Effects of Everolimus on Cellular and Humoral Immune Processes Leading to Chronic Allograft Nephropathy in a Rat Model with Sensitized Recipients
Bibliographic record
Abstract
BACKGROUND: Chronic allograft nephropathy (CAN) remains the most common cause of late graft loss especially in sensitized patients. The aim of this study is to evaluate the therapeutic effect of everolimus on cellular and humoral mechanisms of chronic allograft damage in a rat model with sensitized recipients. METHODS: F344 kidneys were transplanted to LEW.RNU rats. The athymic recipients were reconstituted with 3.5 x 10(7) or 5 x 10(7) presensitized CD4+T-lymphocytes. In the treatment group, everolimus was introduced five weeks posttransplantation. Rats were monitored for peripheral blood lymphocytes, renal function, histological changes in the graft, and the development of donor-specific alloantibodies. RESULTS: Rats developed cell dose-dependent renal failure. Increased urinary albumin excretion and glomerulopathy were frequently accompanied by the development of donor-specific major histocompatibility complex (MHC) alloantibodies. In the everolimus group, five of six animals survived for 20 weeks with stable serum creatinine and displayed neither acute cellular rejection nor CAN. Prolonged survival was accompanied with significantly reduced tubulointerstitial cell infiltrate in the graft. Increased urinary albumin excretion was present in all, acute tubular necrosis in five of six, and glomerular sclerosis in two grafts. MHC alloantibodies were found in four of six animals. CONCLUSION: The used rat model offers the opportunity to study the influence of everolimus on the interaction of humoral and cellular mechanisms involved in chronic renal damage. Everolimus leads to a prolongation of allograft survival, reduced cell infiltrate in the graft, and prevents tubular atrophy and interstitial fibrosis. The development of alloantibodies and albuminuria was not prevented. These data suggest that although cellular rejection is clearly suppressed, humoral mechanisms of CAN cannot be completely controlled by everolimus treatment in the sensitized rat model.
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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) | 0.000 | 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 | 0.000 |
| 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".