TRPC6 single nucleotide polymorphisms and progression of idiopathic membranous nephropathy

Background: Activating mutations in the Transient Receptor Potential channel C6 (TRPC6) cause autosomal dominant focal segmental glomerular sclerosis (FSGS). TRPC6 expression is upregulated in renal biopsies of patients with idiopathic membranous glomerulopathy (iMN) and animal models thereof. In iMN, disease progression is characterized by glomerulosclerosis. In addition, a context-dependent TRPC6 overexpression was recently suggested in complement-mediated podocyte injury in e.g. iMN. Hence, we hypothesized that genetic variants in TRPC6 might affect susceptibility to development or progression of iMN. Methods & Results: Genomic DNA was isolated from blood samples of 101 iMN patients and 292 controls. By direct sequencing of the entire TRPC6 gene, 13 single nucleotide polymorphisms (SNPs) were identified in the iMN cohort, two of which were causing an amino acid substitution (rs3802829; Pro15Ser and rs36111323, Ala404Val). No statistically significant differences in genotypes or allele frequencies between patients and controls were observed. Clinical outcome in patients was determined (remission n = 26, renal failure n = 46, persistent proteinuria n = 29, follow-up median 80 months {range 51-166}). The 13 identified SNPs showed no association with remission or renal failure. There were no differences in genotypes or allele frequencies between patients in remission and progressors. Conclusions: Our data suggest that TRPC6 polymorphisms do not affect susceptibility to iMN, or clinical outcome in iMN

Immunologie in de medische praktijk. III. Lupus erythematodes dissiminatus: gestoorde apoptose?

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Lupus Nephritis

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Discontinuation of immunosuppression in proliferative lupus nephritis: is it possible?

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Renal replacement therapy in lupus nephritis.

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Lupus nephritis: consequence of disturbed removal of apoptotic cells?

In the last decade it has become clear that systemic lupus erythematosus (SLE) is an autoantigen driven T cell dependent autoimmune disease. The nucleosome has been identified as a major autoantigen. Nucleosomes are generated during apoptosis. Either an increased or delayed apoptosis or a reduced clearance of apoptotic cells (which are not mutually exclusive) leads to an increased exposure of (modified, more immunogenic) nucleosomes to the immune system. This generates the formation of nucleosome specific T cells and antinucleosome autoantibodies. After complex formation of antinucleosome or anti-double-stranded (ds)DNA antibodies with nucleosomes, these autoantibodies are targeted to basement membranes, especially the glomerular basement membrane (GBM). This nephritogenic potential is due to the binding of the positively charged histone components of the nucleosome to the negatively charged heparan sulphate (HS) within the GBM. This incites glomerular inflammation

Lupus erythematodes dissiminatus: gestoorde apoptose?

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Behandeling van nefritis bij systemische lupus erythematodes

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Deranged removal of apoptotic cells: its role in the genesis of lupus.

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Treatment of lupus nephritis.

Contains fulltext : 87620.pdf (publisher's version ) (Open Access)Renal involvement in systemic lupus erythematosus patients is a severe disease manifestation characterized by various clinical and histopathological alterations. The revised International Society of Nephrology/Renal Pathology Society 2003 classification defines the subclasses of lupus nephritis (LN) according to their pathological glomerular patterns, which has a crucial impact on the prognosis and treatment options for LN patients. There are widely accepted therapeutic agents available, such as cyclophosphamide, mycophenolate mofetil, azathioprine and corticosteroids. Several trials have tried to determine a gold standard for induction and maintenance therapy in LN, and the place of newer drugs, biologicals, has been investigated. We review recently reported data on current treatment regimens in LN, in particular in the context of the International Society of Nephrology/Renal Pathology Society 2003 classification.1 november 201