Among Patients Meeting the KDIGO CKD Practice Point Criterion for Treatment of Metabolic Acidosis, Higher Serum Bicarbonate Concentrations Are Associated with Slower CKD Progression
Bibliographic record
Abstract
Background: Lower serum bicarbonate concentrations in patients with CKD and metabolic acidosis are associated with worse clinical outcomes including faster CKD progression. Less clear is to what extent raising bicarbonate delays CKD progression. The 2024 KDIGO CKD guideline recommends, as a practice point, the use of pharmacological treatment in patients with serum bicarbonate < 18 mEq/L. We explored the relation between achieved serum bicarbonate and CKD progression using data from the VALOR-CKD study, which evaluated the safety and efficacy of veverimer, a non-absorbed polymer that removes hydrochloric acid from the gastrointestinal tract. In this study, 1,480 patients with CKD (eGFR 20-40 mL/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12-20 mEq/L) were randomized, after a single-blind active treatment period, to veverimer or placebo and followed for a median of 24.5 months. The difference in achieved serum bicarbonate concentrations between treatment groups was only 1.3 mEq/L and the trial failed to show a slowing of CKD progression. Methods: In a post-hoc analysis restricted to patients with baseline serum bicarbonate < 18 mEq/L, we evaluated the relation between the average serum bicarbonate concentration achieved over the course of the randomized treatment period (<20, ≥22 mEq/L, ie > 4 mEq/L serum bicarbonate increase), and CKD progression using a Cox proportional hazards model. CKD progression was defined as the time to the first kidney composite endpoint (KCE) of a confirmed reduction in eGFR ≥40%, ESKD (requiring dialysis or transplantation), or death. Results: The patients who achieved average serum bicarbonate concentrations ≥22 mEq/L, irrespective of treatment received, experienced a significantly reduced risk of KCE, HR=0.52 (CI 0.36 to 0.75), p <0.0005, relative to those with serum bicarbonate concentrations <20 mEq/L. Conclusion: This post-hoc analysis from the VALOR-CKD trial provides supportive evidence that in a CKD population with serum bicarbonate concentrations meeting the KDIGO practice point criterion for treatment of metabolic acidosis (< 18 mEq/L), higher achieved serum bicarbonate concentrations are associated with slower CKD progression.
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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 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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".