Immunoglobulin A-nephropathy: modern view of the problem and treatment options

The presented review discusses the mechanisms of development, the issues of diagnosis and the possibility of therapy for IgAnephropathy. IgA-nephropathy is an immunocomplex lesion of the glomeruli, characterized by the predominant deposition of immunoglobulin A in the mesangia. IgA-nephropathy meets all the criteria of an immune-inflammatory disease and is a common type of chronic glomerulonephritis in all countries of the world. Changes in the molecular structure of IgA, disturbances in the processes of its glycosylation and polymerization, as well as the deposition of polymeric IgAl in the glomerular mesangium underlie the pathogenesis of the disease. There are primary, secondary, sporadic and familial forms of IgA-nephropathy. According to the clinical course, the classical, asymptomatic and atypical variants of the course of IgA-nephropathy are distinguished. Clinical manifestations of IgA-nephropathy consist of macro- or microhematuria, proteinuria and arterial hypertension. The final diagnosis is made with nephrobiopsy. Differential diagnosis is made between urolithiasis, renal tumor, secondary nephropathy, Alport syndrome, disease of thin basement membranes. In the treatment of IgA-nephropathy, blockers of the renin-angiotensin-aldosterone system are used; a positive effect of tonsillectomy is possible. Glucocorticoids and cytostatics are recommended for nephrotic proteinuria, rapid disease progression, or signs of renal activity on morphological examination. The prognosis is good, although approximately 40% of patients develop dialysis-dependent end-stage renal disease after 15 to 20 years. 

1. Shilov E. M., Bobkova I. N., Kolina I. B., Kamishova E. S. Klinicheskie rekomendatsii po diagnostike i lecheniyu IgA-nefropatii [Clinical recommendations for diagnostics and treatment of IgA-nephropathy] // Nefrologiya. 2015; 19 (6): 83-92. (In Russian).

2. Berger J., Hinglais N. Intercapillary deposits of IgAIgG. Paris // J Urol Nephrol. 1968; 74: 694–695.

3. Shilov E. M., Tareeva I. E., Ivanov A. A. Techenie i prognoz mezangioproliferativnogo glomerulonefrita [Progress and prognosis of mesangial proliferative glomerulonephritis] // Terapevtichesky arkhiv. 2002; 6: 11–18 (in Russian).

4. De Menezes Neves P. D. M., Pinheiro R. B. B., Dias C. B. et al. Renal Outcomes in Brazilian Patients with Immunoglobulin A Nephropathy and Cellular Crescentic Lesions // Kidney Blood Press Res. 2020; 45: 431–441. https://doi.org/10.1159/000507251.

5. Woo K. T., Chan C. M., Lim C. et al. A Global Evolutionary Trend of the Frequency of Primary Glomerulonephritis over the Past Four Decades // Kidney Diseases. 2019; 5: 4: 247–258. https://doi.org/10.1159/000500142.

6. Sallustio F., Curci C., Di Leo V. et al. A New Vision of IgA Nephropathy: The Missing Link // International Journal of Molecular Sciences. 2020; 21 (1): 189. https://doi.org/10.3390/ijms21010189.

7. Jaryal A., Vikrant S. Clinical Profile and Outcome of IgA Nephropathy from a Tertiary Care Hospital in North India // Journal of The Association of Physicians of India. 2020; 68: 20.

8. Dobronravov V. A., Muzhetskaya T. O., Lin D. I., Kochoyan Z. S. Immunoglobulin A-nefropatiya v rossiiskoi populyatsii: kliniko-morfologicheskaya prezentatsiya i otdalennyi prognoz [Immunoglobulin A-nephropathy in Russian population: clinical and morphological presentation and long-term prognosis] // Nefrologiya. 2019; 23 (6): 45–60. https://doi.org/10.36485/1561-6274-2019-236-45-60 (in Russian).

9. Evangelista-Carrillo L. A., Monteón-Ramos F. Recurrencia de enfermedades glomerulares en trasplante renal // Revista Mexicana de Trasplantes. 2020; 9: S1: 86–90. https://dx.doi.org/10.35366/93492.

10. Nikolaev A. Yu., Malkoch A. V. IgA-nefropatiya pri sistemnykh zabolevaniyakh, persistiruyuschikh infektsiyakh, khronicheskikh boleznyakh pecheni [IgA-nephropathy in systemic diseases, persistent infections, chronic liver diseases: literature review] // Lechaschi Vrach. 2018; 1: 48-51. (In Russian).

11. Choi J. Y., Yu C. H., Jung H. Y. et al. A case of rapidly progressive IgA nephropathy in a patient with exacerbation of Crohn’s disease // BMC nephrology. 2012; 13 (1): 84.

12. Singh A. K. B., Jeyaruban A. S., Wilson G. J., Ranganathan D. Adalimumab-induced IgA nephropathy // BMJ Case Reports CP. 2019; 12 (3): e226442. http://dx.doi.org/10.1136/bcr-2018-226442.

