IgA Nephropathy: A European Perspective in the Corticosteroid Treatment

Abstract

Background: IgA nephropathy (IgAN) is detected in Europe in 22% of glomerular diseases diagnosed by biopsy. The frequency of IgAN as cause of ESRD in Europe has increased in the last decades, accounting for 35% of young and adult transplanted patients. These data justify the interest for risk factors and a possible therapeutic approach. Summary: Insight into a European perspective of IgAN was allowed by the multicenter study VALIGA, on 1,147 patients, almost all Caucasians, with follow-up of 4.7 years. The predictive value of mesangial hypercellularity (M), segmental sclerosis (S), tubular atrophy interstitial fibrosis (T) as independent biomarkers of progression was validated. Endocapillary hypercellularity was predictive of increased follow-up proteinuria. Two groups of patients selected by a propensity score to perfectly match for histologic features (MEST) and clinical data treated with renin-angiotensin system blockers (RASBs) and corticosteroids, or RASBs alone were compared and a beneficial effect of corticosteroids in addition to RASB was found in patients with proteinuria > 1 g/day, with an initial eGFR < 50 mL/min/1.73 m². On the contrary, the STOP-IgAN RCT found that immunosuppressive therapy in addition to optimal supportive care did not provide substantial kidney-related benefits in European patients with IgAN, because there was no difference in the rate of decrease in eGFR, although corticosteroid/immunosuppressive therapy induced complete remission of proteinuria more frequently than supportive care alone. The NEFIGAN trial evaluated a targeted release formulation of budesonide (TRF budesonide) delivering the drug in the distal ileum. TRF budesonide, additionally to optimized RAS blockade, reduced proteinuria and maintained eGFR in IgAN patients, suggesting a reduced risk of future progression to ESRD. Key Messages: In Europe, there is a reasoned search of a balanced approach to corticosteroid therapy for patients with IgAN, with particular attention to selecting the patients at risk of progression while limiting the unwanted systemic adverse events.

The Emerging Role of Pathogenesis of IgA Nephropathy

“…Additionally, corticosteroids inhibit c-Jun, Fos, and NF-κB pathways, consequently inhibiting inflammatory responses. Due to these corticosteroid effects, they are widely used as in the treatment of autoimmune diseases [ 94 ]. Early studies reported that corticosteroids may improve renal outcomes in these diseases, showing that patients treated with corticosteroids have improved 5-year renal survival and reduced proteinuria, compared with patients treated with supportive therapy [ 95 ].…”

Global glomerulosclerosis proportions above 10% predict nephropathy progression in IgA Nephropathy: a multicenter retrospective analysis with propensity score matching

“…The role of corticosteroid intervention for IgAN remains debated [21][22][23]. In the STOP-IgAN trial, immunosuppressive therapy for high-risk IgAN patients did not signi cantly improve the outcome, and more adverse effects were observed [24,25].…”

Downregulation of PPARα mediates FABP1 expression, contributing to IgA nephropathy by stimulating ferroptosis in human mesangial cells

“…Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis globally, which is a major cause of end-stage renal disease [1,2] . Moreover, approximately 30%-40% of kidney biopsies confirm IgAN, with frequencies in Asia ranging from 22% to 39%, which is higher than those observed in Europe [3,4]. IgA-dominant immunoglobulin deposition in the glomerular mesangial area of the kidney is considered the main cause of IgAN; however, the specific pathogenesis underlying IgAN remains to be elucidated [5,6].…”