Explore a catalyst behind IgA nephropathy

IgAN pathogenesis is driven by a 4-hit autoimmune cascade—think outside the kidneys1,2

MOD video

See the cascade in motion

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

Hit 0

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.