Tubulointerstitial Disease in Lupus Nephritis: Relationship to Immune Deposits, Interstitial Inflammation, Glomerular Changes, Renal Function, and Prognosis

Park, M H; D’Agati, Vivette D.; Appel, Gerald B.; Pirani, Conrad L.

doi:10.1159/000184012

Cited by 126 publications

(69 citation statements)

References 24 publications

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“…Both the number of tubulointerstitial macrophages and proliferating (PCNA-positive) cells correlated with serum creatinine. Two other studies have also reported that interstitial macrophage accumulation correlates with both current and future renal function in patients with lupus nephritis [40, 41]. These studies support the observation that tubulointerstitial changes correlate with renal function better than glomerular changes [21, 22, 23].…”

Section: Discussionsupporting

confidence: 68%

Clinicopathologic Correlations in Lupus nephritis in Lima, Peru

Hurtado

Asato

Escudero

et al. 1999

Nephron

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Background: We assessed whether immunohistologic markers for glomerular or tubulointerstitial injury might provide better correlations with ongoing renal function and disease activity as compared with the WHO classification or the NIH activity and chronicity indices in lupus nephritis. Methods: Thirty-three patients with clinically defined systemic lupus underwent renal biopsy over a 1-year period at Hospital Loayza in Lima, Peru. Biopsy specimens were evaluated for macrophages, proliferating cells, α-actin expression, and type IV collagen deposition in both glomeruli and the tubulointerstitium and the results compared with the current WHO and NIH classifications in relation to the clinical presentation. Results: Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria and hematuria, and worse renal function. An elevated NIH activity index correlated with microhematuria, proteinuria, and impaired renal function, whereas an elevated chronicity index correlated with renal function, hypertension, and microhematuria, but not with proteinuria. The presence of glomerular macrophages correlated with both glomerular α-actin expression and type IV collagen deposition, but did not correlate with renal function or proteinuria. In contrast, interstitial macrophages correlated not only with interstitial collagen deposition and myofibroblast accumulation, but also correlated with both renal function and the presence of nephrotic syndrome. Conclusions: Both the WHO classification and the NIH activity/chronicity indices correlate with clinical manifestations of lupus nephritis. While glomerular macrophage accumulation correlates with mesangial cell activation (α-actin expression) and collagen deposition, and interstitial macrophage accumulation correlates with interstitial fibroblast activation and collagen deposition, only interstitial macrophages correlate with renal function. Of particular interest will be future studies to determine whether these markers correlate with the prognosis.

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Section: Discussionsupporting

confidence: 68%

Clinicopathologic Correlations in Lupus nephritis in Lima, Peru

Hurtado

Asato

Escudero

et al. 1999

Nephron

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“…Our analysis supports the finding of Koeffler et al [15] that the sparse interstitial lymphocyte infiltration does not induce a significant tubular MAC deposition. The hypothesis that only immune complex deposition mediates the tubulointerstitial injury has been already refuted in lupus nephritis [27,28], Also, no corre lation between the tubular MAC and C3 was found in our cases (including 2 lupus nephritis patients). We favor the hypothesis of Biesecker et al [17] that tubulointerstitial inflammation may be mediated by MAC.…”

Section: Discussionmentioning

confidence: 40%

Membrane Attack Complex and Membrane Cofactor Protein Are Related to Tubulointerstitial Inflammation in Various Human Glomerulopathies

Mosolits¹,

Magyarlaki²,

Nagy

1997

Nephron

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Immunohistochemical analysis of the membrane attack complex (MAC) and the membrane cofactor protein (MCP) was performed on the tubuli and cortical vessels of 46 kidney biopsies with various types of human glomerulopathies. Irrespective of the type of glomerulopathy, significant correlations between tubular MAC and interstitial lymphomonocyte infiltration (p < 0.001) and interstitial volume (p < 0.02) were found. Tubular MCP was significantly overexpressed at the site of MAC deposition (p < 0.002). There was no correlation between the vascular MAC and MCP and tubulointerstitial lesions. Since tubular MAC is deposited in inflamed areas of tubulointerstitium, we propose that MAC might contribute to the development of tubulointerstitial inflammatory processes in human glomerulopathies. MCP as a regulatory factor in the tubulointerstitium might abrogate further tissue damage and cell-stimulatory effects of the MAC.

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“…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). Features of chronic tubulointerstitial damage (tubular atrophy and interstitial fibrosis) and active tubulointerstitial damage (interstitial edema, interstitial inflammation, tubular regenerative and degenerative changes, tubulointerstitial immune deposits by immunofluorescence and/or electron microscopy) were graded on a semiquantitative scale of 0-3+ (0 = absent, 1 = mild, 2 = moderate, 3 = severe), with the exception of tubulointerstitial immune deposits, which were graded as absent (-) or present (+).…”

Section: Methodsmentioning

confidence: 99%

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

Yellin

D’Agati

Parkinson

et al. 1997

Arthritis & Rheumatism

147

115

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Objective. To investigate potential mechanisms by which CD40L-mediated signals may be involved in the pathogenesis of lupus glomerulonephritis (GN).Methods. Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens. Immunohistochemical studies were performed on frozen sections utilizing anti-CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we analyzed normal kidney specimens and specimens obtained from patients with IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease, idiopathic membranous GN, and antineutrophil cytoplasmic antibodypositive pauci-immune GN. Staining distribution was noted and staining intensity scored on a semiquantitative scale of 0 (no staining) to 3+ (intense staining).Results. In normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells, endothelial cells, and distal tubules but not proximal tubules. Glomerular and tubular CD40 expression was markedly up-regulated in class I11 and class IV lupus GN, where there was intense staining of crescents, proximal and distal tubules, and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus GN was similar to that in normal kidney. Interstitial mononuclear cells expressing CD40L were present in class IV lupus GN. However, these findings were not unique to lupus GN: up-regulation of CD40 and CD40L expres- Submitted for publication June 3, 1996; accepted in revised form July 17, 1996. sion was similarly observed in other inflammatory renal diseases.Conclusion. This study shows that CD40 is expressed on a variety of renal parenchymal and nonparenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class I11 and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.

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Tubulointerstitial Disease in Lupus Nephritis: Relationship to Immune Deposits, Interstitial Inflammation, Glomerular Changes, Renal Function, and Prognosis

Cited by 126 publications

References 24 publications

Clinicopathologic Correlations in Lupus nephritis in Lima, Peru

Clinicopathologic Correlations in Lupus nephritis in Lima, Peru

Membrane Attack Complex and Membrane Cofactor Protein Are Related to Tubulointerstitial Inflammation in Various Human Glomerulopathies

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

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