Clinical and pathological features of adolescent idiopathic membranous nephropathy and its outcome-affecting factors

doi:10.3877/cma.j.issn.2095-3216.2022.04.001

Abstract

Abstract:

Objective

To analyze the clinical and pathological features, treatment, and prognosis of adolescent idiopathic membranous nephropathy (IMN).

Methods

A retrospective analysis was performed on the basic data, laboratory tests, renal biopsy pathology, and treatment protocols, etc, of 164 adolescent IMN patients aged 13-24 years who were diagnosed by renal biopsy in the Department of Nephrology of Chinese PLA General Hospital from January 1, 2011 to April 30, 2018. The patients were divided into a juvenile group (13-18 years old) of 60 cases and a youth group (19-24 years old) of 104 cases, and followed up for 6-24 months from the time of renal biopsy, and the effectiveness of drug treatments and the prognosis were analyzed.

Results

The patients′ male to female ratio was approximately 1.6∶1. The incidence of hematuria (P=0.002) and eGFR (P=0.002) in the juvenile group were higher than those in the youth group, while the levels of IgA (P=0.017) and IgG (P=0.050) were lower in the juvenile group than in the youth group. The clinical manifestations of both groups were mainly those of nephrotic syndrome, and the most common renal pathological feature was membranous nephropathy stage Ⅱ. The positive rate of serum anti-phospholipase A2 receptor antibody in the juvenile group and the youth group was 44.4% and 40%, respectively. The mean follow-up time of the two groups was 8.5 (6, 24) months, and the overall remission rate of IMN treated with tacrolimus and/or glucocorticoids was 75% in both groups. The 24-month overall remission rates in the juvenile group and the youth group were 85.7% and 96%, respectively (χ²=1.303, P=0.254), while the 24-month complete remission rates were 61.5% and 79.2%, respectively (χ²=1.329, P=0.254). None of the patients in the juvenile and youth groups progressed to end-stage renal disease (ESRD). Univariate Cox regression analysis showed that hematuria and hypoimmunoglobulinemia of IgG (<4.0 g/L) suggested a lower 24-month overall remission rate in the IMN patients. Multivariate Cox regression analysis found that hematuria (HR=0.345, 95%CI: 0.035-0.188, P=0.005) and IgG<4.0 g/L (HR=0.278, 95%CI: 0.034-0.434, P=0.023) were both the independent risk factors of 24-month overall remission rate. Besides, IgG<4.0 g/L (HR=3.538, 95%CI: 1.193-10.499, P=0.028) was also an independent risk factor for the 24-month complete remission rate. The area under the receiver operating characteristic (ROC) curve (AUC) also confirmed that IgG<3.48 g/L (AUC=0.765, specificity 69.4%, sensitivity 88.7%, P=0.001) was the best cut-off point for predicting the 24-month non-remission.

Conclusion

The clinical manifestations in the juvenile group were more severe than those in the youth group. The outcome of the adolescent IMN patients was good at 24 months of follow-up. Hematuria and hypoimmunoglobulinemia of IgG were independent risk factors of the remission rate of the adolescent IMN patients.

Key words: Membranous nephropathy, Adolescent, Clinicopathology, Treatment, Prognosis

Linna Wang, Cunxia Guo, Yan Miao, Suge Tian, Dongge Qiao, Lei Yan, Bing Liu, Qing Zhu, Fengmin Shao, Xiangmei Chen. Clinical and pathological features of adolescent idiopathic membranous nephropathy and its outcome-affecting factors[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(04): 181-190.

