Kidney ACE2 expression: Implications for chronic kidney disease
Bibliographic record
Abstract
Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. Together, tissue expression of ACE2 and TMPRSS2 may determine infection. Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. Accordingly, we obtained renal tubulointerstitial and glomerular microarray expression data and clinical variables from healthy living donors (HLD) and patients with CKD from the European Renal cDNA Bank. ACE2 expression was similar in the tubulointerstitium of the two groups, but greater in females than males in HLD (P = 0.005) and CKD (P < 0.0001). ACE2 expression was lower in glomeruli of CKD patients compared to HLD (P = 0.0002) and lower in males than females. TMPRSS2 expression was similar in the tubulointerstitium but lower in glomeruli of CKD patients compared to HLD (P < 0.0001). There was a strong relationship between ACE2 and TMPRSS2 expression in the glomerulus (r = 0.51, P < 0.0001). In CKD, there was a relationship between tubulointerstitial ACE2 expression and estimated glomerular filtration rate (r = 0.36, P < 0.0001) and age (r = -0.17, P = 0.03), but no relationship with BMI. There were no relationships between TMPRSS2 expression and clinical variables. Genes involved in inflammation (CCL2, IL6, and TNF) and fibrosis (COL1A1, TGFB1, and FN1) were inversely correlated with ACE2 expression. In summary, kidney expression of ACE2 and TMPRSS2 differs in HLD and CKD. ACE2 is related to sex and eGFR. ACE2 is also associated with expression of genes implicated in inflammation and fibrosis.
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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 | 0.096 |
| 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) | 0.001 | 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".