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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2023, Vol. 12 ›› Issue (02) : 61 -66. doi: 10.3877/cma.j.issn.2095-3216.2023.02.001

论著

尿诱骗受体2/肌酐水平与糖尿病肾小管病预后的关系
王卫东1, 陈佳1, 何娅妮2, 陈客宏2,†()   
  1. 1. 400042　重庆，陆军军医大学陆军特色医学中心、大坪医院肾内科
    2. 400042　重庆，陆军军医大学陆军特色医学中心、大坪医院肾内科；400042　重庆，陆军军医大学创伤、烧伤与复合伤国家重点实验室
  • 收稿日期:2022-08-11 出版日期:2023-04-28
  • 通信作者: 陈客宏
  • 基金资助:
    国家自然科学基金项目(82270768); 重庆市科技创新引导课题(2022YSZX-JCX0007CSTB)

Relationship between urinary DcR2/Cr level and prognosis in patients with diabetic tubulopathy

Weidong Wang1, Jia Chen1, Yani He2, Kehong Chen2,†()   

  1. 1. Department of Nephrology, Daping Hospital, Army Specialized Medical Center
    2. Department of Nephrology, Daping Hospital, Army Specialized Medical Center; State Key Laboratory of Trauma, Burns and Complex Injuries; Army Medical University, Chongqing 400042, China
  • Received:2022-08-11 Published:2023-04-28
  • Corresponding author: Kehong Chen
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引用本文：

王卫东, 陈佳, 何娅妮, 陈客宏. 尿诱骗受体2/肌酐水平与糖尿病肾小管病预后的关系[J/OL]. 中华肾病研究电子杂志, 2023, 12(02): 61-66.

Weidong Wang, Jia Chen, Yani He, Kehong Chen. Relationship between urinary DcR2/Cr level and prognosis in patients with diabetic tubulopathy[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(02): 61-66.

目的

探讨尿诱骗受体2/肌酐(DcR2/Cr)水平是否可作为预测糖尿病肾小管病(DT)预后的生物标志物。

方法

纳入2018至2021年经我科病理诊断为DT并留取尿液标本的患者共计65例，对基本资料、实验室检查结果、病理检查等进行回顾性分析，并随访患者、记录终点事件。根据尿DcR2/Cr水平分3组：第1组：DcR2/Cr<321 ng/mmol，第2组：321≤DcR2/Cr≤505 ng/mmol，第3组：DcR2/Cr>505 ng/mmol。使用单因素方差分析、Kruskal-Wallis检验进行组间比较，卡方检验进行率的比较，Cox回归模型分析尿DcR2/Cr与DT预后的关系，数据采用SPSS 26.0统计学软件进行处理。

结果

随着DcR2/Cr水平增高，尿白蛋白肌酐比(ACR)、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、胱抑素C(CYC)、血肌酐水平呈增高趋势，而尿肌酐、估算肾小球滤过率(eGFR)逐渐下降(P<0.05)。血红蛋白、血清白蛋白水平随着DcR2/Cr增高而下降(P<0.05)，甘油三酯、低密度脂蛋白随DcR2/Cr增高而增高(P<0.05)。DcR2/Cr水平与ACR、CYC、NAG均呈正相关(均P<0.01)，但与eGFR呈负相关(P<0.01)。尿DcR2/Cr水平与间质纤维化肾小管萎缩(IFTA)评分、肾动脉玻璃样变评分、肾动脉硬化评分均呈正相关(均P<0.05)。Cox回归模型分析显示，尿DcR2/Cr水平与患者预后呈显著相关(P＝0.001)，其中第3组患者不良预后的发生风险是第1组患者的11.416倍。Kaplan-Meier生存曲线显示患者的DcR2/Cr水平越高，预后越差。受试者工作特征(ROC)曲线分析显示，尿DcR2/Cr的曲线下面积(AUC)最大，高于ACR、CYC和血肌酐。

结论

尿DcR2/Cr水平与DT密切相关，可能是预测DT预后的一个生物标志物。

关键词: 尿, DcR2/Cr, 糖尿病肾小管病, 肾小管间质损伤
Objective

To investigate whether urinary decoy receptor 2/ urine creatinine(DcR2/Cr) could be used as a biomarker to predict the prognosis of diabetic tubulopathy (DT).

