儿童原发性肾病综合征复发相关因素分析及风险预测模型构建

doi:10.12372/jcp.2023.23e0209

摘要/Abstract

摘要：

目的探讨儿童原发性肾病综合征（PNS）复发的相关因素及构建风险预测模型。方法回顾性分析2013年1月至2020年1月入院诊断为PNS患儿的临床资料。随访患儿复发情况，分析影响患儿复发与频复发的危险因素，建立预测模型并进行效能评估。结果纳入392例PNS患儿，男192例、女200例，中位年龄8.0（7.0~10.0）岁。392例患儿中复发266例（67.9%），复发患儿中频复发124例（46.6%）。多因素logistic回归分析发现，发病年龄增大是PNS患儿复发的独立保护因素（P<0.05），临床分型为肾炎型、尿蛋白转阴时间延长是独立危险因素（P<0.05）。回归方程：Logit（P）=-14.27-1.85×（发病年龄）+0.65×（临床分型）+1.71×（尿蛋白转阴时间），模型预测PNS患儿复发的ROC曲线下面积（AUC）为0.90（95%CI：0.88~0.93）。依从性不良、家长PNS疾病了解情况差是PNS患儿频复发的独立危险因素（P<0.05），初次复发时间延长是独立保护因素（P<0.05）。回归方程：Logit（P）=-0.52+0.54×（依从性）+0.51×（家长PNS疾病了解情况）-0.09×（初次复发时间），模型预测PNS患儿频复发的AUC为0.89（95%CI：0.86~0.92）。结论 PNS患儿总体复发率高，与发病年龄、肾炎型、尿蛋白转阴时间密切相关，而患儿依从性、家长PNS疾病了解情况、初次复发时间与频复发相关，应给予针对性干预措施，降低患儿复发率。

关键词: 原发性肾病综合征, 复发, 频复发, 预测模型

Abstract:

Objective To explore the related factors of recurrence and to construct a risk prediction model in children with primary nephrotic syndrome (PNS). Methods The clinical data of children diagnosed with PNS from January 2013 to January 2020 were retrospectively analyzed. The recurrence of PNS children was followed up, the risk factors affecting recurrence and frequent recurrence were analyzed, the prediction model was established and its efficacy was evaluated. Results A total of 392 children with PNS (192 boys and 200 girls) were included and the median age was 8.0(7.0-10.0) years old. Among the 392 children, 266 (67.9%) had recurrence and 124 (46.6%) had frequent recurrence. Multivariate logistic regression analysis showed that the increase of onset age was an independent protective factor for the recurrence of PNS (P<0.05), and nephritis type and the prolonged time of urinary protein turning negative were independent risk factors for the recurrence of PNS (P<0.05). The regression equation was as follows: Logit (P)= -14.27-1.85× (onset age) +0.65× (clinical type) +1.71× (negative conversion time of urine protein), and the area under the receiver operating characteristic (ROC) curve (AUC) by the model was 0.90 (95%CI: 0.88-0.93). Poor compliance and poor parents' understanding of PNS were independent risk factors for frequent recurrence of PNS (P<0.05), and prolonged first recurrence time was an independent protective factor for frequent recurrence of PNS (P<0.05). The regression equation was as follows: Logit (P)= -0.52+0.54×(compliance)+0.51× (parental cognition to PNS) -0.09 × (first recurrence time), and the AUC predicting frequent recurrence in children with PNS was 0.89 (95%CI: 0.86-0.92). Conclusions The overall recurrence rate of PNS children is high, which is closely related to the age of onset, nephritis type and negative conversion time of urine protein, while children's compliance, parental cognition to PNS and first recurrence time are related to frequent recurrence. Targeted intervention measures should be given to reduce the recurrence rate of children.

Key words: primary nephrotic syndrome, recurrence, frequent recurrence, prediction model

郑志方, 敬小青, 刘利蕊, 王文涛. 儿童原发性肾病综合征复发相关因素分析及风险预测模型构建[J]. 临床儿科杂志, 2023, 41(12): 914-918.

ZHENG Zhifang, JING Xiaoqing, LIU Lirui, WANG Wentao. Related factors analysis of recurrence and risk prediction model construction for primary nephrotic syndrome in children[J]. Journal of Clinical Pediatrics, 2023, 41(12): 914-918.

