Trimethylamine-N-oxide is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis

Figures & data

Table 1. Demographic and clinical characteristics of hemodialysis (HD) patients according to different level of trimethylamine oxide.

Variables	Total(n = 69)	TMAO < 15μmol/L(n = 47)	TMAO  ≥ 15μmol/L(n = 22)	p Value
Age (years)	61.28 ± 11.99	60.28 ± 11.13	63.41 ± 13.68	0.316
Male, n (%)	36 (52.2%)	26 (55.3%)	10 (45.5%)	0.093
Dialysis vintages (months)	37 (26.5–81.0)	36.0 (25.0–76.0)	50.0 (30.8–86.8）	0.282
Body mass index, kg/m^2	21.67 ± 3.21	21.52 ± 3.04	21.36 ± 3.61	0.683
Vascular access (AVF %)	57 (82.6%)	39 (83.0%)	18 (81.9%)	1.000
Diabetes, n (%)	9 (13.0%)	7 (14.9%)	2 (9.0%)	0.777
Hypertension, n (%)	61 (88.40%)	41 (87.2%)	20 (90.9%)	0.967
Predialysis SBP	141.98 ± 13.64	141.93 ± 13.56	142.08 ± 14.12	0.967
Predialysis DBP	80.12 ± 9.07	80.65 ± 9.19	78.97 ± 8.91	0.477
IDWG (kg)	2.02 ± 0.88	2.04 ± 0.93	1.97 ± 0.79	0.780
IDH (%)	0.025 (0–0.147)	0.025 (0–0.086）	0.027 (0–0.195)	0.683
NT-proBNP (pg/ml)	2488 (1429–4935)	2075 (1225–4672）	2834 (1557–5146)	0.421
CK-MB (ng/ml)	1.63 (1.26–2.51)	1.55 (1.25–2.1)	1.92 (1.24–3.64）	0.221
TnT (ng/ml)	0.038 (0.027–0.068)	0.038 (0.028–0.065）	0.041 (0.025–0.083)	0.832
hsCRP (mg/L)	3.2 (0.92–5.49)	2.26 (0.78–4.75)	4.07 (1.34–6.05)	0.200
RBC (*10^12/L)	3.53 (3.25–3.81)	3.58 (3.28–3.82)	3.41 (3.21–3.81)	0.571
Hb (g/L)	106 (95.5–115.5)	106.0 (98–116)	102.5 (94–114.3)	0.723
β2MG (mg/L)	17.22 (15.02–18.67)	17.05 (14.27–18.41)	17.90 (15.80–19.15)	0.135
Prealbumin (g/L)	334.45 ± 75.40	333.64 ± 73.93	336.18 ± 80.19	0.897
Alb (g/L)	41.80 ± 4.56	41.80 ± 3.44	42.10 ± 6.37	0.400
Predialysis BUN (mmol/L)	27.97 ± 6.02	28.62 ± 6.30	26.60 ± 5.26	0.200
Predialysis Scr (μmol/L)	1014.19 ± 244.33	1045.70 ± 244.29	947.0 ± 235.88	0.119
Ca (mmol/L)	2.31 ± 0.19	2.29 ± 0.20	2.36 ± 0.17	0.125
P (mmol/L)	1.98 (1.74–2.40)	1.98 (1.68–2.49）	1.95 (1.78–2.27)	0.974
iPTH (ng/L)	353.2 (173.6–616.1)	395.5 (167–594.6)	352.7 (176.58–789.28)	0.616
Ferrintin (μg/L)	264.1 (143.7–443.3)	264.1 (124.6–474.2)	256.1 (186.88–306.5)	0.757
TSAT %	27.0 (22.0–36.5)	29.0 (23.0–38.0)	24 (20.0–30.75)	0.078
CHO (mmol/L)	4.10 (3.56–4.92)	4.92 ± 4.53	4.37 ± 0.99	0.503
LDL (mmol/L)	2.26 (1.76–2.94)	2.19 (1.71–2.5)	2.81(1.87–3.42)	0.093