Methods

A total of 65 patients who were pathologically diagnosed with DT and had urine specimens retained in our department from 2018 to 2021 were included. Basic data, laboratory findings, and pathological information were collected for retrospective analysis. The patients were followed up, and endpoint events were recorded. Aaccording to urinary DcR2/Cr levels, the patients were divided into three groups, group 1 (DcR2/Cr <321 ng/mmol), group 2 (321≤DcR2/Cr≤505 ng/mmol), and group 3 (DcR2/Cr>505 ng/mmol). Univariate analysis of variance and Kruskal Wallis test were used for groups comparison, and chi square test was used for comparison of rates. Cox regression was applied to analyze the relationship between urinary DcR2/Cr level and prognosis of DT. The data was processed with the SPSS 26.0 statistical software.

Results

With the increase of DcR2/Cr level, urinary albumin-to-creatinine ratio (ACR), N-acetyl-β-D-glucosaminidase (NAG), cystatin C (CYC), and serum creatinine tended to increase, while urinary creatinine and estimated glomerular filtration rate (eGFR) gradually decreased (P<0.05). Hemoglobin and serum albumin levels decreased with the increase of urinary DcR2/Cr level (P<0.05), while triglyceride and low density lipoprotein (LDL) increased with the increase of DcR2/Cr (P<0.05). The DcR2/Cr level was positively correlated with ACR (P<0.01), CYC (P<0.01), and NAG (P<0.01), but negatively correlated with eGFR (P<0.01). The urinary DcR2/Cr level was positively correlated with the interstitial fibrosis and tubular atrophy (IFTA) score, renal artery hyalinosis score, and renal atherosclerosis score (all P<0.05). Cox regression analysis revealed a significant correlation between the urinary DcR2/Cr level and the occurrence of adverse prognosis (P=0.001). The risk of adverse prognosis of the group 3 was 11.416 times that of group 1. The Kaplan-Meier survival curve showed that the higher the urinary DcR2/Cr level, the worse the prognosis in the patients. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of urine DcR2/Cr was the largest among ACR, CYC, and SCr.

Conclusion

Urinary DcR2/Cr was closely associated with DT, and may be a biomarker to predict the prognosis of DT.

