Article Text

PDF
247 URINE F2-ISOPROSTANES ARE REDUCED IN LUPUS NEPHRITIS.
  1. C. J. Njoku,
  2. K. S. Patrick,
  3. J. C. Oates
  1. Medical University of South Carolina, Ralph H. Johnson VAMC, Charleston, SC

Abstract

Purpose Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex formation and activation of the innate immune system. An essential player in this response is the generation of reactive intermediates. We have reported increases in nitric oxide (NO) production during the disease activity and inducible NO synthase-dependent increases in urine F2-isoprostanes murine lupus nephritis (LN). F2-isoprostanes are formed by the reaction of arachidonate and reactive oxygen intermediates (ROI). Urine levels are an accepted measure of systemic oxidant stress. We hypothesized that there would be an increase in urine F2-isoprostanes in LN that associates with the degree of glomerular proliferation.

Methods We recruited 19 lupus, 13 LN, and 9 healthy control subjects. Only LN subjects with active disease (requiring significant increases in immunosuppressive therapy) were enrolled. Of these LN subjects, 12 had renal biopsies performed at the time of urine collection. Biopsies were classified by WHO class, activity, and chronicity. Urine F2-isoprostanes were measured by isotopic dilution, immunoaffinity extraction, and gas chromatography-mass spectrometry-negative ion chemical ionization. Standard laboratory measures of SLE disease activity were measured at the time of the study visit. WHO class was scored for analysis according to the extent of proliferation (V = 1, II = 2, III = 3, IV = 4). Results were reported as mean 6 standard error in ng/mg urine creatinine. A Spearman correlation was used to determine relationships between clinical variables and urine F2-isoprostane levels. One-way ANOVA was used to compare F2-isoprostane levels between groups.

Results Urine F2-isoprostane levels were greater in SLE subjects and controls than LN subjects (0.58 6 0.07 vs 0.53 6 0.1 vs 0.34 6 0.06, p = .14 for entire group). Among SLE subjects, the presence of nephritis was associated with lower F2-isoprostane levels (p = .06). Among those with nephritis, the histopathological activity score (a measure of proliferative activity) was significantly negatively correlated with F2-isoprostane levels (r = 2.66, p = .02).

Conclusions These findings did not agree with our hypothesis that F2-isoprostanes would increase with proliferative LN. These results could reflect (1) a reduction in ROI production in proliferative LN or (2) reaction of ROI-reactive nitrogen intermediates. NO production was reported as increased in proliferative LN. Superoxide (SO) generated during proliferative disease may react with NO to form peroxynitrite, making SO unavailable as a substrate for generation of F2-isoprostanes. Future work will focus on markers of peroxynitrite production in this population.

Statistics from Altmetric.com

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.