Clonal Hematopoiesis of Indeterminate Potential Is Associated With a Higher Risk of Incident AKI
Bibliographic record
Abstract
Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related process wherein an acquired driver mutation in a hematopoietic stem cell produces a resilient clonal leukocyte population with dysregulated inflammatory signaling. The presence of CHIP has been associated with the progression of chronic kidney disease. We tested whether CHIP is a novel risk factor for acute kidney injury (AKI) in two community-based cohorts. Methods: We evaluated participants from the Atherosclerosis Risk in Community (ARIC; N = 10,570) and Cardiovascular Health Study (CHS; N = 2,792). We identified somatic DNA mutations in peripheral leukocytes that met established criteria for CHIP using whole exome and whole genome data. AKI events were previously ascertained in both cohorts based on hospitalization codes with additional validation by manual chart review in CHS. We used proportional hazards regression to test associations of CHIP with AKI after adjustment for relevant confounders. Results: CHIP was identified in 7.6% of ARIC participants (median age: 58) and 14.5% of CHS participants (median age: 72). The incidence rate of AKI was higher among persons with CHIP in both cohorts: 12.6 vs. 10.4 events per 1000 person-years in ARIC and 6.6 vs. 4.4 events per 1000 person-years in CHS. In a fixed-effects meta-analysis adjusted for age, age2, sex, and baseline eGFR, the presence of CHIP was associated with an estimated 18% greater risk of AKI (HR 1.18, 95% CI: 1.02 - 1.37). The risk for AKI was greatest for mutations in driver genes other than DNMT3A (non-DNMT3A CHIP; HR 1.29, 95% CI: 1.07 - 1.55). Conclusions: CHIP is associated with a greater risk of incident AKI in two large community-based cohorts. Non-DNMT3A CHIP mutations demonstrate the strongest associations with incident AKI. CHIP may therefore be a novel risk factor for AKI that could partially explain the strong age dependency of this condition. Future studies will elucidate which subtypes of CHIP pose the highest risk of kidney sequelae and in which scenarios emerging treatments for CHIP would be beneficial. Funding: Other NIH Support - NHLBI Trans-Omics for Precision Medicine
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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 | 0.004 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.007 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| 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".