ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewRenal fibrosis characterizes a common endpoint of diverse renal diseases which leads to functional impairment ultimately resulting in terminal renal failure.Recent findingsRecent advances in this field led to the discovery of several novel mediators as well as novel aspects of known mediators. Studies on the origin and role of specific renal cell types involved in renal fibrosis identified bone marrow derived mesangial progenitors and offered substantial evidence for the concept of epithelial to mesenchymal transition. Much progress has also been made in better understanding of the interactions between different mediators and between mediators and renal target cells. Compounds designed on the basis of this current knowledge have proven to be potent inhibitors of the development of renal fibrosis or might even induce resolution of renal fibrosis.SummaryThe number and diversity of recent studies in this field offer hope for new treatment regimes in our clinical efforts towards prevention and regression of progressive fibrosing renal diseases.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewTubulointerstitial injury is characteristic of aging-associated renal injury and progressive renal disease. Salt-sensitive hypertension is also associated with tubulointerstitial inflammation, especially when accompanied by microvascular disease. Here we summarize recent studies on the pathogenesis and consequences of tubulointerstitial disease, emphasizing the role of ischemia and the microvasculature.Recent findingsTubulointerstitial injury occurs via several mechanisms of which one of the most important is chronic ischemia. Recent studies suggest that chronic vasoconstriction may contribute to the renal injury associated with angiotensin II, catecholamines, nitric oxide inhibition, hypokalemia, hyperuricemia, and cyclosporine nephropathy. Salt-sensitivity may result as a consequence of the tubulointerstitial inflammatory response to these conditions, and this appears to be perpetuated by the development of preglomerular vascular disease. With progression of tubulointerstitial disease there is also a loss of peritubular capillaries, and stimulating microvascular growth with angiogenic factors can stabilize renal function in these models.SummaryIschemia secondary to vasoconstriction or to structural changes of the renal vasculature may have important consequences both in terms of mediating salt-sensitive hypertension and renal progression. Angiogenic factors may have potential benefit in preventing or treating these conditions.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewChemokines are members of the largest group of chemotactic cytokines, and were the first shown to be able to engage specific subpopulations of inflammatory cells. Accordingly, our expanding knowledge in chemokine biology has enlarged our understanding of inflammatory cell interactions, lymphopoesis, specificity of cell recruitment, and a variety of human diseases. This review covers recent developments on chemokines in renal diseases.Recent findingsIntrinsic renal cells are capable of chemokine expressionin vitroandin vivo, and the involved induction pathways are becoming increasingly defined. Differential chemokine expression during the time course of disease, followed by an infiltration of cells expressing the corresponding receptors has been described in animal models. Therapeutic efficacy of chemokine blockade has been demonstrated in a variety of disease models, including progressive interstitial fibrosis. Chemokine receptors are differentially expressed and localized to specific parenchymal compartments in human renal diseases, as revealed by studies of renal biopsies, and some functional roles of specific chemokine/receptor interactions can be deduced through the correlation of patterns of expression, genetic variations and disease courses.SummaryChemokines play an important role in renal inflammation. Although the treatment of patients with renal diseases using chemokine receptor blocking agents has not yet reached clinical practice, a recent body of data indicates that human renal disease might be amenable to such approaches.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe rapidly developing field of podocyte cell biology is reviewed, focusing on papers published in the last 12 months.Recent findingsFour areas of particular progress can be discerned. First, podocytes proliferate during early metanephric development, are quiescent after the capillary loop stage, and re-enter the cell cycle only in the disease group termed collapsing glomerulopathy. We have learned that control of the podocyte cell cycle involves both expression of cell-cycle regulating proteins and the process of cytokinesis. Second, the podocyte slit diaphragm is the final component of the filtration barrier. The structure and maintenance of the slit diaphragm has been a major focus of research activity, and a multiplicity of relevant molecular interactions have been defined. Significant advances have been made in understanding the complex and interacting role of nephrin and podocin mutations in the genesis of clinical glomerular disease. Third, several proteins essential to controlling discrete podocyte transcriptional programs have been defined. Finally, conditionally-immortalized podocyte cell lines, derived from mouse and human tissue, have proven their worth as models to advance investigations of podocyte biology.SummaryPodocyte injury occurs as a consequence of genetic mutation, immunological injury, viral infection, or abnormal hemodynamic forces within the glomerulus. As we understand more about the podocyte proteome and cell biology, we gain an increasingly detailed molecular understanding of podocyte structure and function. In this drama we have many molecular players and increasing stretches of molecular dialogue, but the script remains largely to be deciphered. Nevertheless, we do understand the consequences that arise when the podocyte cannot put its best foot (processes) forward.