336-OR: Females Undergoing Islet Transplantation with CNI-Based Immunosuppression May Be at Higher Risk of Renal Function Decline
Bibliographic record
Abstract
Islet transplantation (ITx) is an established treatment for recurrent, severe hypoglycemia in type 1 diabetes, however, requires lifelong immunosuppression (IS) which can be nephrotoxic. We conducted a risk regression to identify factors associated with progression to Stage 3 CKD (S3CKD) or worse post-ITx. We used data from adults undergoing ITx alone at the University of Alberta Hospital between March 11 1999 and Oct 1 2019 with >1 year follow up. IS included tacrolimus and sirolimus/mycophenolate. We identified episodes of irreversible S3CKD as eGFR <60 ml/min/1.73m2 for ≥90d in addition to a final 12m average eGFR below threshold. We conducted multivariable competing risk (death) regression with the covariates: baseline eGFR, age at first ITx, diabetes duration, total ITx count, mean tacrolimus trough levels in year 1 post-ITx, number of acute kidney injury (AKI) events in year 1 post-ITx, sex, baseline hypertension and sirolimus exposure. We identified 199 adults (41% M followed for a median 76.1m [IQR 38.0-131.6]), of which 47.7% progressed to S3CKD within a median 28m [IQR 9-57]. Female sex and more AKI events substantially increased the risk of progression to S3CKD (HR 1.50, [95% CI 1.31,1.80, p =0.004; HR 1.21, [95% CI 1.02, 1.45, p=0.028] respectively). Older age at first-ITx, lower baseline eGFR and longer diabetes duration had modest effect of significance on the risk of progression. Mean tacrolimus level in the first year post-ITx, number of ITx, baseline hypertension and exposure to sirolimus were not significant predictors for the risk of progression to S3CKD. No sex differences were found in risk for Stage 4 or 5 CKD. IS may put female ITx recipients at greater hazard of progressing to S3CKD, independently of other potential risk factors. Further study is required to elucidate this association, which could translate into sex-specific strategies to manage IS post-ITx. Effective IS regimens without nephrotoxicity remain an important goal. Disclosure A.L.J. Carr: None. B.A. Marfil-Garza: None. A. Lam: None. B.L. Anderson: None. D. O'Gorman: None. T. Kin: None. D. Bigam: None. A. Shapiro: Consultant; Vertex Pharmaceuticals Incorporated, Betalin Therapeutics, Hemostemix Inc, ViaCyte, Inc., Aspect Biosystems. P.A. Senior: Consultant; Abbott, Bayer Inc., Dexcom, Inc., Eli Lilly and Company, GlaxoSmithKline plc, Insulet Corporation, Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk Canada Inc. Research Support; Novo Nordisk Canada Inc.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.036 | 0.003 |
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".