RESistance of IgA Nephropathy to Conventional and Newly-approved Therapies: an Observational, Real-life Study (RESIGAN)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 800
- 试验地点
- 2
- 主要终点
- Proportion of patients with persistent proteinuria (>1 g/g) and/or renal dysfunction (>20% eGFR decline) at twelve months from diagnosis.
研究概览
简要总结
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by glomerular mesangial IgA deposits, often with IgG and C3. Despite its prevalence, the pathophysiology of IgAN is poorly understood. The prognosis varies significantly, from benign hematuria to rapidly progressive glomerulonephritis, potentially leading to end-stage renal disease within months. The MEST-C classification enhances prognosis characterization and informs integrated scoring systems; however, while useful for assessing overall prognosis, these scores do not reliably predict treatment responses and are unvalidated for IgA vasculitis nephritis. Given the disease's heterogeneity, treatment options for IgAN, with or without vasculitis, are controversial. Nephroprotective strategies that lower intraglomerular pressure through RAS blockade are essential in managing IgAN. Steroids are considered for rapidly progressive cases, yet their effectiveness in persistent proteinuria despite optimized nephroprotection is debated. Other immunosuppressive therapies, such as B cell targeting and complement inhibition, are under investigation. Recently developed nephroprotective strategies, including SGLT2 inhibitors and endothelin-1 receptor antagonists, may significantly influence future therapeutic approaches. Although available in many European countries, their real-world effectiveness has not been evaluated. Identifying factors linked to persistent proteinuria and renal dysfunction despite optimized nephroprotection is a critical unmet need. We hypothesize that innovative nephroprotective strategies will reduce the risk of persistent proteinuria and renal dysfunction in an IgAN cohort.
详细描述
IgA Nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally, diagnosed by detecting mesangial IgA deposits in the kidneys, often accompanied by IgG and C3. The disease's pathophysiology remains unclear despite its commonality. Prognosis can vary widely, from benign hematuria to rapidly progressive forms leading to end-stage renal disease within months. The MEST-C classification provides histological prognostic factors that enhance prognosis assessment and facilitate the development of integrated scoring systems. However, these scores are limited in predicting treatment responses and lack validation for IgA vasculitis nephritis.
Given the disease's heterogeneity, treatment strategies for IgAN are contentious. Nephroprotective approaches focusing on reducing intraglomerular pressure through RAS blockade play a significant role in management. Steroids are suggested for rapidly progressive disease, but their effectiveness in persistent proteinuria, despite optimized nephroprotection, is debated. Other treatments, including B cell-targeting therapies and complement inhibition, are under investigation. Recent advances in nephroprotection, such as SGLT2 inhibitors and endothelin-1 receptor antagonists, could significantly reshape future therapeutic strategies. While these treatments are widely available in Europe, their real-world effectiveness remains to be evaluated. Identifying factors linked to persistent proteinuria and renal dysfunction despite optimized strategies is a pressing unmet need.
This study hypothesizes that new nephroprotective strategies will influence the risk of persistent proteinuria and renal dysfunction in a real-life cohort of IgAN patients.
Primary Objective: To identify clinical, biological, and histological risk factors for persistent proteinuria and renal dysfunction in IgAN patients.
Secondary Objectives include:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patient: age ≥ 18 years
- •Renal biopsy performed after 2017 showing IgA deposits leading to the diagnosis of IgAN (the date of diagnosis being the index date)
- •Informed patient and who does not object to the use of his data
排除标准
- 未提供
结局指标
主要结局
Proportion of patients with persistent proteinuria (>1 g/g) and/or renal dysfunction (>20% eGFR decline) at twelve months from diagnosis.
时间窗: month 12 from diagnosis
Persistent proteinuria is defined as protein/creatinine ratio \>1 g/g; renal dysfunction is defined as a loss of \>20% eGFR (Estimated Glomerular Filtration Rate) as compared to eGFR measured at baseline.
次要结局
- Proportion of patients with 50% decline in eGFR or end-stage kidney disease at any time during follow-up(Baseline, Month 3, Month 6, Month 12, Month 24, and then each year until the end of follow-up)
- Proportion of patients with persistent proteinuria (>1 g/g) and/or renal dysfunction (>20% eGFR decline) at 6 months from diagnosis(month 6 from diagnosis)
- Proportion of patients with persistent proteinuria (>1 g/g) and/or renal dysfunction (>20% eGFR decline) at twenty-four months from diagnosis.(month 24 from diagnosis)
- Proportion of patients with persistent proteinuria (>1 g/g) and/or renal dysfunction (>20% eGFR decline) at the end of follow-up.(At the end of follow-up, that is at least 2 years from inclusion)
- Proportion of patients experiencing a Major Adverse Renal Event (MARE) by month 12, defined as the initiation of dialysis, receipt of a kidney transplant, or onset of renal failure(month 12 from diagnosis)
- Proportion of patients experiencing a Major Adverse Renal Event (MARE) by month 6, defined as the initiation of dialysis, receipt of a kidney transplant, or onset of renal failure(month 6 from diagnosis)
- Proportion of patients with absence of response to steroids therapy defined as persistent proteinuria or renal dysfunction at the end of steroids treatment(At the end of steroids treatment, that is on average at 6 months from inclusion)
- Proportion of patients with severe hyperkalemia (>6mM/l) evaluated at each visit(Baseline, Month 3, Month 6, Month 12, Month 24, and then each year until the end of follow-up)
- Proportion of patients with severe acute renal failure (KDIGO stage 3) at each visit until the end of follow-up(Baseline, Month 3, Month 6, Month 12, Month 24, and then each year until the end of follow-up)