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewRecent research achievements might considerably alter scientific concepts of pathways involved in tissue injury and repair.Recent findingsAccumulating evidence for an important role of alloantibodies in acute and chronic allograft rejection led to a renewed interest in humoral kidney transplant rejection. Studies reassessing the mechanisms of antibody- and complement-mediated injury now shed new light on the pathogenic mechanisms underlying acute or chronic graft dysfunction and injury. A closer look at humoral effector mechanisms revealed that endothelial cell activation and injury may play a key role in humoral rejection, and further uncovered an important interplay between humoral and cellular alloimmunity. Regeneration of cells after injury has been thought to rely on activation of local progenitor cells. Recent investigation indicates that regeneration of grafted solid organs is not exclusively based on self-renewal of tissues but obviously also involves repopulation of the graft by recipient cells, creating chimerism in the vasculature and other compartments. Besides reparative compensation of cell loss, chimerism of endothelial cells might also alter immunologic properties of the graft, thus favoring adaptation and graft survival. On the other hand, however, myofibroblasts mediating deleterious arterial intimal proliferation may also be of recipient origin. A possible source of graft-repopulating recipient cells are bone marrow-derived adult stem cells with the amazing capacity of differentiating into cell types of all three germ cell layers.SummaryReliable diagnosis of humoral mechanisms in allograft rejection and identification of involved effector mechanisms should provide the basis for development and targeted application of specific anti-humoral treatment. Recently emerged new concepts of mechanisms underlying tissue regeneration might pave the way for entirely new therapeutic approaches in human disease.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewGlomerulonephritis is an important manifestation of small vessel vasculitides such as Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Renal involvement in these diseases is characterized by a pauci-immune segmental necrotizing and crescentic glomerulonephritis that is strongly associated with circulating antineutrophil cytoplasmic autoantibodies. We will review recent advances in understanding the pathogenesis of antineutrophil cytoplasmic autoantibody-related renal vasculitides and innovative approaches to their treatment.Recent findingsAn experimental milestone in antineutrophil cytoplasmic autoantibody research has been reached in the past year. Using an innovative mouse model, investigators from the University of North Carolina in Chapel Hill have recently acquired robust data supporting the pathogenic role of antineutrophil cytoplasmic autoantibodies in the glomerulonephritis and small vessel vasculitis, analogous to those seen in microscopic polyangiitis and Wegener granulomatosis. Novel immunosuppressive approaches have been examined including preliminary studies using biologic agents, such as antagonists of tumor necrosis factor and monoclonal antibodies to B lymphocytes.SummaryRecent insights into the pathogenesis of antineutrophil cytoplasmic autoantibody-related vascular injury and the availability of new biologic, immune response modifiers to complement standard chemical immunosuppressive agents offer exciting new prospects for investigation in the management of patients with small vessel renal vasculitides.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewDiabetic nephropathy is the single most common disorder leading to renal failure. Its annual incidence has more than doubled in the past decade to reach 44% of all end-stage renal disease, despite recent therapeutic advances. Thus, research into diabetic nephropathy pathophysiology that could lead to new treatment approaches is urgently needed and this review aims to summarize the work performed in this area in the past year.Recent findingsThere have been advances in the understanding of diabetic nephropathy pathology. Clearly, structural changes may be advanced before any clinical findings are apparent. Not all functional consequences of the condition are explained by current structural analyses. Genetic studies have connected the disorder risk to multiple candidate genes and a few genetic loci, but the exact genetic predisposition or protectors are not fully described. Perturbations in multiple metabolic pathways are associated with diabetic nephropathy in animals and humans, but their relative importance requires further work. Glycemia and blood pressure control are crucial for diabetic nephropathy prevention and treatment, but new modalities are needed.SummaryRecent advances in molecular biology and genetics will bring new insights to the mechanisms involved in diabetic nephropathy development. This will allow early identification of patients at risk of, or safe from, diabetic nephropathy and will hopefully lead to preventive strategies, based on the understanding of the pathophysiology of the disorder. Meanwhile, aggressive implementation of proven therapies to prevent (glycemic control) and slow (antihypertensive therapy, especially with renin-angiotensin system blockers) the progression of diabetic nephropathy are strongly recommended.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewGiven the continuous relations of blood pressure to cardiovascular risk, any definition of high blood pressure is arbitrary, and based on thresholds at which there is clear evidence that treatment benefits outweigh potential risks. This review examines what constitutes optimal blood pressure.Recent findingsA recent report raised the possibility of an age- and sex-dependent threshold for risk associated with systolic blood pressure, questioning the use of a single threshold (such as 140/90 mmHg) for defining hypertension. Several subsequent studies have questioned this notion and reemphasized that lower blood pressure levels are associated with less morbidity and mortality even within the nonhypertensive range. A recent meta-analysis confirmed that a blood pressure of 115/75 mmHg is associated with minimal vascular mortality and likely constitutes optimal blood pressure. Such blood pressure levels are infrequent in westernized societies. The target blood pressure goal for treated hypertensives is higher at 140/90 mmHg but is infrequently achieved. Select individuals at high absolute risk of cardiovascular disease events and/or with specific conditions (notably diabetes, renal insufficiency and prior vascular disease) may benefit from blood pressure lowering below this threshold.SummaryAt a population level, a blood pressure of 115/75 mmHg seems optimal because it is associated with minimal vascular risk. Over half of all hypertensives do not have their blood pressure controlled underscoring the challenges facing health care providers. Efforts should be strengthened for the primary prevention of hypertension and the promotion of optimal blood pressure through lifestyle measures.

ISSN:1062-4821    

出版商:OVID    

年代:2003

数据来源: OVID