PROTECTing the kidneys in IgA nephropathy

Treatment of IgA nephropathy has traditionally focused on immunosuppression to address the pathogenesis of the disease and kidney-protective strategies, such as modulation of the renin–angiotensin system to prevent disease progression; 40–50% of patients nonetheless develop kidney failure within 10–15 years of diagnosis. 1 Pitcher D Braddon F Hendry B et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023; 18: 727-738 Crossref PubMed Scopus (12) Google Scholar The relatively long duration for progression to kidney failure has been a barrier for executing trials of novel therapies for IgA nephropathy. Identification of earlier surrogate markers of beneficial treatment effect—proteinuria reduction and rate of kidney function decline—has improved trial feasibility and contributed to unprecedented industry interest in drug development in IgA nephropathy. 2 Thompson A Carroll K L AI 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 (99) Google Scholar , 3 Inker LA Mondal H Greene T et al. Early change in urine protein as a surrogate end point in studies of IgA nephropathy: an individual-patient meta-analysis. Am J Kidney Dis. 2016; 68: 392-401 Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar , 4 Inker LA Heerspink HJL Tighiouart H et al. Association of treatment effects on early change in urine protein and treatment effects on GFR slope in IgA nephropathy: an individual participant meta-analysis. Am J Kidney Dis. 2021; 78: 340-349 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar The PROTECT study was designed to address a need for targeted, non-toxic therapies to improve the outcome of patients with IgA nephropathy, a leading cause of kidney failure. 5 Heerspink HJL Radhakrishnan J Alpers CE et al. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet. 2023; 401: 1584-1594 Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trialOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function. Full-Text PDF