Clinical significance of mesangial IgM deposition in patients with IgA nephropathy

Glomerular immunoglobulin G deposition in patients with immunoglobulin A nephropathy (IgAN) has been shown to be associated with adverse renal outcomes. Clinical significance of mesangial immunoglobulin M (IgM) deposition in these patients remains to be proven. One hundred patients who had a diagnosis of IgAN between 2001 and 2017 were enrolled. Patients were divided into two groups based on mesangial IgM deposition status. Groups were compared for demographic, clinical, and pathologic variables at baseline and in follow-up. Cox regression analysis was performed to evaluate the effect of mesangial IgM positivity on renal survival. IgM-positive group included 51% of participants. Baseline demographic and clinical parameters were not significantly different between groups. Mesangial IgM deposition was significantly associated with a higher segmental sclerosis score (p = 0.008). At last visit, median serum creatinine was higher (p = 0.021) and eGFR was lower (p = 0.006) in IgM-positive group. Nineteen (19%) of all patients reached the combined primary outcome which includes doubling in serum creatinine or evolution to ESRD. Cumulative renal survival was lower (p = 0.001) and resistant disease was more frequent in IgM-positive group (p = 0.026). Renal survival at 15 years was 94.2% and 59.7% in IgM-negative and IgM-positive groups, respectively (p = 0.006). Time-averaged proteinuria (HR 2.9; 95% CI 1.9–4.5; p < 0.001) and mesangial IgM deposition (HR, 13.2; 95% CI 1.9–93.1; p = 0.01) were found to be independent predictors of unfavorable renal outcomes. In conclusion, we demonstrated that mesangial IgM deposition independently associated with worse renal outcomes in patients with IgA nephropathy.