摘要:

Clinical immunosuppression must balance the therapeutic goal of reducing host defence with the risk of catastrophic infection or malignancy, plus the non-immune effects of the existing agents. A variety of new agents are now available which improve the chances of achieving these immunosuppressive objectives. Others are promising but remain unproven in the clinic. The general principles of immunosuppression are also becoming clearer, and we are developing more rational approaches. The effects of immunosuppressives on the T cell response, plus studies of the genetic errors which create blocks in the immune response, can now be combined to create an increasingly complete picture of non-redundant, semiredundant, and redundant steps in the T cell response, and how the immunosuppressive agents affect these steps.

ISSN:1420-4096    

DOI:10.1159/000174068

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In recent years, nitric oxide (NO) has been identified as an effector molecule with multiple biological functions. NO production is physiologically involved in the regulation of vascular tone, platelet aggregation and hormone release, in neurotransmission, and in immune defense against several pathogens. However, uncontrolled up-regulation of NO release by cytokine-inducible NO synthases (iNOSs) may cause tissue damage in immune-mediated diseases. In experimental glomerulonephritis, there is now good evidence that glomerular induction of NO synthesis mediates glomerular cell injury. In contrast, an intact constitutive NO release within the glomerular vasculature may be protective by decreasing glomerular capillary pressure. This review discusses the pathophysiological role of NO in glomerulonephritis based on experimental data and provides a perspective for potential anti-inflammatory treatment approaches selectively targeting iNOS overexpression.

ISSN:1420-4096    

DOI:10.1159/000174069

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Enhanced filtered load of proteins in glomerular diseases (overload proteinuria) results in significant increase in the rate of proximal tubular uptake that is true for all proteins tested so far, including albumin. The excess concentration of absorbed proteins in lysosomes may itself lead to cellular damage by spillage of lysosomal enzymes to the cytosol. In vitro evidence is also available of functional alteration of these tubular cells, including upregulation of genes encoding for endothelin-1 (ET-1) and other inflammatory mediators, when they are overloaded in culture with proteins or lipoproteins. This could affect renal function and structure given the inflammatory, growth factor, and vasoactive properties of ET-1. Findings in several experimental models of proteinuric progressive nephropathies have indeed documented enhanced renal ET-1 gene expression and excretion of the peptide into the urine which correlated with proteinuria and the degree of glomerular and tubulointerstitial damage.

ISSN:1420-4096    

DOI:10.1159/000174070

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Specific interactions between cells and components of the surrounding extracellular matrix (ECM) or underlying basement membrane have been shown to modulate cell behaviour, in culluro and in vivo. There is evidence that extensive ‘cross-talk’ occurs between glomerular mesangial cells (MCs), ECM molecules, and soluble mediator substances affecting the proliferative and synthetic-secretory phenotype of MCs. This is likely to be relevant for the behaviour of MCs during embryonic development, disease processes of glomeruli, and tissue repair. The potential biologic and clinical relevance of cell-matrix interactions in the glomerulus are discussed in this brief review of selected aspects of recent investigations concerning the mesangial matrix and its interactions with

ISSN:1420-4096    

DOI:10.1159/000174071

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Correlations between the relative volume of the intertubular capillaries in the renal cortex and the serum creatinine concentration in primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides are reported. In the mesangioproliferative glomerulonephritides, there are significant negative correlations between the number and area of the intertubular capillaries in the cortex and the serum creatinine concentration. In diabetic glomerulosclerosis, renal glomerular amyloidosis, decompensated benign nephrosclerosis, secondary malignant nephrosclerosis, and chronic interstitial nephritis, there is a significant negative correlation between the relative area of the intertubular capillaries and the serum creatinine concentration. Thus, in these diseases, there is progressive narrowing/ obliteration of the postglomerular capillaries which leads to a progressive decrease in glomerular filtration rate and thus to a rise in serum creatinine concentration.