图/表 3

表1

PNS患儿复发/频复发单因素分析"

临床资料	复发组 (n=266)	未复发组 (n=126)	统计量	P	频复发组 (n=124)	非频复发组 (n=142)	统计量	P
年龄($\bar{x} \pm s$)/岁	8.5±1.0	8.6±0.9	t=0.69	0.491	8.5±0.9	8.6±1.0	t=0.61	0.545
性别(男/女)	128/138	64/62	χ²=0.25	0.621	61/63	67/75	χ²=0.11	0.743
居住地为城市[n(%)]	142(53.4)	72(57.1)	χ²=0.49	0.485	64(51.6)	78(54.9)	χ²=0.29	0.589
发病年龄($\bar{x} \pm s$)/岁	3.4±0.5	3.8±0.6	t=7.48	<0.001	3.4±0.5	3.5±0.4	t=1.03	0.304
临床分型[n(%)]			χ²=12.22	<0.001			χ²=1.06	0.304
单纯型	152(57.1)	95(75.4)			75(60.5)	77(54.2)
肾炎型	114(42.9)	31(24.6)			49(39.5)	65(45.8)
依从性良好[n(%)]	215(80.8)	112(88.9)	χ²=4.02	0.045	93(75.0)	122(85.9)	χ²=5.09	0.024
家长PNS疾病了解[n(%)]			χ²=13.45	0.001			χ²=6.41	0.041
好	34(12.8)	35(27.8)			11(8.9)	23(16.2)
一般	98(36.8)	41(32.5)			41(33.1)	57(40.1)
差	134(50.4)	50(39.7)			72(58.1)	62(43.7)
总蛋白($\bar{x} \pm s$)/mg·L^-1	39.8±4.5	40.5±5.0	t=1.42	0.157	39.6±4.3	40.0±4.9	t=0.87	0.388
白蛋白($\bar{x} \pm s$)/mg·L^-1	17.2±3.1	17.3±2.9	t=0.30	0.762	17.1±3.0	17.3±3.2	t=0.40	0.692
白细胞计数($\bar{x} \pm s$)/×10⁹·L^-1	9.2±1.5	9.4±1.2	t=1.02	0.307	9.2±1.7	9.3±1.4	t=0.32	0.752
CRP($\bar{x} \pm s$)/mg·L^-1	18.4±2.2	18.2±2.8	t=1.01	0.315	18.5±2.4	18.3±2.1	t=0.67	0.487
血肌酐($\bar{x} \pm s$)/μmol·L^-1	32.5±3.5	32.9±3.2	t=1.08	0.279	32.5±3.6	32.4±3.2	t=0.26	0.792
血尿素氮($\bar{x} \pm s$)/mmol·L^-1	4.5±0.8	4.5±0.7	t=0.24	0.808	4.6±0.8	4.5±0.8	t=0.14	0.886
总胆固醇($\bar{x} \pm s$)/mmol·L^-1	8.7±1.8	8.8±2.0	t=0.35	0.729	8.8±1.7	8.7±1.9	t=0.50	0.618
三酰甘油($\bar{x} \pm s$)/mmol·L^-1	3.2±0.7	3.1±0.6	t=0.99	0.321	3.1±0.7	3.2±0.7	t=0.24	0.809
IgA($\bar{x} \pm s$)/g·L^-1	1.3±0.3	1.2±0.4	t=0.79	0.428	1.3±0.4	1.3±0.3	t=0.96	0.338
IgM($\bar{x} \pm s$)/g·L^-1	1.5±0.3	2.0±0.5	t=12.57	<0.001	1.4±0.3	1.5±0.4	t=0.88	0.381
IgG($\bar{x} \pm s$)/g·L^-1	2.2±0.6	2.1±0.6	t=0.92	0.361	2.2±0.5	2.2±0.7	t=1.21	0.227
24 h尿蛋白定量($\bar{x} \pm s$)/ mg·kg^-1	128.1±15.7	107.3±11.9	t=13.19	<0.001	131.4±17.2	125.3±15.2	t=3.07	0.002
尿蛋白转阴时间($\bar{x} \pm s$)/d	14.7±2.5	8.4±1.4	t=26.32	<0.001	16.3±2.6	13.2±2.3	t=10.66	<0.001
输注白蛋白[n(%)]	50(18.8)	26(20.6)	χ²=0.19	0.667	22(17.7)	28(19.7)	χ²=0.17	0.681
初次复发时间($\bar{x} \pm s$)/月	-	-	-	-	5.5±1.2	9.9±2.3	t=10.66	<0.001

