The Challenge of Stopping Medications in IgA Nephropathy
Disease progression and symptom recurrence remain persistent concerns for patients with kidney disease. Today, we explore strategies to achieve sustained remission and prevent treatment rebound after medication discontinuation.
Is It Easy to Stop Medications for IgA Nephropathy?
Unfortunately, discontinuing treatment for IgA nephropathy is not straightforward. The most commonly used medications—ACE inhibitors and ARBs (Angiotensin Receptor Blockers)—are foundational therapies that typically require long-term or lifelong use.
Even corticosteroids are difficult to discontinue safely.
The 2025 Chinese IgA Nephropathy Guidelines recommend that after achieving short-term treatment goals with corticosteroid therapy, patients should continue maintenance treatment. The duration of maintenance therapy varies depending on individual patient responses and disease progression as determined by the treating physician.
Corticosteroids carry significant side effects. In IgA nephropathy treatment, the risks often outweigh the benefits, leading to high dropout rates in clinical trials as participants frequently withdraw due to adverse effects.
Mechanistic Limitations of Traditional Therapies
From a mechanistic perspective, corticosteroids and immunosuppressive agents are not ideally suited for IgA nephropathy. These medications primarily target the vascular wall, making them more effective for conditions like minimal change disease, membranous nephropathy, and focal segmental glomerulosclerosis, where the pathological changes occur within the vessel walls.
In IgA nephropathy, however, the primary pathology occurs not within the vascular wall but in the mesangial cells located outside the vessel wall—a distance of just 5 micrometers that significantly reduces the effectiveness of these medications. This spatial limitation has historically prevented corticosteroids from being first-line therapy for IgA nephropathy due to unfavorable risk-benefit ratios.
Targeted Corticosteroid Therapy: A New Approach
To address the high-risk profile of traditional corticosteroids, researchers developed a novel targeted corticosteroid: budesonide enteric-coated capsules (brand name: Nefecon). This targeted formulation reduces systemic side effects while maintaining therapeutic efficacy, successfully achieving a favorable risk-benefit ratio. Recent guidelines now recommend this treatment with a 9-month course duration.
The 9-month duration was established based on clinical trial data from the drug’s pre-market studies.
Do Symptoms Return After Stopping Nefecon?
Recent data from the 2025 European Renal Association Congress (ERA25) provided important insights into this question.
The NefXtend trial, an extension study of Nefecon’s Phase 3 trials, revealed the following results:
After 9 months of treatment with budesonide enteric-coated capsules (16mg daily) followed by drug discontinuation, patients showed:
- Average decline in estimated glomerular filtration rate (eGFR)
- Average increase in proteinuria during the subsequent 15-month observation period
While proteinuria levels remained lower than pre-treatment baselines and kidney function declined more slowly than before treatment, indicating persistent but insufficient benefit that does not support drug discontinuation.
These findings align with previous research presented at the American Society of Nephrology meeting, which showed that after the first treatment course’s effectiveness diminished, a second course provided similar efficacy to the initial treatment.
Addressing the Root Cause: Oxidative Stress
Nefecon, as a targeted therapy, is expensive (approximately $200,000 per course before insurance coverage) and remains costly even after insurance coverage compared to traditional corticosteroids and immunosuppressants. Long-term use would create a significant financial burden for patients.
The Underlying Mechanism
Nefecon targets the disease antigen: galactose-deficient IgA. Normal IgA contains galactose, but in patients with IgA nephropathy, this galactose is missing. The upstream cause of this deficiency is oxidative stress—a reduction in the body’s antioxidant capacity that allows free radicals to attack the immune system’s IgA.
The root causes of oxidative stress include poor lifestyle habits, genetic DNA defects, and environmental factors. While these factors are often beyond direct medical intervention, patients typically address lifestyle issues during treatment. However, oxidative stress remains the primary driver of disease recurrence.
Addressing oxidative stress allows the immune system to function normally, creating conditions for successful drug discontinuation without rebound.
Case Study: IgA Nephropathy Grade 4 Patient Recovery
Patient Background
A 15-year-old female from Qinghai province was diagnosed with IgA nephropathy in 2015. Despite treatment with corticosteroids and immunosuppressants, her proteinuria remained unstable with frequent fluctuations. By 2020 (her fifth year of treatment), proteinuria reached 8.07 grams per day.
(Note: IgA nephropathy typically produces less proteinuria than other kidney diseases because the pathology occurs outside the vascular wall, making protein leakage less severe. Proteinuria exceeding 1 gram usually indicates advanced disease.)
Treatment Approach and Outcome
After achieving proteinuria remission through antioxidant therapy, corticosteroids and immunosuppressants were successfully discontinued.
Rationale for Drug Discontinuation:
- Immunosuppressive therapy repairs vascular wall damage
- Antioxidant therapy prevents continued vascular wall attack
- Without ongoing oxidative damage, maintenance immunosuppression becomes unnecessary
Current Status: The patient has been off corticosteroids and immunosuppressants for three years without recurrence. Recent follow-up shows proteinuria at 0.3 grams per day.
While other supportive measures were implemented, the most critical intervention was detecting, monitoring, and resolving oxidative stress—the true pathological root within medical treatment scope.
Clinical Implementation
Detecting and treating oxidative stress is not an overly complex or proprietary technology. Many experienced clinicians have expertise in this area. Unlike developing new pharmaceutical compounds, antioxidant therapy is accessible to hospitals with strong nephrology departments and integrated medicine programs.
Conclusion
The goal is for all kidney disease patients to be free from oxidative stress and successfully discontinue corticosteroids and immunosuppressants while maintaining disease remission.
This article is adapted from Chinese medical literature and presents current research and clinical approaches to IgA nephropathy treatment. Patients should always consult with their healthcare providers before making any changes to their treatment regimens.
发表回复