Results
Demographic and clinical characteristics according to the degree of glomerular C3deposition at the time of biopsy
According to the scheme, 136 patients were enrolled and followed up 105 months after renal biopsy. The cohort of 136 patients with IgAN was stratified according to C3 deposition on biopsy specimens as either glomerular C3low IgAN (C3 score of 1+ and 2+ on immunofluorescent staining, n=102) or glomerular C3high IgAN (C3 score of 3+ on immunofluorescent staining, n = 34) (Figure 1). We further discovered that patients in C3high group suffered from higher percentage of glomerular IgA, IgM and IgG deposition (Figure 2).
The baseline characteristics of the study population was presented with no significant differences between glomerular C3lowgroup and glomerular C3high group in terms of sex, age, serum C3, blood pressure, erythrocyturia, serum uric acid, serum albumin or blood urea nitrogen (Table 1). At time of biopsy for the overall cohort (n = 136), the median degree of proteinuria was 1.0 g/24h and the mean level of serum creatinine was 77.6 (μmol/L). Patients with C3high IgAN compared to C3low IgAN had a higher serum creatinine (C3high: 89.4 vs. C3low: 74.9 μmol/L, P = 0.008), and a higher degree of proteinuria (C3high: 1.6 vs. C3low: 0.9 g/24h, P <0.001). The estimated glomerular filtration rate (76.0 vs. 100.8 ml/min per1.73 m2, P=0.001) was lower in C3high group (Table 1).
IgAN patients in C3high group presented with severe pathological lesions and suffered more interstitial inflammatory cell infiltration
In consistent with the higher proteinuria level and lower eGFR, IgAN patients in C3high group presented with a higher percentage of mesangial hypercellularity (56.9% versus 27.5%; P=0.003), segmental glomerulosclerosis (41.2% versus 19.6%; P=0.012), severe tubular atrophy/interstitial fibrosis (T2, 44.1% versus 17.6%; P=0. 002), crescents (52.9% versus 33.3%; P=0.042), severe arterial wall thickening (29.4% versus 12.7%; P=0.034), severe arterial hyalinosis (47.1% versus 21.6%; P=0.004) (Table 2). The two groups showed no difference in endocapillary hypercellularity or global glomerulosclerosis. Representative photographs of light microscopy (PAS and Masson) and electron microscopy of the two groups were shown in Figure 3.
To understand inflammatory cell infiltration in these patients, we detected CD68+ macrophages, CD4+, CD8+ T lymphocytes, tryptase+ mast cells, CD20+ B lymphocytes and CD1c+ myeloid dendritic cells in renal biopsies. We found that patients in C3high group presented with intense interstitial macrophages and T lymphocytes infiltration than that in C3low group (Figure 4). Renal tissues were revealed more interstitial tryptase+ mast cells infiltration in the C3high group in renal biopsies of IgAN patients rather than CD20+ B lymphocytes and CD1c+ myeloid dendritic cells (Supplementary figure).