What is IgA (Immunoglobulin A) nephropathy?

From the Guidelines

IgA nephropathy patients with high-risk features should be considered for treatment with delayed-release budesonide, as it has shown a statistically significant 34% reduction in proteinuria from baseline at 9 months, with the potential to improve long-term kidney survival outcomes 1.

Treatment Overview

IgA nephropathy is a kidney disease caused by deposits of immunoglobulin A (IgA) in the glomeruli, leading to inflammation and potential kidney damage over time. Treatment focuses on controlling blood pressure, reducing proteinuria, and slowing disease progression.

First-Line Therapy

First-line therapy includes ACE inhibitors or ARBs such as lisinopril 10-40 mg daily or losartan 50-100 mg daily to control hypertension and reduce protein excretion 1.

Corticosteroid Therapy

For patients with persistent proteinuria >1 g/day despite 3-6 months of optimal supportive care, a 6-month course of corticosteroids may be considered, typically methylprednisolone 0.5-1 g IV for 3 days at months 1,3, and 5, alternating with oral prednisone 0.5 mg/kg every other day 1.

Lifestyle Modifications

Patients should maintain a healthy lifestyle with moderate sodium restriction (<2g/day), protein intake of 0.8-1.0 g/kg/day, and regular exercise.

Monitoring

Regular monitoring of kidney function, blood pressure, and proteinuria is essential, with follow-up every 3-6 months depending on disease severity.

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. Some key points to consider when treating IgA nephropathy include:

• The use of glucocorticoids in IgAN is not established and should be given with extreme caution or avoided entirely in patients with certain conditions, such as eGFR <30 ml/min per 1.73 m2, diabetes, obesity, latent infections, secondary disease, active peptic ulceration, uncontrolled psychiatric disease, or severe osteoporosis 1.
• 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 disease results from abnormal glycosylation of IgA molecules, leading to their deposition in the mesangium, triggering inflammation and scarring.
• While many patients have a benign course, about 30-40% progress to end-stage kidney disease within 20-30 years, making early intervention crucial. In summary, the management of IgA nephropathy should focus on controlling blood pressure, reducing proteinuria, and slowing disease progression, with consideration of treatment with delayed-release budesonide for high-risk patients, and careful monitoring of kidney function and proteinuria 1.

From the Research

Overview of IgA Nephropathy

• IgA nephropathy is a primary glomerulonephritis with a potentially serious prognosis 2
• It is the most common primary glomerulonephritis worldwide 2

Treatment Options

• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are beneficial in treating IgA nephropathy, particularly in patients with hypertension and proteinuria 3, 4
• The combination of ACE inhibitors and ARBs has been shown to have a greater antiproteinuric effect and protect against renal function deterioration 3, 4
• Supportive care, including therapeutic lifestyle changes and excellent blood pressure control, is the cornerstone of treatment for IgA nephropathy 2, 5
• Targeted-release formulation of budesonide may replace systemic corticosteroids in patients with higher proteinuria and active histological lesions 2

Renin-Angiotensin Blockade

• Renin-angiotensin system (RAS) blockade using ACE inhibitors or ARBs is first-line therapy for IgA nephropathy 5
• RAS blockade has been shown to achieve remission in half of IgAN patients, with increasing treatment duration to 6 months improving remission rates 5
• Patients with severe clinical and histological disease are less likely to tolerate and respond to treatment with RAS blockade 5

Predictors of Response to Treatment

• Baseline estimated glomerular filtration rate (eGFR) and serum albumin levels are predictors of response to treatment with RAS blockade 5
• Asymptomatic hyperuricemia and higher proteinuria are associated with a lower likelihood of achieving remission 5
• Certain histological lesions, such as E1 and T1/T2 lesions, are more frequent in patients who fail to achieve remission 5