尿液中蛋白结合毒素水平与上尿路结石的相关性研究

doi:10.3969/j.issn.1674-8115.2024.05.007

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (5): 591-598.doi: 10.3969/j.issn.1674-8115.2024.05.007

• 论著 · 临床研究 • 上一篇

尿液中蛋白结合毒素水平与上尿路结石的相关性研究

王文姬¹(), 钟开义², 李椒纶¹, 周悦玲¹, 黄涛¹, 段丽珠¹, 沈毓琪¹, 李雪竹¹, 丁峰¹, 谢丹庶¹()

^1.上海交通大学医学院附属第九人民医院肾脏内科，上海 200011
^2.海南西部中心医院肾脏内科，儋州 571700

收稿日期:2023-10-16 接受日期:2024-02-23 出版日期:2024-05-28 发布日期:2024-05-28
通讯作者: 谢丹庶 E-mail:codein2004@126.com;melody_hp@163.com
作者简介:王文姬（1980—），女，主治医师，博士；电子信箱：codein2004@126.com。
基金资助:
上海市卫生健康委员会科研项目(202040435);上海交通大学医学院附属第九人民医院临床研究助力计划(JYLJ202218);上海交通大学医学院附属第九人民医院生物样本库专项基金(YBKB202115)

Association between urinary excretion of protein-bound uremic toxins and upper urinary tract calculus

WANG Wenji¹(), ZHONG Kaiyi², LI Jiaolun¹, ZHOU Yueling¹, HUANG Tao¹, DUAN Lizhu¹, SHEN Yuqi¹, LI Xuezhu¹, DING Feng¹, XIE Danshu¹()

^1.Department of Nephrology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
^2.Department of Nephrology, Hainan West Central Hospital, Danzhou 571700, China

Received:2023-10-16 Accepted:2024-02-23 Online:2024-05-28 Published:2024-05-28
Contact: XIE Danshu E-mail:codein2004@126.com;melody_hp@163.com
Supported by:
Project of Shanghai Municipal Health Commission(202040435);Clinical Research Program of Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine(JYLJ202218);Project of Biobank from Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine(YBKB202115)

摘要/Abstract

摘要：

目的·探讨尿液中蛋白结合毒素（protein-bound uremic toxin，PBUT）水平与上尿路结石形成的关系。方法·以海南省儋州市海头镇社区18~80岁居民为研究对象。记录研究对象基本信息和近3 d饮食情况，收集空腹血清和24 h尿液标本，所有对象接受肾脏和输尿管B超检查。将B超检查发现有上尿路结石或有明确上尿路结石病史的对象作为结石组，其他作为非结石组。检测血、尿中结石形成相关的生化指标，通过高效液相色谱检测血、尿中的PBUT（硫酸吲哚酚、3-吲哚乙酸和硫酸对甲酚），以及尿草酸和尿枸橼酸水平。通过多因素Logistic回归分析上尿路结石形成的相关因素。采用Spearman相关性检验分析尿PBUT与尿尿酸、草酸和枸橼酸的相关性。结果·经筛选，共纳入117例研究对象，其中结石组54例，非结石组63例。2组的性别、年龄、血清指标，以及高血压、糖尿病、高尿酸血症/痛风等合并症比例方面差异均无统计学意义。结石组的24 h尿液pH值、钙、尿酸和氯均显著高于非结石组（均P<0.05），而硫酸吲哚酚显著低于非结石组（P<0.05）。多因素Logistic回归分析结果显示，除尿钙外，尿硫酸吲哚酚水平（OR=0.929，95%CI 0.875~0.986，P=0.016）也是上尿路结石形成的独立相关因素。Spearman相关性分析结果显示，24 h尿液中3-吲哚乙酸（r=0.420，P=0.000）和硫酸对甲酚（r=0.307，P=0.001）水平均与草酸呈正相关，硫酸对甲酚水平与尿酸呈正相关（r=0.297，P=0.002），硫酸吲哚酚水平与枸橼酸呈正相关（r=0.289，P=0.002）。结论·在该研究人群中，尿硫酸吲哚酚水平降低可能是上尿路结石形成的独立危险因素，且尿液中PBUT水平与尿酸、草酸、枸橼酸的水平相关。

