Renal Profile Is Altered in Lupus Nephritis
Renal Profile Is Altered in Lupus Nephritis
Introduction: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT-I+II expression profile is altered during lupus nephritis.
Methods: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means of standard statistical methods.
Results: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median number of proximal tubules displaying this MT expression pattern per high-power microscope field (40× magnification), was positively correlated to the creatinine clearance in the lupus nephritis cohort (P = 0.01). Furthermore, a tubular MT score below the median value of the cohort emerged as a significant predictor of a poor renal outcome in renal survival analyses. Thus, patients with a tubular MT score <1.0 had a 6.2-times higher risk of developing end-stage renal disease than patients with a tubular MT score 1.0 (P = 0.03).
Conclusion: Lupus nephritis is associated with significant alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis.
Systemic lupus erythematosus (SLE) is an immune-inflammatory disorder characterized by multiorgan involvement and a chronic relapsing course. Nephritis is a common and serious manifestation of SLE. More than one-half of all SLE patients develop nephritis during their course of illness, and 10% to 25% of these patients progress to end-stage renal disease (ESRD) despite immunosuppressive treatment. A central pathogenic aspect of lupus nephritis is the deposition of immune complexes within glomeruli and tubules. Subsequent inflammatory processes involving complement activation, macrophage recruitment, and generation of reactive oxygen species cause glomerular damage, increased glomerular permeability, and proteinuria. Sustained glomerular and interstitial inflammation stimulates fibrogenesis, eventually leading to renal scarring and compromised renal function.
Metallothioneins (MTs) are nonenzymatic polypeptides of 6 to 7 kDa that bind heavy metals with high affinity and possess a range of anti-inflammatory properties. Due to a high content of cysteines, MTs are potent antioxidants and provide protection against reactive oxygen species-induced cellular damage during experimental inflammation. In addition, MTs have been shown to reduce inflammation through interference with activation of cytotoxic T cells and B cells. Four major MT subfamilies exist in mammals (MT-I, MT-II, MT-III, and MT-IV). Human kidneys express MT-I and MT-II, which have been described as intracellular proteins of proximal tubular cells.
The aim of the present study was to investigate whether the pathogenesis of lupus nephritis involves an altered pattern of renal MT-I+II expression. To our knowledge, this question has not been addressed before. We demonstrate that lupus nephritis is associated with significant alterations in the tubular MT-I+II expression profile. Furthermore, our data indicate that important prognostic information can be deduced from the renal MT-I+II expression pattern in patients with lupus nephritis.
Abstract and Introduction
Abstract
Introduction: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT-I+II expression profile is altered during lupus nephritis.
Methods: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means of standard statistical methods.
Results: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median number of proximal tubules displaying this MT expression pattern per high-power microscope field (40× magnification), was positively correlated to the creatinine clearance in the lupus nephritis cohort (P = 0.01). Furthermore, a tubular MT score below the median value of the cohort emerged as a significant predictor of a poor renal outcome in renal survival analyses. Thus, patients with a tubular MT score <1.0 had a 6.2-times higher risk of developing end-stage renal disease than patients with a tubular MT score 1.0 (P = 0.03).
Conclusion: Lupus nephritis is associated with significant alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis.
Introduction
Systemic lupus erythematosus (SLE) is an immune-inflammatory disorder characterized by multiorgan involvement and a chronic relapsing course. Nephritis is a common and serious manifestation of SLE. More than one-half of all SLE patients develop nephritis during their course of illness, and 10% to 25% of these patients progress to end-stage renal disease (ESRD) despite immunosuppressive treatment. A central pathogenic aspect of lupus nephritis is the deposition of immune complexes within glomeruli and tubules. Subsequent inflammatory processes involving complement activation, macrophage recruitment, and generation of reactive oxygen species cause glomerular damage, increased glomerular permeability, and proteinuria. Sustained glomerular and interstitial inflammation stimulates fibrogenesis, eventually leading to renal scarring and compromised renal function.
Metallothioneins (MTs) are nonenzymatic polypeptides of 6 to 7 kDa that bind heavy metals with high affinity and possess a range of anti-inflammatory properties. Due to a high content of cysteines, MTs are potent antioxidants and provide protection against reactive oxygen species-induced cellular damage during experimental inflammation. In addition, MTs have been shown to reduce inflammation through interference with activation of cytotoxic T cells and B cells. Four major MT subfamilies exist in mammals (MT-I, MT-II, MT-III, and MT-IV). Human kidneys express MT-I and MT-II, which have been described as intracellular proteins of proximal tubular cells.
The aim of the present study was to investigate whether the pathogenesis of lupus nephritis involves an altered pattern of renal MT-I+II expression. To our knowledge, this question has not been addressed before. We demonstrate that lupus nephritis is associated with significant alterations in the tubular MT-I+II expression profile. Furthermore, our data indicate that important prognostic information can be deduced from the renal MT-I+II expression pattern in patients with lupus nephritis.
Source...