#3074 CHANGES IN THE CLINICAL CHARACTERISTICS AND MANAGEMENT OF PATIENTS WITH AHUS OVER 10 YEARS: TRENDS FROM THE GLOBAL AHUS REGISTRY
Bibliographic record
Abstract
Abstract Background and Aims Atypical haemolytic uraemic syndrome (aHUS) is a rare disease predominantly caused by alternative complement pathway dysregulation. Prior to 2011, before the targeted complement inhibitor eculizumab became available, aHUS frequently led to end-stage kidney disease (ESKD) and early death. Treatment with eculizumab led to notable improvements in outcomes; whether patient characteristics and management has continued to change over time is unknown. Using data from the Global aHUS Registry, we assessed clinical characteristics and management of patients with aHUS over 10 years to identify any potential trends. Method All patients enrolled in the Global aHUS Registry from 2012–2022 were included. Patients were categorised according to age at aHUS onset (adult [≥18 years] vs paediatric [<18 years]); onset of aHUS was defined as the earliest of initial symptom presentation, aHUS diagnosis, or first recorded thrombotic microangiopathy (TMA). Patient characteristics were summarised using descriptive analysis. Results Of the 1994 patients enrolled in the registry between 2012 and 2022, 33 (1.7%) were missing data on age at aHUS onset. Of the remaining 1961 patients, 813 (41.5%) were paediatric and 1148 (58.5%) were adult. Changes in patient characteristics and management are presented in Fig. 1. Plasma exchange/plasma infusion (PE/PI) prior to and including the year of enrolment was less common in paediatric than adult patients (58.5% vs. 71.3%) between 2012–2013 and declined substantially in paediatric (19.6%) relative to adult (55.1%) patients by 2020–2022. Similar proportions of paediatric patients required dialysis at the time of enrolment between 2012–2013 (5.1%) and 2020–2022 (5.9%), while numerically lower proportions of adults required dialysis over time (2012–2013, 15.2%; 2020–2022, 6.5%). The rate of paediatric patients requiring a kidney transplant prior and up to enrolment dropped from 2012–2013 (28.4%) to 2020–2022 (5.9%); however, the rate among adult patients remained comparable (2012–2013, 29.2%; 2020–2022, 27.1%). A decrease in the proportion of patients with a reported identified pathogenic variant and/or anti-CFH antibodies was observed in paediatric and adult patients between 2012–2013 (paediatric, 59.1%; adult, 45.5%) and 2020–2022 (paediatric, 49.0%; adult, 30.8%). The proportion of patients with a reported triggering event increased from 2012–2013 (paediatric, 6.3%; adult, 12.4%) to 2020–2022 (paediatric, 9.8%; adult, 28.0%). In this cohort, a total of 1208 patients were treated with eculizumab/ravulizumab between 2012 and 2022 (paediatrics, 476; adults, 732). Between 2012–2013, the median time from aHUS onset to treatment initiation was 94.9 days for paediatric patients (blue) and 51.1 days for adult patients (orange); this fell to 13.1 days in paediatrics and 24.1 days in adults between 2020–2022 (Fig. 2). Conclusion Utilisation of PE/PI to treat aHUS has decreased more in paediatric than adult patients over time. A decreased requirement for transplant in paediatric patients was evident, suggesting more paediatrics are now being diagnosed and treated earlier, leading to better outcomes with fewer patients progressing to renal failure and requiring kidney transplant. The proportion of both paediatric and adult patients with reported pathogenic variants and/or anti-CFH antibodies decreased over time and may reflect the rate at which a clinical constellation consistent with aHUS is identified. Moreover, aHUS may be recognised more frequently in the presence of a triggering condition, or a lower barrier for clinicians to suspect aHUS in recent years. Patients were more rapidly treated with a complement inhibitor, likely due to better awareness in the clinical community around complement inhibitors and the importance of early treatment initiation. Although patients with aHUS are being treated more promptly in recent years than 10 years ago, more work is needed, especially in adults, to move towards optimal clinical practice.
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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".