We can go further in non-immunosuppressive treatment of IgA nephropathy

More than 50 years after the description of IgA nephropathy as Berger's disease, 20–40% of affected individuals still progress to end-stage kidney disease within 10–20 years of diagnosis, which negatively affects life expectancy. 1 Jarrick S Lundberg S Welander A et al. Mortality in IgA nephropathy: a nationwide population-based cohort study. J Am Soc Nephrol. 2019; 30: 866-876 Crossref PubMed Scopus (44) Google Scholar Glucocorticoids can halt progression in some patients but rarely prevent the final development of end-stage kidney disease, and side-effects limit the intensity and duration of treatment. 2 Tesar V Troyanov S Bellur S et al. Corticosteroids in IgA nephropathy: a retrospective analysis from the VALIGA Study. J Am Soc Nephrol. 2015; 26: 2248-2258 Crossref PubMed Scopus (154) Google Scholar , 3 Lv J Wong MG Hladunewich MA et al. Effect of oral methylprednisolone on decline in kidney function or kidney failure in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA. 2022; 327: 1888-1898 Crossref PubMed Scopus (31) Google Scholar A challenge for the assessment of treatment effects in IgA nephropathy is the usual long time-course to traditional outcomes of doubling of serum creatinine, end-stage kidney disease, or death. A breakthrough has been the Kidney Health Initiative (KHI) project that, on the basis of published trials, evaluated and confirmed the predictive value of proteinuria reduction on this combined outcome. This resulted in the KHI recommendation of proteinuria reduction as a surrogate efficacy endpoint for accelerated approval of new therapies for IgA nephropathy by the US Food and Drug Administration (FDA). 4 Thompson A Carroll K A Inker L et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin J Am Soc Nephrol. 2019; 14: 469-481 Crossref PubMed Scopus (77) Google Scholar Since then, an increasing number of new therapies are under investigation for IgA nephropathy. Recently, targeted-release budesonide for a course of 9 months has been approved as the first specific immunosuppressive treatment in IgA nephropathy. 5 Fellström BC Barratt J Cook H 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: 2117-2127 Summary Full Text Full Text PDF PubMed Scopus (203) Google Scholar Sustained proteinuria reduction is essential for the prognosis of IgA nephropathy, 6 Canney M Barbour SJ Zheng Y et al. Quantifying duration of proteinuria remission and association with clinical outcome in IgA nephropathy. J Am Soc Nephrol. 2021; 32: 436-447 Crossref PubMed Scopus (17) Google Scholar which highlights the need for additional non-toxic treatments that can be given in the long term and at different disease stages. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trialOnce-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Full-Text PDF