13. Champtiaux N., Lioté F., El Karoui K. et al. Spondyloarthritis-associated IgA nephropathy // Kidney International Reports. 2020; 5 (6): 813– 820. https://doi.org/10.1016/j.ekir.2020.03.012.

14. Yılmaz F., Keleş M. Familial mediterranean fever and immunoglobulin A nephropathy: A case report and review of the literature // Saudi Journal of Kidney Diseases and Transplantation. 2020; 31 (2): 537–541. https://doi.org/10. 4103/1319-2442.284033.

15. Fu D., Zhong Z., Shi D. et al. ST6GAL1 polymorphisms influence susceptibility and progression of IgA nephropathy in a Chinese Han population // Immunobiology. 2020; 151973. https://doi.org/10.1016/j.imbio.2020.151973.

16. Tao J., Mariani L., Eddy S. et al. JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA Nephropathy // Clinical Journal of the American Society of Nephrology. 2020. https://doi.org/10.2215/CJN.11010919.

17. Makita Y., Suzuki H., Kano T. et al. TLR9 activation induces aberrant IgA glycosylation via APRIL-and IL-6 – mediated pathways in IgA nephropathy // Kidney International. 2020; 97 (2): 340–349. https://doi.org/10.1016/j.kint.2019.08.022.

18. Mizerska-Wasiak M., Gajewski Ł., Cichoń-Kawa K. et al. Serum GDIgA1 levels in children with IgA nephropathy and Henoch-Schönlein nephritis // Central European Journal of Immunology. 2018; 43 (2): 162–167.

19. Irabu H., Shimizu M., Kaneko S. et al. Clinical Significance of Serum Galactose-Deficient IgA1 Level in Children with IgA Nephropathy // Journal of Immunology Research. 2020; 2020. https://doi.org/10.1155/2020/4284379.

20. Abbad L., Monteiro R. C., Berthelot L. Food antigens and Transglutaminase 2 in IgA nephropathy: Molecular links between gut and kidney // Molecular Immunology. 2020; 121: 1–6. https://doi.org/10.1016/j.molimm.2020.02.019.

21. Klimovich V. B., Samoilovich M. P. Immunoglobulin A (IgA) i ego retseptory [Immunoglobulin A (IgA) and its receptors] // Meditsinskaya immunologiya. 2006; 8 (4): 483–500. https://doi.org/10.15789/1563-0625-2006-4-483-500 (in Russian).

22. Kumar N., Arthur C. P., Ciferri C., Matsumoto M. L. Structure of the secretory immunoglobulin A core // Science. 2020; 367 (6481): 1008–1014. https://doi.org/10.1126/science.aaz5807.

23. Bobart S. A., Alexander M. P., Shawwa K. et al. The association of microhematuria with mesangial hypercellularity, endocapillary hypercellularity, crescent score and renal outcomes in immunoglobulin A nephropathy // Nephrology Dialysis Transplantation. 2019. https://doi. org/10.1093/ndt/gfz267. 24. Moran S. M., Cattran D. C. Immunoglobulin A nephropathy: prognosis and management. 2019; 34 (7): 1099–1101. https://doi.org/10.1093/ndt/gfy312.

24. Hizon M. A. P., LiM R. S., Tan Z. K. et al. Epidemiology of glomerulonephritis in Southeast Asia: The gn-special (glomerulonephritis – singaporephilippines epidemiology cohorts in adults) study // Kidney International Reports. 2019; 4: S1– S437. https://doi.org/10.1016/j.ekir.2019.05.408.

25. Zakharova I. N., Osmanov I. M., Machneva E. B. et al. Tsilindry v moche: chto neobkhodimo znat pediatru I nefrologu [Urinary cylinders: what pediatrician and nephrologist need to know] // Meditsinsky Sovet. 2019; 11: 118–125. DOI: https://doi.org/10.21518/2079-701X-2019-11-118-125. (In Russian).

26. Trachtman H. Tonsillectomy for the Management of Immunoglobulin A Nephropathy // JAMA Netw Open. 2019; 2 (5): e194755. https://doi.org/10.1001/jamanetworkopen.2019.4755.

27. Watanabe H., Goto S., Mori H. et al. Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy // Nephrol Dial Transplant. 2017; 32 (12): 2072–2079. https://doi.org/10.1093/ndt/gfw343.

28. Cao Y., Qiao M., Tian Z. et al. Comparative analyses of subgingival microbiome in chronic periodontitis patients with and without IgA nephropathy by high throughput 16S rRNA sequencing // Cell Physiol Biochem. 2018; 47 (2): 774–783. https://doi.org/10.1159/000490029.

29. Russo E., Verzola D., Salvidio G. et al. Longterm blood pressure behavior and progression to end-stage renal disease in patients with immunoglobulin A nephropathy: a singlecenter observational study in Italy // Journal of Hypertension. 2020; 38 (5): 925–935. https://doi.org/10.1097/HJH.0000000000002354.

30. Tan J., Dong L., Ye D. et al. The efficacy and safety of immunosuppressive therapies in the treatment of IgA nephropathy: A network meta-analysis // Scientific reports. 2020; 10 (1): 1–11.