From the Guidelines
Targeting B-cells is not recommended as a standard treatment for IgA Nephropathy, according to the most recent guidelines from KDIGO 1. The primary focus of IgA Nephropathy management should be multifaceted, optimized supportive care, including RAS blockade, blood pressure control, cardiovascular risk minimization, adherence to lifestyle advice, and dietary counseling. Some key points to consider in the management of IgA Nephropathy include:
- RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d.
- If proteinuria stays above 0.75–1 g/d despite at least 90 days of optimized supportive care, the patient may be considered for a 6-month course of glucocorticoid therapy.
- Beyond glucocorticoids, other immunosuppressive therapies, including rituximab, are not recommended in IgA Nephropathy, except in specific cases such as rapidly progressive IgAN. The rationale for not recommending B-cell targeting therapies, such as rituximab, in IgA Nephropathy is based on the lack of sufficient evidence to support their use in this context, as stated in the KDIGO guideline 1. However, research into new therapies for high-risk IgAN patients is ongoing, including drugs that may augment the supportive care approach or more specific approaches, such as therapies targeting B-cell development 1. It is essential to note that treatment decisions should be individualized based on disease severity, rate of progression, and other patient factors, and patients should be monitored for potential side effects of any treatment. In the context of IgA Nephropathy, the use of B-cell targeting therapies, such as rituximab, may be considered in the context of clinical trials or specific patient populations, but it is not a standard treatment approach, as per the KDIGO guideline 1.
From the Research
Targeting B-Cells in IgA Nephropathy
- The effectiveness of targeting B-cells as a strategy to halt the disease process in IgA Nephropathy is being explored in various studies 2, 3, 4, 5, 6.
- IgA Nephropathy is a complex disease characterized by the deposition of immune complexes composed of galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 autoantibodies in the glomeruli, leading to complement-mediated inflammation and potential kidney damage 4, 6.
- Current treatment options for IgA Nephropathy are limited, and there is a need for therapies that directly affect the formation of pathogenic Gd-IgA1 antibodies and anti-Gd-IgA1 antibody-containing immune complexes 6.
Role of B-Cells in IgA Nephropathy
- B-cells play a crucial role in the production of Gd-IgA1 antibodies, which are central to the pathogenesis of IgA Nephropathy 4, 6.
- Depletion or modulation of Gd-IgA1-producing B-cells is a potential therapeutic strategy for IgA Nephropathy, and several monoclonal antibodies are being investigated for this purpose 6.
- Monoclonal antibodies such as rituximab, felzartamab, and narsoplimab may target B-cells and other factors involved in their activation and survival, such as BAFF or APRIL 6.
Evidence for Targeting B-Cells
- Studies have shown that immunosuppressive therapy, including corticosteroids and cytotoxic agents, may have beneficial effects on IgA Nephropathy, although the evidence is not always consistent 3, 5.
- A 2020 Cochrane review found that corticosteroid therapy probably prevents the progression to end-stage kidney disease in patients with IgA Nephropathy and proteinuria, although the evidence for other immunosuppressive agents is less clear 5.
- Emerging therapies, including monoclonal antibodies, may offer new opportunities for targeting B-cells and other components of the immune system involved in IgA Nephropathy 6.