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

doi:10.3969/j.issn.1674-8115.2024.05.007

Abstract

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)

CLC Number:

R692.4

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.

Figures/Tables 5

TrendMD

References 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