Dan Wu1, Xueqian Li1, Xingfeng Yao2, Nan Zhang2, Lei Lei1, Hejia Zhang1, Mengmeng Tang1, Jie Ni1, Chen Ling1, Zhi Chen1, Xiangmei Chen3, Xiaorong Liu4. 1. Department of Nephrology, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China. 2. Department of Pathology, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China. 3. Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Diseases, 28th Fuxing Road, Beijing, 100853, China. 4. Department of Nephrology, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China. lxrbch@sina.com.
Abstract
BACKGROUND: Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children. METHODS: We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90 mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period. RESULTS: A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25 months (interquartile range 18-36 months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029). CONCLUSION: Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.
BACKGROUND: Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children. METHODS: We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90 mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period. RESULTS: A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25 months (interquartile range 18-36 months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029). CONCLUSION:Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.
Entities:
Keywords:
Children; Complement; IgA nephropathy; Oxford classification; Predictive marker
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