{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:39:46Z","timestamp":1791113986482,"version":"4.1.0"},"reference-count":42,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Increased production of tumor necrosis factor-\u03b1 (TNF-\u03b1) in chronic kidney disease may be involved in the progression of renal failure and injury, and cardiovascular disease. We investigated the effect of TNF-\u03b1 neutralization on renal failure, inflammation and fibrosis, and blood pressure in rats with renal failure. &lt;b&gt;&lt;i&gt;Methods and Results:&lt;\/i&gt;&lt;\/b&gt; Renal failure was induced by renal mass reduction and the animals were treated with PEG-sTNFR1, a pegylated form of soluble TNF type 1 receptor that neutralizes TNF-\u03b1, for 6 weeks. Systolic, diastolic and mean arterial pressures were higher in renal failure rats that were associated with increased serum creatinine, albuminuria and renal injury comprised of blood vessel media hypertrophy, focal and segmental glomerulosclerosis, tubular atrophy and interstitial inflammation and fibrosis. These changes were associated with greater levels of TNF-\u03b1, transforming growth factor (TGF)-\u03b21, nuclear transcription factor NF-\u0138B and cytosolic phospho-I\u0138B-\u03b1, and inflammatory markers expression (ICAM-1, VCAM-1 and MCP-1). Moreover, endothelin (ET)-1 production was also increased, whereas nitric oxide (NO) release was decreased. TNF-\u03b1 neutralization reduced hypertension, albuminuria and renal inflammation and fibrosis, which were coupled to a reduction in renal NF-\u0138B activation, inflammatory markers expression, TGF-\u03b21 and ET-1 production, and an increase in NO release. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Neutralization of TNF-\u03b1 in rats with renal failure decreases NF-\u0138B activity that is associated with a reduction in renal TGF-\u03b21 and ET-1 production, and an improvement of NO release. These effects likely reduce renal inflammation and fibrosis, and blood pressure indicating a pivotal role for TNF-\u03b1, at least, in the progression of renal injury.<\/jats:p>","DOI":"10.1159\/000340033","type":"journal-article","created":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T12:41:52Z","timestamp":1342701712000},"page":"151-161","source":"Crossref","is-referenced-by-count":69,"title":["Neutralization of Tumor Necrosis Factor-Alpha Reduces Renal Fibrosis and Hypertension in Rats with Renal Failure"],"prefix":"10.1159","volume":"36","author":[{"given":"Fr\u00e9d\u00e9rick 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