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Title: Corticosteroids worsen proteinuria and increase intraglomerular signaling by NF-ĸB in a model of membranous glomerulonephritis.
Austin Authors: Mudge, Stuart J;Paizis, Kathy ;Auwardt, Russell B;Levidiotis, Vicki;Fraser, Scott A;Power, David Anthony
Affiliation: Department of Nephrology, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 29-Jun-2010
Publication information: Nephron. Experimental Nephrology 2010; 116(2): e23-31
Abstract: Passive Heymann nephritis (PHN) is a model of human membranous glomerulonephritis characterized by heavy proteinuria. We have recently demonstrated activation of NF-κB by podocytes in this model. In this study, therefore, we have determined whether dexamethasone (DEX) and pyrrolidine dithiocarbamate (PDTC), therapies that inhibit NF-κB, influence proteinuria.Twenty-one days after induction of PHN, rats were divided into three groups: group 1 received saline, group 2 received DEX for 7 days, and group 3 received PDTC for 7 days. The effects of these drugs on activation of NF-κB and proteinuria were then determined.DEX administration was associated with a very significant increase in proteinuria, whereas PDTC produced a slight decrease. Within the glomerulus, both agents were associated with increased levels of IL-1β mRNA and protein, compared with untreated rats, and there was increased nuclear localization of p50 in both of the treated groups. Neither agent, therefore, inhibited NF-κB activation within the glomerulus. Both agents produced a decrease in the systemic anti-sheep Ig immune response, and there was reduced interstitial αβ T-cell infiltration compared with controls.These data suggest that agents predicted to inhibit NF-κB might have opposing effects in membranous glomerulonephritis. The use of steroids to treat membranous glomerulonephritis, therefore, might produce unpredictable results, depending on whether suppression of the systemic immune response or inflammatory events within the kidney is more important in a particular patient.
Gov't Doc #: 20588061
DOI: 10.1159/000317128
Type: Journal Article
Subjects: Animals
Dexamethasone.therapeutic use
Disease Models, Animal
Glomerulonephritis, Membranous.drug therapy
Kidney Glomerulus.drug effects.metabolism
NF-kappa B.antagonists & inhibitors.physiology
Proteinuria.chemically induced
Pyrrolidines.therapeutic use
RNA, Messenger.metabolism
Rats, Sprague-Dawley
Signal Transduction.drug effects
Thiocarbamates.therapeutic use
Appears in Collections:Journal articles

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