The Experts below are selected from a list of 24264 Experts worldwide ranked by ideXlab platform
Haiyan Wang - One of the best experts on this subject based on the ideXlab platform.
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corticosteroid therapy in IgA Nephropathy
Journal of The American Society of Nephrology, 2012Co-Authors: Vlado Perkovic, David W Johnson, Mark Woodward, Adeera Levin, Hong Zhang, Haiyan WangAbstract:The benefits and risks of steroids for the treatment of IgA Nephropathy remain uncertain. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized, controlled trials of corticosteroid therapy for IgA Nephropathy published between 1966 and March 2011. We identified nine relevant trials that included 536 patients who had urinary protein excretion >1 g/d and normal renal function. Forty-six (8.6%) of these patients developed a kidney failure event, defined as doubling of the serum creatinine/halving of the GFR or ESRD. Overall, steroid therapy was associated with a lower risk for kidney failure (relative risk, 0.32 [95% confidence interval [CI], 0.15-0.67]; P=0.002) and a reduction in proteinuria (weighted mean difference, -0.46 g/d [95% CI, -0.63 to -0.29 g/d]), with no evidence of heterogeneity in these outcomes. Subgroup analysis suggested that the dose modifies the effect of steroids for renal protection (P for heterogeneity=0.030): Relatively high-dose and short-term therapy (prednisone >30 mg/d or high-dose pulse intravenous methylprednisolone with duration ≤1 year) produced significant renal protection, whereas low-dose, long-term steroid use did not. Steroid therapy was associated with a 55% higher risk for adverse events. The quality of included studies was low, however, limiting the generalizability of the results. In conclusion, steroids appear to provide renal protection in patients with IgA Nephropathy but increase the risk for adverse events. Reliably defining the efficacy and safety of steroids in IgA Nephropathy requires a high-quality trial with a large sample size.
Francesco Scolari - One of the best experts on this subject based on the ideXlab platform.
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the pathophysiology of IgA Nephropathy
Journal of The American Society of Nephrology, 2011Co-Authors: Hitoshi Suzuki, Francesco Scolari, Jan Novak, Jiri Mestecky, Robert J. Wyatt, Krzysztof Kiryluk, Zina Moldoveanu, Andrew B Herr, Matthew B Renfrow, Ali G GharaviAbstract:Here we discuss recent advances in understanding the biochemical, immunologic, and genetic pathogenesis of IgA Nephropathy, the most common primary glomerulonephritis. Current data indicate that at least four processes contribute to development of IgA Nephropathy. Patients with IgA Nephropathy often have a genetically determined increase in circulating levels of IgA1 with galactose-deficient O-glycans in the hinge-region (Hit 1). This glycosylation aberrancy is, however, not sufficient to induce renal injury. Synthesis and binding of antibodies directed against galactose-deficient IgA1 are required for formation of immune complexes that accumulate in the glomerular mesangium (Hits 2 and 3). These immune complexes activate mesangial cells, inducing proliferation and secretion of extracellular matrix, cytokines, and chemokines, which result in renal injury (Hit 4). Recent genome-wide association studies identify five distinct susceptibility loci—in the MHC on chromosome 6p21, the complement factor H locus on chromosome 1q32, and in a cluster of genes on chromosome 22q22—that potentially influence these processes and contain candidate mediators of disease. The significant variation in prevalence of risk alleles among different populations may also explain some of the sizable geographic variation in disease prevalence. Elucidation of the pathogenesis of IgA Nephropathy provides an opportunity to develop disease-specific therapies.
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Familial IgA Nephropathy.
Journal of nephrology, 1999Co-Authors: Francesco ScolariAbstract:To date, more than 90 families with multiple members with IgA Nephropathy have been reported. The case for genetic predisposition as a cause of familial clustering of IgA Nephropathy is supported by several factors, including variable time points in the onset of the disease in relatives with IgA Nephropathy; the presence of abnormalities of IgA production in both affected and unaffected family members; the clustering of the birthplaces of ancestors of large pedigrees containing multiple affected members with IgA Nephropathy, which suggests the existence of a "founder effect". Immunogenetic studies does not conclusively indicate that HLA is involved in the pathogenesis of IgA Nephropathy. The specific mode of inheritance of familial IgA Nephropathy is difficult to establish with certainty. IgA Nephropathy may be a single gene trait with incomplete penetrance. Alternatively, a multifactorial genetic disease could account for the increased prevalence of the disorder among relatives of affected individuals. Clinicians must become aware that IgA Nephropathy may aggregate within families in a substantial number of cases. The availability of multiplex families offers an ideal opportunity to design a molecular genetics approach to map the gene(s) or pathway(s) responsible for the development of IgA Nephropathy.
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Familial clustering of IgA Nephropathy: further evidence in an Italian population.
