Mesangial IgM deposition predicts renal outcome in patients with IgA nephropathy: a multicenter, observational study

Abstract

Mesangial IgM deposition is found in patients with immunoglobulin A nephropathy (IgAN). This study aims to investigate the relationships between mesangial IgM deposition and disease progression in IgAN patients. A total of 1239 patients with biopsy-proven primary IgAN were enrolled in this multicenter, observational study between January 2013 and August 2017. According to the degree of IgM deposition, 1239 patients were divided into three groups: Grade 0 (no or trace; n = 713, 57.55%), Grade 1 (mild; n = 414, 33.41%), Grades 2 + 3 (moderate and marked; n = 112, 9.04%). Using a 1:1 propensity score matching (PSM) method identifying age, gender and treatment modality to minimize confounding factors, 1042 matched patients (out of 1239) with different degrees of IgM deposition were enrolled to evaluate the severity of baseline clinicopathological features and renal outcome: Grade 0 (n = 521, 50.00%), Grade 1 (n = 409, 39.25%), Grades 2 + 3 (n = 112, 10.75%). Kaplan-Meier and Cox proportional hazards analyses were performed to determine whether different degrees of mesangial IgM deposition are associated with varying renal outcomes in IgAN. During a mean follow-up of 48.90 ± 23.86 and 49.01 ± 23.73 months, before and after adjusting for propensity scores, respectively, the rate of complete remission (CR) was progressively lower with increased IgM deposition in both unmatched (63.39%, 46.14%, 45.54%) and matched cohort (61.80%, 46.45%, 45.54%), whereas the proportion of patients progressing to end-stage renal disease (ESRD) showed reverse correlation (P < 0.001). Kaplan-Meier analysis indicated negative correlation between the intensity of mesangial IgM deposits and cumulative renal survival (all P < 0.05). Moreover, Cox regression analysis revealed that the degree of mesangial IgM deposition predicted renal outcome independent of MESTC score and clinical variables in the unmatched (Grade 1, HR, 1.59; 95% CI, 1.11-2.29; P = 0.01; Grades 2 + 3, HR, 1.69; 95% CI, 1.02-2.08; P = 0.04) and matched cohort (Grade 1, HR, 1.84; 95% CI, 1.19-2.85; P = 0.01; Grades 2 + 3, HR, 1.91; 95% CI, 1.01-3.24; P = 0.04). Mesangial IgM deposition is associated with histological activity, clinical severity and renal outcome and is an independent risk factor for poor renal prognosis in IgAN. TRIAL REGISTRATION: TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074 .

Keywords: Clinicopathological features; IgM deposition; Immunoglobulin A nephropathy; Propensity score matching (PSM); Renal outcomes.