慢性肾脏病患者血清HIF-1α、TGF-β1与肾小管间质纤维化及疾病进展的关系

林永强; 陈恬恬; 王超超; 周莹; 蔡小巧; 姜益; 林胜芬

doi:10.16766/j.cnki.issn.1674-4152.002188

慢性肾脏病患者血清HIF-1α、TGF-β1与肾小管间质纤维化及疾病进展的关系

doi: 10.16766/j.cnki.issn.1674-4152.002188

1.
温州市中西医结合医院肾内科，浙江温州 325000
2.
温州医科大学附属第一医院肾内科，浙江温州 325000

基金项目:

浙江省基础公益研究计划项目 LQ19H050002

详细信息

通讯作者:
王超超，E-mail：164459621@qq.com

中图分类号: R692 R692.6
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- 被引次数: 0
出版历程
- 收稿日期: 2021-03-28
- 网络出版日期: 2022-02-15

The relationship between serum HIF-1α, TGF-β1 and renal interstitial fibrosis and disease progression in patients with chronic kidney disease

1.
Nephrology Department, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang 325000, China

摘要

摘要: 目的探讨血清缺氧诱导因子-1α(HIF-1α)、转化生长因子(TGF-β1)与肾小管间质纤维化(TIF)在慢性肾脏病(CKD)患者中的变化及其对疾病进展预测价值。方法选择2019年1月—2020年12月温州市中西医结合医院肾内科收治的CKD患者158例，根据肾小球滤过率(eGFR)值对CKD患者进行分期：1期(38例)、2期(42例)、3期(30例)、4期(28例)、5期(20例)，另选取健康体检者40例为对照组，收集各组临床资料及血液样本，应用酶联免疫吸附法(ELISA)检测CKD患者血清HIF-1α、TGF-β1水平，采用Masson染色评估TIF面积。结果 CKD 1~5期患者HIF-1α[依次为(25.48±4.26)ng/mL、(30.98±5.36)ng/mL、(35.88±6.78)ng/mL、(42.25±5.63)ng/mL、(68.96±6.98)ng/mL]、TGF-β1[依次为(3.98±0.36)ng/mL、(5.23±0.45)ng/mL、(6.78±0.63)ng/mL、(8.96±1.52)ng/mL、(12.97±2.98)ng/mL]显著高于对照组[(12.78±0.69)ng/mL和(1.22±0.15)ng/mL，均P < 0.05]。经Pearson相关性分析显示，血清HIF-1α、TGF-β1与血清CysC、Scr、TIF面积呈正相关(均P < 0.05)。经ROC曲线分析可知，血清HIF-1α、TGF-β1联合诊断可提高TIF诊断灵敏性及特异性。结论血清HIF-1α、TGF-β1水平升高与CKD病情进展及肾间质纤维化相关，并可作为CKD患者TIF病情诊断的预测指标，两者联合检测可提高诊断准确性。
- 慢性肾脏病 /
- 血清缺氧诱导因子-1α /
- 转化生长因子 /
- 肾小管间质纤维 /
- 疾病进展
Abstract: Objective To investigate the changes of serum hypoxia-inducible factor-1α (HIF-1α), transforming growth factor (TGF-β1) and tubular interstitial fibrosis (TIF) in patients with chronic kidney disease (CKD) and their predictive value for disease progression. Methods A total of 158 cases of CKD patients were selected admitted to Department of Nephrology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to December 2020. The patients were staged according to the glomerular filtration rate (eGFR) value: stage 1 (n=38), stage 2 (n=42), stage 3 (n=30), stage 4 (n=28), stage 5 (n=20). Another 40 cases of healthy subjects were selected as control group. The clinical data and blood samples of above groups were collected. The levels of HIF-1α and TGF-β1 were detected with Enzyme-linked immunosorbent assay (ELISA). TIF area was assessed with Masson staining. Results The levels of HIF-1α [(25.48±4.26) ng/mL, (30.98±5.36) ng/mL, (35.88±6.78) ng/mL, (42.25±5.63) ng/mL, (68.96±6.98) ng/mL], TGF-β1 [(3.98±0.36) ng/m, (5.23±0.45) ng/m, (6.78±0.63) ng/m, (8.96±1.52) ng/m, (12.97±2.98) ng/mL] of CKD stage 1-5 were significantly higher than control group [(12.78±0.69) ng/mL and (1.22±0.15) ng/mL, all P < 0.05]. The levels of serum CysC, Scr, HIF-1α, and TGF-β1 of non-TIF group were lower than TIF group (all P < 0.05). The serum HIF-1α, TGF-β1 were positively correlated with serum CysC, Scr, TIF area by Pearson correlate factor analysis (all P < 0.05). The HIF-1α and TGF-β1 can improve the value of early CKD diagnosis by receiver specific curve (ROC). Conclusion The increase of serum HIF-1α and TGF-β1 levels is related to the increase of CysC, Scr and TIF. The serum HIF-1α and TGF-β1 can be used as early CKD serum standards, and the combined detection of the two can improve the diagnostic accuracy.
- Chronic kidney disease /
- Serum hypoxia-inducible factor-1α /
- Transforming growth factor /
- Tubular interstitial fibers /
- Disease progression