American Journal of Kidney Diseases, 1999Co-Authors: Francesco Scolari, Antonio Amoroso, Silvana Savoldi, G. Mazzola, Prati E, B. Valzorio, Battista Fabio Viola, Bossini Nicola, Ezio Movilli, Massimo SandriniAbstract:Several lines of evidence suggest that genetic factors have an important role in the pathogenesis of immunoglobulin A (IgA) Nephropathy. We report the prevalence of familial IgA Nephropathy in a referral center in northern Italy and present the data on HLA genotypes in the families identified. Twenty-six of 185 patients (14%) with IgA Nephropathy investIgAted in Brescia, Italy, were related to at least one other patient with the disease. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta and HLA-DQ alpha and beta genes, as well as polymerase chain reaction-based oligonucleotide typing, was performed in family members. The 26 patients with IgA Nephropathy belonged to 10 families. Familial relationships between the patients varied greatly, ranging from parent-child to sib-pair to more distant familial relationships. No common nephrotoxic factor was identified in the families. The intervals separating the apparent onset of disease in relatives with IgA Nephropathy varied from 8 months to 13 years. In patients with a family history of IgA Nephropathy, there was an increased incidence of HLA-DRB1*08 compared with those with sporadic IgA Nephropathy. The study shows that a significant number of the patients with IgA Nephropathy followed up in Brescia had a family history of disease. The fact that the Italian population, an ethnic group not previously examined, also presents an increased familial susceptibility to IgA Nephropathy suggests that familial predisposition is a very common finding for IgA Nephropathy. Thus, clinicians should become aware that IgA Nephropathy may aggregate within families in a substantial number of cases. In addition, this subgroup of patients with IgA Nephropathy offers an ideal opportunity to elucidate the molecular genetics of this disease.
Vlado Perkovic - One of the best experts on this subject based on the ideXlab platform.
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corticosteroid therapy in IgA Nephropathy
Journal of The American Society of Nephrology, 2012Co-Authors: Vlado Perkovic, David W Johnson, Mark Woodward, Adeera Levin, Hong Zhang, Haiyan WangAbstract:The benefits and risks of steroids for the treatment of IgA Nephropathy remain uncertain. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized, controlled trials of corticosteroid therapy for IgA Nephropathy published between 1966 and March 2011. We identified nine relevant trials that included 536 patients who had urinary protein excretion >1 g/d and normal renal function. Forty-six (8.6%) of these patients developed a kidney failure event, defined as doubling of the serum creatinine/halving of the GFR or ESRD. Overall, steroid therapy was associated with a lower risk for kidney failure (relative risk, 0.32 [95% confidence interval [CI], 0.15-0.67]; P=0.002) and a reduction in proteinuria (weighted mean difference, -0.46 g/d [95% CI, -0.63 to -0.29 g/d]), with no evidence of heterogeneity in these outcomes. Subgroup analysis suggested that the dose modifies the effect of steroids for renal protection (P for heterogeneity=0.030): Relatively high-dose and short-term therapy (prednisone >30 mg/d or high-dose pulse intravenous methylprednisolone with duration ≤1 year) produced significant renal protection, whereas low-dose, long-term steroid use did not. Steroid therapy was associated with a 55% higher risk for adverse events. The quality of included studies was low, however, limiting the generalizability of the results. In conclusion, steroids appear to provide renal protection in patients with IgA Nephropathy but increase the risk for adverse events. Reliably defining the efficacy and safety of steroids in IgA Nephropathy requires a high-quality trial with a large sample size.
Jan Novak - One of the best experts on this subject based on the ideXlab platform.
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Secondary IgA Nephropathy
Kidney International, 2018Co-Authors: Manish K. Saha, Bruce A. Julian, Jan Novak, Dana V. RizkAbstract:IgA Nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culminate in the development of primary IgA Nephropathy. Whether secondary forms of the disease share common pathways triggered by underlying disorders or different mechanisms leading to similar pathologic findings remains to be determined. In this article we describe the most frequent etiologies for secondary IgA Nephropathy and review the available literature for the pathophysiology.
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Glycosylation of IgA1 and pathogenesis of IgA Nephropathy
Seminars in Immunopathology, 2012Co-Authors: Jan Novak, Bruce A. Julian, Jiri Mestecky, Matthew B RenfrowAbstract:IgA Nephropathy, described in 1968 as IgA-IgG immune-complex disease, is an autoimmune disease. Galactose-deficient IgA1 is recognized by unique autoantibodies, resulting in the formation of pathogenic immune complexes that ultimately induce glomerular injury. Thus, formation of the galactose-deficient IgA1-containing immune complexes is a critical factor in the pathogenesis of IgA Nephropathy. Studies of molecular defects of IgA1 can define new biomarkers specific for IgA Nephropathy that can be developed into clinical assays to aid in the diagnosis, assessment of prognosis, and monitoring of disease progression.