表1

表2

表3

参考文献 17

[1]	Boussetta A, Jaber C, Jellouli M, et al. Thromboembolic complications in children with primary nephrotic syndrome: A Tunisian series[J]. Tunis Med, 2022, 100(1): 33-36.
[2]	Chan EY, Yu ELM, Angeletti A, et al. Long-term efficacy and safety of repeated rituximab to maintain remission in idiopathic childhood nephrotic syndrome: an international study[J]. J Am Soc Nephrol, 2022, 33(6): 1193-1207. doi: 10.1681/ASN.2021111472 pmid: 35354600
[3]	耿海云, 陈朝英, 涂娟, 等. 不同方案泼尼松治疗儿童原发性肾病综合征的疗效及复发危险因素分析[J]. 中国当代儿科杂志, 2022, 24(8): 853-857.
[4]	刘钧菲, 刘翠华, 厉洪江, 等. 小儿原发性肾病综合征复发的危险因素logistic回归分析[J]. 中国实用医刊, 2019, 46(22): 13-16.
[5]	中华医学会儿科学分会肾脏病学组. 儿童常见肾脏疾病诊治循证指南(一): 激素敏感、复发/依赖肾病综合征诊治循证指南(试行)[J]. 中华儿科杂志, 2009, 47(3): 167-170.
[6]	何振济, 陈碧, 李辉, 等. 中文版Morisky用药依从性问卷在肾病综合征患儿中的信效度评价及应用[J]. 儿科药学杂志, 2022, 28(6): 25-29.
[7]	Bello-Marquez DC, Nieto-Rios JF, Serna-Higuita LM, et al. Nephrotic syndrome associated with primary atypical hemolytic uremic syndrome[J]. J Bras Nefrol, 2021, 43(3): 440-444. doi: 10.1590/2175-8239-JBN-2020-0050 pmid: 32779691
[8]	Funatogawa T, Narita Y, Tamura A, et al. Use of mycophenolate mofetil in patients with pediatric and adult primary nephrotic syndrome: information from a Japanese hospital claims database[J]. Clin Exp Nephrol, 2022, 26(10): 1005-1013. doi: 10.1007/s10157-022-02233-w pmid: 35579722
[9]	Weber LT, Tönshoff B, Grenda R, et al. Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome[J]. Pediatr Transplant, 2021, 25(3): e13955. doi: 10.1111/petr.v25.3
[10]	Ismail G, Obrișcă B, Jurubiță R, et al. Inherited risk factors of thromboembolic events in patients with primary nephrotic syndrome[J]. Medicina (Kaunas), 2020, 56(5): 242.
[11]	曹杏, 牛文忠, 石新慧, 等. 原发性肾病综合征患儿复发危险因素及预后分析[J]. 新乡医学院学报, 2020, 37(12): 1164-1167.
[12]	刘翠华, 田明, 李玉柳, 等. 激素敏感型肾病综合征患儿复发的预测因素[J]. 中华实用儿科临床杂志, 2017, 32(22): 1744-1746.
[13]	丁峰, 赵爱学. PCT、hs-CRP与Cys-C检测在PNS患儿中的诊断价值探讨[J]. 检验医学与临床, 2021, 18(2): 264-266.
[14]	Dossier C, Delbet JD, Boyer O, et al. Five-year outcome of children with idiopathic nephrotic syndrome: the NEPHROVIR population-based cohort study[J]. Pediatr Nephrol, 2019, 34(4): 671-678. doi: 10.1007/s00467-018-4149-2 pmid: 30552564
[15]	Hao S, Wu Y, Kang Y, et al. A single-center analysis of primary nephrotic syndrome with acute pancreatitis in children[J]. Medicine (Baltimore), 2020, 99(27): e21056. doi: 10.1097/MD.0000000000021056
[16]	Dakshayani B, Lakshmanna M, Premalatha R. Predictors of frequent relapsing and steroid-dependent nephrotic syndrome in children[J]. Turk Pediatri Ars, 2018, 53(1): 24-30. doi: 10.5152/TurkPediatriArs.
[17]	刘钧菲, 刘翠华, 厉洪江, 等. 儿童原发性肾病综合征频繁复发的相关因素分析[J]. 中国实用医刊, 2019, 46(17): 20-22.

因素	偏回归系数	标准误	χ²值	OR(95%CI)	P
发病年龄	-1.85	0.49	13.96	0.16(0.06~0.42)	<0.001
临床分型为肾炎	0.65	0.32	4.14	1.91(1.02~3.55)	0.042
依从性为良好	-0.17	0.66	0.07	0.84(0.23~3.08)	0.794
家长PNS疾病了解情况为差	0.19	0.35	5.34	1.20(0.60~2.41)	0.602
IgM	-0.01	0.05	5.34	0.99(0.90~1.10)	0.878
24h尿蛋白定量	0.10	0.09	5.34	1.11(0.93~1.31)	0.242
尿蛋白转阴时间	1.71	0.21	5.34	5.52(3.67~8.30)	<0.001
常量	-14.27	3.50	16.62	－	<0.001

因素	偏回归系数	标准误	χ²值	OR(95%CI)	P
依从性不良	0.54	0.23	5.65	1.71(1.10~2.66)	0.018
家长PNS疾病了解情况差	0.51	0.22	5.34	1.66(1.08~2.55)	0.021
24 h尿蛋白定量	0.88	0.50	2.99	2.36(0.89~6.23)	0.085
尿蛋白转阴时间	1.11	0.59	3.58	3.04(0.96~9.60)	0.059
初次复发时间	-0.09	0.05	4.36	0.91(0.83~0.99)	0.037
常量	-0.52	0.14	13.80	－	<0.001