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图 1 CKD 1~5期肾间质纤维化面积(Masson染色，×200)

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图 2 CKD 1~5期肾间质纤维化面积

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图 3 血清HIF-1α、TGF-β1诊断CKD患者肾间质纤维化的ROC曲线图

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表 1 各组临床资料及血清HIF-1α、TGF-β1水平比较

组别	例数	性别 (男/女，例)	年龄 (x±s，岁)	SBP (x±s，mm Hg)	DBP (x±s，mm Hg)	血糖 (x±s，mmol/L)	血红蛋白 (x±s，g/L)	血总胆固醇 (x±s，mmol/L)
对照组	40	20/20	50.12±4.26	110.25±3.98	78.96±4.25	5.98±0.63	127.85±5.98	2.89±0.36
CKD 1期	38	18/20	50.72±3.98	129.02±4.88^c	85.96±5.02^c	6.02±0.87	122.25±6.97	4.11±0.58^c
CKD 2期	42	22/20	50.36±4.02	131.02±4.23^c	86.10±4.56^c	6.04±0.96	126.23±5.88	4.78±0.61^cd
CKD 3期	30	16/14	50.41±4.52	133.78±4.69^c	87.96±4.69^c	6.15±0.89	124.10±5.78	4.80±0.63^cde
CKD 4期	28	15/13	50.22±5.36	135.25±3.98^c	88.10±4.89^c	6.23±1.01	125.22±6.02	4.93±0.59^cdef
CKD 5期	20	10/10	51.02±4.98	139.87±4.52^c	88.78±4.52^c	6.18±0.89	123.89±5.78	4.95±0.68^cdefg
统计量		0.396^a	0.135^b	222.27^b	27.625^b	0.248^b	2.345^b	101.88^b
P值		0.995	0.939	< 0.001	< 0.001	0.866	0.075	< 0.001

组别	例数	尿β2-MG (x±s, mg/L)	BUN (x±s, mmol/L)	CysC (x±s, mg/L)	Scr (x±s, μmol/L)	HIF-1α (x±s, ng/mL)	TGF-β1 (x±s, ng/mL)
对照组	40	0.19±0.05	4.63±0.22	0.72±0.18	58.02±6.89	12.78±0.69	1.22±0.15
CKD 1期	38	0.48±0.12^c	4.98±0.28^c	0.93±0.21^c	62.10±5.47^c	25.48±4.26^c	3.98±0.36^c
CKD 2期	42	0.68±0.23^cd	5.02±1.02^cd	1.25±0.69^cd	71.56±6.03^cd	30.98±5.36^cd	5.23±0.45^cd
CKD 3期	30	1.42±0.56^cde	6.98±1.06^cde	1.55±0.23^cde	90.12±6.98^cde	35.88±6.78^cde	6.78±0.63^cde
CKD 4期	28	5.66±1.26^cdef	10.89±2.12^cdef	2.56±0.45^cdef	128.98±12.88^cdef	42.25±5.63^cdef	8.96±1.52^cdef
CKD 5期	20	8.25±2.59^cdefg	15.10±3.26^cdefg	3.89±0.63^cdefg	456.89±20.22^cdefg	68.96±6.98^cdefg	12.97±2.98^cdefg
统计量		112.062^b	66.774^b	28.192^b	168.342^b	166.611^b	66.9724^b
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001
注：^a为χ²值，^b为F值。与对照组比较，^cP < 0.05；与CKD 1期比较，^dP < 0.05；与CKD 2期比较，^eP < 0.05；与CKD 3期比较，^fP < 0.05；与CKD4期比较，^gP < 0.05。1 mm Hg=0.133 kPa。

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表 2 血清HIF-1α、TGF-β1与肾功能相关指标及TIF面积的关系

相关指标	统计量	尿β2-MG	BUN	CysC	Scr	TIF面积
HIF-1α	r值	0.169	0.114	0.698	0.612	0.579
	P值	0.689	0.721	< 0.001	< 0.001	< 0.001
TGF-β1	r值	0.138	0.101	0.669	0.498	0.598
	P值	0.690	0.806	< 0.001	< 0.001	< 0.001

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表 3 血清HIF-1α、TGF-β1对CKD患者肾间质纤维化的预测价值

指标	AUC	灵敏度	特异度	约登指数	P值	95% CI
HIF-1α	0.692	0.682	0.742	0.512	< 0.001	0.547~0.769
TGF-β1	0.728	0.718	0.769	0.559	< 0.001	0.689~0.811
HIF-1α联合TGF-β1	0.826	0.822	0.841	0.623	< 0.001	0.798~0.902

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