Clonal Hematopoiesis of Indeterminate Potential Is Associated with AKI
Bibliographic record
Abstract
Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized risk factor for several chronic diseases of aging including cardiovascular disease and chronic kidney disease. In these contexts, clonal populations of mutated myeloid cells contribute to end-organ damage through inflammatory dysregulation. We recently identified CHIP as a novel risk factor for AKI: it was associated with an increased risk of incident AKI in ICD code-based prospective clinical data from three large cohorts totalling nearly half a million individuals (adjusted hazard ratio: 1.26, 95% CI: 1.19-1.34). Methods: In the current work, we sought to investigate determine whether CHIP was associated with impaired functional recovery from AKI. We first examined the association between CHIP and AKI recovery in the ASSESS-AKI cohort. We then assessed long-term post-AKI outcomes in a mouse model of CHIP (partial Tet2-/- bone marrow transplant) subjected to ischemia reperfusion injury. Results: We identified that certain subtypes of CHIP exhibited a non-resolving pattern of injury and had poorer long-term outcomes after AKI. At 28 days post-ischemic injury, we observed higher levels of kidney injury markers KIM-1 and NGAL as well as more kidney fibrosis in the CHIP mice compared to wild type mice. Kidney macrophage infiltration was markedly increased in CHIP mice at this timepoint, and concomitant upregulation of pro-inflammatory and fibrotic signaling pathways was noted. Conclusions: This work identifies CHIP as a novel and potentially targetable risk factor for impaired recovery from AKI. Funding: NIDDK Support, Other NIH Support - Canadian Institutes of Health Research Project Grant (application # 427810), R01DK132155, 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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.001 | 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".