P0350THE DURATION OF PROTEINURIA REMISSION AND CLINICAL OUTCOMES IN IGA NEPHROPATHY
Notice bibliographique
Résumé
Abstract Background and Aims A relative reduction in proteinuria has been proposed as a surrogate outcome for therapeutic trials in IgA nephropathy. It is currently unknown how long a reduction in proteinuria needs to be maintained in order to mitigate the long-term risk of disease progression. To address this knowledge gap we sought to quantify the association between duration of proteinuria remission and the risk of disease progression in IgA nephropathy. Method In this retrospective multi-ethnic international cohort of adult patients with biopsy-proven IgA nephropathy, we defined proteinuria remission based on three criteria: (i) peak proteinuria on/after biopsy ≥1g/day; (ii) an absolute reduction in proteinuria to <1g/day; (iii) a ≥25% reduction in proteinuria from the peak value. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. The primary outcome was the occurrence of end-stage kidney disease or a sustained 50% reduction in estimated glomerular filtration rate (eGFR). The association between duration of remission and the primary outcome was visualized using restricted cubic splines, and quantified using extended Cox proportional hazards regression models. Results A total of 1864 patients met criteria for remission, which occurred a median of 8.3 months after biopsy (IQR 3.6-22). They had a median age of 36.8 (IQR 29.4-46.6) years and a median eGFR of 78 (IQR 55-104) mL/min/1.73m2. Median proteinuria was 1.54 (IQR 1.09-2.4) g/day at the time of biopsy and 0.55 (IQR 0.33-0.76) g/day at the time of entering remission. During a median follow-up of 3.9 years, 274 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and the primary outcome was non-linear (Figure). Each 3 months in sustained remission up to 51 months was associated with an additional 9% reduction in the risk of disease progression (hazard ratio 0.91, 95% confidence interval 0.89-0.93). In contrast, each additional 3 months in remission beyond 51 months was associated with a smaller non-significant risk reduction (hazard ratio 0.99, 95% confidence interval 0.96-1.03). These finding were robust to multivariable adjustment and were consistent across subgroups based on the MEST histology score, and whether or not the remission occurred while on renin-angiotensin-aldosterone-system blockade or after immunosuppression treatment. Results were similar when relapse was defined as either a 50% or 100% increase in proteinuria from the nadir value after remission to an absolute value of ≥1g/day. Conclusion We observed a strong non-linear dose-response relationship between the duration of proteinuria remission and the risk of disease progression in patients with IgA nephropathy. The ability to quantitate the renal survival benefit related to the duration of remission is an important advance for patients and their physicians. Rather than there being a minimum duration of proteinuria remission in IgA nephropathy, our results demonstrate that even short durations in remission, or small increases in remission duration, are both associated with significant reductions in the risk of disease progression. For future therapeutic trials in IgA nephropathy using proteinuria as a surrogate outcome, our findings illustrate the need to consider the duration of proteinuria reduction, in addition to the magnitude of proteinuria reduction, when evaluating the anticipated treatment effect on long-term clinical endpoints.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».