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References 33

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项目		所有患者	少年组(n＝60)	青少年组(n＝104)	t/Z/χ²值	P值
男性[例(%)]		101(61.5)	35(58.3)	66(63.5)	0.410	0.522
年龄		19.62±3.05	16.13±1.35	21.63±1.6
发病至肾穿时病程(月)		4.0(1.0~5.0)	2.0(0.7~4.0)	2.0(1.0~5.0)	2.656	0.103
抗PLA2R抗体阳性率		42.9%	44.4%	40%	0.046	0.831
抗PLA2R抗体滴度		28.69(6.11~73.21)	27.02(16.77~31.08)	31.5(5.72~73.21)	－0.268	0.793
高血压[例(%)]		65(40.1)	23(38.3)	42(41.1)	0.067	0.796
收缩压(mmHg)		124.02±16.45	123.37±14.32	124.40±17.57	－0.380	0.704
舒张压(mmHg)		77.30±9.76	76.41±9.59	77.82±9.82	－0.884	0.378
肾病综合征[例(%)]		119(72.6)	45(75.0)	74(71.2)	0.283	0.595
血尿[例(%)]		99(60.4)	46(76.6)	59(56.7)	9.327	0.002
血红蛋白(g/L)		131.92±18.16	130.87±17.36	132.53±18.58	－0.562	0.575
血白蛋白(g/L)		25.12±6.96	24.93±6.67	25.22±7.20	－0.258	0.797
24 h尿蛋白(g)		4.76±2.94	4.86±3.24	4.69±2.77	0.336	0.738
血尿素氮(mmol/L)		4.76±5.82	5.37±9.46	4.42±1.62	0.998	0.320
血肌酐(μmol/L)		65.40±25.99	64.13±38.58	66.13±14.87	－0.473	0.637
血尿酸(μmol/L)		345.62±101.31	333.76±98.96	352.08±102.12	－1.079	0.282
胱抑素C		0.91±0.34	0.85±0.26	0.95±0.38	－1.383	0.17
NAG		51.38±43.15	48.44±40.69	53.21±45.19	－0.53	0.597
胆固醇(mmol/L)		7.23±2.42	7.14±2.24	7.27±5.54	－0.311	0.756
三酰甘油(mmol/L)		2.20±1.56	2.08±1.86	2.28±1.37	－0.753	0.452
空腹血糖(mmol/L)		4.76±0.93	4.56±0.81	4.59±0.81	－1.002	0.308
高密度脂蛋白(mmol/L)		1.49±0.81	1.60±0.77	1.43±0.84	1.123	0.264
eGFR[ml/(min·1.73 m²)]		121.29±28.75	134.08±20.85	125.77±12.38	3.195	0.002
免疫学指标(g/L)
	IgA	1.65±0.72	1.47±0.68	1.75±0.73	－2.413	0.017
	IgG	4.53±0.25	4.00±2.13	4.83±0.27	－1.976	0.050
	IgM	1.27±0.69	1.31±0.57	1.24±0.75	0.552	0.582
	C3	1.10±0.37	1.04±0.25	1.12±0.42	－1.429	0.155
	C4	0.24±0.11	0.21±0.07	0.26±0.11	－2.737	0.007

项目		所有患者	少年组(n＝60)	青少年组(n＝104)	t/Z/χ²值	P值
男性[例(%)]		101(61.5)	35(58.3)	66(63.5)	0.410	0.522
年龄		19.62±3.05	16.13±1.35	21.63±1.6
发病至肾穿时病程(月)		4.0(1.0~5.0)	2.0(0.7~4.0)	2.0(1.0~5.0)	2.656	0.103
抗PLA2R抗体阳性率		42.9%	44.4%	40%	0.046	0.831
抗PLA2R抗体滴度		28.69(6.11~73.21)	27.02(16.77~31.08)	31.5(5.72~73.21)	－0.268	0.793
高血压[例(%)]		65(40.1)	23(38.3)	42(41.1)	0.067	0.796
收缩压(mmHg)		124.02±16.45	123.37±14.32	124.40±17.57	－0.380	0.704
舒张压(mmHg)		77.30±9.76	76.41±9.59	77.82±9.82	－0.884	0.378
肾病综合征[例(%)]		119(72.6)	45(75.0)	74(71.2)	0.283	0.595
血尿[例(%)]		99(60.4)	46(76.6)	59(56.7)	9.327	0.002
血红蛋白(g/L)		131.92±18.16	130.87±17.36	132.53±18.58	－0.562	0.575
血白蛋白(g/L)		25.12±6.96	24.93±6.67	25.22±7.20	－0.258	0.797
24 h尿蛋白(g)		4.76±2.94	4.86±3.24	4.69±2.77	0.336	0.738
血尿素氮(mmol/L)		4.76±5.82	5.37±9.46	4.42±1.62	0.998	0.320
血肌酐(μmol/L)		65.40±25.99	64.13±38.58	66.13±14.87	－0.473	0.637
血尿酸(μmol/L)		345.62±101.31	333.76±98.96	352.08±102.12	－1.079	0.282
胱抑素C		0.91±0.34	0.85±0.26	0.95±0.38	－1.383	0.17
NAG		51.38±43.15	48.44±40.69	53.21±45.19	－0.53	0.597
胆固醇(mmol/L)		7.23±2.42	7.14±2.24	7.27±5.54	－0.311	0.756
三酰甘油(mmol/L)		2.20±1.56	2.08±1.86	2.28±1.37	－0.753	0.452
空腹血糖(mmol/L)		4.76±0.93	4.56±0.81	4.59±0.81	－1.002	0.308
高密度脂蛋白(mmol/L)		1.49±0.81	1.60±0.77	1.43±0.84	1.123	0.264
eGFR[ml/(min·1.73 m²)]		121.29±28.75	134.08±20.85	125.77±12.38	3.195	0.002
免疫学指标(g/L)
	IgA	1.65±0.72	1.47±0.68	1.75±0.73	－2.413	0.017
	IgG	4.53±0.25	4.00±2.13	4.83±0.27	－1.976	0.050
	IgM	1.27±0.69	1.31±0.57	1.24±0.75	0.552	0.582
	C3	1.10±0.37	1.04±0.25	1.12±0.42	－1.429	0.155
	C4	0.24±0.11	0.21±0.07	0.26±0.11	－2.737	0.007

