From the Guidelines
IgA nephropathy is a complex disease with variable complication rates, and its management should focus on optimized supportive care, including RAS blockade, blood pressure control, and lifestyle modifications, with consideration of glucocorticoid therapy in high-risk patients, as supported by the most recent evidence from 2023 1.
Disease Overview
IgA nephropathy is the most common form of glomerulonephritis worldwide, characterized by deposits of immunoglobulin A in the glomerular mesangium. The disease typically presents in young adults, often with episodes of visible hematuria during respiratory infections, or with persistent microscopic hematuria and proteinuria.
Complication Rates
Complications of IgA nephropathy vary widely, with approximately 30-40% of patients progressing to end-stage renal disease (ESRD) within 20-30 years of diagnosis. Hypertension develops in about 60% of patients and correlates with disease progression. Nephrotic syndrome occurs in 5-10% of cases and indicates a poorer prognosis. Acute kidney injury can occur during episodes of gross hematuria in 25% of patients but is usually reversible.
Risk Factors for Progression
Risk factors for progression include persistent proteinuria >1g/day, hypertension, reduced GFR at diagnosis, and certain histological features like tubular atrophy and interstitial fibrosis. The International IgAN Prediction Tool, available at Calculate by QxMD, can be used to assess disease prognosis, but it is essential to note that neither this calculator nor the MEST-C score nor the presence or number of crescents can determine the likely impact of any particular treatment regimen 1.
Treatment
Treatment focuses on blood pressure control with ACE inhibitors or ARBs, and immunosuppressive therapy with corticosteroids may be considered for patients with persistent proteinuria despite optimal supportive care. The use of glucocorticoids in IgAN is supported by recent evidence, including the TESTING study, which showed a significant reduction in composite outcome with steroid treatment over a median 4.2-year follow-up 1. However, the use of glucocorticoids should be done with caution, considering the potential for serious adverse events, and alternative therapies, such as targeted-release glucocorticoids like budesonide, may be considered.
Pathogenesis
The pathogenesis involves abnormal glycosylation of IgA molecules, leading to their deposition in the mesangium and subsequent inflammation and scarring, which explains the variable clinical course and complication rates observed in different patients.
Key Considerations
- Optimized supportive care, including RAS blockade, blood pressure control, and lifestyle modifications, is essential for managing IgA nephropathy.
- Glucocorticoid therapy may be considered for patients with persistent proteinuria despite optimal supportive care, but its use should be done with caution.
- Alternative therapies, such as targeted-release glucocorticoids like budesonide, may be considered for patients with high-risk features.
- The International IgAN Prediction Tool can be used to assess disease prognosis, but its limitations should be recognized.
From the Research
Description of IgA Nephropathy
- IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to end-stage renal disease in 20-30% of patients 2.
- It is a very common glomerulonephritis among young adults, but the best therapeutic approach has not been fully elucidated 3.
- IgAN is characterized by the deposition of immunoglobulin A (IgA) antibodies in the glomeruli, leading to inflammation and damage to the kidneys.
Complication Rates
- 15-50% of patients with IgAN develop loss of renal function in 10-20 years, and the rest experience remission or mild proteinuria/hematuria 4.
- The complication rates vary depending on the severity of the disease and the effectiveness of treatment.
- Patients with severe chronic renal failure have a poorer prognosis, with a 6-year renal survival rate of 50-57% 5.
Treatment and Management
- The optimal treatment for IgAN is uncertain, but supportive therapies such as angiotensin blockade should be considered as first-line therapy for patients with urine protein >0.5 g/day and/or blood pressure >140/90 mm Hg 2.
- Corticosteroids could be considered as add-on or monotherapy for patients with urine protein >1 g/day with preserved renal function 2.
- Immunosuppressive therapy, including corticosteroids and azathioprine, may be effective in reducing proteinuria and stabilizing renal function in IgAN 3, 5.
- Non-immunosuppressive therapy, such as renin-angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers (ARB), fish oil, statins, and antiplatelets, may also be beneficial in managing IgAN 4.