ISSN:0250-8095    

DOI:10.1159/000168643

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0250-8095    

DOI:10.1159/000168644

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The glomerular capillary wall imposes a remarkably efficient barrier to the passage of proteins the size of albumin and larger. The development of heavy proteinuria signifies impairment in the function of this barrier. Because endogenous proteins of graded size are heterogeneous with respect to their molecular charge, and undergo extensive tubular reabsorption, they are not useful for quantifying the extent of barrier dysfunction. An alternative approach is to determine the fractional clearance of uncharged and nonreabsorbable polymers of graded size. When combined with a hydrodynamic theory of solute transport through a heteroporous membrane, the intrinsic properties of healthy and diseased glomerular capillary walls can be inferred. This approach reveals the nephrotic range proteinuria that attends membranous nephropathy to be associated with impairment of both the size- and charge-selective properties of glomerular capillary walls.

ISSN:0250-8095    

DOI:10.1159/000168645

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Glomerular epithelial cells contribute significantly to the hydraulic and macromolecular permeability properties of the glomerulus. Because of their location as the terminal element in the filtration barrier and their elaborate cytoskeleton, they are likely to participate in the regulation of filtration. In disease, alterations of the glomerular epithelial cells may lead to simplification and retraction of foot processes, resulting in a decreased density of slit diaphragms and decreased by hydraulic conductivity. In addition, denudation of epithelial cells from the basement membrane results in increased macromolecular permeability at those sites and accounts for much of the proteinuria in a variety of types of renal disease.

ISSN:0250-8095    

DOI:10.1159/000168646

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Mediators of immune glomerular injury may be divided into primary and secondary. Primary mediators include antibody and T cells and secondary include complement, infiltrating inflammatory cells, such as neutrophils, monocytes/macrophages and platelets, coagulation system, resident glomerular cells including mesangial, endothelial and epithelial cells, reactive oxygen metabolites, eicosanoids, proteolytic enzymes and a host of cytokines. Following initiation of immune glomerular injury with primary mediators, which in most cases is antibody, a complex set of interactions involving some or all of the secondary mediators occurs in the glomerulus, ultimately leading to the clinical manifestations of glomerular injury. The precise sequence and the mechanisms of these interactions are not fully defined but are under intense study. The identity of the putative antigens and why and how an autoimmune response develops are also not fully known.

ISSN:0250-8095    

DOI:10.1159/000168647

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Proteinuria is the primary manifestation of a variety of glomerular diseases which are characterized clinically by the nephrotic syndrome. In many cases there is little effective treatment for the primary disease process. However, reduction of proteinuria can frequently improve the hypoalbuminemia, hyperlipidemia and edema which are responsible for the morbidity of the nephrotic syndrome. Proteinuria can be reduced in nephrotic humans and experimental animal models by restriction of dietary protein intake, nonsteroidal anti-inflammatory drug, and by angiotensin-converting enzyme inhibitors. Each of these therapies modifies the activity of locally acting glomerular hormones, autocoids, suggesting that there is a component of proteinuria which is hormonally mediated. The effects of dietary protein, nonsteroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors on nephrotic proteinuria and their potential hormonal mechanisms of action is the subject of this review.

ISSN:0250-8095    

DOI:10.1159/000168648

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The nephrotic syndrome is a consequence of urinary loss of intermediate sized plasma proteins and the resulting homeostatic responses to those losses. Plasma protein composition is changed greatly. Intermediate sized proteins, including albumin, transferrin, IgG, hormone binding proteins, and low molecular weight inhibitors of the clotting cascade, are lost in the urine and their concentration in plasma reduced. Synthesis of many proteins secreted by the liver is increased either at the level of transcription or posttranscriptionally. Synthesis of several liver-derived proteins is increased in the absence of their urinary loss, suggesting that hypoalbuminemia or reduced plasma oncotic pressure (Π) stimulates the production or reduces the rate of catabolism of these proteins. Their plasma levels, including those of lipoproteins and elements of the coagulation cascade, are increased. Plasma Πfalls and plasma viscosity increases because of the replacement of intermediate sized plasma proteins by larger ones. The plasma concentration of several proteins lost in the urine but not secreted by the liver, such as erythropoietin and IgG, are not defended by increased synthesis, suggesting that increased synthesis of plasma proteins is primarily confined to the liver. Loss of both liver-derived and non-liver-derived proteins may cause reduced immunity, anemia, and deficiency syndromes. Urinary loss of albumin alone is not responsible for decreased plasma Π. The relationship between plasma protein concentration and Πis greatly disturbed in nephrotic rats. In contrast, the relationship between Πand plasma protein concentration is nearly the same in rats with hereditary analbuminemia (NAR) and normal rats, despite the absence of albumin from the plasma of NAR. When proteinuria is induced in NAR the relationship between plasma protein concentration and Πbecomes identical to that in nephrotic animals, although no albumin was lost in the urine o

ISSN:0250-8095    

DOI:10.1159/000168649

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The nephrotic syndrome can profoundly affect metabolism and regulation of protein or protein-bound hormones or prohormones. The present paper provides an overview of the published studies on erythropoietin, vitamin D and thyroid metabolism as well as hypothalamic-pituitary-gonadal axis in nephrotic syndrome. On each occasion the clinical significance and practical implications of the reported abnormalities are emphasized. In addition, attention is drawn to the areas needing further investigations.

ISSN:0250-8095    

DOI:10.1159/000168650

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Nephrotic syndrome is defined by proteinuria, hypoalbuminemia, edema and hypercholesterolemia. Evidence from both the experimental and clinical literature suggests that high lipid levels are not only a marker of disease, but also contribute to the process of glomerulosclerosis. Lipid mediators, including eicosanoids, platelet-activating factor, and chemotactic factors, can contribute by effecting leukocyte infiltration, mesangial proliferation, extracellular matrix protein production, vasoreactivity, and coagulation. Infiltrating macrophages may play a central role in these processes. Therapeutic maneuvers aimed at the correction of lipid abnormalities may halt or slow the progression of nephrotic syndrome to end-stage renal disease.

ISSN:0250-8095    

DOI:10.1159/000168651

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Tubulointerstitial disease is an invariant finding in proteinuric renal disease regardless of the underlying disease or the compartment in which the disease originates. Such histologic changes are functionally significant in that scores of such injury rather than glomerular histologic injury correlate with decrements in GFR. Proteinuria, the consequence of a loss of glomerular permselectivity incurred by glomerular diseases, also provides an index of renal functional decline. This review provides evidence that proteins leaked into the urinary space may directly or indirectly provoke tubulointerstitial injury, a linkage that may underlie the functional significance of proteinuria and tubulointerstitial disease. This review also highlights two products of nitrogen metabolism, ammonia and nitric oxide, in the pathogenesis of tubulointerstitial disease.

ISSN:0250-8095    

DOI:10.1159/000168652

出版商:S. Karger AG    

年代:1993

数据来源: Karger