Expected and verified benefits from old and new corticosteroid treatments in IgA nephropathy: from trials in adults to new IPNA-KDIGO guidelines

IgA nephropathy in children has a potential progression risk over decades of adult life. For this reason, pediatric nephrologists tend to treat the disease from the onset, aiming at halting the pathogenetic processes, based on expert opinion and general confidence with steroids for the lack of large pediatric controlled studies. Glucocorticosteroids are widely used, although without full comprehension of the fine molecular effects on IgAN, mostly based on trials performed in adults. In this review, a critical analysis of adult data is provided for extrapolating information useful for children, with a parallel evaluation of the results of the TESTING Trial, employing oral methylprednisolone, and of the NEFIgArd Trial, using enteric release budesonide. Patients’ characteristics and the scheme of the two studies are surprisingly similar: Nefecon and methylprednisolone showed 40–50% proteinuria reduction from baseline, with a fast effect of methylprednisolone (3–6 months) and a similar effect on renal function decline. Large genome-wide studies, above-risk alleles, also discovered risk loci targetable by multiple drugs particularly those involved in the modulation of the mucosal immunity priming of B-cells toward the production of galactose deficient IgA1 (Gd-IgA1). The new KDIGO 2024 guidelines under public review in recent months will lower the proteinuria threshold for treatment to 0.5 mg/mg and consider the value of Nefecon in reducing the levels of Gd-IgAI1. The choice between old and new corticosteroids in treating children with IgAN is approaching. In the near future, the genetic data, complemented by blood and urine biomarkers, could be included in tools to guide therapeutic choices and monitoring.