk factors are poorly characterized. This analysis describes CV and TE outcomes in the Cure GlomeruloNephropathy (CureGN) Network. Prospective cohort study. CureGN is a prospective cohort study of children and adults with biopsy-proven minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy (IgAN)/vasculitis (IgAV). Data from 2,545 children and adults (23% MCD, 23% MN, 25% FSGS, 29% IgAN/IgAV) was analyzed. Estimated glomerular filtration rate (eGFR), proteinuria, serum albumin, tobacco use, body mass index, hypertension, renin-angiotensin-aldosterone system. CV and TE events. Kaplan–Meier curves were used to estimate cumulative incidence, and multivariable Cox proportional hazards models were fitted to estimate associations of histologic diagnosis, age, sex, and race. Laboratory and other clinical data were evaluated separately in models adjusted for base model covariates. Median follow-up time was 4.6 years (IQR 2.7-6.1). The cumulative incidence of first CV and TE event postbiopsy was 3% and 2% in children and 10% and 5% in adults, respectively. No association between GD subtype and risk of CV or TE event was detected. Older age and Black race were associated with higher risk of first CV and TE event {hazard ratio (HR) (95% confidence interval {CI}) per 5 years, CV = 1.17 (1.12-1.23); TE = 1.11 (1.05-1.18); for Black race, CV = 1.62 (1.03-2.56), TE = 2.25 (1.27-4.01)}. Lower eGFR, higher urinary protein-creatinine ratio (UPCR), and lower serum albumin levels at enrollment were associated with higher risk of first CV and TE event (eGFR per 10 mL/min/1.73 m2, CV = 0.87 [0.81-0.93], TE = 0.80 [0.73-0.88]; UPCR per mg/mg, CV = 1.04 [1.02-1.07], TE = 1.03 [1.00-1.07]; serum albumin per g/dL, CV = 0.75 [0.59-0.95], TE = 0.71 [0.53-0.96]). Age of cohort, duration of follow-up. In CureGN, elevated risk of incident CV and TE events is associated with severity of kidney disease rather than GD subtype.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".