Kidney Week Educational Symposia-Current Therapies and Treatment Responses in Primary Focal Segmental Glomerulosclerosis and IgA Nephropathy

Video Transcription

Video Summary

This ASN Kidney Week 2021 educational symposium reviews treatment goals and current/near-future therapies for primary focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), emphasizing traditional endpoints (complete/partial remission, proteinuria reduction, kidney failure, death) while noting growing attention to patient-reported outcomes and validated surrogate endpoints (proteinuria and eGFR change) that accelerate trials.<br /><br />For FSGS, the speaker stresses it is a histologic lesion, not a single disease, best classified by etiology: primary (putative circulating factor), genetic (over 50 genes; collagen IV variants common in adult familial disease), APOL1 risk genotypes requiring a “second hit” (e.g., HIV/COVID-associated collapsing glomerulopathy), and secondary/adaptive forms (hyperfiltration, obesity, drugs/viruses). Distinguishing primary vs secondary is crucial because immunosuppression is reserved for primary disease. Universal supportive care includes RAAS blockade, BP/volume control, cardiovascular risk management, and emerging use of SGLT2 inhibitors (DAPA-CKD subgroup signals benefit but underpowered in FSGS). Sparsentan (dual ARB/endothelin antagonist) showed greater short-term proteinuria reduction than irbesartan in DUET; phase 3 DUPLEX is ongoing. Primary FSGS therapy remains high-dose prednisone (low complete remission; partial remission still improves long-term outcomes), with calcineurin inhibitors for steroid-resistant disease (responses often partial and relapse common; nephrotoxicity limits use). Rituximab/cyclophosphamide have limited evidence in steroid-resistant FSGS; trial enrollment and precision-medicine approaches (transcriptomics/biomarkers) are highlighted.<br /><br />For IgAN, diagnosis requires kidney biopsy; pathogenesis follows the “four-hit” model (galactose-deficient IgA1, autoantibodies, immune complexes, complement/inflammation). Risk stratification uses MEST-C scoring and the International IgA Prediction Tool to guide shared decision-making, though not to mandate therapy. KDIGO-based management prioritizes optimized supportive care (ACEi/ARB when proteinuria ≥0.5 g/day; “high risk” if ≥1 g/day despite care). Steroids may be considered for high-risk patients but toxicity is significant, especially with low eGFR; STOP-IgAN and TESTING trials showed mixed efficacy and notable adverse events. Alternative phenotypes (minimal-change-like IgAN, RPGN with crescents, gross hematuria–associated AKI, IgA vasculitis, IgA-dominant infection-related GN) require different approaches; immunosuppression is generally avoided in IgA-dominant infection-related GN. Emerging therapies include SGLT2 inhibitors (dapagliflozin benefited biopsy-proven IgAN in DAPA-CKD) and multiple phase 2/3 agents (targeted budesonide/“nefacon,” sparsentan, complement inhibitors, endothelin antagonists, B-cell/APRIL pathway drugs).

Asset Subtitle

Moderators: Michelle O'Shaughnessy

Speakers:

Introduction - Michelle O'Shaughnessy
Current Therapies and Treatment Response in FSGS - J. Ashley Jefferson
Current Therapies and Treatment Response in IgAN - Jai Radhakrishnan

Meta Tag

Date 11/5/2021

Pathway 1 Glomerular Diseases

Session ID 406550

Session Type ES - Educational Symposium

Keywords

ASN Kidney Week 2021

focal segmental glomerulosclerosis (FSGS)

IgA nephropathy (IgAN)

proteinuria reduction

eGFR surrogate endpoints

RAAS blockade (ACEi/ARB) supportive care

SGLT2 inhibitors (dapagliflozin, DAPA-CKD)

sparsentan (dual endothelin/angiotensin receptor antagonist)

immunosuppression (prednisone, calcineurin inhibitors, steroids)

IgAN four-hit pathogenesis model and MEST-C risk stratification