Background Presence of vascular microthrombotic lesions in lupus nephritis (LN), with or without antiphospholipid antibodies (aPL), may relate to worse renal outcome. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear.
Objectives The aim of this study was to analyze renal vascular involvement in MRL/lpr mice and its association to the degree of renal inflammation, presence of aPL and renal function.
Methods We used 12-20-week old female MRL/lpr mice with nephritic lesions (n=41). The pattern of renal vascular disease, acute and chronic glomerular and tubulointerstitial lesions were analyzed by using H&E and PAS staining. Immunohistochemistry (IHC) techniques were used to detect CD41, fibrinogen (FGN), complement (C3) and macrophages. Expression of CD41 was detected indicating the presence of platelet thrombi. Expression of FGN, C3 and intraglomerular macrophagic infiltration (Mac-2) were quantified using Image J software. Periglomerular macrophagic F4/80 was quantified as the percentage of positive glomeruli. Renal function was assessed by measuring levels of serum creatinine (Crs) and proteinuria. Serum levels of a-dsDNA and anticardiolipin (aCL) antibodies were quantified by ELISA. Association between categorical variables was tested by the X2 test. For continuous variables, comparisons were carried out using t-test. A Spearman’s rank test was used for correlations among different parameters. P<0.05 was considered significant. Statistical analysis was performed using advanced SPSS software version 11.
Results Mice with microthrombotic renal vascular lesions showed a greater degree of periglomerular macrophage infiltration (55.4%vs34.9%; p=0.002). All mice had detectable a-dsDNA or aCL IgG, but no relationship between both autoantibody titer and TMA or CD41+ was found. Proteinuria was positively correlated to the proportion of sclerotic glomeruli (r=0.4; p=0.01), glomerular macrophage infiltration (r=0.46; p=0.004) and was higher in mice with diffuse proliferative glomerular lesions (340.8vs110.8; p=0.02). Correlation between renal vascular lesions and complement deposits, level of proteinuria or Crs was not found.
Conclusions Presence of microthrombotic renal vascular lesions is associated to a higher degree of macrophage infiltration in lpr model of LN. Although a direct impact on proteinuria or renal function could not be demonstrated this model allows analyzing the impact of anti-thrombotic and anti-inflammatory interventions on renal inflammation.
Disclosure of Interest: None Declared
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