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The Four-Hit Hypothesis & The Role Of APRIL In IgA Nephropathy

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The Four-Hit Hypothesis & The Role Of APRIL In IgA Nephropathy

Background:

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. It is characterized by the deposition of galactose-deficient IgA1 (Gd-IgA1) in the glomerular mesangium. The current understanding is that IgA nephropathy occurs due to a multi-hit mechanism, also known as the four-hit hypothesis. In addition, multiple observations support the role of APRIL (A Proliferation Inducing Ligand) in the pathogenesis of IgAN. Increased APRIL levels have been demonstrated in patients with IgAN and correlate with disease severity (proteinuria and eGFR) and increased expression of Gd-IgA1.1

Did You Know?

Therapeutic strategies inhibiting APRIL have the potential to limit IgA and, therefore, Gd-IgA1 production by autoimmune-associated plasma cells. 1

Why Attend This Webinar?

The goal of this webinar is to provide a detailed overview of the Four-Hit hypothesis as well as explain the role of APRIL in disease pathogenesis.  

What You Will Learn

The “four-hit hypothesis” of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. 1 Elevated serum levels of APRIL are observed in patients with IgAN and correlate with disease severity. 1

  References:

  1. Cheung CK et al. Nephrol. 2024; 3:1346769

Dana Rizk

Dana Rizk, MD

Professor of Medicine, Division of Nephrology Director of Clinical Trials, Division of Nephrology Medical Director, Clinical Trials Administrative Office

University of Alabama at Birmingham (UAB)*

Dr Dana Rizk is Tenured Professor of Medicine in the Division of Nephrology at the University of Alabama at Birmingham (UAB). She also serves as Director of Clinical Trials Research in the Division of Nephrology and as Medical Director for the Clinical Trials Administrative Office (part of the CCTS) at UAB.
She has a passion for education and has served as a member of the Clinical Competency Committees for the Internal Medicine as well as the Nephrology Programs. She is the recipient of several teaching awards.
Her clinical and research interests revolve around glomerular diseases and, in particular IgA Nephropathy (IgAN). She has served as the site principal investigator on many clinical trials and is part of several multi-disciplinary translational research projects focused on the role of biomarkers in the diagnosis and prognosis of IgAN. Her research efforts have resulted in more than 60 peer-reviewed publications in prestigious medical journals including the New England Journal of Medicine.

Sayna Norouzi

Sayna Norouzi, MD

Assistant professor Medicine and clinical nephrologist

Loma Linda University Medical Center*

Dr. Sayna Norouzi is an assistant professor Medicine and clinical nephrologist at Loma Linda university medical center. She completed her fellowship at Baylor College of Medicine in Houston, TX. She is the founder and director of glomerular diseases clinics in Loma Linda. She is also the co-director of online GlomCon Glomerular Diseases fellowship program. She has been selected as the educator of the year for three consecutive years and is a member of Alpha Omega Alpha medical honor society. She is a special interest in glomerular diseases and is involved in multiple research projects and clinical trials.

Hannah N. Lambert

Hannah N. Lambert, PharmD

Nephrology Medical Science Liaison
Otsuka Pharmaceutical Development & Commercialization, Inc.*

Hannah N. Lambert is a Medical Science Liaison at Otsuka Pharmaceutical Development and Commercialization. She earned her Doctor of Pharmacy and completed her clinical residency training at Xavier University of Louisiana College of Pharmacy in New Orleans, LA. Prior to joining Otsuka, Dr Lambert was a clinical pharmacist at Ochsner Health in Digital Medicine.

Marla Dallal

Marla Dallal, PharmD, RPH

Nephrology Senior Medical Science Liaison
Otsuka Pharmaceutical Development & Commercialization, Inc.*

Marla Dallal, PharmD, RPH is a Medical Science Liaison at Otsuka Pharmaceutical Development and Commercialization covering Southern California. She earned her Doctor of Pharmacy degree from the University of Southern California, School of Pharmacy in Los Angeles. While in pharmacy school, Dr Dallal pursued various clinical internships within the acute care and ambulatory care settings at Cedars-Sinai Medical Center and Kaiser Permanente. Prior to joining Otsuka, Dr Dallal held various positions within Medical Affairs at Amgen Inc covering the cardiometabolic and nephrology therapeutic areas. She also served as a preceptor at Amgen Inc, where she instructed pharmacy students on Advanced Pharmacy Practice rotations. She is currently licensed as a pharmacist in the state of California with the National Association Board of Pharmacy.

*Drs Dana Rizk and Sayna Norouzi are paid consultants of Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC). Drs Hannah Lambert and Marla Dallal are employees of OPDC.

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