RESUMEN
BACKGROUND: Complement activation is thought to be pathologically important in IgA nephropathy (IgAN). Although C3 deposition in the mesangium is found in IgAN, the origin of C3 is not clear. We recently demonstrated intraglomerular C3 synthesis in the human kidney; however, the activation and pathological role of locally synthesized C3 remains unclear. Here we performed nonradioactive in situ hybridization for C3 mRNA and immunohistochemistry for C3 and its activation products, such as C3d and membrane attack complex (MAC), to determine whether locally produced C3 in glomeruli was activated in IgA nephropathy. METHODS: Renal samples from 14 patients with IgAN and 5 with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidneys with tumors served as normal controls. RESULTS: C3 mRNA was not detected in glomeruli in control tissue and MCNS, but was strongly expressed in resident glomerular cells of IgAN, including mesangial cells, glomerular epithelial cells and the cells of Bowman's capsule. Examination of serial sections disclosed that more than 70% of cells positive for C3 mRNA were also stained for C3 protein, C3d, and MAC. Double staining for in situ hybridization and immunohistochemistry also revealed that those C3 mRNA signals were present in intraglomerular cells positive for C3. The expression of C3 mRNA and MAC in glomeruli correlated significantly with the degree of mesangial matrix expansion. CONCLUSIONS: Our results demonstrated that locally synthesized C3 is activated in the glomeruli of IgAN and that its expression correlated with the severity of mesangial matrix expansion. These findings suggest that activation of C3 may be involved in tissue injury in IgAN through the formation of membrane attack complex.
Asunto(s)
Complemento C3/biosíntesis , Complemento C3d/biosíntesis , Complejo de Ataque a Membrana del Sistema Complemento/biosíntesis , Glomerulonefritis por IGA/inmunología , Glomérulos Renales/inmunología , Adolescente , Adulto , Biopsia , Activación de Complemento/fisiología , Complemento C3/análisis , Complemento C3d/análisis , Complejo de Ataque a Membrana del Sistema Complemento/análisis , Femenino , Glomerulonefritis por IGA/patología , Humanos , Inmunohistoquímica , Hibridación in Situ , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Nefrosis Lipoidea/inmunología , ARN Mensajero/análisis , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Tubulointerstitial inflammation and fibrosis are the main pathological features of chronic renal allograft rejection, which is characterized by accumulation of extracellular matrix protein. Heat shock protein 47 (HSP47), known as a collagen-specific stress protein, is thought to be a molecular chaperone during the processing and/or secretion of procollagen. HSP47 is thought to be involved in the progression of fibrosis, but its expression in chronic renal allograft rejection is still unknown. METHODS: We examined the expression of HSP47 together with that of alpha-smooth muscle actin (alpha-SMA), a marker of myofibroblasts, and CD68, a marker of macrophages, by immunohistochemistry in allograft kidney tissues. Uninvolved portions of surgically removed kidneys with tumours served as control tissue. RESULTS: Expression of HSP47 was detected in the interstitium of fibrotic regions of allograft kidneys. Cells positive for HSP47 were also stained for alpha-SMA and type I collagen, and the expression of HSP47 correlated with the degree of interstitial fibrosis. Furthermore, the expression of HSP47 correlated with the number of infiltrating macrophages. In contrast, HSP47 and alpha-SMA were not expressed in the control tissues, sections of 1 h post-transplantation biopsy specimens and acute allograft rejection without fibrosis. CONCLUSION: Our results suggest that HSP47 may contribute to the progression of interstitial fibrosis in allograft renal tissues.
Asunto(s)
Actinas/metabolismo , Rechazo de Injerto/metabolismo , Proteínas de Choque Térmico/metabolismo , Trasplante de Riñón , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores , Biopsia , Colágeno/metabolismo , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Proteínas del Choque Térmico HSP47 , Humanos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana Edad , Miofibrillas/metabolismo , Miofibrillas/patología , Trasplante HomólogoRESUMEN
BACKGROUND: Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis. METHODS: We determined the expression of HSP47 and HSP70 (nonspecific for collagen synthesis) by immunohistochemistry in peritoneal tissues of patients on CAPD. The tissue for collagen III, alpha-smooth muscle actin (alpha-SMA), and CD68 (a marker for macrophages) were also stained. Thirty-two peritoneal samples were divided into three groups (group A1, 11 patients who had no ultrafiltration loss; group A2, 9 patients who had ultrafiltration loss; and group B, 12 specimens who had end-stage renal disease prior to induction of CAPD. RESULTS: In group B, staining for HSP47, HSP70, and collagen III in peritoneal tissues was faint, and only a few cells were positive for alpha-SMA and CD68. In contrast, HSP47, HSP70, and collagen III were expressed in areas of thickened connective tissues in fibrotic peritoneal specimens of CAPD patients. The expression level of HSP47, HSP70, collagen III, and alpha-SMA and the number of CD68-positive cells in group A2 were significantly higher than those in groups A1 and B. HSP47/HSP70-positive cells were mesothelial cells, adipocytes, and alpha-SMA-positive myofibroblasts. Furthermore, the expression level of HSP47 was significantly higher in peritoneal specimens from patients with refractory peritonitis than without it and was significantly higher in patients with more than 60 months of CAPD therapy than that in patients with less than 60 months of CAPD. CONCLUSION: Our results indicate that CAPD therapy may induce HSPs in the peritoneal tissue, and that peritonitis in CAPD patients may be associated with the progression of peritoneal sclerosis at least through HSP47 expression and chronic macrophage infiltration. Our data also suggest that the progression of peritoneal sclerosis in such patients is associated with deterioration of peritoneal ultrafiltration function.
