Clinical significance of changes of serum TFF3 and VASH-1 levels in diabetic nephropathy patients

doi:10.3877/cma.j.issn.1674-0785.2021.07.006

Abstract

Abstract:

Objective

To investigate the relationship among serum TFF3 and VASH-1 levels and diabetic nephropathy.

Methods

A total of 203 patients with type 2 diabetes admitted to Lanzhou First People's Hospital from January 2018 to June 2020 were selected, including 73 patients complicated with diabetic nephropathy (nephropathy group) and 130 patients without diabetic nephropathy (simple diabetes group). The nephropathy group was further divided into CKD stage 1/2 group (25 cases), CKD stage 3/4 group (32 cases), and CKD stage 5 group (16 cases) according to the staging criteria for CKD. Another 65 healthy volunteers were selected as a control group. Serum TFF3 and VASH-1 levels were detected, and clinical data were collected to analyze the relationship among TFF3, VASH-1, renal function indexes, and the incidence of diabetic nephropathy.

Results

Serum level of TFF3 in the nephropathy group was significantly higher than those of the simple diabetic group and control group (P＜0.05), and VASH-1 level was significantly lower than those of the simple diabetic group and control group (P＜0.05). TFF3 increased with the increase of CKD stage (P＜0.05), while VASH-1 decreased with the increase of CKD stage (P＜0.05). In the nephropathy group, TFF3 was positively correlated with BUN, Scr, and 24-h urine protein (r=0.769, 0.753, and 0.772, respectively, P＜0.05), but negatively correlated with eGFR (r=-0.862, P＜0.05). VASH-1 was negatively correlated with BUN, Scr, and 24-h urine protein (r=-0.786, -0.765, and -0.753, respectively, P＜0.05), but positively correlated with eGFR (r=0.819, P＜0.05). Multivariate Logistic regression analysis showed that hypertension (OR=1.680, 95%CI: 1.318-2.043, P=0.005), high insulin resistance index (OR=1.652, 95%CI: 1.313-1.991, P=0.003), high TFF3 (OR=1.619, 95%CI: 1.312-1.927, P=0.002) were risk factors for diabetic nephropathy, while high VASH-1 (OR=0.604, 95%CI: 0.405-0.898, P=0.001) was a protective factor.

Conclusion

The levels of serum TFF3 increase and those of serum VASH-1 decrease in diabetic nephropathy patients. High level of TFF3 and low level of VASH-1 may be associated with the incidence of diabetic nephropathy and the degree of renal function injury.

Key words: Diabetic nephropathy, Trefoil factor 3, Vasohibin 1

Xinmei Huang, Jingyan Lu, Hongmei Gao, Yarong Si, Shoupin Xie, Huaqin Chen. Clinical significance of changes of serum TFF3 and VASH-1 levels in diabetic nephropathy patients[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(07): 509-514.

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Figures/Tables 4

项目	肾病组（73例）	单纯糖尿病组（130例）	对照组（65例）	统计值	P值
年龄（岁， $x ¯$ ±s）	62.61±5.16	61.35±5.03	61.84±5.14	F=0.653	0.316
男［例（%）］	41（56.16）	85（65.38）	37（56.92）	χ²=2.215	0.330
2型糖尿病病程（年， $x ¯$ ±s）	6.35±1.32	5.02±1.05	-	t=7.880	＜0.001
合并高血压［例（%）］	45（61.64）	60（46.15）	-	χ²=4.492	0.034
合并高脂血症［例（%）］	23（31.51）	43（33.08）	-	χ²=0.053	0.819
合并冠心病［例（%）］	13（17.81）	32（24.62）	-	χ²=1.256	0.262
收缩压（mmHg， $x ¯$ ±s）	152.35±16.35^ab	135.26±10.65^a	120.31±7.49	F=16.352	＜0.001
舒张压（mmHg， $x ¯$ ±s）	100.03±8.65^a	99.35±7.92^a	82.35±6.39	F=10.352	＜0.001
TC（mmol/L， $x ¯$ ±s）	5.29±0.51^a	5.21±0.46^a	4.25±0.32	F=9.356	＜0.001
TG（mmol/L， $x ¯$ ±s）	1.82±0.35^a	1.80±0.32^a	1.53±0.29	F=6.168	＜0.001
HDL-C（mmol/L， $x ¯$ ±s）	1.25±0.20^a	1.30±0.21^a	1.86±0.39	F=7.352	＜0.001
LDL-C（mmol/L， $x ¯$ ±s）	3.26±0.62^a	3.23±0.59^a	2.51±0.41	F=5.165	＜0.001
FPG（mmol/L， $x ¯$ ±s）	8.32±1.29^a	8.15±1.06^a	4.22±0.69	F=23.165	＜0.001
2hPG（mmol/L， $x ¯$ ±s）	12.74±1.60^a	12.41±1.32^a	8.12±1.36	F=15.263	＜0.001
FINS（mmol/L， $x ¯$ ±s）	10.65±2.35^a	10.05±2.19^a	5.26±0.49	F=19.352	＜0.001
HbA1c（%， $x ¯$ ±s）	8.32±1.42^a	8.16±1.36^a	5.12±0.71	F=18.263	＜0.001
BUN（mmol/L， $x ¯$ ±s）	37.12±2.01^ab	13.25±4.16^a	6.12±1.15	F=20.351	＜0.001
Scr（μmol/L， $x ¯$ ±s）	163.24±30.59^ab	136.35±21.35^a	83.26±13.26	F=32.165	＜0.001
24 h尿蛋白（g/24 h， $x ¯$ ±s）	3.02±0.89^ab	0.10±0.03^a	0.05±0.02	F=76.297	＜0.001
eGFR［ml/（min·1.73 m²）， $x ¯$ ±s］	65.12±20.13^ab	98.15±7.42^a	105.26±6.35	F=42.168	＜0.001
HOMA-IR（ $x ¯$ ±s）	3.94±0.75^ab	3.64±0.35^a	0.99±0.03	F=26.352	＜0.001
TFF3（μg/L， $x ¯$ ±s）	35.26±6.19^ab	10.21±3.31^a	7.16±2.25	F=38.165	＜0.001
VASH-1（ng/L， $x ¯$ ±s）	322.01±33.02^ab	405.32±54.12^a	568.95±85.23	F=46.265	＜0.001

