Is One Allele Enough to Cause APOL1-Associated Nephropathy?
Bibliographic record
Abstract
Introduction: The high risk APOL1 genotype are associated with an increased risk of developing non-diabetic kidney disease. In the post-kidney transplant setting, a high-risk donor APOL1 genotype (but not recipient genotype) is associated with an increased risk of graft failure and proteinuria, indicating that it is local glomerular APOL1 gene expression that confers disease rather than systemic gene expression. Here, we present 2 patients that developed post-transplant focal segmental glomerulosclerosis (FSGS) after an initial diagnosis and treatment of Antibody-mediated rejection (AMR). Case Description: Two patients with end stage kidney disease, highly sensitized, received deceased donor kidney transplants from African American donors (one in 2019 and the other a regraft in 2020). Donors were without discernable proteinuria on urine dipstick. Initial post tranasplant courses were complicated by AMR treated as per center protocol. Tissue-based whole biopsy gene expression studies on kidney biopsy specimens (MMdx, using Molecular Microscope, Alberta, Canada) confirmed AMR along with grossly elevated interferon-γ gene expression. Subsequently each developed nephrotic range proteinuria with biopsy-confirmed FSGS and ongoing AMR . In both patients, in the absence of a prior history of FSGS and a delayed development of proteinuria in the first case (2019, patient1), an absence of recurrence in the first allograft in the second case (2020, patient2), a diagnosis of donor-derived APOL-1 nephropathy was considered and retrospective donor genotyping revealed the intermediate G1/G0 genotype. See Figure for more details. Discussion: We hypothesize that extreme local interferon-γ activation due to AMR was the primary trigger that could have resulted in local APOL-1 gene activation and subsequent podocytopathy. Similar data was recently reported by Shetty et al, in a kidney transplant patient with COVID associated collapsing nephropathy and G1/G0 donor genotype. Based upon these data we hypothesize that the G1/G0 genotype may represent intermediate risk for podocytopathies. Further research is needed in this area to confirm these initial associations.
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 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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".