Prospective associations between the CKD-mineral bone disorder and metabolic acidosis
Bibliographic record
Abstract
BACKGROUND: The common chronic kidney disease (CKD)-associated complications of mineral bone disorder (MBD) and metabolic acidosis share some biochemical features that physiologic studies suggest may be linked by the effects of progressive acidosis on bone and kidney. To explore this further, we examined prospective associations between key elements of the CKD-MBD and the subsequent appearance of subclinical and clinical metabolic acidosis in patients with stage 3/4 CKD. METHODS: Post hoc analysis of 1993 CAN AIM TO PREVENT participants followed for 2.86 years per participant. Mixed-effects linear and logistic regression were used to evaluate prospective associations between phosphate, calcium, 25(OH)D, PTH, and FGF-23 with (1) declining plasma bicarbonate, (2) subclinical metabolic acidosis (bicarbonate 22-24 mmol/L), and (3) clinical metabolic acidosis (bicarbonate < 22 mmol/L). RESULTS: Each mmol/L increase in phosphate predicted a lower bicarbonate (- 1.29 mmol/L (95% CI - 1.61, - 0.98; p < 0.001)), and increased odds for subclinical (OR 1.92 (1.32, 2.79); p = 0.001) and clinical metabolic acidosis (OR 5.03 (3.16, 7.93); p < 0.001). Each mmol/L increase in calcium predicted a higher bicarbonate (2.70 mmol/L (2.11, 3.30; p < 0.001)), and decreased odds for subclinical (OR 0.23 (0.11, 0.46); p < 0.001) and clinical metabolic acidosis (OR 0.15 (0.06, 0.37); p < 0.001). Each unit increase in log-transformed 25(OH)D predicted a higher bicarbonate (0.38 mmol/L (0.23, 0.53); p < 0.001)), and decreased odds for subclinical (OR 0.67 (0.56, 0.80); p < 0.001) and clinical metabolic acidosis (OR 0.65 (0.50, 0.82); p < 0.001). Log-PTH exhibited a non-linear relationship with acidosis risk: moderate elevations were associated with reduced acidosis risk (OR 0.60 (0.40, 0.90); p = 0.013), while higher levels predicted an increased risk for subclinical (OR 1.42 (1.02, 1.98); p = 0.041) but not clinical metabolic acidosis (OR 1.44 (0.93, 2.24); p = 0.103). No significant associations were found between log-FGF-23 and acidosis risk (OR 1.02 (0.88, 1.19); p = 0.767). CONCLUSION: Key elements of the CKD-MBD were independently and prospectively associated with the subsequent development of subclinical and clinical metabolic acidosis. Future studies could examine whether a causal relationship exists between progressive metabolic acidosis and the CKD-MBD.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 |
| 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".