Association Between Indoxyl Sulfate and Dialysis Initiation and Cardiac Outcomes in Chronic Kidney Disease Patients

Figures & data

Table 1 Clinical Characteristics Stratified According to Indoxyl Sulfate Levels

	Low Indoxyl Sulfate (n=44)	High Indoxyl Sulfate (n=45)	p-value
Age	67.36 ± 14.57	59.71 ± 14.81	0.016
Diabetes mellitus	20 (45.45%)	25 (55.56%)	0.346
Creatinine (mg/dL)	2.56 ± 2.53	5.57 ± 2.77	<0.001
eGFR (mL/min/1.73m2)	32.52 ± 12.08	12.46 ± 9.11	<0.001
Calcium (mg/dL)	9.24 ± 1.47	9.03 ± 1.07	0.448
Phosphate (mg/dL)	3.55 ± 0.64	4.74 ± 1.25	<0.001
Albumin (g/dL)	4.04 ± 0.32	3.91 ± 0.36	0.086
Hemoglobin (g/dL)	11.82 ± 1.75	10.15 ± 0.49	<0.001
C-reactive protein (mg/L)	14.04 (11.84)	20.9 (18.8)	<0.001
ABI	1.06 ± 0.16	1.07 ± 0.14	0.756
CAVI	7.76 ± 1.45	8.67 ± 1.46	0.012
LVDd	4.78 ± 0.92	4.88 ± 0.80	0.621
LVDs	3.09 ± 1.04	3.09 ± 0 0.73	0.979
LVEF	62.56 ± 13	64.02 ± 12	0.595
LVMI	116.12 ± 37	121.92 ±36	0.465
LAVI	29.49 ± 12	36.29 ± 15	0.029
E/A	1.01 ± 0.37	0.98 ± 0.42	0.738
E/e’	15.82 ± 6.5	17.39 ± 6.16	0.269
GLS (%)	−16.87 ± 5.32	−14.9 ± 4.09	0.125
Reduced LVEF	5 (11.36%)	7 (15.56%)	0.567
LVH	25(57%)	37 (82.2%)	0.013
LA enlargement	12 (27.2%)	25 (55.5%)	0.010
Impaired LV strain	20 (45.5%)	30 (66.7%)	0.025

Note: Data are presented as mean ± SD, median (IQR).

Abbreviations: ABI, ankle-brachial index; CAVI, cardio-ankle vascular index; eGFR, estimated glomerular filtration rate; GLS, global longitudinal strain; LAVI, left atrial volume index; LVEF, left ventricular ejection fraction; LVDd, left ventricular diastolic dimension; LVDs, left ventricular systolic dimension; LVH, left ventricular hypertrophy; LVMI, left ventricular mass index.

Table 2 Univariate and Multivariate Linear Regression Analyses for Indoxyl Sulfate

	Univariate Analysis		Multivariate Analysis
	r	p-value	r	p-value
Age	−0.19	0.005	−0.06	0.271
Creatinine	2.16	<0.001	1.49	<0.001
Calcium	−1.23	0.164
Phosphate	4.47	<0.001	0.04	0.97
Albumin	−2.34	0.428
Hemoglobin	−2.44	<0.001	−1.76	0.002
ABI	11.33	0.166
CAVI	0.04	0.955
LVDd	1.23	0.314
LVDs	1.07	0.361
LVEF	−0.01	0.918
LVMI	0.02	0.45
LAVI	0.04	0.574
E/A	0.62	0.82
E/e’	0.05	0.756
GLS (%)	0.62	0.01	0.42	0.033

Abbreviations: ABI, ankle-brachial index; CAVI, cardio-ankle vascular index; GLS, global longitudinal strain; LAVI, left atrial volume index; LVEF, left ventricular ejection fraction; LVDd, left ventricular diastolic dimension; LVDs, left ventricular systolic dimension; LVMI, left ventricular mass index.

Figure 1 Linear regression curve. Relationship between serum levels of indoxyl sulfate and global longitudinal strain.

Table 3 Univariate and Multivariate Cox Proportional Hazards Models of Dialysis Initiation During Follow-Up

	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p-value	HR (95% CI)	p-value
Age (years)	1.03 (1.01–1.05)	0.005	0.98 (0.96–1.01)	0.194
Male	1.18 (0.60–2.39)	0.480
Diabetes mellitus	0.95 (0.48–1.86)	0.884
Smoking	1.17 (0.28–4.91)	0.829
RAAS inhibitors	0.22 (0.09–0.54)	0.001	0.45 (0.17–1.16)	0.099
Creatinine (mg/dL)	1.17 (1.10–1.25)	< 0.001	1.1 (0.98–1.22)	0.093
Indoxyl sulfate (mg/L)	1.08 (1.05–1.11)	< 0.001	1.04 (1.01–1.08)	0.022
CAVI	0.99 (0.78–1.27)	0.984
GLS	1.11 (1.02–1.19)	0.010	1.00 (0.90–1.11)	0.931
LVEF (%)	0.97 (0.95–0.99)	0.035	0.96 (0.93–0.99)	0.033

Abbreviations: CAVI, cardio-ankle vascular index; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; RAAS, renin-angiotensin-aldosterone system.

Figure 2 Kaplan–Meier curves of cumulative event-free survival for dialysis according to low- and high- indoxyl sulfate group.

Table 4 Cox Univariate and Multivariate Regression Analyses for Predictors of Cardiovascular Events

	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p-value	HR (95% CI)	p-value
Age (years)	1.08 (1.02–1.13)	0.004	1.05 (0.97–1.13)	0.225
Male	3.94 (0.89–17.47)	0.071
Smoking	1.19 (0.16–9.03)	0.868
Creatinine (mg/dL)	1.03 (0.99–1.06)	0.067
Indoxyl sulfate (mg/L)	0.92 (0.83–1.00)	0.069
ABI	6.21 (0.03–11.84)	0.495
CAVI	1.72 (1.10–2.69)	0.017	1.15 (0.69–1.90)	0.580
LVEF (%)	0.96 (0.93–0.99)	0.011	0.98 (0.89–1.08)	0.736
LVMI (g/m2)	1.01 (0.99–1.02)	0.261
LAVI (mL/m2)	1.02 (0.99–1.05)	0.184
GLS (%)	1.21 (1.02–1.42)	0.026	1.26 (1.01–1.59)	0.045

Abbreviations: ABI, ankle-brachial index; CAVI, cardio-ankle vascular index; GLS, global longitudinal strain; LAVI, left atrial volume index; LVMI, left ventricular mass index.

Figure 3 Kaplan–Meier curve of the cumulative cardiovascular event-free survival stratified by GLS (preserved and impaired GLS groups).