Mineralocorticoid receptor antagonism for non-diabetic kidney disease
Notice bibliographique
Résumé
The use of mineralocorticoid receptor antagonists (MRAs) in preclinical models of non-diabetic chronic kidney disease (CKD) has consistently shown a beneficial effect by preventing renal structural injury, reducing albuminuria and preserving renal function. In this context, MR activation in non-epithelial cells contributes to renal injury through the activation of inflammatory and fibrotic pathways, increasing oxidative stress and modulating renal hemodynamics. The protective effects of MRAs in animal models of CKD are not restricted to the kidney. Cardiovascular benefits, such as the prevention of cardiac fibrosis, hypoperfusion and vascular calcification, have also been observed. The translation of these preclinical findings into clinical practice has been difficult, mainly due to the lack of clinical studies testing the efficacy of steroidal MRAs in CKD patients due to their contraindication because of an increased risk of hyperkalemia in these patients. Here, we review the latest preclinical evidence showing new mechanisms by which MR inhibition results in beneficial effects against cardiorenal damage in non-diabetic kidney disease. Moreover, we summarize the clinical trials testing the safety and efficacy of steroidal and non-steroidal MRAs in patients with advanced non-diabetic CKD. PLAIN ENGLISH SUMMARY: The mineralocorticoid receptor (MR) is known for its role in the regulation of sodium and potassium balance in the distal tubules of the kidney. However, under pathological conditions the activation of the MR in other renal cell types (including the vasculature and immune cells) leads to harmful effects, damaging the main structural components of the kidney, and ultimately causing renal dysfunction. Over the past 20 years, several studies performed in mouse and rat models of non-diabetic kidney disease have shown that using a specific drug class that inhibits the MR (MR antagonists: MRAs) positively impacts the preservation of the kidney structure and helps to prevent the decline of renal function, thus positioning MRAs as a good therapeutic option against kidney diseases from non-diabetic origin. In addition, the use of MRAs also benefited the cardiovascular system health as shown by improved cardiac structural and functional parameters as well as preventing the calcification of blood vessels. Nevertheless, an important barrier to translating these findings into clinical practice is that the use of MRAs could lead to increased serum potassium levels, particularly in kidney disease patients, an adverse effect that could lead to life-threatening cardiac arrhythmias. In this review, we summarize the latest data in animal models showing new evidences of MR benefits in non-diabetic kidney disease. In addition, we review the clinical trials that evaluated the safety and efficacy of MRAs in patients with advanced non-diabetic kidney disease including those that tested a new generation of MRAs (non-steroidal MRAs) and are expected to reduce the frequency of adverse effects while retaining their renal and cardiovascular benefits.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».