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the pathophysiology of IgA Nephropathy
Journal of The American Society of Nephrology, 2011Co-Authors: Hitoshi Suzuki, Francesco Scolari, Jan Novak, Jiri Mestecky, Robert J. Wyatt, Krzysztof Kiryluk, Zina Moldoveanu, Andrew B Herr, Matthew B Renfrow, Ali G GharaviAbstract:Here we discuss recent advances in understanding the biochemical, immunologic, and genetic pathogenesis of IgA Nephropathy, the most common primary glomerulonephritis. Current data indicate that at least four processes contribute to development of IgA Nephropathy. Patients with IgA Nephropathy often have a genetically determined increase in circulating levels of IgA1 with galactose-deficient O-glycans in the hinge-region (Hit 1). This glycosylation aberrancy is, however, not sufficient to induce renal injury. Synthesis and binding of antibodies directed against galactose-deficient IgA1 are required for formation of immune complexes that accumulate in the glomerular mesangium (Hits 2 and 3). These immune complexes activate mesangial cells, inducing proliferation and secretion of extracellular matrix, cytokines, and chemokines, which result in renal injury (Hit 4). Recent genome-wide association studies identify five distinct susceptibility loci—in the MHC on chromosome 6p21, the complement factor H locus on chromosome 1q32, and in a cluster of genes on chromosome 22q22—that potentially influence these processes and contain candidate mediators of disease. The significant variation in prevalence of risk alleles among different populations may also explain some of the sizable geographic variation in disease prevalence. Elucidation of the pathogenesis of IgA Nephropathy provides an opportunity to develop disease-specific therapies.
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Treatment of IgA Nephropathy
Vnitrni lekarstvi, 2008Co-Authors: Karel Matousovic, Jiri Mestecky, Milan Tomana, Jan NovakAbstract:IgA Nephropathy is the most common cause of chronic renal failure among primary glomerulonephritides. During the last decade, there was a remarkable progress in understanding its pathogenesis. A number of therapeutic trials has been published that shed light on its treatment. ACEI and AT1R antagonists (sartans) or their combination represent the cornerstone of therapy of IgA Nephropathy. However, this treatment is not given to patients having optimal blood pressure, normal glomerular filtration rate, proteinuria less than 0.3 g/24 h, mild abnormalities in renal biopsy, and stationary course of the disease. The medication is administered in a maximal tolerated dose to patients with active, progressing disease. ACEI and AT1R antagonists are also drugs of the first choice in patients with proteinuric IgA Nephropathy. However, if proteinuria does not decrease significantly within 3 months from the beginning of this treatment, administration of glucocorticosteroids is recommended. On the basis of prospective, controlled clinical trials and metaanalyses of other therapeutic studies, it has been concluded that glucocorticosteroids decrease proteinuria and slow down the decline of renal function. A complete remission of proteinuria is the aim of the treatment. The effectiveness of cyclophosphamide in active forms of IgA Nephropathy, described in some studies, was not confirmed by metaanalyses. Nevertheless, cyclophosphamide may be effective in some patients with rapidly deteriorating renal function and active morphological findings with cellular extracapillary proliferation.
Hong Zhang - One of the best experts on this subject based on the ideXlab platform.
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corticosteroid therapy in IgA Nephropathy
Journal of The American Society of Nephrology, 2012Co-Authors: Vlado Perkovic, David W Johnson, Mark Woodward, Adeera Levin, Hong Zhang, Haiyan WangAbstract:The benefits and risks of steroids for the treatment of IgA Nephropathy remain uncertain. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized, controlled trials of corticosteroid therapy for IgA Nephropathy published between 1966 and March 2011. We identified nine relevant trials that included 536 patients who had urinary protein excretion >1 g/d and normal renal function. Forty-six (8.6%) of these patients developed a kidney failure event, defined as doubling of the serum creatinine/halving of the GFR or ESRD. Overall, steroid therapy was associated with a lower risk for kidney failure (relative risk, 0.32 [95% confidence interval [CI], 0.15-0.67]; P=0.002) and a reduction in proteinuria (weighted mean difference, -0.46 g/d [95% CI, -0.63 to -0.29 g/d]), with no evidence of heterogeneity in these outcomes. Subgroup analysis suggested that the dose modifies the effect of steroids for renal protection (P for heterogeneity=0.030): Relatively high-dose and short-term therapy (prednisone >30 mg/d or high-dose pulse intravenous methylprednisolone with duration ≤1 year) produced significant renal protection, whereas low-dose, long-term steroid use did not. Steroid therapy was associated with a 55% higher risk for adverse events. The quality of included studies was low, however, limiting the generalizability of the results. In conclusion, steroids appear to provide renal protection in patients with IgA Nephropathy but increase the risk for adverse events. Reliably defining the efficacy and safety of steroids in IgA Nephropathy requires a high-quality trial with a large sample size.