Key words: Urine, DcR2/Cr, Diabetic tubulopathy, Renal tubular interstitial injury
表1 3组糖尿病肾小管病患者临床基本资料比较
临床资料 DcR2/Cr1组(n＝21) DcR2/Cr2组(n＝22) DcR2/Cr3组(n＝22) 合计(n＝65) F/χ2值 P值
年龄(岁) 52.4±8.7 51.7±11.7 53.8±10.4 52.7±10.3 0.406 0.668b
男性[例(%)] 17(81.0) 18(81.8) 13(59.1) 48(73.8) 3.753 0.153c
体重指数(kg/m2) 26.0±2.3 24.1±2.4 24.3±2.9a 24.7±2.7 3.310 0.044b
收缩压(mmHg) 140.6±21.3 143.1±21.2 144.3±26.2 144.5±23.5 0.047 0.954b
舒张压(mmHg) 80.1±14.5 78.9±10.6 77.9±12.2 79.6±12.9 0.394 0.676c
蛋白尿[例(%)] 20(95.2) 21(95.5) 22(100.0) 63(96.9) 1.057 0.589c
下肢水肿[例(%)] 13(61.9) 17(77.3) 16(72.7) 46(70.8) 1.288 0.525c
高血压[例(%)] 18(85.7) 20(90.9) 18(81.8) 56(86.2) 0.767 0.681c
贫血[例(%)] 7(33.3) 14(63.6)a 15(68.2)a 36(55.4) 6.197 0.045c
低白蛋白血症[例(%)] 4(19.0) 11(50.0) 9(40.9) 24(36.9) 4.647 0.098c
冠心病[例(%)] 2(9.5) 2(9.1) 2(9.1) 6(9.2) 0.003 0.998c
脑血管疾病[例(%)] 1(4.8) 2(9.1) 3(13.6) 6(9.2) 1.011 0.603c
慢性肝病[例(%)] 0 3(13.6) 1(4.5) 4(6.2) 3.608 0.165c
糖尿病视网膜病变[例(%)] 11(57.9) 16(76.2) 16(72.7) 43(69.4) 1.753 0.416c
表2 3组糖尿病肾小管病患者实验室检查资料比较
实验室检查资料 DcR2/Cr1组(n＝21) DcR2/Cr2组(n＝22) DcR2/Cr3组(n＝22) 合计(n＝65) F/H值 P值
尿蛋白定量(g/L) 1.28(0.5，3.0) 2.5(1.2，4.3) 3.8(1.4，6.1)a 2.0(0.9，4.8) 5.291 0.071d
ACR[mg/(g·Cr)] 801(222，2534) 2385(1045，4110) 4743(2242，6237)a 2352(779.3，4492.5) 14.651 0.001d
NAG(U/L) 21.2(17.1，36.4) 28.2(18.9，37.7) 55.9(23.5，78.5)a 28.4(17.9，48.2) 9.581 0.008d
血红蛋白(g/L) 131.6±23.6 117.4±20.5a 103.7±25.2a 114.9±26.0 8.409 0.001c
血肌酐(μmol/L) 86.1(70.6，112.7) 113.1(84.7，144.5)a 121.1(84.3，165.9)a 101.7(81.6，137.8) 7.666 0.022d
胱抑素C(mg/L) 1.4(1.1，1.6) 1.5(1.3，1.8) 2.0(1.5，2.3)ab 1.6(1.3，2.0) 13.473 0.001e
eGFR[ml/(min·1.73 m2)] 77.2±19.2 64.6±26.2a 57.6±28.5a 68.2±26.3 6.945 0.002c
血清白蛋白(g/L) 35.7±7.1 32.7±6.3a 28.5±8.7a 32.9±7.7 3.306 0.043c
总胆固醇(mmol/L) 4.4(3.6，4.9) 4.8(3.8，5.9) 5.5(4.2，7.2) 4.7(4.1，5.9) 4.630 0.099d
甘油三酯(mmol/L) 1.8(1.0，2.8) 1.6(1.0，2.0) 2.3(1.5，3.2)b 1.9(1.3，2.7) 7.125 0.028d
高密度脂蛋白(mmol/L) 1.1±0.2 1.1±0.2 1.2±0.3 1.1±0.3 0.375 0.689c
低密度脂蛋白(mmol/L) 2.6(2.3，3.2) 3.0(2.3，3.8) 3.4(2.7，4.8)a 2.9(2.5，3.8) 6.852 0.033d
空腹血糖(mmol/L) 7.7±3.6 7.0±3.5 7.9±4.1 8.4±4.1 0.438 0.647c
糖化血红蛋白(%) 7.8(6.6，9.4) 8.1(6.9，9.1) 8.0(6.6，9.5) 7.9(6.6，9.5) 0.171 0.918d
表3 3组糖尿病肾小管病患者随访资料
随访情况 DcR2/Cr1组(n＝21) DcR2/Cr2组(n＝22) DcR2/Cr3组(n＝22) 合计(n＝65) H/χ2值 P值
随访时间(月) 11.0(5.5，18.5) 10.5(6.0，24.2) 9.5(6.0，13.5) 10.0(6.0，17.5) 2.237 0.327d
终点事件[例(%)] 3(1 4.3) 8(36.4) 17(77.3)ab 28(43.1) 17.995 <0.001c
表4 尿诱骗受体2/肌酐水平与临床病理指标的相关性
指标 尿诱骗受体2/肌酐水平
r值 P值
NAG 0.408 0.002
尿白蛋白肌酐比 0.476 <0.001
胱抑素C 0.466 <0.001
估算的肾小球滤过率 －0.408 0.001
肾小管萎缩与间质纤维化 0.381 0.002
肾小球损伤 0.308 0.012
肾动脉玻璃样变 0.268 0.031
肾动脉硬化 0.25 0.045
图1 3组糖尿病肾小管患者终点的预测(Kaplan-Meier生存曲线分析)
表5 尿诱骗受体2/肌酐水平与糖尿病肾小管病预后的多因素Cox回归模型分析
组别 未校正HR值(95%CI) P值 模型校正后HR值(95%CI)a P值
DcR2/Cr 1组 1.0(参照)   1.0(参照)  
DcR2/Cr 2组 1.957(0.513~7.466) 0.326 1.137(0.288~4.485) 0.854
DcR2/Cr 3组 10.550(2.931~37.982) <0.001 11.416(2.763~47.175) 0.001
图2 尿诱骗受体2/肌酐等指标预测糖尿病肾小管预后的ROC曲线分析
表6 尿诱骗受体2/肌酐等指标对糖尿病肾小管预后的预测价值
生物标志物 最佳截断值 敏感性 特异性 约登指数 曲线下面积
尿DcR2/Cr 389.0 82.1% 74.3% 0.564 0.811
ACR 1958.3 89.3% 62.9% 0.522 0.789
胱抑素C 1.545 78.6% 68.6% 0.472 0.795
血肌酐 68.68 92.9% 40.0% 0.329 0.687
[1]
Reed J, Bain S, Kanamarlapudi V. A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives [J]. Diabetes Metab Syndr Obes, 2021, 14: 3567-3602.
[2]
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.
[3]
