{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:49Z","timestamp":1785434929195,"version":"3.56.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009077","name":"Otsuka America Pharmaceutical, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009077","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Immunoglobulin A nephropathy (IgAN) is a primary glomerulonephritis characterized by IgA-dominant or co-dominant mesangial immune deposits seen on routine immunofluorescence staining of kidney biopsy tissue. Approximately 40% of patients develop kidney failure within 10\u00a0years of diagnosis. IgAN has a variable clinical presentation ranging from the characteristic synpharyngitic macroscopic haematuria to persistent microscopic haematuria with or without proteinuria, often accompanied by reduced kidney function if disease recognition is delayed. Recent data from the UK National Registry of Rare Kidney Diseases underscores the need for early diagnosis, prompt management and stringent proteinuria reduction to avoid kidney failure throughout an affected patient's lifetime. Until recently, there had been a paucity of disease-specific treatment options. However, elucidation of IgAN pathophysiology, data from genome-wide association studies and the Kidney Health Initiative (that identified change in proteinuria as an acceptable surrogate endpoint for clinical trials) have revolutionized the IgAN therapeutic landscape. Beyond systemic steroids, we now have a targeted-release formulation of budesonide, which is thought to act primarily on the gut-associated lymphoid tissue to reduce the production of pathogenic galactose-deficient IgA1. It was the first US Food and Drug Administration\u2013approved IgAN treatment. B cells and plasma cells that play a central role in the production of galactose-deficient IgA1 and its autoantibody are being targeted using B cell activating factor and a proliferation-inducing ligand cytokine inhibitors as well as CD38-positive plasma cell\u2013depleting drugs. Recognizing the role of the alternative complement cascade in IgAN-mediated glomerular injury and inflammation identified new potential therapeutic targets and ultimately led to the approval of a complement factor B inhibitor, iptacopan. Other non-immunosuppressive treatments are also available or being investigated with the aim of reducing proteinuria and slowing chronic kidney disease progression, including endothelin A receptor antagonists. In this article we review current clinical trials in IgAN and critically examine what they teach us about IgAN pathogenesis.<\/jats:p>","DOI":"10.1093\/ndt\/gfaf144","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:37:38Z","timestamp":1753961858000},"page":"i35-i45","source":"Crossref","is-referenced-by-count":5,"title":["What do clinical trials teach us about the pathophysiology of human IgA nephropathy?"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6155-1555","authenticated-orcid":false,"given":"Raghunandan","family":"Konda","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Rajasekaran","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]},{"name":"Renal Medicine Associates , Albuquerque, NM ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-2811","authenticated-orcid":false,"given":"Dana V","family":"Rizk","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham , Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"2026022304271280100_bib1","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.amjms.2020.10.003","article-title":"IgA nephropathy: an interesting autoimmune kidney disease","volume":"361","author":"Rajasekaran","year":"2021","journal-title":"Am J Med 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