2,024 research outputs found
C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis
Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure
Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review
Background/Aims: Interferon treatment of malignant or viral diseases can be accompanied by various side-effects including nephro-toxicity. Methods: We report on a 68-year-old Caucasian male who received dual therapy with pegylated interferon 2a plus ribavirin for chronic hepatitis C. Results: After three months of antiviral therapy, the patient developed acute kidney failure (serum creatinine up to 6 mg/dL) with mild proteinuria (500 mg daily) and haematuria. Immediate immunosuppressive therapy with high-dose intravenous steroids did not improve kidney function. Kidney biopsy was consistent with acute tubular necrosis without glomerular abnormalities. He started long-term peritoneal dialysis (four regular exchanges) to provide both dialysis adequacy and ascites removal. Kidney function gradually improved over the following months (serum creatinine around 2 mg/dL) and peritoneal dialysis was continued with two exchanges daily. The temporal relationship between the administration of the drug and the occurrence of nephro-toxicity, and the absence of other obvious reasons for acute tubular necrosis support a causative role for pegylated interferon; benefit on kidney disease was noted after withdrawal of antiviral agents. An extensive review of the literature on acute tubular necrosis associated with interferon-based therapy, based on in vitro data and earlier case-reports, has been made. The proposed pathogenic mechanisms are reviewed. Conclusions: Our case emphasizes the importance of monitoring renal function during treatment of chronic hepatitis C with antiviral combination therapy as treatment may precipitate kidney damage at tubular level
Activation of human endogenous retrovirus K (HERV-K) and cellular modifications in human melanoma cell line: transcriptional profiling analysis
A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology
TLR-4 and VEGF polymorphisms in chronic periaortitis
Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP
Contraception in chronic kidney disease: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology
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Rituximab as Maintenance Treatment for Systemic Lupus Erythematosus: A Multicenter Observational Study of 147 Patients.
OBJECTIVE: The efficacy of rituximab (RTX) in systemic lupus erythematosus (SLE) is a subject of debate. This study was undertaken to investigate the outcomes of RTX treatment in a European SLE cohort, with an emphasis on the role of RTX as a maintenance agent. METHODS: All patients with SLE who were receiving RTX as induction therapy in 4 centers were included. Patients who received a single course of RTX and those who received RTX maintenance treatment (RMT) were followed up after treatment. Disease flares during the follow-up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs. RESULTS: Of 147 patients, 27% experienced treatment failure at 6 months. In a multivariate analysis, a low number of previous immunosuppressive therapies (P = 0.034) and low C4 levels (P = 0.008) reduced the risk of treatment failure. Eighty patients received RMT over a median of 24.5 months during which 85 relapses, mainly musculoskeletal, were recorded (1.06 per patient). At the time of the last RTX course, 84% of the patients were in remission. Twenty-eight (35%) of 80 patients never experienced a flare during RMT and had low damage accrual. Active articular disease at the time of the first RTX administration was associated with a risk of flare during RMT (P = 0.011). After RMT, relapse-free survival was similar to that in patients receiving a single RTX course (P = 0.72). CONCLUSION: RMT is a potential treatment option for patients with difficult-to-treat disease. Relapses occur during RMT and are more likely in those with active articular disease at the time of the first RTX administration. Relapse risk after RMT remains high and apparently comparable to that seen after a single RTX course
Treatment of doxorubicin resistant MCF7/Dx cells with nitric oxide causes histone glutathionylation and reversal of drug resistance.
Acquired drug resistance was found to be suppressed in the doxorubicin-resistant breast cancer cell line MCF7/Dx after pre-treatment with GSNO (nitrosoglutathione). The effect was accompanied by enhanced protein glutathionylation and accumulation of doxorubicin in the nucleus. Among the glutathionylated proteins, we identified three members of the histone family; this is, to our knowledge, the first time that histone glutathionylation has been reported. Formation of the potential NO donor dinitrosyl–diglutathionyl–iron complex, bound to GSTP1-1 (glutathione transferase P1-1), was observed in both MCF7/Dx cells and drug-sensitive MCF7 cells to a similar extent. In contrast, histone glutathionylation was found to be markedly increased in the resistant MCF7/Dx cells, which also showed a 14-fold higher amount of GSTP1-1 and increased glutathione concentration compared with MCF7 cells. These results suggest that the increased cytotoxic effect of combined doxorubicin and GSNO treatment involves the glutathionylation of histones through a mechanism that requires high glutathione levels and increased expression of GSTP1-1. Owing to the critical role of histones in the regulation of gene expression, the implication of this finding may go beyond the phenomenon of doxorubicin resistance
ANCA-associated vasculitis in childhood: Recent advances
Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort
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