肾小球C3沉积在儿童原发性膜性肾病中临床及预后意义

doi:10.12372/jcp.2022.22e0410

摘要/Abstract

摘要：

目的探索肾小球C3沉积对儿童原发性膜性肾病（PMN）患者临床、病理特征及预后的影响。方法回顾性分析2008年1月至2020年12月经肾穿刺诊断为PMN患儿的临床资料。根据肾脏病理免疫荧光染色肾小球C3染色强度患儿分为低强度组（LI组，C3+）和高强度组（HI组，C3++或+++），比较两组基线时临床病理特征及治疗转归，分析PMN患儿进展至终末期肾病（ESRD）的影响因素。结果共纳入213例患儿。LI组92例，HI组121例。与LI组相比，HI组年龄较大，24 h尿蛋白定量较高，血清白蛋白和eGFR水平较低，大量蛋白尿、IgG免疫荧光染色强度+++、IFTA分级为中度的比例较高，差异均有统计学意义（P<0.05）。LI组环磷酰胺的使用率高于HI组，差异有统计学意义（P<0.05）。经43.0（13.0~85.0）个月的随访，LI组92例患儿完成随访，1例进展至ESRD；68例转归为完全缓解（CR）和部分缓解（PR），24例为未缓解（NR）。经57.0（20.0~86.0）个月的随访，HI组121例患儿完成随访，5例进展至ESRD；86例转归为CR和PR，35例为NR。Log-rank检验发现，基线时eGFR≤90 mL·min^-1·1.73 m^-2，达ESRD时间较短，差异有统计学意义（P<0.05）。多因素Cox回归分析发现，基线时eGFR增加是延长患儿病情进展至ESRD的独立保护因素（HR=0.96，95%CI：0.929~0.987），而肾小球C3沉积与ESRD的发生无关。结论广泛的肾小球C3沉积不是儿童PMN患者肾衰竭的预测因子。

关键词: 原发性膜性肾病, C3沉积, 儿童

Abstract:

Objective To investigate the effect of glomerular C3 deposition on clinical and pathological features and prognosis of primary membranous nephropathy (PMN) in children. Methods The clinical data of children diagnosed with PMN by renal puncture from January 2008 to December 2020 were retrospectively analyzed. According to the intensity of glomerular C3 staining by immunofluorescence of renal pathology, the children were divided into low-intensity group (LI group, C3+) and high-intensity group (HI group, C3++ or +++). The clinicopathological features at baseline and treatment outcomes were compared between the two groups. The influencing factors of PMN progressing to end-stage renal disease (ESRD) were analyzed. Results A total of 213 children were included. There were 92 children in LI group and 121 children in HI group. Compared with the LI group, the HI group was older, the 24h urine protein quantity was higher, the serum albumin and eGFR levels were lower, the proportion of massive proteinuria, IgG immunofluorescence staining intensity +++, and IFTA moderate grade were higher, and the differences were statistically significant (P<0.05). The utilization rate of cyclophosphamide in LI group was higher than that in HI group, and the difference was statistically significant (P<0.05). After 43.0 (13.0-85.0) months of follow-up, 92 patients in the LI group completed the follow-up, and one patient progressed to ESRD. Sixty-eight children had complete response (CR) and partial response (PR), and 24 had no response (NR). After 57.0 (20.0-86.0) months of follow-up, 121 patients in HI group completed the follow-up, and five patients progressed to ESRD. Eighty-six children had CR and PR, and 35 had NR. The log-rank test showed that when baseline eGFR≤90 mL·min^-1·1.73 m^-2, the time of progression to ESRD was shorter, and the difference was statistically significant (P<0.05). Multivariate Cox regression analysis showed that increased eGFR at baseline was an independent protective factor for delaying the progression to ESRD (HR=0.96, 95% CI: 0.929-0.987), while glomerular C3 deposition was not associated with the occurrence of ESRD. Conclusions Extensive glomerular C3 deposition is not a predictor of renal failure in children with PMN.

Key words: primary membranous nephropathy, C3 deposition, child

王忍, 夏正坤, 张沛, 高春林. 肾小球C3沉积在儿童原发性膜性肾病中临床及预后意义[J]. 临床儿科杂志, 2022, 40(12): 899-904.

WANG Ren, XIA Zhengkun, ZHANG Pei, GAO Chunlin. Clinical and prognostic significance of glomerular C3 deposition in children with primary membranous nephropathy[J]. Journal of Clinical Pediatrics, 2022, 40(12): 899-904.

