Non-immunosuppressive treatment for IgA nephropathy

Area of Science:

• Nephrology
• Immunology
• Pharmacology

Background:

• IgA nephropathy (IgAN) is a leading cause of kidney failure, affecting 20-40% of patients within 25 years.
• Non-immunosuppressive treatments are crucial for managing IgAN by controlling blood pressure and reducing proteinuria, while avoiding immunosuppression risks.
• Existing clinical trial data for IgAN management is often limited by small sample sizes and short durations, leading to conflicting evidence.

Purpose of the Study:

• To evaluate the efficacy and safety of non-immunosuppressive therapies for IgA nephropathy (IgAN) in adults and children.
• To systematically review all non-immunosuppressive interventions, including antihypertensives, anticoagulants, dietary changes, tonsillectomy, and herbal medicines.

Main Methods:

• A comprehensive search of the Cochrane Kidney and Transplant Register of Studies up to December 2023.
• Inclusion of randomized controlled trials (RCTs) and quasi-RCTs involving adults and children with biopsy-proven IgAN.
• Data extraction and quality assessment by two independent reviewers, with meta-analysis using random-effects models and GRADE for evidence certainty.

Main Results:

• Renin-angiotensin system (RAS) inhibition likely reduces proteinuria (moderate certainty) but shows little effect on kidney failure or serum creatinine doubling (low certainty).
• Tonsillectomy may increase remission rates for proteinuria and microscopic hematuria in Japanese IgAN patients (low certainty), but generalizability is unclear.
• Other interventions like anticoagulants, fish oil, and traditional Chinese medicines showed minimal benefits compared to placebo, with no clear advantage over standard care.

Conclusions:

• Antihypertensive therapies, particularly RAS inhibitors, appear to be the most beneficial non-immunosuppressive treatment for IgAN, with benefits likely outweighing harms.
• The evidence for tonsillectomy's efficacy in IgAN is limited and primarily based on Japanese populations; its recommendation is uncertain due to inconsistent findings and potential harms.
• Robust RCT evidence is lacking for most other non-immunosuppressive treatments, necessitating further research to establish their efficacy and safety in IgAN management.