Role of Regulatory T Cells in Pathogenesis of Primary IgA Nephropathy
GlomerulonephritisIGAAlong structural IgA abnormalities, hyperproduction of IgA is thought to play a role in the pathogenesis of primary IgA nephropathy. CD4+CD25+Fox3P regulatory T cells are instrumental in suppressing adaptative immune responses, including B cells production of immunoglobulins. We, the researchers at Centre Hospitalier Universitaire de Saine Etienne, will test the hypothesis that IgA production in patients with IgA nephropathy is dysregulated because of a quantitative and/or qualitative defect of CD4+CD25+FoxP3+ regulatory T cells.
Autonomic Nervous System (ANS) and Renal Function in Immunoglobin A (IgA) Nephropathy
IGA GlomerulonephritisThe estimation of the cardiovascular risk in the general population must take into account small renal disturbances, as the microalbuminuria. Conversely certain parameters of the cardiovascular risk influence the evolution of renal diseases, for example the arterial high blood pressure. The measure of the activity of the autonomous nervous system, and especially the quantification of its variability, is a means to estimate the cardiovascular risk. The investigators formulate the hypothesis that the variability of the autonomous nervous system is an additional clinical element for the evaluation of the evolutionary risk of renal diseases. The aim of this study is to compare the variability of the autonomous nervous system during the various evolutionary stages of the renal disease. The renal disease studied will be IgA nephropathy (IgNA). IgNA is a histologically defined glomerulonephritis (rela biopsy) by the presence of deposits immunoglobulin A (IgA) in the renal mesangium (at list 1+) by immunofluorescence.
Study of Genetic Anomalies of Complement Related Proteins in Patients With IgA Glomerulonephritis...
IGA GlomerulonephritisOBJECTIVES: I. Determine whether allelic differences associated with the fourth component of complement, type-1 complement receptor expressed on erythrocytes, and Fc receptor FcgRIII contribute to the pathogenesis of IgA glomerulonephritis (IgA-N). II. Compare genetic anomalies of these key components in immune complex processing and clearance between juvenile vs adult onset IgA-N vs normal controls.
Longterm Renal Oucomes of STOP-IgAN Trial Participants
IgA NephropathyIgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis in the Western world. Although most IgAN patients take a benign longterm course, about 20-30% progress to end-stage renal disease (ESRD) over 20 years. The majority of current treatment recommendations is based on weak evidence. In the randomized, controlled Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgAN (STOP-IgAN) trial, the investigators analyzed whether additional immunosuppression on top of standardized supportive care provides renal benefits in patients with progressive IgAN. Patients with persisting proteinuria >0.75 g/d (n=162) despite optimized supportive treatment including control of blood pressure and proteinuria, were randomized to either continue on supportive care or to receive additional immunosuppression during the 3-year trial phase. It was observed that immunosuppressive therapy in addition to optimized supportive care led to more full clinical remissions, but eventually did not better preserve renal function, did not better save patients from ESRD development and evoked more adverse effects such as infections, weight gain and diabetes. Aim of this planned study is to analyze renal outcome measures and adverse effects in the longterm observation of all randomized STOP-IgAN participants to ascertain quality and strength of the original trial results. By its observational nature, this quality control study includes the 162 IgAN patients (with the exception of drop-out patients) that had been previously randomized into the original STOP-IgAN trial. Information on serum creatinine, proteinuria, ESRD, death, relevant adverse events such as major cardiovascular events, osteoporosis, osteonecrosis, bone fractures, diabetes, malignancies and interim treatment will be collected as available from existing routine records until March 31, 2018. Primary endpoint is the time to the first occurring event of the binary composite of all-cause death, ESRD or decline in estimated glomerular filtration rate (eGFR) by at least 40% as compared to enrollment into the original trial. Secondary outcome measures comprise the individual components of the primary endpoint, absolute eGFR at the end of observation, proteinuria and adverse events. Information on specific treatments with renin-angiotensin-system (RAS)-blocking agents and/or interim immunosuppression will also be collected. All data will be recorded in a pseudonymous fashion in a central electronic data base located at the PI's site.
