肾小球皮质密度对随访5年的IgA肾病不良预后的预测△

doi:10.24920/J1001-9294.2017.021

摘要/Abstract

摘要：

目的评估肾小球皮质密度（glomerular density, GD）是否可以作为估测肾小球滤过率（estimated glomerular filtration rate，eGFR）在30到60 ml/(min·1.73 m2)的IgA肾病患者以及随访中时间平均蛋白尿< 0.5 g/d患者预后不良的独立危险因素。方法入组2000年1月至2010年12月在本院经肾脏穿刺诊断为IgA肾病、且随访时间大于5年的173例患者。主要终点事件为随访5年后eGFR较基线值下降大于30%。采用ROC曲线计算GD的诊断界值，采用Kaplan-Meier生存分析及Cox回归分析评估预后。结果随访期间14.5%的患者eGFR下降超过30%。GD对于IgA肾病预后的诊断界值为1.99/mm2（ROC下曲线面积=0.90, 敏感性=84.0%，特异性=81.8%）。对于eGFR在30到60 ml/(min·1.73 m2)的IgA肾病患者，更多的低GD患者（GD<1.99 / mm2）发生终点事件（低GD组6例，高GD组1例）。对于时间平均蛋白尿< 0.5 g/d的患者, 低GD 组的eGFR下降更显著[4.5±16.7 ml/(min·1.73 m2) 与 -8.1±21.4 ml/(min·1.73 m2), P = 0.038]；低GD组中2例患者随访中出现终点事件，而高GD组无终点事件发生。结论 GD是eGFR在30到60 ml/(min·1.73 m2)及随访中时间平均蛋白尿<0.5 g/d的IgA肾病患者的独立危险因素。

关键词: 肾小球皮质密度, IgA肾病, 肾脏预后

Abstract: Objective

To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m², or for patients with time-average proteinuria < 0.5 g/d.

Methods

A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis.

Results

A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm² (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm²) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m²(six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m² vs. -8.1±21.4 ml/min per 1.73 m², P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did.

Conclusion

GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m²of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Key words: glomerular density, IgA nephropathy, renal progression

Chen Zhen-jie, Li Hang, Cai Jian-fang, Zhang Xin, Li Chao, Zou Pei-mei, Li Ming-xi, Chen Li-meng, Li Xue-mei, Li Xue-wang, Wen Yu-bing. The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy^△[J].Chinese Medical Sciences Journal, 2017, 32(3): 145-151.

图/表 5

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Characteristics	All patients	Glomerular density		t value	P value
Characteristics	All patients	≤2.18/mm²	>2.18/mm²	t value	P value
n Age^§ (yrs)	173	58	115
n Age^§ (yrs)	36.2 ± 9.9	36.6 ± 9.3	36.0±10.3	–0.25	0.001
Male [n (%)]	74 (42.8)	25 (43.1)	49 (42.6)		0.54
Diabetes [n (%)]	15 (8.7)	3 (5.2)	12 (10.4)		0.19
Hypertension [n (%)]	71 (41.0)	31 (53.4)	40 (34.8)		0.014
Body mass index^§ (kg/m²)	24.5 ± 3.9	24.3 ± 3.6	24.5 ± 4.1	–0.12	0.75
Mean arterial pressure^§ (mm Hg)	96.0 ± 13.3	98.4 ± 14.2	94.8 ± 12.6	2.17	0.09
Proteinuria [g/d, median (Q1, Q3)]	2.0 (0.9, 4.0)	2.2 (1.0, 3.8)	2.0 (0.9, 4.0)		0.94
eGFR^§ (ml/min per 1.73 m²)	80.0 ± 25.4	67.9 ± 22.0	86.0 ± 24.9	–4.73	<0.001
Serum creatinine^§ (μmol/L)	100.3 ± 39.8	113.0 ± 39.0	89.8 ± 27.8	3.99	<0.001
Uric acid^§ (μmol/L)	361.0 ± 109.2	405.8 ± 114.2	338.3 ± 99.6	5.08	<0.001
Total cholesterol [mmol/L, median (Q1, Q3)]	5.6 (4.7, 6.7)	5.6 (4.7, 6.6)	5.5 (4.7, 6.8)		0.94
Triglycerides^§ (mmol/L)	2.2 ± 1.2	2.1 ± 1.2	2.2 ± 1.2	–0.33	0.48
Pathological variables
Glomerular density^§ (per mm²)	2.7 ± 1.1	1.5 ± 0.4	3.3 ± 0.9	–8.21	<0.001
Global glomerulosclerosis^§ (%)	26.1 ± 18.4	40.8 ± 18.8	18.6 ± 13.0	8.19	<0.001
Maximal glomerular diameter^§ (μm)	216.3 ± 25.8	224.1 ± 22.6	212.4 ± 26.4	2.57	0.004
M1 [n (%)]	102 (59.0)	35 (60.3)	67 (58.3)		0.46
E1 [n (%)]	52 (30.1)	15 (25.9)	37 (32.2)		0.25
S1 [n (%)]	163 (94.2)	56 (96.6)	107 (93.0)		0.29
T1 [n (%)]	58 (33.5)	21 (36.2)	37 (32.2)		0.36
T2 [n (%)]	17 (9.8)	14 (24.1)	3 (2.6)		<0.001

