摘要:

There is ample evidence to support the recommendation of renin-angiotensin system blockade therapy as the standard of care for strategies aimed at preserving renal function in chronic renal disease. Nevertheless, despite the well established antihypertensive effects of these drugs, the use of renin-angiotensin system blockers in renal transplantation has been quite limited so far, nephrologists being afraid of the possibility of inducing renal insufficiency in patients with a single kidney transplant. However, current knowledge of the ability of these agents to control blood pressure and urinary protein excretion, as well as post-transplant erythrocytosis, effectively in kidney transplant recipients suggests that it is now time to apply renin-angiotensin system blockers to the field of renal transplantation.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The limited availability of donor organs restricts the number of kidney transplantations performed per year. One novel solution to this shortage envisions ‘growing' new kidneysin situvia xenotransplantation of renal primordia. To be successful, such an approach would require the following criteria to be met: that transplants are ‘grown' in a location that renders their subsequent excretory function possible; that developed transplants have normal morphology and function; that transplanted metanephroi become well integrated into the host, in terms of inducing a state of immune tolerance and being vascularized by host vessels; and that source material for metanephros transplants is easy to access. This review summarizes recent work addressing these issues.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Conversion of mesenchyme to epithelium in the metanephric kidney is clearly a multimolecular, multistep and partly redundant process. The present short review focuses on a neglected morphological aspect of kidney differentiation: the development of two transitory mesenchymal condensations that precede epithelial differentiation of nephrons. The first appearing condensate covers the tips of the collecting ducts and is termed a cap condensate. In the early kidney rudiment this structure has been referred to as a primary or early condensate. A few cells of the cap condensate (maybe only four to six cells), situated at the lateral edge of the cap, start proliferating rapidly and form a pretubular aggregate (or pretubular condensate), which converts to secretory nephron epithelia and finally segregates to different tubule segments. Throughout nephrogenesis, the cap condensates and pretubular aggregates are clearly distinguishable structures that show only partly overlapping gene expression profiles. Apart from being the source for the pretubular aggregates, the role of the cap condensate is unknown. It is now proposed that the cap regulates ureteric branching morphogenesis.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Hepatocyte growth factor (HGF) and its specific c-met receptor constitute a paired signaling system that plays an important role in renal development and in the maintenance of normal adult kidney structure and functions. HGF elicits potent mitogenic, motogenic, morphogenic, and antiapoptotic activities in renal tubular epithelial cells. The nature of these pleiotropic actions renders it to be specifically suited to preserve and to reconstitute the structural and functional integrity of renal tubules after acute renal injury. Emerging evidence also indicates that both endogenous and exogenous HGF are beneficial by inhibiting the onset and progression of chronic renal diseases in various animal models. Administration of exogenous HGF protein, or its gene, effectively inhibits the activation of matrix-producing myofibroblasts, attenuates extracellular matrix deposition and interstitial fibrosis, and suppresses profibrogenic cytokine transforming growth factor-β1 and its type I receptor expressionin vivo. Hence, although more studies are warranted to further clarify its role in various chronic renal fibrosis models, delivery of either HGF or its gene may hold promise as a novel therapeutic strategy for promoting initial protection and subsequently regenerative repair after acute insult, and for ameliorating renal fibrosis and kidney dysfunction in chronically diseased conditions.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Bone morphogenetic proteins are members of the transforming growth factor-β superfamily of cytokines and consist of a group of at least 15 morphogens involved in intracellular messaging through complex bone morphogenetic protein receptor mediated Smad signaling. Bone morphogenetic protein-7 knockout mice die shortly after birth due to uremia, demonstrating that this morphogenetic protein is essential for renal development. Recent investigations have characterized renal bone morphogenetic protein-7 receptors, shown exogenous bone morphogenetic protein-7 to prevent fibrogenesis associated with ureteral obstruction, indicated a loss of renal bone morphogenetic protein-7 associated with diabetic nephropathy, and an improvement in glomerular pathology in rodent streptozocin-induced diabetes with bone morphogenetic protein-7 treatment. In addition, this morphogenetic protein has been shown to reduce glomerulonephritis and tubulointerstitial fibrosis in a murine model of lupus nephritis as well as decrease the peritrabecular fibrosis associated with murine high turnover renal osteodystrophy. Finally, we review the effects of bone morphogenetic protein-7 on vascular calcification in an animal model, a potential complication of this therapy given its osseous morphogenetic effect.