Achieving remission in immunoglobulin A nephropathy (IgAN) does not eliminate the risk of disease recurrence or progressive kidney damage, according to a prospective cohort study of 1,069 adults with biopsy-confirmed IgAN. Over a median follow-up of 6.3 years, 33% of patients experienced relapse, with a median time to first relapse of 2.3 years. Relapse was associated with significantly worse kidney outcomes: 42% of patients who relapsed experienced kidney failure or a 50% decline in estimated glomerular filtration rate (eGFR), compared with 8% of those who maintained remission. Patients who relapsed also experienced a faster annual decline in eGFR (-2.3 vs -1.0 mL/min/1.73 m²).

These findings reinforce the importance of continued monitoring even after remission is achieved. Higher proteinuria and lower eGFR at remission were associated with increased relapse risk, while achieving proteinuria below 0.3 g/day was linked to better relapse-free outcomes. Patients who achieved remission with corticosteroids also showed higher relapse rates, although the observational findings do not establish causation. While the single-center study involved only Chinese patients, its findings highlight the potential value of stricter proteinuria targets, long-term surveillance, and individualized follow-up strategies to help identify recurrence and protect kidney function.

Reference: Shen X, Chen P, Hui M, et al. Association Between Relapse and Long-Term Kidney Outcomes in IgA Nephropathy. Kidney Med. 2025 Sep 15;7(11):101104. doi: 10.1016/j.xkme.2025.101104.

A comprehensive review of immunoglobulin A nephropathy (IgAN) treatment highlights the expanding role of targeted therapies in reducing proteinuria and slowing kidney disease progression while potentially limiting exposure to systemic corticosteroids. An interim analysis of the phase 3 APPLAUSE-IgAN trial found that the complement factor B inhibitor iptacopan achieved a 38.3% lower mean 24-hour urinary protein-to-creatinine ratio than placebo at nine months, with no unexpected safety findings reported. Iptacopan subsequently received traditional FDA approval in July 2026 to slow kidney function decline in adults with primary IgAN at risk of disease progression. The phase 3 PROTECT trial also demonstrated substantial proteinuria reductions with sparsentan, a dual endothelin and angiotensin receptor antagonist, compared with irbesartan (49.8% vs 15.1% from baseline). Additional investigational treatments targeting a proliferation-inducing ligand and other complement pathways showed encouraging results in earlier-stage studies, although the phase 3 ARTEMIS-IgAN trial of narsoplimab was discontinued after failing to meet its primary endpoint. The review also highlights targeted-release budesonide as an alternative approach to immunosuppression, while emphasizing that systemic glucocorticoids remain associated with significant adverse effects, particularly infections.

As targeted therapies expand, treatment decisions must balance kidney protection with potential risks. Optimized supportive care remains foundational, including blood pressure control, dietary sodium restriction, weight management, and maximally tolerated renin-angiotensin-aldosterone system inhibition. Sodium-glucose cotransporter-2 inhibitors offer additional kidney protection, supported by a prespecified DAPA-CKD analysis reporting a 71% relative reduction in the primary composite kidney outcome among patients with IgAN. Persistent proteinuria, declining estimated glomerular filtration rate, hematuria, and Oxford MEST-C biopsy findings can help identify patients requiring closer monitoring or additional treatment. However, specific considerations include infection risk, adverse effects, medication costs, and uncertainty surrounding long-term outcomes. Because this review reflects clinical trial findings and regulatory information available at publication, clinicians should consult current treatment guidelines and prescribing information before incorporating newer therapies into practice.

Reference: Scarpioni R, Valsania T. IgA nephropathy: what is new in treatment options? Kidney Dial. 2024 Dec;4(4):223-245. doi: 10.3390/kidneydial4040019.

Investigators of a retrospective study of 130 patients with biopsy-confirmed immunoglobulin A nephropathy (IgAN) found that sustained proteinuria during follow-up was a stronger predictor of kidney disease progression than proteinuria at diagnosis. Conducted at a Malaysian medical center, the study followed patients for a median of 7.5 years and evaluated the combined outcome of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease. Overall, 26.2% of patients reached this endpoint. Although median proteinuria at diagnosis was 2.4 g/day, median time-averaged proteinuria during follow-up declined to approximately 0.7 g/day. Time-averaged proteinuria was the only independent predictor of kidney disease progression in multivariable analysis (hazard ratio, 2.23; 95% CI, 1.57-3.16; P < .001). In contrast, proteinuria measured at diagnosis was not significantly associated with long-term outcomes. The estimated 10-, 20-, and 30-year rates of survival without the combined kidney endpoint were 80%, 53%, and 25%, respectively.

Monitoring proteinuria trends over time may provide a more accurate assessment of progression risk than relying on baseline measurements alone. Regular evaluation of urinary protein excretion, eGFR, and blood pressure can help identify patients who remain at risk despite initially favorable findings or improvements following treatment. Although hypertension, reduced baseline kidney function, and certain Oxford MEST-C biopsy findings were associated with progression in unadjusted analyses, sustained proteinuria emerged as the strongest independent prognostic marker. The results support treatment strategies focused on achieving and maintaining proteinuria reduction, alongside ongoing assessment of kidney function and cardiovascular risk. However, the study's retrospective, single-center design, relatively small sample, and variation in immunosuppressive treatment limit generalizability and prevent conclusions about treatment effectiveness. Prospective studies are needed to determine how best to incorporate long-term proteinuria measurements into individualized risk assessment and treatment decisions.

Reference: Mohd R, Mohammad Kazmin NE, Abdul Cader R, et al. Long term outcome of immunoglobulin A (IgA) nephropathy: A single center experience. PLoS One. 2021 Apr 8;16(4):e0249592. doi: 10.1371/journal.pone.0249592.