Search

The need for early nephrology referral. The incidence of end-stage renal disease is increasing. Progression to end stage can be slowed if kidney damage is detected at an early stage. Prognosis and outcomes in patients with chronic kidney disease have been related to the quality of predialysis care and the timing of referral. Many patients with chronic kidney disease are referred to a nephrologist close to commencement of renal replacement therapy. This leads to suboptimal management of complications of chronic renal insufficiency, and increased morbidity and mortality of patients on renal replacement therapy. This article addresses the evidence that examines the view that patients need to be referred early in order to avoid complications of chronic renal insufficiency. Early referral can be achieved through improved communication between primary health care givers and nephrology services. A multidisciplinary approach has a significant impact on outcomes. In the face of rising incidence of chronic kidney disease, early referral of all patients is not possible. Therefore, identification of patients at risk for rapid deterioration of renal function is important in order to rationalize and reduce health care expenditure. [ABSTRACT FROM AUTHOR]

Investigates the mechanisms whereby filtered transferrin iron and intracellular iron cause damage in the rat remnant kidney model of chronic renal disease. Model and animals; Lysosomal studies; Analytic techniques; Fragility of lysosomes expressed by different formulas.

Presents the abstract 'Reconstitution of CD4+ T Cells Reduces Renal Injury in Scid Mice With Adriamycin Nephropathy,' by Yiping Wang, Lukas Kairaitis, Yuet-Ching Tay, Yang Wang, Ling Zheng and David C.H. Harris.

The role of tubulointerstitial inflammation. Exploration of the role of tubulointerstitial inflammation in experimental chronic renal disease (CRD) is an essential step to understanding and finding new treatments for human CRD. Adriamycin nephrosis (AN) is an experimental analogue of human focal glomerular sclerosis and tubulointerstitial inflammation. Using murine and rat AN, we have systematically investigated the pathogenic roles of chemokines, costimulatory molecules, and inflammatory cells, such as macrophages and effector and regulatory T lymphocytes. The profile of humoral and cellular mediators was studied in vitro and in vivo. The pathogenic significance of various factors was investigated by DNA vaccination, leukocyte reconstitution and depletion, retroviral transduction, and blockade with monoclonal antibodies. Renal cortical and tubular cell CC-chemokines, including MCP-1, RANTES, and MIP-1α, were up-regulated via mediation of NFκB, and contributed to disease by attracting inflammatory cells into the interstitium. The role of these chemokines was confirmed by DNA vaccination. CD40-CD40L costimulation signals were involved in expansion and activation of the inflammatory infiltrate, whereas PD-1 signals were inhibitory, and CD28-B7 appeared to have a neutral effect. Macrophage and CD8+ T cells were shown to be effectors of injury, whereas CD4+CD25+ and γδ T cells acted as regulatory cells. FoxP3 transduction was able to convert naïve T cells to CD4+CD25+ regulatory T cells. There is a broad range of humoral and cellular factors involved in the pathogenesis of experimental CRD, some of which are potential targets for treatment of human CRD. [ABSTRACT FROM AUTHOR]

Examines the role of CD4[sup+] T cells to disease progression and loss of renal function in chronic proteinuric renal disease (CPRD). Combination of adriamycin and CD4[sup+] depletion mice; Effects of CD4 depletion on recruitment of inflammatory cells; Number of inflammatory infiltrates.

Lipopolysaccharide-induced MCP-1 gene expression in rat tubular epithelial cells is nuclear factor-κB dependent. Background. Endotoxin is an important factor in the development of acute renal failure related to infection and in acceleration of chronic nephritis. Lipopolysaccharide (LPS; the major component of endotoxin) is one of the most potent triggers for renal cells to produce monocyte chemoattractant protein-1 (MCP-1), a key cytokine involved in immune cell recruitment into the renal interstitium in acute and chronic renal diseases. Knowledge about the transcriptional regulation of MCP-1 in renal tubular epithelial cells in response to LPS is incomplete. Methods. Transcriptional regulation of MCP-1 was investigated in rat proximal tubule cells (PTCs) in primary culture and was exposed to LPS using electromobility shift assay and supershift analysis for nuclear factor-κB (NF-κB) and Western blot for the NF-κB inhibitory protein IκB. To prove the role for NF-κB, activator protein (AP-1), and sequence-specific transcription factor (Sp1), mutation and deletion analysis was performed using a 3.5 kb fragment of rat MCP-1 5′-flanking region inserted into a luciferase reporter construct transfected into tubular epithelial cell line (NRK-52E). Results. LPS increased NF-κB in a dose- and time-dependent manner, which paralleled that of MCP-1 mRNA expression. IκBα decreased within 30 minutes of LPS treatment, but returned to basal levels by two hours. IκBβ levels were depressed within one hour and remained low throughout the culture period after LPS stimulation. The activity of the transfected 5′-flanking region of the MCP-1 gene increased nearly threefold after LPS stimulation. Mutation or deletion of NF-κB binding sites, located in the enhancer region of the 5′-flanking region, resulted in a total loss of LPS-induced increase in luciferase activity. Mutation of putative AP-1 and Sp1... [ABSTRACT FROM AUTHOR]