Heyan Wu1,2, Xiang Fang1, Zhengkun Xia3, Chunlin Gao4, Yingchao Peng1, Xiaojie Li1, Pei Zhang1, Qianghuining Kuang1, Ren Wang5, Meiqiu Wang1. 1. Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China. 2. Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China. 3. Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China. njxzk@126.com. 4. Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China. shuangmu34@163.com. 5. Department of Pediatrics, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Abstract
BACKGROUND: The long-term renal outcome for IgA nephropathy (IgAN) in large cohorts of children remains unclear. IgAN is a progressive disease, to explore novel biomarkers is necessary for predicting the disease activity and progression of IgAN. In addition, there is a hot debate on when to treat with immunosuppression in children. We aimed to confirm the long-term renal survival, find some undetected risk factors and investigate when to treat with immunosuppression can benefit for renal outcome in Chinese children. METHODS: 1243 Children with IgAN were enrolled and a follow-up of at least 1 year after a biopsy from 2000 to 2017. Long-term renal survival, undetected risk factors and the renal survival of immunosuppressive and non-immunosuppressive therapy were evaluated. The primary endpoint of the study was a combined outcome of either ≥50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) or death. RESULTS: The median follow-up time were 86.8 months (interquartile range 54.7-140.2 months). The 5-, 10- and 15-year renal survival rates were 95.3%, 90.3% and 84%, respectively. Cox multivariate regression and Kaplan-Meier analysis showed that hypertension, hyperuricemia, high 24 h urine protein (24 h-UP) levels, lower initial eGFR, high urine C3 levels, high retinol-binding protein (RBP) levels, segmental glomerulosclerosis (S) and tubular atrophy and interstitial fibrosis (T) were associated with renal outcome. The statistically significant predictive perfect power for renal outcome was RBP ≥ 0.7µg/ml (AUC = 0.899, sensitivity = 84.00%, specificity = 86.00%), 24 h-UP ≥ 1 g/24 h (AUC = 0.722, sensitivity = 84.20%, specificity = 52.70%), eGFR < 60 ml/min/1.73 m2 (AUC = 0.718, sensitivity = 81.30%, specificity = 39.20%) and S1 lesion (AUC = 0.703, sensitivity = 75.50%, specificity = 65.10%).Children with urinary RBP ≥ 0.7µg/ml were associated with a 2.513-fold risk than patients with urinary RBP < 0.7µg/ml (P = 0.003). Our study suggested that immunosuppressive therapy may reduce the risk of progression in IgAN children had both eGFR > 50 ml/min/1.73 m2 and proteinuria of at least 1 g/day. CONCLUSIONS: This is the first report that the 15-year renal survival rate of children with IgAN in China was 84%. At the same time, this is the first study to reveal that urinary RBP ≥ 0.7µg/ml may indicate a poor renal outcome. In addition, this study supports immunosuppressive therapy for IgAN children had both proteinuria ≥1 g/day and initial eGFR > 50 ml/min/1.73m2.
BACKGROUND: The long-term renal outcome for IgA nephropathy (IgAN) in large cohorts of children remains unclear. IgAN is a progressive disease, to explore novel biomarkers is necessary for predicting the disease activity and progression of IgAN. In addition, there is a hot debate on when to treat with immunosuppression in children. We aimed to confirm the long-term renal survival, find some undetected risk factors and investigate when to treat with immunosuppression can benefit for renal outcome in Chinese children. METHODS: 1243 Children with IgAN were enrolled and a follow-up of at least 1 year after a biopsy from 2000 to 2017. Long-term renal survival, undetected risk factors and the renal survival of immunosuppressive and non-immunosuppressive therapy were evaluated. The primary endpoint of the study was a combined outcome of either ≥50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) or death. RESULTS: The median follow-up time were 86.8 months (interquartile range 54.7-140.2 months). The 5-, 10- and 15-year renal survival rates were 95.3%, 90.3% and 84%, respectively. Cox multivariate regression and Kaplan-Meier analysis showed that hypertension, hyperuricemia, high 24 h urine protein (24 h-UP) levels, lower initial eGFR, high urine C3 levels, high retinol-binding protein (RBP) levels, segmental glomerulosclerosis (S) and tubular atrophy and interstitial fibrosis (T) were associated with renal outcome. The statistically significant predictive perfect power for renal outcome was RBP ≥ 0.7µg/ml (AUC = 0.899, sensitivity = 84.00%, specificity = 86.00%), 24 h-UP ≥ 1 g/24 h (AUC = 0.722, sensitivity = 84.20%, specificity = 52.70%), eGFR < 60 ml/min/1.73 m2 (AUC = 0.718, sensitivity = 81.30%, specificity = 39.20%) and S1 lesion (AUC = 0.703, sensitivity = 75.50%, specificity = 65.10%).Children with urinary RBP ≥ 0.7µg/ml were associated with a 2.513-fold risk than patients with urinary RBP < 0.7µg/ml (P = 0.003). Our study suggested that immunosuppressive therapy may reduce the risk of progression in IgANchildren had both eGFR > 50 ml/min/1.73 m2 and proteinuria of at least 1 g/day. CONCLUSIONS: This is the first report that the 15-year renal survival rate of children with IgAN in China was 84%. At the same time, this is the first study to reveal that urinary RBP ≥ 0.7µg/ml may indicate a poor renal outcome. In addition, this study supports immunosuppressive therapy for IgANchildren had both proteinuria ≥1 g/day and initial eGFR > 50 ml/min/1.73m2.
Entities:
Keywords:
Chinese children; IgA nephropathy; Long-term observation; Renal survival; Undetected risk factors
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