Half a century of IgA nephropathy: achievements, frustrations and challenges

Keywords: IgA nephropathy, biomarkers, immune system, proteinuria, gut, therapeutic approach

Abstract

IgA nephropathy is the most common glomerulonephritis worldwide. This disease has a tremendous economic impact because renal replacement therapy is expensive and hard-to-reach. It also represents a social problem because children and young adults in their second and third decades of life are affected by the IgA nephropathy, and it is the most active period of human life with highest work productivity. Many retrospective studies have shown that 40% of biopsy-proven IgA nephropathy patients develop end-stage kidney disease in 20 years after their biopsy disease.

The biomarker research in IgA nephropathy has experienced a major splash in recent years with great number of scientific reports. Individual biomarkers often lack sensitivity and specificity with impairment of disease specificity as a consequence. The review describes a novel approach based on a panel of biomarkers for pathogenic process of IgA nephropathy. Integration of genetic, clinical, and bioinformatics data sets could optimize the specific value of each biomarker in a multimarker panel. This is a inspirational and promising approach for precision medicine and personalized therapy in IgA nephropathy.

Half a century into the original description of IgA nephropathy, there is still no specific therapy for this condition Although the scarcity in treatment advances could be related to the disease’s complex pathogenesis. The evolution of different therapeutic approaches is reviewed over time and resulted in the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Glomerulonephritis that presently is being updated, and provide collation of recent data on various forms of immunosuppressive agents. Existing approaches to treatment of IgA nephropathy are described with focus primarily on innovative therapeutic strategies currently being evaluated in IgA nephropathy that were not discussed in the 2012 Kidney Disease Improving Global Outcomes Clinical Practice Guidelines.

Downloads

Download data is not yet available.

References

Soares MFS, Roberts ISD. Histologic Classification of IgA Nephropathy: Past, Present, and Future. Sem in Nephrol. 2018; 38(5):477-84. doi: 10.1016/j.semnephrol.2018.05.017

Schena FP, Cox SN. Biomarkers and Precision Medicine in IgA Nephropathy. Sem in Nephrol. 2018;38(5):521-30. doi:10.1016/j.semnephrol.2018.05.022.

Berger J, Hinglais N. Intercapillary deposits of IgA-IgG. J Urol Nephrol (Paris). 1968;74:69-95 [in French].

Schena FP, Nistor I. Epidemiology of IgA Nephropathy: A Global Perspective. Semin in Nephrol. 2018; 38(5):435-42. doi:10.1016/j.semnephrol.2018.05.013

Leung, JC, Chan, LY, Saleem, MA, Mathieson, PW, Tang, SC, and Lai, KN. Combined blockade of angiotensin II and prorenin receptors ameliorates podocytic apoptosis induced by IgA-activated mesangial cells. Apoptosis. 2015;20:907-20. doi: 10.1007/s10495-015-1117-1

Tang SCW. An Overview of IgA Nephropathy: 50 Years On. Seminars in nephrology. 2018;38(5):433-34. doi: 10.1016/j.semnephrol.2018.05.024

Coppo R, Troyanov S, Bellur S et al. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int. 2014; 86: 828-36. doi:  [10.1038/ki.2014.63]

Kawamura T, Yoshimura M, Miyazaki Y et al. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy. Nephrol Dial Transplant. 2014; 29:1546-53. doi: 10.1093/ndt/gfu020

Hoshimo Y, Kaga T, Abe Y, Endo M, Wakai S, Tsuchiya K et al. Renal biopsy findings and clinical indicators of patients with hematuria without overt proteinuria. Clin Exp Nephrol. 2015;19:918-24. doi:  [10.1007/s10157-015-1090-6]

 Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997;29:829-42.

Lee SMK. Prognostic indicators of progressive renal disease in IgA nephropathy: emergence of a new histologic grading system. Am J Kidney Dis. 1997; 29: 953-58

 Barbour SJ, Espino-Hernandez G, Reich H et al. Oxford derivation, North-American validation and VALIGA consortia. The MEST score provides earlier risk prediction in IgA nephropathy. Kidney Int. 2016;89:167-175. doi: 10.1038/ki.2015.322

 Lv J, Zhang H, Wong MG, et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017;318(5):432-42. doi:  [10.1001/jama.2017.9362]

Trimarchi H, Barratt J, Cattran DC et al. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017; 91: 1014-21. doi: 10.1016/j.kint.2017.02.003.

