Clonal Hematopoiesis of Indeterminate Potential and Progression of CKD
Bibliographic record
Abstract
Key Points Non- DNMT3A clonal hematopoiesis of indeterminate potential was associated with CKD progression in a meta-analysis of 5654 individuals with CKD. In an adenine-induced CKD mouse model, Tet2 -clonal hematopoiesis of indeterminate potential was linked to lower GFR, increased kidney inflammation, tubular injury, and fibrosis. Background Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. CHIP has been associated with incident AKI and kidney function decline in the general population, particularly mutations in CHIP genes other than DNMT3A (termed non- DNMT3A CHIP). Previous studies of CHIP in individuals with CKD had limited sample sizes and conflicting findings. Methods We examined CHIP and CKD progression in four CKD cohorts ( N =5654): the Chronic Renal Insufficiency Cohort, the African American Study of Kidney Disease, individuals with CKD from the BioVU biorepository, and the Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events. Primary outcomes were incident CKD progression (50% eGFR decline or kidney failure) and eGFR slope over time. In addition, kidney function and pathology were assessed in a Tet2 -CHIP mouse model of CKD induced by dietary adenine. Results Across all cohorts, the average age was 66±11 years, with an average baseline eGFR of 43±15 ml/min per 1.73 m 2 , and 24% had CHIP. After meta-analysis, non- DNMT3A CHIP was associated with a 64% higher relative risk of incident CKD progression (hazard ratio, 1.64; 95% confidence interval, 1.00 to 2.68), with the strongest effect observed in individuals with baseline eGFR 30–60 ml/min per 1.73 m 2 (hazard ratio, 1.85; 95% confidence interval, 1.18 to 2.90). Non- DNMT3A CHIP carriers also exhibited a faster eGFR decline ( β , −0.62±0.28 ml/min per 1.73 m 2 per year; P = 0.03). In a dietary adenine mouse model of CKD, Tet2 -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis. Conclusions Non- DNMT3A CHIP was associated with CKD progression among individuals with CKD. Furthermore, Tet2 -CHIP mouse models support a causal role in kidney injury.
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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 | 0.005 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.014 |
| Bibliometrics | 0.002 | 0.002 |
| 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".