Treatment of immunoglobulin A nephropathy: Current perspective and future prospects

Abstract

Immunoglobulin (Ig) A nephropathy is the most common type of primary glomerulonephritis globally. It typically manifests with microscopic hematuria and a spectrum of proteinuria, although rapidly progressive glomerulonephritis may occur in rare instances. Deposition of IgA in the mesangium seems to be the underlying disease mechanism. Despite current treatment, IgA nephropathy may progress into end-stage renal disease, indicating the necessity for the development of new therapeutic agents. Lifestyle modifications and anti-proteinuric treatment are recommended, and steroids have shown to be beneficial to high risk groups. Nevertheless, other conventional immunosuppressive agents, such as cyclophosphamide and mycophenolate mofetil, may be considered, despite the lack of sufficient evidence to support their efficacy. A considerable proportion of cases remain unresponsive to these treatments, underscoring the need for novel therapeutic approaches. There are several promising immunosuppressive drugs, such as B-cell lineage depleting agents or complement system inhibitors, that are currently undergoing clinical trials. These therapies may be considered for use in selected cases.

Keywords: Immunoglobulin A nephropathy; Telitacicept; Complement inhibitors; B-cell lineage depletion; Anti-proteinuric treatment

Core Tip: Immunoglobulin A nephropathy represents the most prevalent form of primary glomerulonephritis, with the potential for progression to end-stage renal disease. Lifestyle modifications, dietary alterations and anti-proteinuric pharmacological agents have been demonstrated to induce clinical remission in most cases. However, some cases do not respond to supportive therapy. Short term use of corticosteroids should be considered in unresponsive cases. However, novel therapeutic strategies are required for patients with steroid-refractory disease. B-cell lineage depletion therapies and complement system inhibitors represent promising avenues for future research and may be considered in cases of persistent disease despite guideline-directed medical treatment.