项目	肾病组（73例）	单纯糖尿病组（130例）	对照组（65例）	统计值	P值
年龄（岁， $x ¯$ ±s）	62.61±5.16	61.35±5.03	61.84±5.14	F=0.653	0.316
男［例（%）］	41（56.16）	85（65.38）	37（56.92）	χ²=2.215	0.330
2型糖尿病病程（年， $x ¯$ ±s）	6.35±1.32	5.02±1.05	-	t=7.880	＜0.001
合并高血压［例（%）］	45（61.64）	60（46.15）	-	χ²=4.492	0.034
合并高脂血症［例（%）］	23（31.51）	43（33.08）	-	χ²=0.053	0.819
合并冠心病［例（%）］	13（17.81）	32（24.62）	-	χ²=1.256	0.262
收缩压（mmHg， $x ¯$ ±s）	152.35±16.35^ab	135.26±10.65^a	120.31±7.49	F=16.352	＜0.001
舒张压（mmHg， $x ¯$ ±s）	100.03±8.65^a	99.35±7.92^a	82.35±6.39	F=10.352	＜0.001
TC（mmol/L， $x ¯$ ±s）	5.29±0.51^a	5.21±0.46^a	4.25±0.32	F=9.356	＜0.001
TG（mmol/L， $x ¯$ ±s）	1.82±0.35^a	1.80±0.32^a	1.53±0.29	F=6.168	＜0.001
HDL-C（mmol/L， $x ¯$ ±s）	1.25±0.20^a	1.30±0.21^a	1.86±0.39	F=7.352	＜0.001
LDL-C（mmol/L， $x ¯$ ±s）	3.26±0.62^a	3.23±0.59^a	2.51±0.41	F=5.165	＜0.001
FPG（mmol/L， $x ¯$ ±s）	8.32±1.29^a	8.15±1.06^a	4.22±0.69	F=23.165	＜0.001
2hPG（mmol/L， $x ¯$ ±s）	12.74±1.60^a	12.41±1.32^a	8.12±1.36	F=15.263	＜0.001
FINS（mmol/L， $x ¯$ ±s）	10.65±2.35^a	10.05±2.19^a	5.26±0.49	F=19.352	＜0.001
HbA1c（%， $x ¯$ ±s）	8.32±1.42^a	8.16±1.36^a	5.12±0.71	F=18.263	＜0.001
BUN（mmol/L， $x ¯$ ±s）	37.12±2.01^ab	13.25±4.16^a	6.12±1.15	F=20.351	＜0.001
Scr（μmol/L， $x ¯$ ±s）	163.24±30.59^ab	136.35±21.35^a	83.26±13.26	F=32.165	＜0.001
24 h尿蛋白（g/24 h， $x ¯$ ±s）	3.02±0.89^ab	0.10±0.03^a	0.05±0.02	F=76.297	＜0.001
eGFR［ml/（min·1.73 m²）， $x ¯$ ±s］	65.12±20.13^ab	98.15±7.42^a	105.26±6.35	F=42.168	＜0.001
HOMA-IR（ $x ¯$ ±s）	3.94±0.75^ab	3.64±0.35^a	0.99±0.03	F=26.352	＜0.001
TFF3（μg/L， $x ¯$ ±s）	35.26±6.19^ab	10.21±3.31^a	7.16±2.25	F=38.165	＜0.001
VASH-1（ng/L， $x ¯$ ±s）	322.01±33.02^ab	405.32±54.12^a	568.95±85.23	F=46.265	＜0.001

组别	例数	TFF3（μg/L）	VASH-1（ng/L）
CKD 1~2期组	25	31.81±0.85	350.12±4.16
CKD 3~4期组	32	35.26±2.58^a	315.83±10.15^a
CKD 5期组	16	40.65±0.88^ab	290.45±1.84^ab
F值		42.532	50.358
P值		＜0.001	＜0.001

