Predictors of glomerular IgA immunostaining patterns and disease progression in IgA nephropathy patients; a 13-year study of clinical and morphological features of renal biopsies

Introduction: IgA nephropathy (IgAN) is a common primary glomerulonephritis with highly heterogeneous clinical and histopathological features. The MEST-C scoring system has been developed to improve prognostic assessment but lacks elements related to immunostaining study. Objectives: This study aimed to investigate the association between the immunofluorescence (IF) deposits’ patterns of IgA (mesangiocapillary versus pure mesangial) with demographic, clinical, biochemical, and morphological parameters of MEST-C classification in IgAN patients. Patients and Methods: This retrospective, cross-sectional study was conducted on 268 biopsy-proven cases of IgAN from July 2009 to July 2022 at a single laboratory in Isfahan in Iran. The demographic, clinical, and laboratory data including age, gender, serum creatinine, and proteinuria were collected from the biopsy request forms. The morphological parameters of MEST-C classification and IF study patterns were collected from the biopsy reports. Results: The average age of all patients was 37.7 ± 13.47 years, with 67% being males. The mean serum creatinine and proteinuria levels were 1.43 mg/dL and 1730.94 mg/day, respectively. MEST-C score analysis revealed that 171 patients (63.8%) had mesangial expansion (M1), while 105 patients (39.2%) exhibited endocapillary hypercellularity (E1). Additionally, segmental glomerulosclerosis (S1) and tubular atrophy/interstitial fibrosis (T1 and T2) was observed in 160 biopsy samples (59.7%). Moreover, crescent (C) formation was noted in 76 (28.4%) of biopsies. Data analysis using univariate logistic regression demonstrated that E, T, and C on morphology, complement C3, IgG, IgM deposits on IF, and the total MEST score were all associated with an increased risk for mesangiocapillary deposits of IgA. However, using the multivariate method, the results indicated that only the total MEST score (OR: 2.4), presence of crescent (OR: 3.22), presence of endocapillary hypercellularity (OR: 4.86), tubular atrophy/interstitial fibrosis grade II (OR: 34.4), and IgG deposition (OR: 3.37) were independent risk factors for mesangiocapillary deposits of IgA. Conclusion: The total MEST score is significantly higher in mesangiocapillary patterns. Furthermore, the presence of E1, T2, and C1-2 morphological parameters of the updated Oxford classification in renal biopsies are independent risk factors for IgA mesangiocapillary deposits. Hyperactivation of immunoglobulins and the complement system appears to contribute to mesangial-capillary proliferation.