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Explore a catalyst behind IgA nephropathy

IgAN pathogenesis is driven by a 4-hit autoimmune cascade—think outside the kidneys^1,2

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The pathogenesis of IgA Nephropathy

https://player.vimeo.com/video/1079783838

MOD Video

See the cascade in motion

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The APRIL (A PRoliferation-Inducing Ligand) cytokine is a key driver of IgAN pathogenesis and plays a role in the initiation of the 4-hit cascade.^1-3

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Pre-Hit 1:

APRIL is one of the factors that triggers the 4-hit pathogenic cascade.³

Hit 1:

Production of Gd-IgA1.^1,2

Hit 2:

Persistently elevated levels of Gd-IgA1 trigger autoantibody production.^1,2

Hit 3:

The proliferated Gd-IgA1 binds to the newly generated autoantibodies to form immune complexes.^1,2

Hit 4:

The pathogenic immune complexes are deposited into glomerular tissue, activating an inflammatory immune response.^1,2

Role of APRIL

APRIL is a sustaining factor in the 4-hit pathogenic cascade, advancing IgAN disease progression.^1,2

About APRIL

IgAN burden and management

With IgAN, the timeline of kidney disease progression is often aggressive.⁴

IgAN burden

Resources

Enhancing awareness of IgAN is critical to improving diagnosis and management.

IgAN Resources

APRIL=A PRoliferation-Inducing Ligand; Gd-IgA1=galactose-deficient immunoglobulin A1; IgA=immunoglobulin A; IgAN=immunoglobulin A nephropathy; MOD=mechanism of disease.

References: 1. Suzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22(10):1795-1803. 2. Gutiérrez E, Carvaca-Fontán F, Luzardo L, Morales E, Alonso M, Praga M. A personalized update on IgA nephropathy: a new vision and new future challenges. Nephron. 2020;144(11):555-571. 3. Cheung CK, Barratt J, Lafayette R, et al. Targeting APRIL in the treatment of glomerular diseases. Kidney Int. 2024. doi:10.1016/j.kint.2024.08.012. 4. Pitcher D, Braddon F, Hendry B, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18(6):727-738. 5. Cheung CK, Barratt J, Liew A, Zhang H, Tesař V, Lafayette R. The role of BAFF and APRIL in lgA nephrology: pathogenic mechanisms and targeted therapies. Front Nephrol. 2024;3:134‌6769. 6. Caster DJ, Abner CW, Walker PD, et al. Clinicopathological characteristics of adult IgA nephropathy in the United States. Kidney Int Rep. 2023;8(9):1792-1800. 7. Rajasekaran A, Julian BA, Rizk DV. IgA nephropathy: an interesting autoimmune kidney disease. Am J Med Sci. 2021;361(2):176-194. 8. Lai KN, Tang SC, Schena FP, et al. IgA nephropathy. Nat Rev Dis Primers. 2016;2:16001. 9. Cattran DC, Floege J, Coppo R. Evaluating progression risk in patients with immunoglobulin A nephropathy. Kidney Int Rep. 2023;8(12):2515‌-2528. 10. Donadio JV, Bergstralh EJ, Grande JP, Rademcher DM. Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy. Nephrol Dial Transplant. 2002;17(7):1197-1203. 11. Reich HN, Troyanov S, Scholey JW, Cattran DC; Toronto Glomerulonephritis Registry. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007;18(12):3177‌-3183. 12. Coppo R, D’Arrigo G, Tripepi G, et al. Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update. Nephrol Dial Transplant. 2020;35(6):1002-1009.