#1643 Long-term cohort study on the prognostic impact of mesangial IgM deposition in IgA nephropathy

Abstract Background and Aims The prognostic importance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) is not well-understood and is subject to ongoing debate. Moreover, mesangial IgM deposition could also reflect lectin complement system activation. Thus, our study sought to examine the long-term prognostic implications of mesangial IgM deposition in a cohort of IgAN patients. Method We carried out a single-center retrospective study involving 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. The follow-up period extended until the onset of end-stage kidney disease (ESKD), death, or January 2021, with a median duration of 7 years. An independent pathologist assessed the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions using a detailed protocol. Results In our study, 70% (n = 65) of patients exhibited mesangial IgM-positive deposits, while 30% (n = 28) did not show IgM deposition. Both IgM-positive and IgM-negative groups were comparable in terms of age (40 vs 43 years, p 0.6), sex (69 vs 64% male, p 0.6), arterial hypertension prevalence (69 vs 64%, p 0.6), Charlson comorbidity scores (2 vs 1, p 0.3), kidney function (eGFR 46 vs 55 mL/min, p 0.1 and proteinuria 1.2 vs 0.7, p 0.1), pathology findings (including Oxford MEST-C score, IgG and C3 immune deposition), TEM analysis, as well as in their treatment with renin-angiotensin-system inhibitors (63 vs 71%, p 0.4) and immunosuppression (39 vs 39%, p 0.9), and mortality rates (11 vs 7%, p 0.5). However, a notable difference emerged in the progression to ESKD, with 37% of IgM-positive patients advancing to this stage compared to only 11% of those in the IgM-negative group (p 0.01). The multivariate Cox proportional hazards regression analysis identified lower eGFR (HR 0.94, 95% CI: 0.92, 0.97), higher Oxford MEST-C score (HR 1.53, 95% CI: 1.16, 2.02), and mesangial IgM deposits (HR 4.75, 95% CI: 1.25, 17.99) as independent predictors of reduced kidney survival. Conclusion Our study identifies mesangial IgM deposition as a potential risk factor for ESKD in advanced IgAN, suggesting a need for further investigation. Future research should explore whether IgM's activation of the lectin complement pathway and resultant damage, as proven in ischemia-reperfusion injury models, are applicable to IgAN.