Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.
View Article and Find Full Text PDFBackground: In membranous nephropathy, the development of glomerular lesions is related to the formation of immune complexes at subepithelial sites. These deposits are associated with modifications in the fibrinolytic activity of glomerular cells leading to the appearance of fibrin degradation products in the deposits and the urine. A previous study has shown that immune complexes interact with glomerular epithelial cells (GEC) through the neonatal Fc receptor (FcRn).
View Article and Find Full Text PDFThe renin-angiotensin system (RAS) has become increasingly complex. New components have been identified, and additional roles for angiotensin peptides and their receptors are being uncovered. A functional (pro)renin receptor has been cloned that acts as (pro)renin cofactor on cell surface, enhancing the efficiency of angiotensinogen cleavage by (pro)renin and unmasking prorenin catalytic activity.
View Article and Find Full Text PDFRev Med Interne
October 2003
Introduction: Hemophagocytic lymphohistiocytosis syndrome (HLS) is defined by activated macrophage proliferation. These cells phagocyte the blood elements. This syndrome can be primary as an autosomal recessive disease or secondary to neoplasia, immune diseases or infections-viral, parasitary or bacterian.
View Article and Find Full Text PDFBackground: Mice transgenic for growth hormone develop mesangial proliferation, glomerular hypertrophy, and progressive glomerular sclerosis suggesting that the growth hormone-insulin-like growth factor I (IGF-I) pathway plays an important role. Therefore, we studied the impact of variable concentrations of 22 kD, 20 kD growth hormone, as well as of the growth hormone receptor antagonist pegvisomant (B2036-PEG), on both the growth hormone receptor (GHR/GHBP) gene expression and growth hormone binding protein (GHBP) formation in a human glomerular mesangial cell line. Further, the impact on collagen, IGF-I and IGF binding protein-1 (IGFBP-1) formation was studied.
View Article and Find Full Text PDFThe role of proteases and of antiproteases in the progression of renal disease is well established. Most studies have focused on the serine-proteases of the plasmin/plasminogen activator system and on matrix metalloproteases. Recently, renin, an aspartyl-protease, has attracted much attention because of the role of angiotensin II in the progression of renal lesions and because of the discovery of a functional renin receptor.
View Article and Find Full Text PDFIn France, 45,000 patients are treated by hemodialysis and/or transplantation for chronic renal failure. Every year 7,000 new patients need such a therapeutic approach. The estimated cost of this pathology is about 1% of the total amount of the budget of social security, even though the number of patients is limited.
View Article and Find Full Text PDFPurpose Of Review: The renin-angiotensin system plays a major role in the control of blood pressure and of salt balance, but it is also involved in physiological and pathological processes, development, inflammation and cardiac hypertrophy. A concept has emerged suggesting that these effects are due to a local activation of the renin-angiotensin system. The search for a receptor of renin was based on the idea that tissue (pro)renin is taken up from the circulation and on data suggesting that renin has cellular effects independent of angiotensin II.
View Article and Find Full Text PDFA false hyperchloremia in a patient with a history of depression suspected bromide intoxication. The diagnosis was confirmed by an increased bromide concentration > 20 mmoL.L-1.
View Article and Find Full Text PDFBackground: Haemolytic uraemic syndrome (HUS) is a rare and severe disease of various aetiologies in adults. The effect of fresh frozen plasma (FFP) infusion in adults suffering from HUS is not well defined. The aim of this retrospective study was to analyse the causes of HUS in adults admitted in a single renal intensive care unit (ICU) and to determine the life and renal prognosis factors, while most patients (78%) received FFP infusion.
View Article and Find Full Text PDFRenin is an aspartyl protease essential for the control of blood pressure and was long suspected to have cellular receptors. We report the expression cloning of the human renin receptor complementary DNA encoding a 350-amino acid protein with a single transmembrane domain and no homology with any known membrane protein. Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
February 2002
Our previous study demonstrated that the GR is expressed in the human kidney glomerulus. The function of the GR of glomerular cells might be affected by the concentration of intracellular glucocorticoids, which is modulated by 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). Because the expression of 11betaHSD2 in the glomerular cells remains unclear, we used competitive RT-PCR and immunoblotting to detect the expression of 11betaHSD2 mRNA and protein in isolated human glomeruli, in whole kidney cortex as a positive control, and in a human glomerular visceral epithelial cell line.
View Article and Find Full Text PDFThe urokinase receptor (uPAR) is a multifunctional molecule involved in pericellular, fibrinolytic, and proteolytic activities, as well as in cell adhesion and chemotaxis and may play a role in the pathogenesis of tissue remodeling occurring during glomerulonephritis. We analyzed sequentially the expression of uPAR by immunohistochemistry and in situ hybridization in an accelerated model of nephrotoxic nephritis in rats. A strong induction of uPAR mRNA expression was observed in glomeruli as soon as 1 h after nephrotoxic serum injection.
View Article and Find Full Text PDFBackground: Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis.
View Article and Find Full Text PDFThis is the first retrospective study aimed to analyze the clinical symptoms, the etiology, the morbidity and the lethality of acute renal failure in patients over 80 years. The criterion of inclusion was the occurrence of acute renal failure defined on the basis of high plasma creatinine associated with normal kidney size in patients of this class of age who had been hospitalized in an intensive care unit between October 1971 and September 1996. In the case of a preexisting moderate nephropathy, acute renal failure was defined by an increase of plasma creatinine of at least 50% over its basal value.
View Article and Find Full Text PDFTissue-specific expression patterns of the paired type IV collagen genes COL4A5 and COL4A6 form the basis for organ involvement in X-linked Alport syndrome, a disorder in which these genes are mutated. We investigated the proximal promoter region of COL4A5 and COL4A6 using glomerular visceral epithelial cells, in which COL4A5 alone is transcribed; keratinocytes, in which the genes are co-transcribed; and additional model cell lines. By RNase protection assays, the intergenic region is 292 base pairs.
View Article and Find Full Text PDFBackground: Renal impairment, usually due to tubulointerstitial and rarely glomerular disorders occurs in 10 to 30% of patients with primary Sjögren's syndrome. Extracapillary proliferation may also be observed.
Case Report: A 62-year-old woman with primary Sjogren's syndrome diagnosed 12 years earlier, developed microscopic polyangeitis leading to rapidly progressive renal failure.
Matrix metalloproteinase 2 (MMP2) has been reported to be secreted by collagen-stimulated platelets, and active MMP2 has been shown to play a role in platelet aggregation. It has been demonstrated that MMP2 activation is dependent on the complex (membrane type 1 [MT1]-MMP/tissue inhibitor of MMP2 [TIMP2]) receptor and MMP2. We have investigated human platelets as a possible source of MT1-MMP, and we have studied its role in MMP2 activation and in platelet aggregation.
View Article and Find Full Text PDFPlasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis. The progression of renal lesions to fibrosis involves several mechanisms, among which the inhibition of extracellular matrix (ECM) degradation appears to play an important role. Two interrelated proteolytic systems are involved in matrix degradation: the plasminogen activation system and the matrix metalloproteinase system.
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