Indoxyl sulfate and high-density lipoprotein cholesterol in early stages of chronic kidney disease

Figures & data

Table 1. Patients characteristics.

	Overall (n = 205)	CKD1 (n = 96)	CKD2 + 3 (n = 109)	p value
Demographics
Age, y	43.27 ± 13.80	41.46 ± 13.84	44.87 ± 13.66	0.077
Sex (men/women)	96/109	46/50	50/59	0.781
Smoking History (%)	27 (13.2%)	15 (15.6%)	12 (11.0%)	0.409
Anthropometric Measurements
Systolic BP, mmHg	131.48 ± 17.36	128.92 ± 13.87	133.73 ± 19.73	0.108
Diastolic BP, mmHg	82.87 ± 11.48	81.48 ± 10.19	84.09 ± 12.43	0.072
BMI, kg/m^2	24.24 ± 3.69	24.23 ± 3.41	24.26 ± 3.93	0.948
Underlying Kidney Disease (n, %)
Glomerular disease	164 (80.0%)	84 (87.5%)	80 (73.4%)
Diabetic nephropathy	16 (7.8%)	3 (3.1%)	13 (11.9%)
Hypertensive nephropathy	7 (3.4%)	2 (2.1%)	5 (4.6%)
Polycystic kidney disease	1 (0.5%)	1 (1.0%)	0
Others	1 (0.5%)	0	1 (0.9%)
Unknown	16 (7.8%)	6 (6.3%)	10 (9.2%)
Comorbidity (n, %)
Hypertension	97 (47.3%)	33 (34.4%)	64 (58.7%)	0.001
Diabetes	29 (14.1%)	9 (9.4%)	20 (18.3%)	0.073
Gout	6 (2.9%)	2 (2.1%)	4 (3.7%)	0.687
CVD	7 (3.4%)	1 (1.0%)	6 (5.5%)	0.124
Laboratory Tests
Hemoglobin, g/L	131.00 ± 19.17	136.45 ± 14.77	126.16 ± 21.29	<0.001
HbA1c, %	5.67 ± 0.94	5.54 ± 0.87	5.79 ± 0.99	0.047
Albumin, g/L	33.72 ± 8.52	33.84 ± 8.68	33.61 ± 8.43	0.842
pre-Albumin, g/L	0.29 ± 0.07	0.29 ± 0.06	0.29 ± 0.07	0.613
BUN, mmol/L	5.96 ± 2.76	4.60 ± 1.28	7.17 ± 3.13	<0.001
Scr, μmol/L	80.50 (64.0-108.8)	64.00 (55.5-76.5)	107.00 (85.3-130.3)	<0.001
UA, μmol/L	360.64 ± 99.00	328.04 ± 86.56	389.62 ± 100.69	<0.001
eGFR, ml/min/1.73m^2	84.59 ± 26.20	107.88 ± 11.32	64.30 ± 16.92	<0.001
Urine protein, g/d	1.38 (0.74-2.81)	1.23 (0.69-2.67)	1.71 (0.95-3.16)	0.085
IS, μg/ml	1.24 ± 1.37	0.94 ± 0.66	1.50 ± 1.74	0.007
TC, mmol/L	5.56 ± 2.00	5.62 ± 2.04	5.52 ± 1.97	0.722
TG, mmol/L	1.77 (1.25-2.67)	1.72 (1.19-2.53)	1.91 (1.30-2.78)	0.533
HDL-c, mmol/L	1.25 ± 0.42	1.33 ± 0.45	1.19 ± 0.39	0.017
LDL-c, mmol/L	3.36 ± 1.70	3.33 ± 1.71	3.37 ± 1.69	0.871
hsCRP, mg/L	1.20 (0.43-2.38)	1.00 (0.48-2.20)	1.40 (0.40-2.63)	0.168

Continuous data expressed as mean ± standard deviation or median [interquartile range]; Categorical data expressed as count (percentage).

p value: CKD2 + 3 group vs. CKD1 group.

CKD: chronic kidney disease; BP: blood pressure; BMI: body mass index; HbA1c: glycated hemoglobin; BUN: blood urea nitrogen; Scr: serum creatinine; UA: uric acid; eGFR: estimated glomerular filtration rate; IS: indoxyl sulfate; TC: total cholesterol; TG: triglycerides; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; hsCRP: high- sensitivity C-reactive protein.

Table 2. Correlation of high IS levels with other variables.

Variables	r	p value
eGFR	−0.245	<0.001
Systolic BP	0.221	0.001
Diastolic BP	0.143	0.040
Hypertension History	0.216	0.002
CVD History	0.230	0.001
Hemoglobin	−0.157	0.025
Albumin	0.280	<0.001
BUN	0.242	<0.001
Scr	0.222	0.001
HDL-c	−0.244	0.001
hsCRP	0.168	0.019
Urine protein	−0.254	<0.001

IS: indoxyl sulfate; HDL-c: high-density lipoprotein cholesterol; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; BP: blood pressure; BUN: blood urea nitrogen; Scr: serum creatinine; hsCRP: high- sensitivity C-reactive protein.

Figure 1. Trend of HDL-c levels in the four IS quartiles.* vs. quartle1, p < 0.05.

Table 3. Logistic regression of low HDL-c incidence with IS levels increment.

	OR (95%CI)	p value
Model 1	1.56 (1.07–2.27)	0.018
Model 2	1.55 (1.05–2.30)	0.028
Model 3	1.71 (1.13–2.59)	0.010
Model 4	1.57 (1.02–2.41)	0.039

Model 1. Crude;.

Model 2. Adjusted for hypertension history, diabetes history, gout history, smoking history and CVD history, age, sex, Systolic BP, Diastolic BP and BMI;.

Model 3. Model 2 further adjusted for hemoglobin, HbA1c, albumin and hsCRP;.

Modle 4. Model 3 further adjusted for eGFR, BUN, Scr, UA and 24 h urine protein.

Table 4. Risk factors predicting for CKD stage 3.

variables	OR(95%CI)	p value
HDL-c	0.15 (0.04–0.57)	0.006
IS	1.67 (1.06–2.63)	0.027
Systolic BP	1.04 (1.01–1.06)	0.003
Hemoglobin	0.98 (0.95–1.00)	0.004
Urine protein	1.23 (1.08–1.40)	0.002

Adjusted for medical history of primary hypertension, diabetes, gout and CVD, sex, age,

BMI, diastolic BP, HbA1c, albumin, pre-albumin, TG, TC, LDL-c and hsCRP.

CKD: chronic kidney disease; HDL-c: high-density lipoprotein cholesterol; IS: indoxyl sulfate; BP: blood pressure.

Data availability statement

The datasets used and analyzed during the current study are available from the corresponding authors on reasonable request.