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recent treatment for IgA Nephropathy

Sean Barbour, John Feehally
PURPOSE OF REVIEW: The treatment of IgA nephropathy (IgAN) has been limited by several controversies in the literature, including the benefits of corticosteroids in addition to optimized renin-angiotensin system blockers (RASBs), in those with lower estimated glomerular filtration rate (eGFR), or in different ethnic groups. Recent studies have attempted to address these issues. RECENT FINDINGS: Two observational studies suggest the efficacy of corticosteroids in those with lower eGFR, but with a higher risk of adverse events...
April 8, 2017: Current Opinion in Nephrology and Hypertension
Ali I Al-Lawati, Heather N Reich
The most common primary glomerular disease globally is IgA nephropathy (IgAN). It is often a slowly progressive disease, and ∼40% of patients will progress to kidney failure. Due to a lack of large clinical trial networks and a lack of surrogate markers of treatment efficacy, there are relatively few large multicenter clinical trials in IgAN. Given that both the pathogenesis and progression of IgAN are linked to defects in mucosal immune regulation and inflammation, use of immunosuppression to prevent kidney failure is well founded...
January 1, 2017: Nephrology, Dialysis, Transplantation
Rosanna Coppo
Recent data suggest that gut-associated lymphoid tissue (GALT) plays a major role in the development of immunoglobulin A (IgA) nephropathy (IgAN). A genome-wide association study showed that most loci associated with the risk of IgAN are also associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier and regulation of response to gut pathogens. Studies involving experimental models have demonstrated a pivotal role of intestinal microbiota in the development of IgAN in mice producing high levels of IgA and in transgenic mice overexpressing BAFF, a B-cell factor crucial for IgA synthesis, indicating the role of genetic background, B-cell activity, GALT intestinal immunity and diet...
April 7, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Thomas Rauen, Jürgen Floege
Immunoglobulin A nephropathy (IgAN) is the most frequently occurring primary glomerulonephritis in Caucasian and Asian populations. Nonetheless, therapeutic recommendations are based on weak evidence, large controlled trials are scarce and, in particular, the additional value of immunosuppression beyond comprehensive supportive measures is not well-established. The use of immunosuppressants is supported by experimental insights into IgAN pathogenesis that suggest an autoimmune component in disease development...
March 14, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Ruhao Yang, Xuan Xu, Huiling Li, Jinwen Chen, Xudong Xiang, Zheng Dong, Dongshan Zhang
The role of p53 in renal fibrosis has recently been suggested, however, its function remains controversial and the underlying mechanism is unclear. Here, we show that pharmacological and genetic blockade of p53 attenuated renal interstitial fibrosis, apoptosis, and inflammation in mice with unilateral urethral obstruction (UUO). Interestingly, p53 blockade was associated with the suppression of miR-215-5p, miR-199a-5p&3p, and STAT3. In cultured human kidney tubular epithelial cells (HK-2), TGF-β1 treatment induced fibrotic changes, including collagen I and vimentin expression, being associated with p53 accumulation, p53 Ser15 phosphorylation, and miR-199a-3p expression...
February 27, 2017: Scientific Reports
Maria F Soares, Ian S D Roberts
PURPOSE OF REVIEW: To provide an update on recent developments since the publication of the Oxford Classification of IgA nephropathy and to consider lesions that were not included in the original classification. RECENT FINDINGS: Over 20 validation studies of the Oxford Classification have been published. Tubular atrophy/interstitial fibrosis is consistently the strongest predictor of renal survival, whereas mesangial hypercellularity predicts rate of loss of renal function...
May 2017: Current Opinion in Nephrology and Hypertension
Rigas G Kalaitzidis, Anila Duni, Georgios Liapis, Olga Balafa, Sofia Xiromeriti, Paulos Karolos Rapsomanikis, Moses S Elisaf
Treatment with oral anticoagulants has been associated with worsening kidney function in patients with chronic kidney disease (CKD) as well as among patients without underlying CKD. Thus, anticoagulant-related nephropathy (ARN) is an increasingly recognized entity nowadays, mainly associated with warfarin anticoagulation. Recent evidence indicates that patients treated with the direct anticoagulants may also be at risk of ARN. However, the true incidence of anticoagulant-related nephropathy is difficult to determine...
