Prognostic evaluation of pediatric IGA nephropathy using histological criteria including macrophage accumulation.

Background: There is no histological classification to predict disease flare in children with IgA nephropathy (IgAN). As macrophage (MQ) accumulation correlates with histological injury, we investigated new histological criteria to predict disease flare in pediatric IgAN. Method(s): A total of 73 children with biopsy proven IgAN underwent 2 years of steroid treatment followed by a protocol biopsy and then steroid tapering. The non-flare group successfully discontinued steroid treatment (N=61, 20.1+/-9.2 years at biopsy); the flare group exhibited increased proteinuria during the taper or cessation of treatment (N=12, 11.6+/-2.3 years at biopsy, p<0.05). Histological findings were evaluated using Oxford classification. Macrophage number and phenotype was assessed by immunofluorescence. Result(s): At first (diagnostic) biopsy, urine findings were comparable between the two groups, but the flare group had a higher serum IgA level (279+/-83 vs 214+/-87 mg/dL; P<0.05). Biopsies revealed no difference in mesangial proliferation (M), endocapillary proliferation (E), glomerulosclerosis (S), tubulointerstitial fibrosis (T), and crescent formation (C); however, the flare group had more total MQ (CD68+ cells) (p<0.05) and M1 MQ (CD68+CD86+ cells) (p<0.05). In addition, M1 MQ correlated with glomerular M, E, S, C lesions (all P<0.01). At second (protocol) biopsy, the flare group had more severe S (p<0.01) and T (p<0.05) lesions, and more glomerular and interstitial M2 MQ (CD68+CD163+ cells) (both p<0.01 vs non-flare group). In addition, M2 MQ correlated with S and T lesions (both p<0.001). ROC analyses revealed glomerular MQ number >2.2 cells at first biopsy could predict disease flare by sensitivity of 83%. Conclusion(s): MQ accumulation is a potential marker to predict disease flare in pediatric IgAN. The number of glomerular M1 MQ in active lesions at the first biopsy was related to flare occurrence, while glomerular and interstitial accumulation of M2 MQ in chronic lesions