Asunto(s)
Proteínas HSP70 de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/biosíntesis , Fallo Renal Crónico/metabolismo , Diálisis Peritoneal Ambulatoria Continua , Peritoneo/metabolismo , Actinas/análisis , Adulto , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biopsia , Colágeno/análisis , Colágeno/biosíntesis , Eosina Amarillenta-(YS) , Femenino , Fibroblastos/química , Fibroblastos/metabolismo , Glucosa/análisis , Proteínas del Choque Térmico HSP47 , Proteínas HSP70 de Choque Térmico/análisis , Proteínas de Choque Térmico/análisis , Hematoxilina , Humanos , Técnicas para Inmunoenzimas , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Peritoneo/química , Peritoneo/patología , Esclerosis , Coloración y Etiquetado , UltrafiltraciónRESUMEN
We report a case of renal papillary necrosis with diabetes mellitus which was treated with prostaglandin E1. An intravenous infusion of 40 mg/day prostaglandin E1 was given for 14 days in an attempt to improve renal circulation. Treatment resulted in an improved creatinine clearance, renal plasma flow and renogram, and proteinuria was decreased. The administration of prostaglandin E1 produced an improvement in renal haemodynamics and can be considered as a possible therapy for renal papillary necrosis in diabetic patients.
Asunto(s)
Alprostadil/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Necrosis Papilar Renal/complicaciones , Necrosis Papilar Renal/tratamiento farmacológico , Anciano , Creatinina/orina , Femenino , Humanos , Necrosis Papilar Renal/fisiopatología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Flujo Plasmático Renal/efectos de los fármacos , Vasodilatadores/uso terapéuticoRESUMEN
The presence of nitric oxide (NO) in the kidney has been implicated in the pathogenesis of human glomerulonephritis. However, the exact type of glomerular cells that express NO synthase (NOS) and the NOS isoform involved in the local production of NO has not been identified in the human diseased kidney. We examined the expression of three isoforms of NOS, inducible NOS (iNOS), endothelial NOS (eNOS) and brain NOS (bNOS) in the renal tissue of patients with IgA nephropathy (IgAN, N = 10), lupus nephritis (LN, N = 5), membranous nephropathy (MN, N = 5) and minimal change nephrotic syndrome (MCNS, N = 5). Sections were immunostained and the correlation between the expression of each NOS and the degree of glomerular injury in that section was also examined. Normal portions of surgically resected kidneys served as controls. eNOS was present in glomerular endothelial cells and endothelium of cortical vessels in the control and diseased kidneys. iNOS was localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased glomeruli, whereas immunostaining for iNOS was hardly detected in control kidneys. In addition, the expression pattern of eNOS in each glomerulus was the reverse of that of iNOS. In IgAN and LN, the extent of staining for eNOS correlated negatively with the degree of glomerular injury, while the extent of staining for iNOS correlated positively with the degree of glomerular injury in the same tissues. bNOS was not detected in normal or nephritic glomeruli. Our results indicate the presence of a NO pathway in human diseased kidney, and suggest that NO derived from eNOS and iNOS may be involved in the progression of renal diseases and that NO derived from each NOS may play an important role in different way in human inflamed glomeruli.
Asunto(s)
Glomerulonefritis/enzimología , Óxido Nítrico Sintasa/metabolismo , Adulto , Glomerulonefritis/patología , Humanos , Inmunohistoquímica/métodos , Riñón/enzimología , Riñón/patología , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Coloración y Etiquetado , Distribución TisularRESUMEN
Plasma exchange is used frequently in renal diseases for the removal of the humoral components of immune responses. Various pathological circulating factors are recognized in primary and secondary renal diseases. Recent advances in medical technology have allowed a wider clinical application of plasmapheresis in the clinical management of a variety of conditions. However, the clinical efficacy of plasmapheresis in renal diseases is still controversial. In this article, we review the therapeutic use of apheresis in different renal diseases.