ISSN:1420-4096    

DOI:10.1159/000174072

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The German Collaborative Glomerulonephritis Therapy Study, which celebrated its 10th anniversary in 1996, has collected data on more than 1,000 patients with biopsy-proven glomerulonephritis. 929 patients could be evaluated and 500 were treated according to at least one of various protocols developed for a randomized controlled trial. Current results show that prednisolone is effective in minimal-change nephropathy, and in combination with other immunosuppressants it can reduce proteinuria in individual cases of focal and segmental glomerulosclerosis, membranous glomerulonephritis and nephrotic IgA nephropathy. The majority of tested treatment protocols did not prove to be superior to symptomatic therapy for long-term outcome.

ISSN:1420-4096    

DOI:10.1159/000174073

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The objective of immunosuppressive therapy in nephrology is to prevent autoimmune diseases and to suppress kidney allograft rejections while sparing other effects. Increased clarification of the underlying immune mechanism has made specific immunodulation possible using chimeric proteins in which the variable domains of an immunoglobulin are replaced by extracellular domains of cell surface molecules or cytokines. The immunosuppressive effects of fusion proteins such as CTLA-4 IgG, CD40 IgG, interleukin (IL)-10 IgG, IL-2 IgG or tumor necrosis factor (TNF)-receptor IgG have been proven in various animal models. Moreover, the application of TNF-receptor IgG successfully limited the OKT3-induced cytokine release syndrome in kidney graft recipients. It seems likely that recombinant proteins with increasingly effective suppression of specific elements of the immune response will become an essential element in clinical protocols.

ISSN:1420-4096    

DOI:10.1159/000174074

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The hemolytic uremic syndrome is the most frequent cause of acute renal failure in childhood. In the vast majority of patients, the syndrome of acute hemolysis, thrombopenia and renal dysfunction is preceded by an episode of diarrhea with or without bloody stools. This colitis is caused by different strains of Escherichia coli which produce shiga like toxins. These toxins are responsible for both hemolysis and renal disease. There are good reasons for distinguishing patients with D (+) HUS and those without prodromal diarrhea [D (-) HUS], especially since the outcome in the latter group is less predictable and on average fairly unfavorable. D (+) HUS has also been labeled ‘typical HUS’ and D (-) HUS as ‘atypical HUS’. This has led to some oversimplification, in that atypical has become synonymous with poor outcome. Our experience comprises 20 D (-) HUS patients, of whom 14 did extremely well. Scrutinizing the data of our patients lead to the conclusion that, within the D (-) group, some have a ‘typical course’ and display complete cure whereas those with an ‘atypical course’ either die or have

ISSN:1420-4096    

DOI:10.1159/000174075

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The molecular genetic defect of many hereditary nephropathies has been assigned to a specific chromosomal region or has even been identified. While the localization of a gene permits an indirect genotype analysis to estimate the risk status of a close relative of a patient with a proven clinical diagnosis, it is not possible to confirm a diagnosis in case of inconclusive clinical data. In some nephropathies, the gene has been cloned and mutations identified. By demonstrating the molecular genetic defect in these patients, the diagnosis can be ensured and an easily assessible method of carrier detection can be offered. The possibilities and limitations of DNA diagnosis in some important nephropathies are outlined.

ISSN:1420-4096    

DOI:10.1159/000174076

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The hepatitis C virus is a 9.4-kb single-stranded positive RNA virus. After infection, more than 80% of patients develop a chronic carrier state. The diagnosis is based on the detection of hepatitis C virus antibodies and of HCV RNA. Recently, methods have been established to quantify HCV RNA levels and determine HCV genotypes. Interferon treatment gives long-term response in 10-20% of individuals. Low transaminase levels, low levels of viremia and low histological activity are positive predictive parameters for treatment response. In contrast, cirrhosis, high ferritin levels and associated markers of autoimmunity are negative predictors of treatment response. At present, the combination of interferon with the nucleoside analogue ribavirin is being evaluated. Endstages of hepatitis-C-induced cirrhosis are treated with liver transplantation. Reinfection of the graft occurs regularly, the clinical implications of which are not yet clear. Our knowledge of the spontaneous course and treatment response of hepatitis C infection in hemodialysis patients is limited.

ISSN:1420-4096    

DOI:10.1159/000174077

出版商:S. Karger AG    

年代:1996

数据来源: Karger