 Alamartine E, Sauron C, Laurent B, et al. The use of Oxford classification of IgA nephropathy to predict renal survival. Clin J Am Soc Nephrol. 2011;6:2384-88. doi:  [10.2215/CJN.01170211]

 Cook T, Roberts IS, Feehally J, Barratt J. Evidence-based classification of glomerular pathology. Kidney Int. 2014;86:1059. doi: 10.1038/ki.2014.248

 Glassock RJ. Glomerular disease: targeted steroid therapy for IgA nephropathy. Nat Rev Nephrol. 2017;13:390-92. doi: 10.1038/nrneph.2017.65

 Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;3:69-75. doi:  [10.1097/MOG.0000000000000139]

 Evenepoel P, Poesen R, and Meijers B. The gut-kidney axis. Pediatr Nephrol. 2017; 32: 2005-14. doi: 10.1007/s00467-016-3527-x

Forbes JD, Van Domselaar G, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol. 2016;7:1081. doi:  [10.3389/fmicb.2016.01081]

 Fellström BC, Barratt J, Cook H, Coppo R, Feehally J, de Fijter JW et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017;389:2117-27. doi.org/10.1016/S0140-6736(17)30550-0

Yanagawa H, Suzuki H, Suzuki Y, Kiryluk K, Gharavi AG, Matsuoka K et al. A panel of serum biomarkers differentiates IgA nephropathy from other renal diseases. PLoS One. 2014; 9: e98081.  doi.org/10.1371/journal.pone.0098081 Available from https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098081

 Berthoux F, Suzuki H, Mohey H, Maillard N, Mariat C, Novak J et al. Prognostic value of serum biomarkers of autoimmunity for recurrence of IgA nephropathy after kidney transplantation. J Am Soc Nephrol. 2017; 28: 1943-50. doi:  [10.1681/ASN.2016060670]

 Barratt J, Tang SCW. Treatment of IgA Nephropathy: Evolution Over Half a Century. Semin in Nephrol. 2018 September; 38(5):531-40. doi: 10.1016/j.semnephrol.2018.05.023.

 Liu LL, Wang LN, Jiang Y et al. Tonsillectomy for IgA nephropathy: a meta-analysis. Am J Kidney Dis. 2015;65:80-7. doi: 10.1053/j.ajkd.2014.06.036

 Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines–application to the individual patient. Kidney Int. 2012;82:840-56. doi: 10.1038/ki.2012.280

 Hou JH, Le WB, Chen N et al. Mycophenolate mofetil combined with prednisone versus full-dose prednisone in IgA nephropathy with active proliferative lesions: a randomized controlled trial. Am J Kidney Dis. 2017;69:788-95. doi: 10.1053/j.ajkd.2016.11.027

 Rauen T, Fitzner C, Eitner F et al. Effects of two immunosuppressive treatment protocols for IgA nephropathy. J Am Soc Nephrol. 2018;29:317-25. doi: 10.1681/ASN.2017060713

 Glassock RJ. Moderator's view: treatment of IgA nephropathy-getting comfortable with uncertainty. Nephrol Dial Transplant. 2016;31:1776-80. doi: 10.1093/ndt/gfw284

 Sherlock ME, MacDonald JK, Griffiths AM, Steinhart AH, Seow CH. Oral budesonide for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2015;10:CD007698 doi: 10.1002/14651858.CD007698.pub3 Available from https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007698.pub3/full

Ring T, Pedersen BB, Salkus G, Goodship, TH. Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum? Clin Kidney J. 2015; 8: 489-91. doi:  [10.1093/ckj/sfv076]

 Lafayette RA, Canetta PA, Rovin BH et al. A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol. 2017;28:1306-13. doi: 10.1681/ASN.2016060640  

Gao R, Wu W, Wen Y, Li X. Hydroxychloroquine alleviates persistent proteinuria in IgA nephropathy. Int Urol Nephrol. 2017;49:1233-41. doi: 10.1007/s11255-017-1574-2


Abstract views: 360
PDF Downloads: 15599
Published
2018-09-30
How to Cite
Lapchynska, I. (2018). Half a century of IgA nephropathy: achievements, frustrations and challenges. Ukrainian Journal of Nephrology and Dialysis, (3(59), 50-60. https://doi.org/10.31450/ukrjnd.3(59).2018.08