Glomerular Permselectivity Associates With Higher Risk of Kidney Failure and Death in Type 2 Diabetes
Bibliographic record
Abstract
Background: Hydrodynamic models of hindered solute transport are used to characterize the size selective properties of the glomerular barrier. One model assumes the glomerular capillary is perforated by restrictive cylindrical pores of identical pore radius and a parallel shunt pathway of nonrestrictive pores characterized by a parameter, ωo, that estimates the fraction of total filtrate passing through the shunt. We reported previously that type 2 diabetes (T2D) associated with an increase in to. Here we examine whether ωo associates with incident kidney failure or death in Pima Indians with T2D. Methods: Iothalamate GFR and fractional clearance of dextrans of graded sizes were measured in 185 adults (74 men, 111 women) with T2D. ωo was computed from the dextran sieving data. Hazard ratios (HR) for kidney failure or death were expressed per 1 standard deviation (SD) increase of ωo by Cox regression after adjusting for age, sex, GFR, ACR, HbA1c and mean arterial blood pressure (MAP). Results: At baseline, mean age (±SD) was 43±10 years, diabetes duration 8.8±8.7 years, HbA1c 8.9±2.4%, MAP 93±12 mm Hg, GFR 147±46 ml/min, and median (IQR) ACR was 41 (10-229) mg/g. During a median follow-up of 29 years, 70 participants developed kidney failure and 134 died, 60 after developing kidney failure. Baseline ωo was higher in participants who developed kidney failure (0.00262 ± 0.00095 vs 0.00204 ±0.00077, P=0.0016) or died (0.00240 ± 0.00086 vs 0.00188 ± 0.00097, P=0.015). After adjustment, each 1 SD increase in baseline ωo associated with increased risk of kidney failure (HR: 1.60, 95% CI 1.20-2.14) and death (HR: 1.34, 95% CI 1.06-1.68) [Table]. Conclusions: Enhanced transglomerular passage of test macromolecules associated with kidney failure and death, independent of albuminuria and GFR, suggesting that mechanisms responsible for impaired glomerular barrier size selectivity are important determinants of adverse health outcomes in T2D. Funding: NIDDK Support, Other NIH Support - N01-DK-6-2285 and N01-DK-7-2291 Hazard ratio for kidney failure and death according to baseline shunt coefficient (ωo)
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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 | 0.001 |
| 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".