{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:27:19Z","timestamp":1792643239373,"version":"4.5.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The expanding therapeutic armamentarium for IgA nephropathy (IgAN) has brought to the forefront a key strategic dilemma: whether to intervene simultaneously on IgAN-specific pathogenic mechanisms and the downstream, non-specific consequences of nephron loss, or to follow a sequential, stepwise approach in which therapies are added only as residual risk becomes evident. This debate article contrasts these philosophies. Proponents of early, combined treatment, in line with KDIGO 2025 guidance, argue that the traditional paradigm of first maximizing \u2018supportive\u2019 care\u2014renin\u2013angiotensin system blockade, strict blood pressure and sodium control, and more recently SGLT2 inhibitors and mineralocorticoid receptor antagonists\u2014before initiating immunosuppressive or other disease-directed agents embeds harmful delay. They emphasize that IgAN is driven by continuous immune activity, with ongoing production of pathogenic IgA, immune complex formation, complement activation, and glomerular injury that proceeds even when proteinuria is hemodynamically reduced. Once a critical threshold of nephron loss is crossed, self-perpetuating hyperfiltration, fibrosis, and microvascular rarefaction limit reversibility. Advocates of a more sequential strategy highlight heterogeneity in disease course, the risks and costs of polypharmacy, and the need for individualized escalation based on dynamic risk assessment. Together, the opposing yet complementary viewpoints underscore that future algorithms will likely integrate baseline risk stratification, evolving biomarkers of immune activity and chronic damage, and patient preferences to balance early, comprehensive disease control against overtreatment and toxicity in IgAN.<\/jats:p>","DOI":"10.1093\/ckj\/sfag035","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T12:40:20Z","timestamp":1770468020000},"source":"Crossref","is-referenced-by-count":1,"title":["Simultaneous or sequential treatment of IgA nephropathy - specific disease drivers and non-specific consequences of nephron loss?"],"prefix":"10.1093","volume":"19","author":[{"given":"Jonathan","family":"Barratt","sequence":"first","affiliation":[{"name":"University of Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Floege","sequence":"additional","affiliation":[{"name":"RWTH Aachen University Hospital Department of Nephrology and Department of Cardiology, , Aachen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-1996","authenticated-orcid":false,"given":"Carmine","family":"Zoccali","sequence":"additional","affiliation":[{"name":"Institute of Biology and Molecular Genetics (BIOGEM) , Ariano Irpino ,","place":["Italy"]},{"name":"Renal Research Institute , New York ,","place":["USA"]},{"name":"IPNET, Via Torrione 42, 89125 , Reggio Calabria ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lafayette","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University , Stanford, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"2026052110520022700_bib1","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.kint.2025.04.003","article-title":"Executive summary of the KDIGO 2025 Clinical Practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV)","volume":"108","author":"Floege","year":"2025","journal-title":"Kidney Int"},{"key":"2026052110520022700_bib2","doi-asserted-by":"publisher","first-page":"ii47","DOI":"10.1093\/ckj\/sfad201","article-title":"Expanding options of supportive care in IgA nephropathy","volume":"16","author":"Maixnerova","year":"2023","journal-title":"Clin Kidney J"},{"key":"2026052110520022700_bib3","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41572-023-00476-9","article-title":"IgA nephropathy","volume":"9","author":"Stamellou","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"2026052110520022700_bib4","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.kint.2025.01.014","article-title":"Treatment of patients with IgA nephropathy: a call for a new paradigm","volume":"107","author":"Floege","year":"2025","journal-title":"Kidney Int"},{"key":"2026052110520022700_bib5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.2215\/CJN.0000000000000135","article-title":"Long-term outcomes in IgA nephropathy","volume":"18","author":"Pitcher","year":"2023","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026052110520022700_bib6","doi-asserted-by":"publisher","first-page":"sfae394","DOI":"10.1093\/ckj\/sfae394","article-title":"First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors","volume":"18","author":"Schanz","year":"2025","journal-title":"Clin Kidney J"},{"key":"2026052110520022700_bib7","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2147\/CEOR.S389456","article-title":"Cost-effectiveness analysis of Nefecon versus best supportive care for people with immunoglobulin A nephropathy (IgAN) in the United States","volume":"15","author":"Ramjee","year":"2023","journal-title":"Clinicoecon Outcomes Res"},{"key":"2026052110520022700_bib8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12882-021-02353-7","article-title":"Immunoglobulin A nephropathy and ischemic heart disease: a nationwide population-based cohort study","volume":"22","author":"Jarrick","year":"2021","journal-title":"BMC Nephrol"},{"key":"2026052110520022700_bib9","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1001\/jamainternmed.2019.0600","article-title":"Evaluating a new international risk-prediction tool in IgA nephropathy","volume":"179","author":"Barbour","year":"2019","journal-title":"JAMA Intern. 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