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).