Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Factors of Vitamin C Renal Leak
Bibliographic record
Abstract
Reduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C excretion: a renal leak. We hypothesized that vitamin C renal leak may be the consequence of disease-mediated dysregulation affecting the renal tubules, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. The study objective was to investigate the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal storage disease associated with renal tubular dysfunction and low plasma vitamin C concentration. This was a non-randomized cross-sectional cohort study of males with Fabry disease (n = 34) and healthy male controls (n = 33). To determine primary outcome of vitamin C renal leak, matched urine and fasting plasma vitamin C measurements were obtained following an overnight fast. Based on data from healthy men, vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 µM. Exploratory outcomes assessed the association between renal leak and clinical parameters; and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. Proof-of-concept studies were conducted using two mouse models. Compared with healthy men, Fabry cohort had 16-fold higher odds of renal leak (6% vs 52%: OR16, P < 0.001). Renal leak was associated with higher protein creatinine ratio (p = 0.01), lower hemoglobin (p = 0.002) and hematocrit (p = 0.008). Renal leak, but not plasma vitamin C, was associated with a non-synonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (p = 0.01 and p = 0.47 respectively). Using two mouse models, we recapitulated the relationships between renal leak, dysregulated vitamin C renal reabsorption and low plasma vitamin C concentrations. Increased prevalence of vitamin C renal leak in Fabry disease may result from dysregulated vitamin C renal physiology, with significant clinical and genomic associations. Renal leak may be more sensitive than plasma vitamin C in evaluating genomic associations in small cohorts. Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20,892–1372.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".