关键词: 蛋白结合毒素, 上尿路结石, 肾小管分泌, 硫酸吲哚酚, 3-吲哚乙酸, 硫酸对甲酚

Abstract:

Objective ·To investigate the relation between urinary excretion of protein-bound uremic toxins (PBUTs) and upper urinary tract calculus. Methods ·Residents aged 18?80 years in the community of Haitou, Danzhou city in Hainan Province were recruited. Basic information and diet for the last 3 d of the subjects were recorded. Their fasting sera and 24-hour urine samples were collected, and they also underwent ultrasound examination of kidneys and ureters. The subjects with upper urinary calculi detected by ultrasound or a clear history of upper urinary calculi were selected as the calculus group, and the others as the non-calculus group. The biochemical indicators related to the formation of calculus in blood and urine were detected, and the levels of PBUTs, including indoxyl sufate (IS), indole-3-acetic acid (IAA), and p-cresol sulfate (PCS) in blood and urine, as well as oxalic acid and citric acid in urine were detected by high-performance liquid chromatography. The related factors of upper urinary tract calculus formation were analyzed by multivariate Logistic regression. The correlations of urine PBUTs with urine uric acid, oxalic acid, and citric acid were analyzed by Spearman correlation test. Results ·A total of 117 participants were screened out with 54 people in the calculus group and 63 people in the non-calculus group. There were no significant differences between the two groups in terms of gender, age, serum indicators, and prevalence of complications such as hypertension, diabetes, and hyperuricemia/gout. The 24-hour urine pH, calcium, uric acid, and chlorine in the calculus group were significantly higher than those in the non-calculus group (all P<0.05), while IS was significantly lower than that in the non-calculus group (P<0.05). Multivariate Logistic regression analysis showed that urinary IS (OR=0.929, 95%CI 0.875?0.986, P=0.016) was related to the calculus formation independently, in addition to urinary calcium. The Spearman correlation analysis results showed that the levels of IAA (r=0.420, P=0.000) and PCS (r=0.307, P=0.001) in 24-hour urine were positively correlated with oxalic acid, PCS was positively correlated with uric acid (r=0.297, P=0.002), and IS was positively correlated with citric acid (r=0.289, P=0.002). Conclusion ·In the population, a decrease in urinary excretion of IS may be an independent risk factor for the formation of upper urinary tract calculus, and PBUTs levels are correlated with levels of uric acid, oxalic acid, and citric acid.

Key words: protein-bound uremic toxin (PBUT), upper urinary tract calculus, renal tubular secretion, indoxyl sufate (IS), indole-3-acetic acid (IAA), p-cresol sulfate (PCS)

中图分类号:

R692.4

王文姬, 钟开义, 李椒纶, 周悦玲, 黄涛, 段丽珠, 沈毓琪, 李雪竹, 丁峰, 谢丹庶. 尿液中蛋白结合毒素水平与上尿路结石的相关性研究[J]. 上海交通大学学报（医学版）, 2024, 44(5): 591-598.

WANG Wenji, ZHONG Kaiyi, LI Jiaolun, ZHOU Yueling, HUANG Tao, DUAN Lizhu, SHEN Yuqi, LI Xuezhu, DING Feng, XIE Danshu. Association between urinary excretion of protein-bound uremic toxins and upper urinary tract calculus[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(5): 591-598.

