Acute Calcitriol‐Mediated PTH Suppression is Attenuated by High Phosphate Diet in Experimental Model of CKD
Bibliographic record
Abstract
Background Chronic kidney disease (CKD) patients have impaired phosphate and calcium excretion as well as vitamin D deficiency, which exacerbates secondary hyperparathyroidism (SHPT). A decrease in renal CYP27B1 conversion of calcifediol leads to reduced levels of calcitriol. SHPT leads to increased bone resorption and is a risk factor for vascular calcification and cardiovascular disease in the CKD population. The effectiveness of calcitriol in managing SHPT is problematic, as significant resistance develops with chronic therapy; a condition that can lead to parathyroidectomy. Aim Determine the time course and impact of increasing dietary phosphate on calcitriol‐induced suppression of PTH in experimental CKD. Methods In Sprague Dawley rats (N=10), a 0.25% adenine 0.5% phosphate diet was fed for 4–5 weeks to generate stable CKD. A single oral calcitriol dose (160ng/kg) was given pre‐CKD, and at 1, 3, and 5 (off adenine) weeks of CKD induction (0.5% dietary phosphate). From 7–8 weeks rats were given increased dietary phosphate (1.0%) and the response to calcitriol was re‐assessed. Changes in circulating PTH, fibroblast growth factor 23 (FGF‐23), calcium and phosphate in response to the biweekly sham or calcitriol dosing were assessed at 0, 4, 8 and 24 hours. Results In CKD rats, PTH increased from 80±25.8 pg/mL to 221±66.7 pg/mL (week 5) and FGF‐23 from 421±26.0 pg/mL to 6803±1510.2 pg/mL (week 5). The two week 1% phosphate markedly increased PTH to 1342±310 pg/mL (8 weeks) and FGF‐23 to 14490±4980.8 pg/mL (7 weeks). In CKD rats on a low phosphate diet, the biweekly calcitriol dose reduced PTH by up to 44% and raised FGF‐23 by 82% whereas in rats on high dietary phosphate PTH was no longer responsive to calcitriol suppression. Conclusion Responses to calcitriol therapy were attenuated with increasing dietary phosphate and increasing CKD severity. This study supports the importance of dietary phosphate restriction in the CKD population to limit the impact of PTH responsiveness and mineral bone disease in this population. Significance Characterization of calcitriol resistance will help to develop new dosing strategies for vitamin D receptor agonists in this population and prevent SHPT and parathyroidectomies. Support or Funding Information Funded by the Canadian Institutes of Health Research This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".