摘要:

It has long been known that a number of diseases affecting the kidney are the result of genetic defects passed on through the generations. Whereas some of these defects are rare, others, eg, the cystic diseases, are among the most common. Our understanding of the underlying pathobiology in these disorders based on physiologic and cell biologic studies is variable—we suspect that the V2 vasopressin receptor is defective in nephrogenic diabetes insipidus; we know that the glomerular basement membrane in Alport syndrome is abnormal; we suspect that a tumor suppressor gene is defective in Wilms tumor; and we lack a unifying hypothesis regarding cystic degeneration of the kidney. The advent and rapid progress of molecular biology have permitted an entirely new approach to understanding these diseases, allowing the expected identification of mutations in the V2 receptor, the unexpected finding that a novel collagen gene is responsible for many Alport syndrome cases, and the somewhat less-unexpected finding that only one of several genes responsible for renal cancers has been identified. Further, we are beginning to unravel the complex pathways responsible for cystic changes in the kidney. This review integrates these molecular biologic discoveries with the known pathobiology of disease to achieve a more complete understanding of the whole process.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

An emerging viewpoint states that localization of antibodies, T cells, and macrophages within the kidney occurs through specific receptor-mediated interactions to initiate nephritis. The initial events involve loss of tolerance with activation of autoreactive B cells, autoreactive T cells, or both. Many pathogenic autoantibodies form immune deposits either by binding directly to renal antigens or by complexing with endogenous antigens with affinity for renal antigens. Autoreactive T-cell infiltration requires both the presence of specific antigens and costimulatory factors expressed by cells capable of antigen presentation. It is particularly noteworthy that some of the antigen targets of the nephritogenic immune response involve either cell surface molecules or matrix components with functional properties, raising the possibility that ligation of these components could serve to modulate the local inflammatory response. Furthermore, specific perturbations within endogenous cells, resulting directly from these interactions, probably influence subsequent inflammatory-fibrogenic events. In this review, we focus on recent work relating to the loss of tolerance leading to the emergence of autoreactive B and T lymphocytes; specific autoantibody and T-cell interactions within the kidney; and the active participation of endogenous cells in the initiation of the nephritogenic response.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Cytokines play pivotal roles in most physiologic and pathologic processes. This paper reviews recent data on the role of cytokines in mediating renal inflammatory diseases. These data show that cytokines are involved in every phase of inflammatory injury. Cytokines induce expression of major histocompatibility complex class II and adhesion molecules on renal cells and are thereby involved in antigen presentation and leukocyte localization. Cytokines also induce the synthesis of leukocyte chemoattractants, eg, interleukin-8 and monocyte chemotactic peptide-1, in renal cells. Finally, cytokines, and in particular, platelet-derived growth factor and transforming growth factor-β, appear to play a role in the long-term consequences of renal inflammation such as the induction of cell proliferation and the accumulation of extracellular matrix, both of which characterize glomerular and tubulointerstitial fibrosis. Better understanding of the disturbances of the cytokine network in renal inflammation may ultimately lead to novel therapeutic approaches to renal disease.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

This paper briefly reviews recent experimental data derived from work in animals and cell cultures that have increased our understanding of the pathobiologic pathways leading to focal sclerosis. These pathways include glomerular visceral epithelial cell damage, leukocyte infiltration, hyperplasia and matrix accumulation in the mesangium, and endothelial injury.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Advances in cell and molecular biology have generated fresh insights into the mechanisms of glomerular injury, a field with very few substantial advances in the past 20 years. Currently, the nature of renal antigens involved in the immune reaction is being identified, as in the case of Goodpasture antigen. Many recent studies focus on T-cell and macrophage functions in glomerulonephritis that initiate acute inflammatory events and determine glomerular disease progression. Recent data established that after inflammatory cell migration to the glomerulus, subsequent damage depends on cell adhesion to cytokine-activated endothelial cells, a process mediated by a variety of specialized molecules. It seems easy to predict that within the next few years these studies will have a major impact on the way these diseases are treated. Already, evidence indicates that, in experimental animals, monoclonal antibodies blocking adhesive molecules prevent or reduce glomerular damage. Cytokines and growth factors, by promoting resident cell proliferation and modulating extracellular matrix synthesis and metabolism, modulate acute glomerular injury and subsequent scarring. Recent studies have established that glomerular injury is related to urinary protein excretion, an issue that has been approached in humans by combining studies on barrier size selectivity with morphometry. An emerging concept suggests that leaking of proteins through the glomerular capillary has an intrinsic renal toxicity that is likely due to proximal tubular over-reabsorption of the abnormally filtered macromolecules. Data are also accumulating that may soon link the degree of tubulointerstitial injury with glomerular damage and subsequent development of renal scarring.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The key change in diabetic glomerulopathy is accumulation of extracellular material. Basement membrane thickening and matrix expansion develop concomitantly. In insulin-dependent diabetic patients persistent microalbuminuria is associated with an early stage of glomerulopathy. Albuminuria in non-insulin-dependent patients does not always reflect glomerulopathy. Renal and glomerular hypertrophy in the early stages of insulin-dependent diabetes mellitus is unlikely to play a dominant role in the development of glomerulopathy. Loss of capillary surface, closely associated with loss of glomerular function, is only partly explained by mesangial expansion—glomerular occlusion plays an important role. Possible mechanisms of albuminuria are qualitative changes of the basement membrane, eg, loss of proteoglycans and excess glycosylation; epithelial cell changes; new vessel formation; remodeling of glomerular structures; and impeded function of juxtaglomerular arterioles. The interplay among abnormalities in individual compartments of the diabetic kidney should be explored.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

In the past few years, advances in molecular and cellular immunology have greatly enhanced our understanding of the immunopathogenesis of tubulointerstitial nephritis and vasculitis. This review focuses on recent observations regarding nephritogenic tubulointerstitial antigens, their expression and presentation by tubular epithelial cells, the subsequent immune response, and the factors that serve to modulate this response. The latter part of this review summarizes recent findings regarding the role of autoantibodies in the immunopathogenesis of vasculitis.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID