From the Guidelines
The primary focus of IgA nephropathy management should be multifaceted, optimized supportive care, including RAS blockade as much as tolerated or allowed, blood pressure control, cardiovascular risk minimization, adherence to lifestyle advice, including dietary counselling, smoking cessation, weight control, and exercise as appropriate. The treatment of IgA nephropathy focuses on controlling blood pressure, reducing proteinuria, and preserving kidney function. First-line therapy includes angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), which reduce proteinuria and slow disease progression 1.
Key Considerations
- Blood pressure should be maintained below 130/80 mmHg.
- RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d.
- For patients with persistent proteinuria >0.75-1 g/d despite at least 90 days of optimized supportive care, a 6-month course of glucocorticoid therapy may be considered 1.
- Lifestyle modifications are also important, including sodium restriction, moderate protein intake, smoking cessation, and weight management.
Immunotherapy
- Beyond glucocorticoids, other immunosuppressive therapies are not recommended in IgAN, including azathioprine, cyclophosphamide (except in the setting of rapidly progressive IgAN), calcineurin inhibitors (CNIs), and rituximab 1.
- The use of mycophenolate mofetil (MMF) in IgAN is not recommended in non-Chinese patients.
Emerging Therapies
- A number of new therapies for high-risk IgAN patients are currently being evaluated, including drugs that may augment the supportive care approach (sodium-glucose co-transporter-2 [SGLT2] inhibitors, sparsentan, atrasentan, hydroxychloroquine) or more specific approaches (e.g., enteric-coated budesonide, various complement inhibitors, therapies targeting B-cell development) 1.
Recent Developments
- The FDA granted accelerated approval of delayed-release budesonide for primary IgA nephropathy with a UPCR > 1.5 g/g, with preliminary results showing a statistically significant 34% reduction in proteinuria from baseline at 9 months in patients in the intervention arm 1.
Monitoring and Follow-up
- Regular monitoring of kidney function, proteinuria, and blood pressure is essential, with follow-up every 3-6 months.
- The treatment approach should be tailored based on disease severity, as IgA nephropathy ranges from benign forms to rapidly progressive glomerulonephritis, with about 20-40% of patients eventually progressing to end-stage kidney disease over 20-25 years.
From the Research
Treatment Options for IgA Nephropathy
- The treatment of IgA nephropathy can be based on the severity of clinical and histological features, with different therapeutic regimens selected accordingly 2.
- For patients with normal renal function and proteinuria <1 g/24-h, no treatment may be necessary, while those with normal renal function and proteinuria >1 g/24-h may receive angiotensin-converting enzyme inhibitors (ACEi) and corticosteroids 2.
- Patients with baseline serum creatinine (Scr) <2.5 mg/dL, proteinuria >3.5 g/24-h, and severe histological lesions may receive ACEi, corticosteroids, and other immunosuppressive drugs 2.
- The KDIGO Clinical Practice Guideline for Glomerulonephritis recommends long-term ACE-I or ARB treatment when proteinuria is more than 1 g/day, with up-titration of the drug, and a 6-month course of corticosteroid therapy for patients with GFR >50 ml/min and proteinuria persistently higher than 1 g/day 3.
Progressive Treatment Approach
- A progressive treatment approach can be taken, which takes into account the time the IgAN is recognized and the clinical conditions present at that time 3.
- This approach includes:
- Annual controls for patients with macro-microscopic haematuria and proteinuria less than 0.3 g/day.
- ACE-I and/or ARB with titration of the drugs for patients with proteinuria between 0.3 and 0.9 g/day.
- A 6-month course of corticosteroids, in addition to ACE-I and/or ARB, for patients with proteinuria higher than 1 g/day, arterial hypertension, and GFR up to 30 ml/min.
- ACE-I/ARB, dialysis, and kidney transplantation for patients with GFR less than 30 ml/min.
New Therapies and Treatment Paradigm
- A new treatment paradigm is proposed, which combines therapies with different mechanisms of action to target the immune components and the chronic kidney disease components of IgAN in parallel to preserve long-term kidney survival 4.
- New therapies, such as sodium-glucose transporter-2 inhibitors, sparsentan, nefecon, and iptacopan, have been approved or are being evaluated for the treatment of IgAN 4.
Role of Angiotensin Antagonists and Fish Oil
- Angiotensin antagonists, such as ACE-I and ARB, have a definite role in treating IgAN, particularly the hypertensive and proteinuric forms 5.
- Fish oil may have a good rationale for renal inflammation and prevention of cardiovascular morbidity, but published reports have given conflicting conclusions 5.