图/表 5

参考文献 39

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Characteristic	All (n=117)	Calculi group (n=54)	Non-calculi group (n=63)	P value
Male/n(%)	66 (56.4)	35 (64.8)	31 (49.2)	0.090
Age/year	50.21±13.63	51.72±10.33	48.90±15.89	0.267
Hypertension/n(%)	34 (29.1)	18 (33.3)	16 (25.4)	0.346
Diabetes/n(%)	8 (6.8)	5 (9.3)	3 (4.8)	0.337
Hyperuricemia/gout/n(%)	9 (7.7)	6 (11.1)	3 (4.8)	0.254
Family history of upper tract urinary calculi/n(%)	11 (9.4)	5 (9.3)	6 (9.5)	0.781
Daily water intake/L	0.70±0.45	0.63±0.43	0.73±0.47	0.382
Meat to vegetable ratio/(g·g^-1)	0.52±0.18	0.52±0.11	0.53±0.21	0.697

Characteristic	All (n=117)	Calculi group (n=54)	Non-calculi group (n=63)	P value
Male/n(%)	66 (56.4)	35 (64.8)	31 (49.2)	0.090
Age/year	50.21±13.63	51.72±10.33	48.90±15.89	0.267
Hypertension/n(%)	34 (29.1)	18 (33.3)	16 (25.4)	0.346
Diabetes/n(%)	8 (6.8)	5 (9.3)	3 (4.8)	0.337
Hyperuricemia/gout/n(%)	9 (7.7)	6 (11.1)	3 (4.8)	0.254
Family history of upper tract urinary calculi/n(%)	11 (9.4)	5 (9.3)	6 (9.5)	0.781
Daily water intake/L	0.70±0.45	0.63±0.43	0.73±0.47	0.382
Meat to vegetable ratio/(g·g^-1)	0.52±0.18	0.52±0.11	0.53±0.21	0.697

Serum parameter	All (n=117)	Calculi group (n=54)	Non-calculi group (n=63)	P value
Creatinine/(μmol·L^-1)	68.77±15.21	70.15±13.39	67.59±16.63	0.366
eGFR/[mL·(min·1.73 m²)^-1]	95.67±17.67	94.11±18.40	97.25±16.94	0.361
Uric acid/(μmol·L^-1)	351.27±96.75	366.37±113.93	338.33±77.79	0.130
Glucose/(mmol·L^-1)	5.52±2.32	5.29±1.13	5.71±3.18	0.318
Albumin/(g·L^-1)	43.22±3.61	43.29±4.12	43.15±3.03	0.838
Potassium/(mmol·L^-1)	4.46±0.68	4.36±0.75	4.56±0.60	0.106
Sodium/(mmol·L^-1)	141.40±1.88	141.69±1.83	141.16±1.91	0.133
Chloride/(mmol·L^-1)	103.49±2.49	103.89±2.83	103.14±2.13	0.107
Calcium/(mmol·L^-1)	2.35±0.09	2.33±0.09	2.36±0.09	0.083
Phosphorus/(mmol·L^-1)	1.26±0.58	1.33±0.85	1.20±0.21	0.290
Magnesium/(mmol·L^-1)	0.90±0.06	0.90±0.06	0.90±0.07	0.803
IS/(μmol·L^-1)	1.40 (0.92, 2.25)	1.40 (1.09, 2.70)	1.40 (0.78, 2.09)	0.306
IAA/(μmol·L^-1)	2.50 (1.91, 3.62)	2.35 (1.81, 3.30)	2.62 (1.94, 3.66)	0.567
PCS/(μmol·L^-1)	5.15 (2.06, 12.06)	5.10 (2.15, 10.05)	5.66 (1.95, 12.13)	0.971

