What is IgA (Immunoglobulin A) nephropathy?

From the Guidelines

IgA nephropathy is a kidney disease characterized by the deposition of immunoglobulin A (IgA) in the glomeruli, leading to inflammation and potential kidney damage over time, with treatment focusing on controlling blood pressure, reducing proteinuria, and slowing disease progression 1.

Key Aspects of IgA Nephropathy

• The disease is diagnosed through biopsy, with histologic scoring via the MEST-C system, and prognosis assessment using the International IgAN Prediction Tool 1.
• Management involves multifaceted, optimized supportive care, including RAS blockade, blood pressure control, cardiovascular risk minimization, and lifestyle advice such as dietary counseling, smoking cessation, weight control, and exercise 1.
• RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d, and proteinuria reduction to under 1 g/d is a surrogate marker of improved kidney outcome in IgAN 1.

Treatment Considerations

• For patients with persistent proteinuria >0.75-1 g/d despite optimized supportive care, a 6-month course of glucocorticoid therapy may be considered, but with caution in certain patient populations such as those with eGFR <30 ml/min per 1.73 m2, diabetes, obesity, or latent infections 1.
• The use of glucocorticoids in IgAN is not established, and they should be given with extreme caution or avoided entirely in certain patients, highlighting the need for careful consideration of the risks and benefits 1.
• Other immunosuppressive therapies, including azathioprine, cyclophosphamide, calcineurin inhibitors, and rituximab, are not recommended in IgAN, except in specific cases such as rapidly progressive IgAN 1.

Emerging Therapies

• New therapies for high-risk IgAN patients are being evaluated, including sodium-glucose co-transporter-2 inhibitors, sparsentan, atrasentan, hydroxychloroquine, and targeted-release glucocorticoids like budesonide, which has shown potential in reducing proteinuria with fewer adverse events 1.
• The FDA has granted accelerated approval of delayed-release budesonide for primary IgA nephropathy with a UPCR > 1.5 g/g, offering a potential new treatment option for patients with this condition 1.

From the Research

Definition and Overview of IgA Nephropathy

• IgA nephropathy, also known as Immunoglobulin A nephropathy, is the most common form of primary glomerulonephritis worldwide 2, 3, 4, 5, 6.
• It is characterized by the deposition of IgA antibodies in the glomeruli, leading to inflammation and damage to the kidneys 6.

Prognosis and Progression

• The prognosis of IgA nephropathy is generally good, with 15-year rates of kidney survival usually well in excess of 70% 2.
• However, progression to end-stage renal disease can occur, especially in patients with heavy proteinuria and/or elevated serum creatinine levels 4, 5.
• The rate of progression can be slow, and spontaneous remission of disease activity can occur in some patients 2.

Treatment and Management

• The mainstay of therapy for IgA nephropathy is optimized supportive care, including measures to lower blood pressure, reduce proteinuria, and minimize lifestyle risk factors 2, 5.
• Nephroprotective therapies, such as renin-angiotensin-aldosterone system blockade, can help slow the progression of kidney damage 4, 6.
• Immunosuppression, such as corticosteroid therapy, may be considered in some patients, especially those with heavy proteinuria or rapid decline in renal function 2, 5.
• Newer therapies, such as sodium-glucose transporter-2 inhibitors and complement inhibitors, are being evaluated and may offer promising treatment options for IgA nephropathy 3, 6.