Perkins BA, Ficociello LH, Roshan B, et al. In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria [J]. Kidney Int, 2010, 77(1): 57-64.
[4]
Zeni L, Norden AGW, Cancarini G, et al. A more tubulocentric view of diabetic kidney disease [J]. J Nephrol, 2017, 30(6): 701-717.
[5]
Tang SCW, Leung JCK, Lai KN. Diabetic tubulopathy: an emerging entity [J]. Contrib Nephrol, 2011, 170: 124-34.
[6]
Mottl AK, Kwon K-S, Mauer M, et al. Normoalbuminuric diabetic kidney disease in the US population [J]. J Diabetes Complications, 2013, 27(2): 123-127.
[7]
Zhan M, Usman I, Yu J, et al. Perturbations in mitochondrial dynamics by p66Shc lead to renal tubular oxidative injury in human diabetic nephropathy [J]. Clin Sci (Lond), 2018, 132(12): 1297-1314.
[8]
Muñoz-Espín D, Cañamero M, Maraver A, et al. Programmed cell senescence during mammalian embryonic development [J]. Cell, 2013, 155(5): 1104-1118.
[9]
He S, Sharpless NE. Senescence in health and disease [J]. Cell, 2017, 169(6): 1000-1011.
[10]
Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan [J]. Nature, 2016, 530(7589): 184-189.
[11]
Kimberley FC, Screaton GR. Following a TRAIL: update on a ligand and its five receptors [J]. Cell Res, 2004, 14(5): 359-372.
[12]
Chen J, Zhang WW, Chen KH, et al. Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy [J]. Am J Physiol Renal Physiol, 2017, 313(2): F273-F281.
[13]
Tervaert TW, Mooyaart AL, Amann K, et al. Pathologic classification of diabetic nephropathy [J]. J Am Soc Nephrol, 2010, 21(4): 556-563.
[14]
Methven S, Gasparini A, Carrero JJ, et al. Routinely measured iohexol glomerular filtration rate versus creatinine-based estimated glomerular filtration rate as predictors of mortality in patients with advanced chronic kidney disease: a Swedish chronic kidney disease registry cohort study [J]. Nephrol Dial Transplant, 2017, 32(Suppl 2): ii170-ii179.
[15]
Hwang JH, Lee JP, Kim CT, et al. Urinary periostin excretion predicts renal outcome in IgA nephropathy [J]. Am J Nephrol, 2016, 44(6): 481-492.
[16]
胡威，陈佳，林利容，等. 尿DcR2/Cr评价IgA肾病肾小管间质损伤程度[J]. 第三军医大学学报，2017, 39(20): 2030-2034.
[17]
Levey AS, Inker LA, Matsushita K, et al. GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration [J]. Am J Kidney Dis, 2014, 64(6): 821-835.
[18]
Chien Y, Scuoppo C, Wang X, et al. Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity [J]. Genes Dev, 2011, 25(20): 2125-2136.
[19]
Chen K, Dai H, Yuan J, et al. Optineurin-mediated mitophagy protects renal tubular epithelial cells against accelerated senescence in diabetic nephropathy [J]. Cell Death Dis, 2018, 9(2): 105.
[20]
Tramonti G, Kanwar YS. Review and discussion of tubular biomarkers in the diagnosis and management of diabetic nephropathy [J]. Endocrine, 2013, 43(3): 494-503.
[21]
López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging [J]. Cell, 2013, 153(6): 1194-1217.
[22]
Jia C, Ke-Hong C, Fei X, et al. Decoy receptor 2 mediation of the senescent phenotype of tubular cells by interacting with peroxiredoxin 1 presents a novel mechanism of renal fibrosis in diabetic nephropathy [J]. Kidney Int, 2020, 98(3): 645-662.
[23]
Chen J, Chen KH, Wang LM, et al. Decoy receptor 2 mediates the apoptosis-resistant phenotype of senescent renal tubular cells and accelerates renal fibrosis in diabetic nephropathy [J]. Cell Death Dis, 2022, 13(6): 522.
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