肾穿后治疗方案(以缓解方案为准，例)	少年组(n＝25)	青年组(n＝48)	χ²值	P值
非免疫抑制治疗	1	7	0.958^a	0.328
糖皮质激素	5	7	2.698^b	0.100
他克莫司	6	10	0.278^b	0.598
糖皮质激素+他克莫司	6	10	0.278^b	0.598
糖皮质激素+霉酚酸酯	2	3		1.000^c
糖皮质激素+来氟米特	3	3	－	0.399^c
糖皮质激素+环孢素	0	2	－	0.304^c
糖皮质激素+环磷酰胺	0	2	－	0.304^c
雷公藤	0	1	－	1.000^c
3种^d	2	3	－	1.000^c

肾穿后治疗方案(以缓解方案为准，例)	少年组(n＝25)	青年组(n＝48)	χ²值	P值
非免疫抑制治疗	1	7	0.958^a	0.328
糖皮质激素	5	7	2.698^b	0.100
他克莫司	6	10	0.278^b	0.598
糖皮质激素+他克莫司	6	10	0.278^b	0.598
糖皮质激素+霉酚酸酯	2	3		1.000^c
糖皮质激素+来氟米特	3	3	－	0.399^c
糖皮质激素+环孢素	0	2	－	0.304^c
糖皮质激素+环磷酰胺	0	2	－	0.304^c
雷公藤	0	1	－	1.000^c
3种^d	2	3	－	1.000^c

项目		少年组	青年组	CR		PR		无缓解(失访)		肾穿前使用免疫抑制剂		复发		CR时间(月)	PR时间(月)
项目		少年组	青年组	少年组	青年组	少年组	青年组	少年组	青年组	少年组	青年组	少年组	青年组	CR时间(月)	PR时间(月)
例数		25	48	7	17	10	23	8	8	2	9	1	2
治疗方案(例)
	NIAT	1	7	0	4	1	2	0	1	0	0	0	0	7(4~12.5)	7(4.3~11)
	G	5	7	1	0	2	5	2	2	0	1^a	0	1	3	3(2, 4)
	T	6	10	0	2	3	7	3	1	0	0	1	1	9(8~10)	7(4~10)
	G+T	6	10	2	4	2	6	2	2	1^b	2^bc	0	0	15(5.5~21)	4(3，10)
	G+L	2	4	1	1	1	2	0	1	0	2^ab	0	0	5.5(4.5~6.5)	3.5(3~5.3)
	G+M	2	3	1	2	0	1	1	0	1^b	2^b	0	0	7(6.5~9.0)	3.5(2.8~4.3)
	G+CsA	0	2	0	0	0	0	0	1	0	1^a	0	0
	G+CTX	0	1	0	1	0	0	0	0	0	1^a	0	0
	雷公藤	0	1	0	0	0	0	0	1	0	0	0	0
	3种	2	3	1	3	1	0	0	0	0	0	0	2
	4种	1	0	1	0	0	0	0	0	0	0	0	0

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