Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease.
Kidney Int
; 96(4): 1030-1036, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31377056
ABSTRACT
Bardoxolone methyl attenuates inflammation by inducing nuclear factor erythroid-derived 2-related factor 2 and suppressing nuclear factor κB. The Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes (BEACON) trial was a phase 3 placebo-controlled, randomized, double-blind, parallel-group, international, multicenter trial in 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease. BEACON was terminated because of safety concerns, largely related to a significant increase in early heart failure events in patients randomized to bardoxolone methyl. Bardoxolone methyl resulted in increased estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. Herein, we present post hoc analyses characterizing the relation between the urine albumin-to-creatinine ratio and eGFR. The urine albumin-to-creatinine ratio and eGFR were assessed every four weeks through Week 12, followed by assessments every eight weeks thereafter, and 4 weeks after the last dose of bardoxolone methyl was administered. The initial increases in urine albumin-to-creatinine ratio observed in patients randomized to bardoxolone methyl were attenuated after six months. Multivariable regression analysis identified baseline eGFR and eGFR over time as the dominant factors associated with change in the urine albumin-to-creatinine ratio. Relative to placebo, bardoxolone methyl resulted in a significant decrease in albuminuria when indexed to eGFR (least-squared means -0.035 [95% confidence interval -0.031 to -0.039]). Thus, among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl, changes in albuminuria are directly related to changes in eGFR, challenging the conventional construct that increases in albuminuria universally reflect kidney injury and denote harm.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácido Oleanólico
/
Creatinina
/
Diabetes Mellitus Tipo 2
/
Nefropatías Diabéticas
/
Albuminuria
/
Fallo Renal Crónico
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Kidney Int
Año:
2019
Tipo del documento:
Article
País de afiliación:
Dinamarca