Abstract 1084: Differential Expression Of MicroRNAs In Patients With End Stage Renal Disease Target The Klotho/FGF23 Signaling Axis And May Attenuate Left Ventricular Hypertrophy
Bibliographic record
Abstract
Introduction: Conventional hemodialysis (CHD) is the standard method of dialysis with concomitant changes in the cardiovascular system that may result in left ventricular hypertrophy (LVH). Importantly, increased frequency of dialysis reduces cardiac complications by regulating fluid status. Klotho and Fibroblast Growth Factor 23 (FGF23) has been shown to be expressed in a reciprocal fashion in patients with end-stage renal disease with LVH. Research Questions/Hypothesis: The Klotho/FGF23 axis may be regulated by circulating microRNAs (miRs) in CHD patients that transition to nocturnal hemodialysis (NHD) thereby regulating the development of LV mass. Goals/ Aims: To define alterations in expression of circulating miRs in patients transitioning from CHD to NHD and correlate the miR signatures with alterations in LV mass. Methods/Approach: Total RNA was isolated from serum of patients undergoing CHD and NHD and used to define the differential expression of miRs via microarray analysis. In parallel, circulating levels of Klotho and FGF23 were measured via ELISA analysis. Results/Data: We identified miRs with differential expression patterns in CHD vs NHD that targeted the Klotho/FGF23 axis. In patients with ≥10% increase or decrease of LV mass, a subset of miRs were identified that regulated the Klotho/FGF23 axis, namely let-7 members, miR-200c, miR-1 and miR-30c. There was no significant correlation between Klotho levels and LV mass in ESRD patients (p >0.05). However, we observed an association between FGF23 levels and LV mass in patients who were treated with NHD such that there were increased circulating FGF23 levels with increased LV mass, and vice versa (p=0.008, two-way ANOVA). Conclusion: Our novel findings have identified the differential expression of miRs in patients that transition from CHD to NHD with concomitant alterations in LV mass. Therapeutic delivery of miR antagomirs or mimics may mitigate cardiac hypertrophy in patients with renal disease by regulating the Klotho/FGF23 axis.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".