Serum parameter	All (n=117)	Calculi group (n=54)	Non-calculi group (n=63)	P value
Creatinine/(μmol·L^-1)	68.77±15.21	70.15±13.39	67.59±16.63	0.366
eGFR/[mL·(min·1.73 m²)^-1]	95.67±17.67	94.11±18.40	97.25±16.94	0.361
Uric acid/(μmol·L^-1)	351.27±96.75	366.37±113.93	338.33±77.79	0.130
Glucose/(mmol·L^-1)	5.52±2.32	5.29±1.13	5.71±3.18	0.318
Albumin/(g·L^-1)	43.22±3.61	43.29±4.12	43.15±3.03	0.838
Potassium/(mmol·L^-1)	4.46±0.68	4.36±0.75	4.56±0.60	0.106
Sodium/(mmol·L^-1)	141.40±1.88	141.69±1.83	141.16±1.91	0.133
Chloride/(mmol·L^-1)	103.49±2.49	103.89±2.83	103.14±2.13	0.107
Calcium/(mmol·L^-1)	2.35±0.09	2.33±0.09	2.36±0.09	0.083
Phosphorus/(mmol·L^-1)	1.26±0.58	1.33±0.85	1.20±0.21	0.290
Magnesium/(mmol·L^-1)	0.90±0.06	0.90±0.06	0.90±0.07	0.803
IS/(μmol·L^-1)	1.40 (0.92, 2.25)	1.40 (1.09, 2.70)	1.40 (0.78, 2.09)	0.306
IAA/(μmol·L^-1)	2.50 (1.91, 3.62)	2.35 (1.81, 3.30)	2.62 (1.94, 3.66)	0.567
PCS/(μmol·L^-1)	5.15 (2.06, 12.06)	5.10 (2.15, 10.05)	5.66 (1.95, 12.13)	0.971

24-hour urinary parameter	All (n=117)	Calculi group (n=54)	Non-calculi group (n=63)	P value
Urine volume/mL	1 400.7±600.1	1 495.3±736.4	1 321.3±447.7	0.137
pH	6.16 (5.77, 6.54)	6.35 (6.04, 6.66)	6.01 (5.61, 6.40)	0.010
Potassium/mmol	31.90±19.10	34.81±23.94	29.40±13.37	0.127
Sodium/mmol	107.44±53.00	116.03±51.99	100.08±53.15	0.104
Chloride/mmol	115.08±57.43	129.21±62.71	102.97±49.88	0.013
Calcium/mmol	3.49±1.81	3.89±1.81	3.15±1.74	0.027
Phosphorus/mmol	17.43 (12.87, 21.98)	17.41 (12.80, 19.17)	17.51 (11.70, 20.79)	0.870
Magnesium/mmol	2.78±1.29	2.93±1.20	2. 64±1.35	0.239
Urea/mmol	229.90 (171.70, 288.10)	240.60 (191.68, 289.51)	217.14 (153.66, 280.62)	0.241
Uric acid/mmol	2 284.7±1 296.8	2 648.6±1 549.0	1 972.9±938.6	0.006
Creatinine/μmol	9 316.4±3 989.1	9 988.9±4 259.4	8 740.1±3 678.5	0.091
UACR/(mg·g^-1)	7.57 (2.67, 12.46)	8.69 (3.93, 16.78)	7.07 (4.52, 10.41)	0.153
IS/μmol	63.20 (18.67, 107.72)	46.56 (35.95, 74.38)	83.39 (32.91, 97.33)	0.040
IAA/μmol	34.65 (20.67, 48.62)	37.32 (22.18, 55.34)	32.90 (26.63, 46.08)	0.754
PCS/μmol	110.78 (71.88, 222.37)	117.58 (63.71, 265.36)	110.78 (78.83, 178.35)	0.593
Oxalic acid/μmol	0.154 (0.129, 0.295)	0.121 (0.149, 0.254)	0.156 (0.123, 0.298)	0.068
Citric acid/μmol	6.001 (3.098, 8.359)	5.443 (3.118, 7.495)	6.120 (3.081, 8.622)	0.743
Urea creatinine ratio	28.63±10.02	27.67±7.93	29.44±11.52	0.344

尿液中蛋白结合毒素水平与上尿路结石的相关性研究

Association between urinary excretion of protein-bound uremic toxins and upper urinary tract calculus

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Metrics

Urinary solute	IS		IAA		PCS
Urinary solute	r	P value	r	P value	r	P value
Uric acid	0.031	0.739	0.142	0.234	0.297	0.002
Oxalic acid	0.143	0.123	0.420	0.000	0.307	0.001
Citric acid	0.289	0.002	0.221	0.062	0.188	0.050

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