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Renal cell carcinomas account for 80-85% of all primary renal neoplasms. Recent identification ofVHL,c-metandTSCas candidate genes mutated in various types of renal carcinomas has greatly enhanced our understanding of the pathogenesis of renal carcinomas and has provided novel therapeutic options for patients with renal cancer. Furthermore, developments in angiogenesis and in tumor immunology have given us additional treatment modalities for cancer patients, especially those with renal cancer. This review highlights the genetic abnormalities seen in renal cell carcinomas and reviews current and future therapeutic options.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Ischemic injury to the kidney is associated with high morbidity and mortality. Improving the ability of the kidney to tolerate ischemic injury would have important implications. A significant amount of data now exists to suggest that there may be intrinsic mechanisms brought to bear by the kidney when exposed to a toxic or ischemic insult, which protect it against a subsequent exposure to ischemia. While it is frequently stated that this phenomenon, termed ischemic preconditioning, was first described in the heart, in fact there is almost a century of literature on the kidney that supports the concept that prior injury protects against a second insult. The protective effect of preconditioning is greater than most reported protective effects with pharmacological interventions in animals. There is compelling evidence in other organs that preconditioning occurs in humans. It therefore behoves us to understand the endogenous processes that the kidney has developed to protect itself against an ischemic insult. Armed with this understanding we can then attempt to mimic these processes and thereby prevent and treat ischemic acute renal failure.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Growth factors and cytokines play a crucial role in the progression of renal diseases. A growing body of evidence has been obtained from experimental studies, suggesting that manipulation of the activity of growth factors and cytokines is a potential form of therapy for renal diseases. To preserve the renal function structure in progressive renal diseases, this approach is achieved by inhibition of apoptosis of renal intrinsic cells and by decrease in the fibrotic signal. Inhibition of transforming growth factor beta, platelet-derived growth factor, interleukin-1 and tumor necrosis factor alpha, and supplementation of hepatocyte growth factor, vascular endothelial growth factor and bone morphogenic protein-7 may be beneficial. Recent progress in therapeutic implements including humanized antibodies, chimeric soluble receptors, aptamers, antisense oligonucleotides, and gene therapy allow us to target the causal molecules. Administration of a combination of growth factors and cytokines is a potential therapeutic approach. Targeting signal transduction molecules and their co-factors and regulators is another possibility because the signals from various growth factors use a common pathway. Thus, targeting growth factors and cytokines in renal diseases could be a promising therapeutic approach.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Angiotensin II and endothelin-1 can both be regulated by nuclear factor-κB. They are to varying degrees also capable of activating nuclear factor-κB and increasing the expression of nuclear factor-κB dependent genes. Angiotensin II related vascular effects are in part mediated by endothelin-1. Nitric oxide synthase inhibition facilitates angiotensin II related effects, which can be inhibited both by angiotensin II type 1 receptor blockers and by endothelin system inhibitors. This supports the notion that a combined therapeutic strategy of inhibiting angiotensin II and endothelin-1 generation or blocking their effects at the receptor level would be superior to either strategy alone. Animal studies are encouraging but not without conflicting results. Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers have a superb track record in experimental animal models and in a host of clinical studies. Selective and nonselective blockers of the endothelin-1 receptors are important research tools and are also undergoing clinical trials. Inhibitors of the endothelin converting enzyme have been developed. The recent elucidation of the endothelin converting enzyme's physical structure should facilitate the development of still more novel compounds to inhibit endothelin-1 generation.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Although the kidney strives to maintain its perfusion within tight boundaries, considerable blood flow fluctuations do occur. The reasons for this are the rather slow acting compensatory mechanisms of renal blood flow autoregulation, the effects of renal nerves, hormonal influences, etc. It seems that variations in renal perfusion can exert a major influence on renal excretory functions, on renin release and on blood pressure. The clinical importance of renal blood flow variability is not fully understood. In many situations, the absence of normal cardiovascular oscillations seems to be a risk factor. Large fluctuations in perfusion pressure to the kidney, however, in the long run, may induce target organ damage.

ISSN:1062-4821    

出版商:OVID    

年代:2002

数据来源: OVID