Characteristics	Unadjusted	Model 1	Model 2	Model 3	Model 4
Glomerular density (per mm²)
>2.18/mm²	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)
≤2.18/mm²	12.41 (4.26, 36.18)	14.05 (4.79, 41.21)	13.14 (4.08, 42.39)	10.80 (3.03, 8.45)	7.21 (1.82, 28.52)
Age		0.94 (0.90, 0.99)	0.92 (0.87, 0.98)	0.93 (0.88, 1.00)	0.94 (0.89, 1.00)
Gender		1.49 (0.66, 3.34)	2.18 (0.85, 5.57)	2.11 (0.80, 5.58)	2.14 (0.81, 5.66)
Hypertension			0.80 (0.33, 1.80)	0.85 (0.32, 2.31)	0.90 (0.34, 2.38)
Proteinuria			1.12 (0.95 ,1.32)	1.09 (0.89, 1.34)	1.13 (0.91, 1.40)
eGFR			0.98 (0.96, 1.00)	0.99 (0.97, 1.01)	0.99 (0.97, 1.02)
Corticosteroids			4.38 (1.23, 15.53)	4.33 (1.07, 17.46)	6.16 (0.40, 27.11)
RAS blockers			0.65 (0.08, 5.53)	0.64 (0.07, 6.21)	0.84 (0.08, 8.76)
Immunosuppressive agents			2.27 (0.79, 6.55)	2.18 (0.70, 6.74)	2.08 (0.66, 6.57)
M1				1.07 (0.42, 2.73)	1.13 (0.44, 2.94)
E1				1.03 (0.40, 2.69)	1.19 (0.45, 3.20)
S1				0.87 (0.08, 9.98)	0.80 (0.07, 9.75)
T1-2				1.02 (0.98, 1.06)	1.01 (0.97, 1.05)
Maximal glomerular diameter				1.00 (0.98, 1.03)	1.01 (0.99, 1.03)
Global glomerulosclerosis percent					1.02 (1.00, 1.06)

Characteristics	Glomerular density		t value	P value
Characteristics	≤1.99/mm²	>1.99/mm²	t value	P value
Age^§ (yrs)	33.8±9.2	41.7±10.4	-2.66	0.01
Male [n (%)]	10 (45.5)	10 (45.5)		1.00
Body mass index^§ (kg/m²)	23.3±3.6	25.4±4.4	-1.74	0.09
Mean arterial pressure^§ (mm Hg)	99.6±14.4	98.2±10.9	0.36	0.72
Proteinuria^§ (g/d)	3.9±2.9	2.7±2.5	1.51	0.14
eGFR^§ (ml/min per 1.73 m²)	46.8±7.8	51.2±9.0	-1.72	0.09
Uric acid^§ (μmol/L)	460.5±84.4	408.2±91.2	1.98	0.06
Total cholesterol^§ (mmol/L)	6.3±1.6	5.7±1.5	1.37	0.18
Triglycerides^§ (mmol/L)	2.3±1.3	2.6±1.2	-0.72	0.47
Pathological variables
Maximal glomerular diameter^§ (μm)	224.8±26.9	211.8±19.8	1.61	0.08
M1 [n (%)]	14 (63.6)	9 (40.9)		0.13
E1 [n (%)]	8 (36.4)	7 (31.8)		0.75
S1 [n (%)]	22 (100.0)	21 (95.5)		0.31
T1 [n (%)]	11 (50.0)	10 (45.5)		0.76
T2 [n (%)]	6 (27.3)	5 (22.7)		0.73

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