项目	TFF3		VASH-1
项目	r值	P值	r值	P值
BUN	0.769	＜0.001	-0.786	＜0.001
Scr	0.753	＜0.001	-0.765	＜0.001
24 h尿蛋白	0.772	＜0.001	-0.753	＜0.001
eGFR	-0.862	＜0.001	0.819	＜0.001

项目	β值	SE	Wald χ²值	OR值	95%CI	P值
2型糖尿病病程	0.323	0.273	1.400	1.381	0.846~1.916	0.816
合并高血压	0.519	0.185	7.870	1.680	1.318~2.043	0.005
HOMA-IR	0.502	0.173	8.420	1.652	1.313~1.991	0.003
收缩压	0.259	0.231	1.257	1.296	0.843~1.748	0.862
TFF3	0.482	0.157	9.425	1.619	1.312~1.927	0.002
VASH-1	-0.505	0.163	9.599	0.604	0.405~0.898	0.001

References 22

1	Zhang L, Long J, Jiang W, et al. Trends in chronic kidney disease in China [J]. N Engl J Med, 2016, 375(9): 905-906.
2	Belle NM, Ji Y, Herbine K, et al. TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths [J]. Nat Commun, 2019, 10(1): 4408.
3	Du TY, Luo HM, Qin HC, et al. Circulating serum trefoil factor 3 (TFF3) is dramatically increased in chronic kidney disease [J]. PLoS One, 2013, 8(11): e80271.
4	Sato Y. The vasohibin family: a novel family for angiogenesis regulation [J]. J Biochem, 2013, 153(1): 5-11.
5	Watatani H, Maeshima Y, Hinamoto N, et al. Vasohibin-1 deficiency enhances renal fibrosis and inflammation after unilateral ureteral obstruction [J]. Physiol Rep, 2014, 2(6): e12054.
6	中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版) [J]. 中华糖尿病杂志, 2018, 10(1): 4-67.
7	Khwaja A. KDIGO clinical practice guidelines for acute kidney injury [J]. Nephron Clin Pract, 2012, 120(4): 179-184.
8	程莹, 李宁娜, 游志清, 等. 三种CKD-EPI公式与改良MDRD公式诊断糖尿病肾病一致性分析 [J]. 中国全科医学, 2016, 19(29): 3584-3588.
9	Zhang J, Liu J, Qin X. Advances in early biomarkers of diabetic nephropathy [J]. Rev Assoc Med Bras, 2018, 64(1): 85-92.
10	Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities [J]. Clin J Am Soc Nephrol, 2017, 12(12): 2032-2045.
11	Krüger K, Schmid S, Paulsen F, et al. Trefoil factor 3 (TFF3) is involved in cell migration for skeletal repair [J]. Int J Mol Sci, 2019, 20(17): 4277.
12	Liu J, Kim SY, Shin S, et al. Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis [J]. Exp Mol Med, 2018, 50(8): 1-11.
13	Tanaka K, Sugiyama H, Yamanari T, et al. Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy [J]. Nephrology (Carlton), 2018, 23(9): 855-862.
14	Lebherz-Eichinger D, Tudor B, Ankersmit HJ, et al. Trefoil factor 1 excretion is increased in early stages of chronic kidney disease [J]. PLoS One, 2015, 10(9): e0138312.
15	Ninomiya Y, Ozawa S, Oguma J, et al. Expression of vasohibin-1 and -2 predicts poor prognosis among patients with squamous cell carcinoma of the esophagus [J]. Oncol Lett, 2018, 16(4): 5265-5274.
16	Zhang B, Wu Z, Xie W, et al. The expression of vasohibin-1 and its prognostic significance in bladder cancer [J]. Exp Ther Med, 2017, 14(4): 3477-3484.
17	Huang W, Ren Y, Liu H. Vasohibin 1 inhibits Adriamycin resistance in osteosarcoma cells via the protein kinase B signaling pathway [J]. Oncol Lett, 2018, 15(4): 5983-5988.
18	Ren H, Shao Y, Wu C, et al. VASH-1 regulates oxidative stress and fibrosis in diabetic kidney disease via SIRT1/HIF1α and TGFβ1/Smad3 signaling pathways [J]. Front Mol Biosci, 2020, 7: 137.
19	Hinamoto N, Maeshima Y, Yamasaki H, et al. Exacerbation of diabetic renal alterations in mice lacking vasohibin-1 [J]. PLoS One, 2014, 9(9): e107934.
20	Tanimura S, Tanabe K, Miyake H, et al. Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model [J]. Am J Physiol Renal Physiol, 2019, 317(2): F264-F274.
21	Carriazo S, Vanessa Perez-Gomez M, Ortiz A. Hypertensive nephropathy: a major roadblock hindering the advance of precision nephrology [J]. Clin Kidney J, 2020, 13(4): 504-509.
22	Magee C, Grieve DJ, Watson CJ, et al. Diabetic nephropathy: a tangled web to unweave [J]. Cardiovasc Drugs Ther, 2017, 31(5-6): 579-592.

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