IgA NEPHROPATHY MOD VIDEO

There may be a hidden culprit in IgA nephropathy: the gut

IgA nephropathy is thought to primarily originate in the ileum.1

See the role the gut plays in IgA nephropathy

~33%

of patients with IgA nephropathy will experience recurrence of the disease after kidney transplantation, indicating that the source of disease is extrarenal in origin.14,15

IgA NEPHROPATHY MECHANISM OF DISEASE

Human IgA exists as 2 subclasses, IgA1 and IgA2, and is further differentiated by site of production.1,16,17

iga nephropathy mucosal surfaces
While most serum IgA is synthesized in the bone marrow, the majority of overall IgA is produced at mucosal surfaces, including the gut1,16-18
Iga1 synthesis at mucosal surfaces
IgA1 produced in the mucosal tissue in the gut differs structurally from serum IgA1 and is specifically implicated in IgAN pathophysiology16,17

Mucosally synthesized IgA1 is relatively poorly galactosylated compared with systemically synthesized IgA116,17,19

peyers patches iga nephropathy if we cannot do
Peyer’s patches at mucosal surfaces in the ileum are a predominant source of galactose-deficient mucosal-type IgA11,16
immune complex iga nephropathy
When elevated levels of galactose-deficient mucosal-type IgA1 occur in the systemic circulation, autoantibodies bind to the hinge region of galactose-deficient IgA1, developing pathogenic immune complexes1,16,17,19
renal function deterioration iga nephropathy

These immune complexes containing pathogenic galactose-deficient IgA1 are deposited in the glomerular mesangium, which may eventually lead to deterioration in renal function17,19,20

A better understanding of the pathophysiology of IgA nephropathy may help provide targets for future treatment exploration

IgA=immunoglobulin A; IgAN=immunoglobulin A nephropathy; MOD=mechanism of disease.

References

1. Barratt J, Rovin BH, Cattran D, et al. Kidney Int Rep. 2020;5(20):1620-1624. doi:10.1016/j.ekir.2020.08.009

2. Hastings MC, Bursac Z, Julian BA, et al. Kidney Int Rep. 2017;3(1):99-104. doi:10.1016/j.ekir.2017.08.008

3. Schena FP. Am J Med. 1990;89(2):209-215. doi:10.1016/0002-9343(90)90300-3

4. Barratt J, Feehally J. Semin Nephrol. 2011;31(4):349-360. doi:10.1016/j.semnephrol.2011.06.006

5. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(suppl 2):259-274.

6. IgA Nephropathy Foundation of America, Inc. The Voice of the Patient: Externally Led Patient-Focused Drug Development Meeting on IgA Nephropathy. https://nkf.egnyte.com/dl/aHGCS6tPNM/?. Accessed August 18, 2021.

7. Penfold RS, Prendecki M, McAdoo S, Tam FWK. Int J Nephrol Renovasc Dis. 2018;11:137-148. doi:10.2147/IJNRD.S129227

8. Arroyo AH, Bomback AS, Butler B, et al. Clin Nephrol. 2015;84(3):145-155. doi:10.5414/CN108556

9.Rauen T, Wied S, Fitzner C, et al; for the STOP-IgAN Investigators. Kidney Int Supp.2020;98(4):1044-1052. doi:10.1016/j.kint.2020.04.046

10. Lafayette RA, Kelepouris E. Am J Nephrol. 2018;47(suppl 1):43-52. doi:10.1159/000481636

11. United States Renal Data System (USRDS). 2018 USRDS Annual Data Report. Vol 2. 2018; chap 9. Accessed April 7, 2021. https://usrds.org/media/1734/v2_c09_esrd_costs_18_usrds.pdf.

12. Golestaneh L, Alvarez PJ, Reaven N, et al. Am J Manag Care. 2017;23(10 Suppl):S163-S172.

13. Knoop T, Vikse BE, Svarstad E, Leh S, Reisæter AV, Bjørneklett R. Am J Kidney Dis. 2013;62(5):883-890. doi:10.1053/j.ajkd.2013.04.019

14. Ponticelli C, Glassock RJ. Clin J Am Soc Nephrol. 2010;5(12):2363-2372. doi:10.2215/CJN.06720810

15. Ponticelli C, Traversi L, Banfi G. Pediatr Transplantat. 2004:8(4):334-338. doi:10.1111/j.1399-3046.2004.00177.x

16. He J-W, Zhou X-J, Lv J-C, Zhang H. Theranostics. 2020;10(25):11462-11478. doi:10.7150/thno.49778

17. Cheung CK, Barratt J. 2020. Accessed April 7, 2021. https://www.uptodate.com/contents/pathogenesis-of-iga-nephropathy?search=pathogenesis%20of%20iga%20nephropathy&source=search_result&selectedTitle=1~126&usage_type=default&display_rank=1.

18. Reinholdt J, Husby S. In: Morteau O, ed. Oral Tolerance: The Response of the Intestinal Mucosa to Dietary Antigens. Landes Bioscience; 2003.

19. Floege J. J Am Soc Nephrol. 2019;30(7):1139-1141. doi:10.1681/ASN.2019040373

20. Wehbi B, Oblet C, Boyer F, et al. J Am Soc Nephrol. 2019;30(7):1238-1249. doi:10.1681/ASN.2018111089

21. Thompson A, Carroll K, Inker LA, et al. Clin J Am Soc Nephrol. 2019;14(3):469-481. doi:10.2215/CJN.08600718

22. Ibrahim A, Garg AX, Knoll GA, Akbari A, White CA. Am J Transplant. 2013;13(3):708-713. doi:10.1111/ajt.12050

23. Levey AS, Gansevoort RT, Coresh J, et al. Am J Kidney Dis. 2020;75(1):84-104. doi:10.1053/j.ajkd.2019.06.009

24. Goto M, Wakai K, Kawamura T, Ando M, Endoh M, Tomino Y. Nephrol Dial Transplant. 2009;24(10):3068-3074. doi:10.1093/ndt/gfp273

25. Brantsma AH, Atthobari J, Bakker SJ, de Zeeuw D, de Jong PE, Gansevoort RT. J Am Soc Nephrol. 2007;18(2):637-645. doi:10.1681/ASN.2006070738