February 4, 2017: International Urology and Nephrology
Yuko Shima, Koichi Nakanishi, Masashi Sato, Taketsugu Hama, Hironobu Mukaiyama, Hiroko Togawa, Ryojiro Tanaka, Kandai Nozu, Mayumi Sako, Kazumoto Iijima, Hiroyuki Suzuki, Norishige Yoshikawa
BACKGROUND: Despite a low incidence, nephrotic syndrome (NS) can present with IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of pediatric patients with IgAN presenting with NS (NS-IgAN) at onset have not been fully elucidated. METHODS: We retrospectively analyzed 426 patients, and compared clinical and pathological (Oxford) findings between those with NS-IgAN and those with non-NS-IgAN. RESULTS: Among 426 patients, 30 (7...
October 6, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Rosanna Coppo
IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to ESRD. The immune and autoimmune responses that characterize IgAN indicate a potential benefit for corticosteroids. The 2012 Kidney Disease Improving Global Outcome (KDIGO) guidelines suggest giving corticosteroids to patients with rather preserved renal function (GFR>50 ml/min per 1.73 m(2)) and persistent proteinuria >1 g/d, despite 3-6 months of optimized supportive care with renin-angiotensin system blockers...
January 2017: Journal of the American Society of Nephrology: JASN
Tomohiro Terasaka, Haruhito A Uchida, Ryoko Umebayashi, Keiko Tsukamoto, Keiko Tanaka, Masashi Kitagawa, Hitoshi Sugiyama, Hiroaki Tanioka, Jun Wada
BACKGROUND: A link between IgA nephropathy and Crohn's disease has recently been reported. Other researchers hypothesize that intestine-derived IgA complexes deposit in glomerular mesangial cells, eliciting IgA nephropathy. Intestinal mucosal plasma cells mainly secrete IgA2. Nevertheless, IgA1 deposition is strongly implicated as being the primary cause of IgA nephropathy. CASE PRESENTATION: A 46-year-old Japanese man developed IgA nephropathy 29 years ago, following tonsillectomy...
September 5, 2016: BMC Nephrology
Na Liu, Yingfeng Shi, Shougang Zhuang
BACKGROUND: Autophagy is the degrading process of protein and organelles mediated by lysosomes. This process is involved in purging senescent organelles and subversive proteins while maintaining the stability of the intracellular environment. This phenomenon is highly conservative, existing in nearly every species, and is involved in cell growth, proliferation and tumorigenesis. SUMMARY: In recent decades, with the discovery of autophagy-related genes and proteins in conjunction with the improvement in detection methods, the study of autophagy is constantly achieving new breakthroughs...
April 2016: Kidney Diseases
Richard J Glassock
A Polar Views discussion by Pozzi and Rauen et al. on the interpretation and clinical application of the recently published Supportive Versus Immunosuppressive Therapy of Progressive IgA Nephropathy (STOP-IgAN) trial has elucidated important points concerning potential strengths and weaknesses of this landmark randomized trial. This critical examination of the impact of steroid monotherapy or steroid plus an immunosuppressive (IS) agent compared with 'supportive' therapy with inhibitors of the renin-angiotensin system (RAS) has enhanced our appreciation of the importance of rigorous application of titrated RAS inhibition in high-risk patients with persistent proteinuria >0...
November 2016: Nephrology, Dialysis, Transplantation
Thomas Rauen, Frank Eitner, Christina Fitzner, Jürgen Floege, Claudio Pozzi
A comprehensive supportive therapy approach constitutes the mainstay treatment of IgA nephropathy (IgAN) patients. In our recent Supportive versus immunosuppressive Therapy Of Progressive IgA Nephropathy (STOP-IgAN) trial, we systematically selected for patients at high risk of a progressive disease course and evaluated the effect of immunosuppression, combined with supportive care, on renal end points in these patients. There was a higher rate of full clinical remission and transient proteinuria reduction in immunosuppressed patients...
