Diffuse proliferative lupus nephritis: Identification of specific pathologic features affecting renal outcome

Abstract

Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Predominance of CD8+ T lymphocytes among periglomerular infiltrating cells and link to the prognosis of class III and class IV lupus nephritis

“…Among all the examined glomeruli, 22.6 Ϯ 27.5% (mean Ϯ SD) had cellular crescents and 8.5 Ϯ 13.8% had Bowman's capsule rupture. The mean Ϯ SD renal activity and chronicity index values were, respectively, 8.1 Ϯ 4.6 and 2 Ϯ 1.3 (19).…”

“…Bowman's capsule rupture and cellular crescents were evaluated after staining with periodic acid-Schiff. Renal activity and chronicity indices were calculated according to the method described by Austin et al (19).…”

“…To examine whether the kidney-infiltrating immune cells are involved in the pathogenesis of lupus nephritis, we examined correlations between the numbers of different kidney-infiltrating cell subsets and the activity or chronicity of lupus nephritis as assessed by the histopathologic scoring system described by Austin et al (19). Interestingly, the best correlation found was between the total number of renal CD8ϩ T cells and the activity index (r ϭ 0.63, P ϭ 0.0007) (Figure 2).…”

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

“…* The activity index and chronicity index were determined as described in ref. 25. The presence or absence of tubulointerstitial immune deposits (TI deposits) and the total tubulointerstitial score (total TI score) were determined as described in Patients and Methods.…”

“…To examine relationships between CD40 expression and particular histopathologic lesions in lupus GN, the activity index and chronicity index were scored according to National Institutes of Health (NIH) criteria (25) ( Table 2). Moreover, to determine if there is a relationship between CD40 expression and severity of tubulointerstitial damage in lupus and nonlupus renal diseases, a detailed analysis of tubulointerstitial injury was conducted (26).…”