IgA Nephropathy, Lymphocyte Homing and IgA Class Switch
IgA NephropathyIgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and it represents an important cause of end-stage kidney failure. This disease was described as a distinct entity in 1968 by J Berger and N Hinglais. The aetiology and the pathogenesis remain still obscure. Clinical observations and immunisation studies indicate that IgAN represents a dysregulation of the immune system, rather than an intrinsic renal abnormality. Twenty years ago, some authors proposed the mucosa-bone marrow axis to explain the pathogenesis of the disease. Mucosal IgA plasmocytes are displaced and take up residence in systemic sites. The unusual characteristics featured by the IgA produced by these cells (charge, size, glycosylation) drive their accumulation, deposition and mesangial activation characteristic of IgAN. Evidence is emerging that altered lymphocyte homing may ultimately explain this aberrant localization.
Probiotics in IgA Nephropathy
IgA NephropathyRecent studies have shown an increased gastrointestinal reactivity and increased intestinal permeability in IgA nephropathy (IgAN). Probiotic supplementation is known to impact the gastrointestinal immune system possibly by improvement of both the immunologic and the non-immunologic intestinal barrier. Probiotic supplementation should thus theoretically have an effect on IgAN. In this study the investigators will study the efficacy and safety of Lactobacillus reuteri.
The Correlation of Periostin and Renal Pathology in Chronic Kidney Disease Patients
Lupus NephritisIgA NephropathyThe purpose of this study is to determine the location of periostin and urine periostin level in patients with lupus nephritis and IgA nephropathy.
An Observational Study of IgA Nephropathy: Pathological Variants and Clinical Data
IgA NephropathyThe pathological variants of IgA nephropathy identified by the Oxford classification may be related to the clinical data at presentation and follow-up, including proteinuria and renal function. This study is aimed to identify the potential relationship between pathological variants and clinical data in IgA nephropathy.
A Survey of Factors Affecting an Early or Delayed Diagnosis of IgA Nephropathy
IgA NephropathyThis is a survey of factors which affect a pathologically defined early or delayed diagnosis of IgA nephropathy in Guangdong General Hospital, Guangzhou, China. An early or delayed diagnosis of IgA nephropathy is pathologically defined using the recently published Oxford classification of IgA nephropathy. The factors to be surveyed include health examination including urine test, socioeconomic status of patients including education,etc.
Establishment of the Human Intestinal and Salivary Microbiota Biobank - Kidney Diseases
Autosomal Dominant Polycystic Kidney Disease (ADPKD)Advanced-Chronic Kidney Disease (CKD)2 moreThis is a prospective, clinical, multicentre study aimed to collect biological samples and study microbiota from subjects suffering from chronic kidney disease and from healthy volunteers. Microbiota is a complex consortium of microorganisms, located at the mucosal level (in particular intestinal, oral and vaginal) having a key role in human health and in the onset of several diseases. Microbiota alterations have been found in several diseases (gastrointestinal, metabolic, renal, oncological, gynaecological). The study will allow to: Provide biological samples (faeces, saliva, blood, urine) from healthy volunteers and patients suffering from chronic renal diseases to the first Italian microbiota biobank; Study microorganisms using different in vitro and in vivo techniques; Study the link between the microbiota and the disease. This study is part of the BIOMIS project (Project Code: ARS01_01220), presented as part of the "Avviso per la presentazione di progetti di ricerca industriale e sviluppo sperimentale nelle 12 aree di specializzazione individuate dal PNR 2015-2020" and admitted to funding under the National Operational Program "Ricerca e Innovazione" 2014-2020 by directorial decree of MIUR - Department for Higher Education and Research - n. 2298 of 12 September 2018. BIOMIS includes several clinical studies that enrol patients with different pathologies to collect and store biological samples and study microbiota.