Metabolic Acidosis Is Associated with CKD Progression: A Longitudinal Analysis of >100,000 US Community-Based Patients
Bibliographic record
Abstract
Background: To delay the progression of CKD, it is imperative to identify modifiable risk factors and then to evaluate efficacy of interventions. Here we assess the role of metabolic acidosis as an independent risk factor for CKD progression in patients (pts) with non-dialysis-dependent CKD Stages 3-5. Methods: De-identified electronic medical records (Optum® EMR), 2007-2019 were queried to identify pts with non-dialysis CKD Stages 3-5, (2 consecutive eGFR values >10 and <60 mL/min/1.73m2 90-365 days apart) followed by 2 consecutive serum bicarbonate values 28-365 days apart, both 12 to <22 mEq/L (metabolic acidosis) or 22 to <30 mEq/L (normal serum bicarbonate) and ≥2 yrs of post-index data or death within 2 yrs. Pts (N = 136,067) were followed for up to 11.5 yrs for evidence of CKD progression, measured as a ≥40% decline in eGFR from baseline and as progression of ≥ 1 CKD stage from baseline using laboratory data. We describe outcomes at 2 yrs and used Cox proportional hazards models over the entire follow-up period to examine potential confounders: age, sex, race/ethnicity, eGFR, log albumin-creatinine ratio, diabetes, hypertension, heart failure, and weighted Charlson Comorbidity Index. Results: 75,127 pts (55%) progressed 1 or more CKD stages within 2 yrs. The incidence of CKD progression within 2 years was significantly higher in pts with metabolic acidosis compared to pts with normal serum bicarbonate, irrespective of the endpoint (≥40% decline in eGFR: 38.3% vs. 20.4%, P< 0.0001; progression of ≥ 1 CKD stage: 66.7% vs. 54.5%, P< 0.0001). During the up to 11.5-yrs of follow-up (median 4.2 yrs), serum bicarbonate was independently associated with CKD progression; hazard ratios per 1 mEq/L increase in serum bicarbonate were 0.969, CI: 0.965-0.973 for a ≥40% decline in eGFR and 0.975, CI: 0.972-0.977 for progression ≥1 CKD stage. Conclusions: In pts with non-dialysis CKD, serum bicarbonate levels below 22 mEq/L were independently associated with increased risk of CKD progression. Large randomized trials targeting treatment of metabolic acidosis to slow CKD progression are needed. There was a 2.5-3.0% risk reduction for a ≥40% decrease in eGFR or progression by ≥1 CKD stage for every 1 mEq/L increase in serum bicarbonate. Funding: Commercial Support - Tricida, Inc.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".