Serum steroid metabolome pattern is associated with the response to prednisolone therapy of male patients with IgA nephropathy

IgA nephropathy (IgAN) is characterized by the deposition of galactose-deficient IgA1 (Gd-IgA1)-containing immune complexes into kidney mesangium leading to glomerular inflammation and injury. In patients with active IgAN non-responding to renin-angiotensin system blocking drugs (RASBs), corticosteroids (CSs) are recommended. Although CSs reduce significantly serum levels of Gd-IgA1, IgA-containing immune complexes, and proteinuria, their clinical effect in IgAN is variable. Because IgAN patients exhibit abnormal serum concentration of several endogenous steroid metabolites, some of which exhibit immuno-protective/regulating functions, we analyzed serum metabolites which could predict clinical response to CS therapy. This prospective study was performed in 18 male IgAN patients to identify potential biomarkers for personalized CS therapy. Using LC-MS set of 85 steroid metabolites was tested in the sera of IgAN patients before CS therapy initiation to identify those with statistically different level in patients clinically responding and not-responding to CS therapy. Responders were those subjects whose proteinuria decrease below 1 g/day after 6-12 months of CS therapy. Statistical analysis revealed significant and clinically relevant differences in the steroid profile between responders and non-responders. The key and consistent finding across the entire analysis is that non-responder status is associated with globally higher level of almost all analyzed steroids. The response of IgAN patients to CS therapy could be predicted by measuring the serum levels of selected steroid metabolites to receive steroid profile. Observation needs to be confirmed in large cohorts of various ethnic origin to be applicable for routine clinical protocols.