August 11, 2016: Nephrology, Dialysis, Transplantation
Michio Fukuda, Osamu Hotta, Masashi Mizuno, Yoshiaki Ogiyama, Nobuyuki Ohte
Proportions of elderly aged ≥65 and ≥75 within Japan will increase to 30 and 20 %, respectively, in 2025, when "Baby-Boom Generations" will reach the age of 75 years. Okabayashi and colleagues report that even in elderly patients with IgA nephropathy (IgAN), immunosuppressive treatment can reduce proteinuria, with no adverse events. Their findings remind us of recent finding from STOP-IgAN study; additional immunosuppressive therapy to intensive supportive care [specifically renin-angiotensin system (RAS) inhibitors (RASi)] did not improve the outcome...
December 2016: Clinical and Experimental Nephrology
Dita Maixnerova, Colin Reily, Qi Bian, Michaela Neprasova, Jan Novak, Vladimir Tesar
We have summarized the latest findings on markers for progression of immunoglobulin A (IgA) nephropathy (IgAN), the most common primary glomerulonephritis with a high prevalence among end-stage renal disease (ESRD) patients. The clinical predictors of renal outcome in IgAN nephropathy, such as proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR) at the time of the diagnosis, are well known. The Oxford classification of IgAN identified four types of histological lesions (known as the MEST score) associated with the development of ESRD and/or a 50 % reduction in eGFR...
August 2016: Journal of Nephrology
Seung Seok Han, Seung Hee Yang, Murim Choi, Hang-Rae Kim, Kwangsoo Kim, Sangmoon Lee, Kyung Chul Moon, Joo Young Kim, Hajeong Lee, Jung Pyo Lee, Ji Yong Jung, Sejoong Kim, Kwon Wook Joo, Chun Soo Lim, Shin-Wook Kang, Yon Su Kim, Dong Ki Kim
TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD...
November 2016: Journal of the American Society of Nephrology: JASN
Jürgen Floege, Thomas Rauen
The optimal role of immunosuppressive therapy in the treatment of IgA nephropathy is controversial. Results of a recently completed randomized controlled trial provide strong support for comprehensive supportive care rather than immunosuppressive therapy in patients at high risk for progression.
January 2016: Kidney International
Claudio Pozzi, Cristina Sarcina, Francesca Ferrario
IgA Nephropathy leads young people to dialysis more often than other glomerular diseases, because often diagnosis and therapy are made late. Nephrologists waive to treat IgAN pts with chronic renal insufficiency, believing that treatment may not be effective and safe. Moreover, studies in IgAN pts with reduced renal function are lacking. Small studies seem to indicate a possible utility of RAS blockers and corticosteroids in these patients. Recently, VALIGA study showed that corticosteroids and immunosuppressants were more frequently used in pts with eGFR <30 ml/min than in those with eGFR >30 ml/min (60 vs...
August 2016: Journal of Nephrology
Claudio Pozzi
The therapy of IgA nephropathy (IgAN) is cause for debate among nephrologists. Since the early 1980s, many therapeutic attempts have been proposed, but most of them did not prove efficacy. The recent KDIGO Clinical Practice Guideline for Glomerulonephritis recommend long-term ACE-I or ARB treatment when proteinuria is more than 1 g/day, with up-titration of the drug. For patients with GFR >50 ml/min and proteinuria persistently higher than 1 g/day, they suggest a 6-month course of corticosteroid therapy...
February 2016: Journal of Nephrology
Liyu He, Xiaofei Peng, Guoyong Liu, Chengyuan Tang, Hong Liu, Fuyou Liu, He Zhou, Youming Peng
IgA nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Recently studies show that inflammation may involve in the progression of renal glomerulosclerosis and tubulointerstitial scarring in IgAN. This study was designed to evaluate the renoprotective effect of triptolide on IgAN rat model. IgAN was induced in Sprague-Dawley rats by oral and intravenous immunization with BSA for 12 weeks. Rats were treated with triptolide (200 μg/kg/d intragastrically) from 12 to 28 weeks...
2015: Immunopharmacology and Immunotoxicology
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