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项目	LI组(n=92)	HI组(n=121)	统计量	P
年龄[M(P₂₅~P₇₅)]/岁	15.0(12.3~16.0)	16.0(14.0~17.0)	Z=3.23	0.001
男性[n(%)]	47(51.1)	72(59.5)	χ²=1.50	0.220
收缩压[M(P₂₅~P₇₅)]/mmHg	120.0(110.0~126.0)	120.0(110.0~130.0)	Z=0.43	0.667
舒张压[M(P₂₅~P₇₅)]/mmHg	74.0(68.0~80.0)	73.0(70.0~80.0)	Z=0.28	0.783
24 h尿蛋白定量[M(P₂₅~P₇₅)]/g·L^-1	1.7(0.9~2.8)	3.2(1.8~6.3)	Z=4.73	<0.001
血尿[n(%)]	54(58.7)	90(74.4)	χ²=5.87	0.015
蛋白尿严重程度[n(%)]			χ²=14.10	<0.001
大量蛋白尿	42(45.7)	86(71.1)
非大量蛋白尿	50(54.3)	35(28.9)
血清白蛋白(x±s)/g·L^-1	34.4±7.7	28.4±6.1	t=4.70	<0.001
eGFR/ mL·min^-1·1.73 m^-2	166.0(141.7~198.3)	149.9(137.7~181.0)	Z=2.35	0.019
病理分期[n(%)]			χ²=1.07	0.785
Ⅰ期	25(27.2)	27(22.3)
Ⅱ期	38(41.3)	58(47.9)
Ⅲ期	25(27.2)	31(25.6)
IV期	4(4.3)	5(4.1)
IgG染色强度[n(%)]			χ²=4.17	0.041
++	88(95.7)	106(87.6)
+++	4(4.3)	15(12.4)
IFTA分级[n(%)]			χ²=2.53	0.282
轻度	80(87.0)	97(80.2)
中度	1(1.1)	5(4.1)
重度	11(12.0)	19(15.7)

项目	LI组(n=92)	HI组(n=121)	统计量	P
随访时间[M(P₂₅~P₇₅)]/月	43.0(13.0~85.0)	57.0(20.0~86.0)	Z=1.16	0.248
末次随访eGFR[M(P₂₅~P₇₅)]/mL·min^-1·1.73 m^-2	138.1(131.0~147.0)	135.0(122.6~149.8)	Z=1.84	0.066
末次随访24h尿蛋白[M(P₂₅~P₇₅)]/g·L^-1	0.4(0.3~2.1)	0.6(0.3~3.1)	Z=1.18	0.237
治疗方案[n(%)]
他克莫司	35(38.0)	47(38.8)	χ²=0.01	0.905
环磷酰胺	13(14.1)	5(4.1)	χ²=6.75	0.009
吗替麦考酚酯	13(14.1)	24(19.8)	χ²=1.19	0.276
利妥昔单抗	5(5.4)	10(8.3)	χ²=0.64	0.424
保守治疗	32(34.8)	42(34.7)	χ²=0.00	0.991
进展至ESRD(n)	1(1.1)	5(4.1)	χ²=0.83	0.362
转归[n(%)]			χ²=2.30	0.317
CR	29(31.5)	27(22.3)
PR	39(42.4)	59(48.8)
NR	24(26.1)	35(28.9)

因素		达ESRD时间(M±SE)	χ²值	P
性别	男	57.0±5.8	2.78	0.095
	女	44.0±6.3
发病年龄	≤13岁	41.0±5.6	1.46	0.228
	>13岁	58.7±6.1
血白蛋白	≤25 g·L^-1	43.3±6.0	2.12	0.145
	>25 g·L^-1	57.8±7.4
基线eGFR	≤90 mL·min^-1·1.73 m^-2	13.0±2.1	165.00	<0.001
	>90 mL·min^-1·1.73 m^-2	55.1±7.9
IgG染色强度	++	54.9±7.4	0.21	0.644
	+++	46.4±5.6
C3染色强度	<++	49.9±7.9	0.77	0.381
	≥++	57.5±4.3
病理分期	Ⅰ期	42.1±4.3	0.78	0.421
	Ⅱ期	56.3±5.5
	Ⅲ期	59.7±7.7
	IV期	58.3±8.3
24 h尿蛋白定量	<50 mg·kg^-1	50.0±6.4	0.80	0.371
	≥50 mg·kg^-1	55.2±7.9