Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

Abstract

IntroductionMicrothrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN.MethodsKidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data.ResultsMicrothrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome.ConclusionsMicrothrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series.

Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis

“…Indeed, according with data previously reported in human and mice models (18, 45, 46), proteinuria levels correlated with macrophagic infiltration.…”

C4d in Native Glomerular Diseases

“…In addition, intensity of glomerular C4d staining was associated with lower serum C3, higher LN activity index, and greater proteinuria [64]. However, in another study using CD61+ platelets as marker for microthrombi and CD68 as marker for macrophage infiltration, it was found that microthrombi associate with macrophage infiltration but not with C4d (via IHC) [65].…”

Editorial: Macrophages and Dendritic Cells in Motion: Tracking Inflammation and Fibrosis

“…In their study, which appears in this issue of Arthritis & Rheumatology , Sahu et al describe 3 renal dendritic cell (DC) populations and 2 renal macrophage populations (). Their work represents a comprehensive first look at the potential phenotypic and functional heterogeneity that has been denoted by the term “macrophage” in many studies of biopsy specimens obtained from patients with lupus (). As shown in Table , Sahu and colleagues used several well‐established markers to delineate murine renal myeloid cells ().…”

“…What is the significance of increased numbers of renal macrophages in lupus nephritis? In studies of renal biopsy specimens obtained from patients with lupus, increased numbers of macrophages correlated with the severity of renal damage (). Hill et al determined that increased numbers of glomerular macrophages were the most sensitive glomerular morphologic variable in initial biopsy specimens obtained from patients with newly diagnosed renal disease, and that in biopsy specimens obtained after 6 months of therapy, the presence or absence of glomerular monocytes was a significant prognostic indicator of poor clinical and outcome parameters.…”