Clinical features
Clinical features at biopsy and during follow-up were shown in Table 1. In this retrospective cohort study, a total of 1243 Chinese children with IgAN who underwent renal biopsy in Jinling Hospital were enrolled. At the time of renal biopsy,the mean age of children was 14±4years, with male (68%) predominance. The average value of MBP was 89±16 mmHg, the initial eGFR was 102±20 ml/min per 1.73m2, and initial proteinuria was 0.6 (interquartile ranges, 0.3–1.4) g/day per 1.73m2. The median duration of follow-up was 7.2 (4.6–11.7) years, with 171 children reaching the primary outcome (ESRD, n= 82;≥50% eGFR decline, n= 89). During the follow-up period, 70% of children were treated with RASB, 45% were treated with GC, and 19% received GC combined other immunosuppressive drugs.
Pathological Findings
Pathological findings were shown in Table 2. According to Oxford classification,29% of the children showed M1, 35% showed E1, 37% showed S1, 23% showed T1, 4.3% showed T2, 44 % showed C1 and 4.6% showed C2. The distribution of the percentage of crescents observed in every child was shown in Fig.1. Of 48.6% children with any cellular/ fibrocellular crescents, 28% had crescents in<10% of glomeruli, whereas 9.4% had a fraction of glomeruli with crescents one tenth or more, 6.6% had a fraction of glomeruli with crescents one sixth or more, and only 4.6% had a fraction of glomeruli with crescents one fourth or more. The percentage of immunoglobulins deposited only in the mesangial region was 68%, while 32% of immunoglobulins were deposited in both the mesangial and capillary loop regions. 25% of children showed positive glomerular staining for IgG, 44% showed positive glomerular staining for IgM,84% showed positive glomerular staining for C3, and 1.1% showed positive glomerular staining for C4.The immunofluorescence intensity of IgA was between 1+ and 3+, including 5.6% of 1+, 13% of 2+ and 81% of 3+.
Effects of Different Kidney Biopsy Time on the Variables in Oxford Classification
The median time (12 months) of onset to renal biopsy was selected as the cut-off point to analyze the effect of biopsy time on variables in the Oxford classification From Table3. It showed that when the time of onset to renal biopsy was less than 12 months, the patient's lesions were milder, dominated by S0(c2=354.5, P<0.001), T0 (c2=323.3, P<0.001), and C0(c2=437.6, P<0.001). On the contrary, when the time of onset to renal biopsy was longer than 12 months, the lesions were corrected mainly by S1,T1-2 and C1-2. With regard to E and M lesions, there was no significant difference in time from onset to renal biopsy within available data.
Associations Between Clinical And Histologic Variables
Linear regression analysis of Oxford classification with the most robust indicators for estimating renal decline (eGFR, MAP and proteinuria) was performed to explore the correlation between Oxford classification and clinical indicators. As shown in Table 4, Children with S, T and C lesions were associated with a reduced initial eGFR at the time of biopsy. All histological lesions (M1, E1, S1, T1–2, and C1-2) were associated individually with a higher initial proteinuria at the time of biopsy. All histological lesions except S1 were associated with higher initial MAP at the time of biopsy.
Renal Survival IgAN Children According To Oxford Classification
As presented in Fig.2, the Kaplan-Meier analyses revealed that lesion S (Log-Rank, χ2=14.796, P<0.001; Fig.2C) and T (χ2=48.976, P<0.001; Fig.2D) were each associated with renal survival. However, lesions M (χ2=1.459, P=0.177, Fig.2A), E (χ2=2.399, P=0.331, Fig.2B) and C (χ2=6.218, P=0.054, Fig.2E) were not associated with renal outcome.
Associations Between Pathologic Features and Renal Outcome
The associations between pathological features and renal outcomes were analyzed in a COX regression model (Table 5). With univariate COX regression model, renal outcome from a combined event were both associated significantly with lesions S (HR3.5, 95%CI 2.3~5.3, P<0.001),T (HR 2.6, 95%CI 2.1~3.3, P<0.001) and C(HR 2.1, 95%CI 1.5~2.8, P=0.045). However, the lesion of M(HR 1.8, 95%CI 1.3~2.3, P= 0.115), and E(HR 1.4, 95%CI 0.9~2.1, P=0.326) were not associated with renal outcome. In the multivariate COX regression model, when adjusted for initial clinical data set (eGFR, MAP, and proteinuria),only S(HR2.7, 95%CI1.8~4.2, P<0.001) and T (HR6.6, 95%CI 3.9~11.3, P<0.001) lesions remained as independent predictors of renal outcome.
Predictive value of lesion M,E and C between immunosuppressive and without immunosuppressive groups
We further assessed the predictive value of lesion (M,E and C) in children who received no immunosuppressive treatment to assess their natural predictive value. Children with crescent who didn’t receive immunosuppressive therapy experienced worse survival from the combined event (Fig.3E), but this difference disappeared after received immunosuppression (Fig.3F).The predictive value of lesion M and E were not changed by adding immunosuppressive treatment (Fig.3A-D).