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Proteinuria, renal function, and serum autoantibody levels were monitored. Renal histopathology, immune complex deposition, and immunohistochemistry were analyzed at various time points. Targeted microarray analysis was performed on renal tissue, with subsequent real-time PCR analysis of several differentially expressed genes.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Treatment with spironolactone was well tolerated by the mice throughout the course of their disease progression, with no significant differences in azotemia or serum potassium levels between vehicle-treated and spironolactone-treated animals. By 36 weeks of age, fewer spironolactone-treated mice developed nephrotic range proteinuria as compared with the control mice (control 70.8%, 25 mg\/kg spironolactone 51.3%, and 50 mg\/kg spironolactone 48.6%). Compared with control mice, mice treated with 25 mg\/kg spironolactone had significantly lower serum anti-single-stranded DNA levels (2,042 \u03bcg\/ml versus 1,036 \u03bcg\/ml; <jats:italic>P<\/jats:italic> = 0.03) and anti-double-stranded DNA levels (3,433 \u03bcg\/ml versus 614 \u03bcg\/ml; <jats:italic>P<\/jats:italic> = 0.05). Spironolactone-treated mice exhibited decreased histopathologic evidence of inflammation and tissue damage, as compared with control mice. Additionally, spironolactone treatment resulted in decreased expression in the kidney of several inflammatory and proapoptotic genes, including those encoding interferon-\u03b3, B lymphocyte stimulator (BlyS), tumor necrosis factor related apoptosis inducing ligand (TRAIL), tumor necrosis factor related weak inducer of apoptosis (TWEAK), and Fas ligand.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Aldosterone receptor blockade is safe and well tolerated in progressive murine lupus nephritis, and it results in decreased levels of clinical proteinuria, lower serum levels of autoantibodies, and decreased kidney damage. It appears to modulate inflammatory changes during the progression of glomerulonephritis and may also have a previously undescribed role in attenuating apoptosis.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2353","type":"journal-article","created":{"date-parts":[[2008,1,15]],"date-time":"2008-01-15T19:15:12Z","timestamp":1200424512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The role of aldosterone blockade in murine lupus nephritis"],"prefix":"10.1186","volume":"10","author":[{"given":"Seetha U","family":"Monrad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D","family":"Killen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Bradke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana J","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,1,15]]},"reference":[{"key":"2203_CR1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/j.1440-1797.2005.00392.x","volume":"10","author":"S Tang","year":"2005","unstructured":"Tang S, Lui SL, Lai KN: Pathogenesis of lupus nephritis: an update. 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