Clonal Hematopoiesis of Indeterminate Potential Is Associated with Kidney Disease Progression in a Multi-Cohort Meta-Analysis of Individuals with CKD
Bibliographic record
Abstract
Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging caused by acquired mutations in blood stem cells. CHIP causes myriad end-organ damage, including a doubling of the risk of cardiovascular disease independent of traditional risk factors. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with a greater effect for CHIP driven by mutations in genes other than DNMT3A (non-DNMT3A CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes. Methods: In this study, we examine the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients: the Chronic Renal Insufficiency Cohort (CRIC), the African American Study of Kidney Disease (AASK), the Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT), and BioVU (total N = 4853). The primary outcome was CKD progression (composite of 50% kidney function decline or end-stage kidney disease). Analyses were adjusted for age, age2, sex, self-reported race, and the following baseline parameters: eGFR, proteinuria, smoking status, BMI, diabetes status, hypertension, and cardiovascular disease history. Results: Across all cohorts, the average age was 67.4 years, the average baseline eGFR was 41.2 ml/min/1.73m2, and 25% had CHIP. In a random-effects meta-analysis, non-DNMT3A CHIP was associated with a 59% increased risk of incident CKD progression (HR 1.59, 95% CI: 1.01-2.51). This effect was slightly more pronounced in the subgroup with baseline eGFR ≥ 30 ml/min/1.73m2 (HR 1.77, 95% CI: 1.06-2.98). Conclusions: Non-DNMT3A CHIP is a potentially targetable novel risk factor for CKD progression in a multi-cohort meta-analysis. Funding: NIDDK Support, Other NIH Support - Canadian Institutes of Health Research Project Grant (application # 427810), R01DK132155, R01DK125782, Government Support - Non-U.S.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.015 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".