"STOP-IgAN"

BACKGROUND: The administration of corticosteroids in addition to supportive care to delay progressive immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, remains controversial. This is partly due to the paucity of well-designed randomized controlled trials and well-known corticosteroid-related side effects. As a result, clinical equipoise in corticosteroid therapy exists depending on geographical regions and the clinician's preference. SUMMARY: Better understanding around the pathogenesis of IgAN has prompted several clinical trials exploring the effects of immunosuppressive agents including corticosteroids...

The role of immunosuppression in the management of IgA nephropathy remains highly controversial. The Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) trial suggested that there was no benefit with the addition of immunosuppression to intensive supportive care, in terms of renal outcome. In this edition of Kidney International, Rauen et al. report long-term outcomes from the STOP-IgAN trial.

BACKGROUND: Inhibitors of the renin-angiotensin system (RAS) are cornerstones of supportive therapy in patients with IgA nephropathy (IgAN). We analyzed the effects of single versus dual RAS blockaQueryde during our randomized STOP-IgAN trial. METHODS: STOP-IgAN participants with available successive information on their RAS treatment regimen and renal outcomes during the randomized 3-year trial phase were stratified post hoc into two groups, i.e. patients under continuous single or dual RAS blocker therapy over the entire 3 years of the trial phase...

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN...

Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and a leading cause of end-stage renal disease. Particularly challenging to the clinician is the early identification of patients at high risk of progression, an estimation of the decline in renal function, and the selection of only those that would benefit from additional immunosuppressive therapies. Nevertheless, the pathway to a better prognostication and to the development of targeted therapies in IgAN has been paved by recent understanding of the genetic and molecular basis of this disease...

BACKGROUND: Immunosuppressive agents have been widely used in the treatment of IgA nephropathy (IgAN), but the efficacy and safety remain controversial. The recent STOP-IgAN and TESTING studies have again focused attention on the application of immunosuppressive agents in IgAN. This study investigated the benefits and risks of immunosuppressive agents in IgAN. METHODS: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with any other non-immunosuppressive agents for treating IgAN...

BACKGROUND: The Oxford classification of IgA nephropathy (IgAN) defines histologic criteria (MEST-C) that provide prognostic information based on the kidney biopsy. There are few data on the predictive impact of this classification in randomized clinical trial settings. METHODS: We performed an exploratory analysis of MEST-C scores in 70 available renal biopsies from 162 randomized STOP-IgAN trial participants and correlated the results with clinical outcomes. Analyses were performed by researchers blinded to the clinical outcome of the patients...

BACKGROUND/AIMS: The addition of immunosuppression to supportive care reduces proteinuria in a subset of patients with IgA nephropathy (IgAN) but is associated with an increased rate of adverse events. The present work investigates whether urinary biomarkers are able to identify subjects who benefit from immunosuppression and to predict the progression of disease in a sub-cohort of the STOP-IgAN trial. METHODS: Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and the product of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 (TIMP2•IGFBP7) were measured in all available urine samples obtained at the time point of enrollment in the STOP-IgAN trial (n=113)...

BACKGROUND: IgA nephropathy (IgAN) is detected in Europe in 22% of glomerular diseases diagnosed by biopsy. The frequency of IgAN as cause of ESRD in Europe has increased in the last decades, accounting for 35% of young and adult transplanted patients. These data justify the interest for risk factors and a possible therapeutic approach. SUMMARY: Insight into a European perspective of IgAN was allowed by the multicenter study VALIGA, on 1,147 patients, almost all Caucasians, with follow-up of 4...

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric therapies (typically renin- angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone, and indeed, several trials have demonstrated renoprotective effects following the use of oral corticosteroids...

IgA nephropathy, identified 50 years ago in France, is the most frequent glomerular disease worldwide. The course is variable, but in most of the cases there is a relentless decline in renal function, reaching end-stage renal failure in 10-60% of the cases after 10 years and in 40% after 20 years. These data justify the interest for finding a suitable therapeutic approach particularly in progressive cases. A supportive care, including renin-angiotensin system inhibitors is the priority in cases with slowly declining renal function, particularly when developing proteinuria...

BACKGROUND/AIMS: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naive T cells to initiate and terminate immune responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene locus are associated with several autoimmune diseases...

IgA nephropathy is an immune-mediated chronic glomerulonephritis with a great variability in clinical presentation and outcome. The disease can progress to end-stage renal failure in 25% of patients. For this reason we should identify patients with potential to progress. Most important risk factors for progression are persistent proteinuria, hypertension, decreased renal function and some histological lesions. The actually suggested treatment is summarized in KDIGO Clinical Practice Guideline from 2012. They suggest to give firstly non-specific supportive treatment (especially renin-angiotensin system blocking agents)...

The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2 : 6-month corticosteroid monotherapy; GFR=30-59 ml/min per 1.73 m2 : cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone)...

The role of immunosuppression in IgAN remains controversial despite a growing evidence base of randomized controlled trials (RCTs). In IgAN with nephrotic syndrome the role for corticosteroids is limited to cases with minimal change on light microscopy. In crescentic IgAN, the use of immunosuppression is supported only by anecdotal data, and outcome may be poor especially when glomerular filtration rate is impaired severely at presentation or there are pathologic features of chronic injury. In slowly progressive IgAN, prediction of outcome now is based both on clinical and pathologic features...

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...

Bronchoesophageal fistulae are a rare complication of tuberculosis. Traditionally they are managed by either thoracotomy with resection and closure of the fistulous tract or by taking a more conservative approach of giving standard treatment for tuberculosis while ensuring nutritional support through a nasogastric tube. We report a young student with disseminated tuberculosis complicated by a bronchoesophageal fistula. He was managed conservatively with anti-tuberculous chemotherapy and nutrition administered through a percutaneous endoscopic gastrostomy tube...

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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...

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a 6-month course of corticosteroids (CS) for IgA nephropathy (IgAN) patients with persistent proteinuria ≥1 g/day despite 3-6 months of renin-angiotensin system (RAS) blockers and glomerular filtration rate (GFR) >50 mL/min/1.73 m2 In December 2015, Rauen et al. (N Engl J Med 2015; 373: 2225-2236) published an article entitled 'Intensive supportive care plus immunosuppression in IgA nephropathy' (STOP-IgAN), which presented results from 379 IgAN patients from 32 nephrology centres in Germany...