IL-1 Inhibition and Vascular Function in CKD.
J Am Soc Nephrol
; 28(3): 971-980, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-27647856
ABSTRACT
Vascular endothelial dysfunction and increased arterial stiffness contribute to increased cardiovascular risk in patients with CKD who exhibit chronic systemic inflammation. Because chronic inflammation contributes to vascular dysfunction, blocking inflammation may reduce cardiovascular risk in patients with CKD. In a two-site, double-blind trial, we randomized 42 adult patients with stage 3-4 CKD who were already receiving optimal background therapy to receive either IL-1 trap rilonacept or placebo for 12 weeks. Coprimary end points included change in brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV) after 4, 8, and 12 weeks. Exploratory end points included change in high-sensitivity C-reactive protein (hsCRP), FMDBA after acute ascorbic acid infusion, and vascular endothelial cell protein expression of NADPH oxidase. Participants were 63±11 (mean±SD) years of age and 24% were women; mean eGFR was 38±13 ml/min per 1.73 m2 Compared with placebo, rilonacept improved FMDBA (baseline 3.36%±2.06% [mean±SD], 12 weeks 2.45%±2.29% with placebo and baseline 3.75%±3.12%, 12 weeks 4.86%±3.20% with rilonacept; P<0.01), without changing aPWV (P=0.56). Rilonacept also reduced hsCRP levels (median [interquartile range]) (baseline 4.60 [1.90-8.22] mg/L, 12 weeks 2.16 [0.92-7.38] mg/L; P<0.01) and endothelial cell NADPH oxidase expression (P<0.05). Acute infusion of ascorbic acid to inhibit superoxide production associated with a nonsignificant trend toward increased FMDBA in the placebo group (P=0.07) but not the rilonacept group (P=0.56). Rilonacept was well tolerated (five adverse events versus two with placebo). In conclusion, treatment with an IL-1 trap improved FMDBA without changing aPWV and reduced systemic inflammation in patients with CKD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
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Endotélio Vascular
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Interleucina-1
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Insuficiência Renal Crônica
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Inflamação
Tipo de estudo:
Clinical_trials
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Am Soc Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article