Research Viewpoints IgA Nephropathy: An Update

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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 DOI 10.1159/000509997

IgA nephropathy (IgAN) is a common disorder that progresses to kidney failure in about 30% of patients followed for 2 decades or more. It also commonly recurs in transplanted kidneys. It can only be diagnosed by kidney biopsy. The pathology, pathogenesis, and prognosis are fairly well understood, but etiology and treatment are not.

Gutierrez and colleagues from Spain have prepared a masterful review and update of this clinicopathological entity. This “blog” cannot really do justice to their high-quality review. It is timely, authoritative, and comprehensive. It clearly shows how much we have learned, but also identifies the many remaining unresolved questions about this enigmatic disease. I will focus here on only a few issues.

The comments on the growing understanding of the role of complement activation (alternative and lectin pathways) were of particular interest on account of their therapeutic implications. The new information on hematuria as a prognostic factor is long overdue. The contribution of the OXFORD-MEST-C classification of pathology is now widely recognized as having significant prognostic value, but its incorporation into treatment decisions and clinical trials has been slow, and until recently very inadequate. New validated tools combining clinical features with kidney pathology are now emerging, and once randomized clinical trials (RCTs) have evaluated their utility in treatment decision making, advances in our understanding of treatment regimens will likely occur.

One of the main challenges in IgAN is how to move beyond non-disease-specific therapies, such as renin-angiotensin system inhibition, which are only effective in about 50% of cases. The role of steroids and the optimum dose and duration of such therapy remains uncertain. The results of the low-dose oral methylprednisolone trial (TESTING-II) and the trial of specially formulated budesonide (NEFIGARD) will help to inform us concerning the rational use of steroids in IgAN. Hydroxychloroquine is becoming a mainstay of treatment, but this is based on only limited RCT data. The use of chemical or biological immunosuppression in IgAN remains uncertain (MMF might be effective in Asians with IgAN). Many novel drugs are currently being studied, including those that affect the complement system. These studies are well outlined in the review.

Altogether, the future appears bright for the resolution of the numerous uncertainties underlying prognosis and therapy in IgAN. The era of disease non-specific therapy may be drawing to a close as the data supporting a tailored (personalized) disease-specific approach to treatment of IgAN emerge from ongoing RCTs. This review certainly provides a degree of optimism that progressive CKD can be altered in many cases of IgAN in the not too distant future.