TMAO: trimethylamine-N-oxide; AVF: arteriovenous fistula；SBP: systolic blood pressure; DBP: diastolic blood pressure; IDWG: interdialytic weight gain; IDH (%): incidence of interdialytic hypotension; NT-proBNP: N-Terminal pro-brain natriuretic peptide; CK-MB: creatine kinase isoenzyme; TnT: troponin I; hsCRP: high sensitivity C-reactive protein; iPTH: immunoreactive parathyroid hormone; RBC: red blood cell; Hb: hemoglobin; β2MG:β2 microglobulin; Alb: albumin; BUN: blood urea nitrogen; Scr: creatinine; Ca: calcium; P: phosphorus; TSAT: transferrin saturation; CHO: cholesterol; LDL: low-density lipoprotein.

Figure 1. Kaplan–Meier estimates for hospitalization events by the cutoff values of TMAO. Maintenance hemodialysis patients with serum TMAO levels (≥15 μmol/L) had more hospitalization events. (log-rank p = 0.0004).

Table 2. Univariate Cox regression analysis for factors predicting hospitalization events.

Covariates	Unit of increase	HR (95% CI)	p Value
Age	1yr	1.034 (0.991–1.079)	0.124
Sex	Male	1.062 (0.465–2.426)	0.887
Dialysis vintage	1 mo	0.998 (0.991–1.006)	0.628
BMI (kg/m^2)	<20	1.000	0.766
	20 ≤ BMI<24	1.095 (0.398–3.013)	0.861
	>24	0.779 (0.270–2.245)	0.643
Vascular access	AVF versus CVC	2.102 (0.871–5.071)	0.098
Diabetes	Yes versus no	2.491 (0.988–6.279)	0.053
Hypertension	Yes versus no	3.267 (0.441–24.199)	0.247
IDWG	1kg	0.819 (0.515–1.303)	0.400
IDH	1%	0.182 (0.009–3.748)	0.270
NT-proBNP (pg/ml)	<1000	1.000	0.437
	1000 ≤ NT-proBNP <10000	0.241 (0.025–2.322)	0.218
	≥10000	0.570 (0.169–1.918)	0.364
CK-MB	1 ng/ml	1.163 (0.982–1.378)	0.080
hsCRP	1 mg/L	1.013 (0.998–1.029)	0.085
Hb	1g/L	0.999 (0.973–1.025)	0.921
Albumin	1 g/L	1.001 (0.918–1.090)	0.988
Predialysis creatinine	1μmol/L	0.999(0.998–1.001)	0.569
iPTH	1 ng/L	1.000 (0.999–1.001)	0.852
P	1mmol/L	1.695 (0.980–2.934)	0.059
Ca	1mmol/L	0.376 (0.044–3.206)	0.371
LDL	1mmol/L	1.062 (0.879–1.283)	0.534
TMAO(entered as categorical variable)	High versus low	2.303 (1.031–5.144)	0.042

BMI: body mass index; SBP systolic blood pressure; DBP: diastolic blood pressure; AVF: arteriovenous fistula; CVC: central venous catheter; IDWG: interdialytic weight gain; IDH (%): incidence of interdialytic hypotension; NT-proBNP: N-Terminal pro-brain natriuretic peptide; CK-MB: creatine kinase isoenzyme; hsCRP: high sensitivity C-reactive protein; iPTH: immunoreactive parathyroid hormone; Hb: hemoglobin; Alb: albumin; Scr:creatinine; Ca: calcium; P: phosphorus; LDL: low-density lipoprotein; TMAO: trimethylamine-N-oxide; HR: hazard ratio.

Table 3. Multivariate Cox regression analysis for factors predicting hospitalization events.

Covariates	Model 1	p Value	Model 2	p Value	Model 3	p Value
	HR (95% CI)		HR (95% CI)		HR (95% CI)
Age	1.025 (0.981–1.072)	0.267	1.031 (0.989–1.075)	0.152
Male	1.393 (0.660–2.941)	0.384
TMAO (entered as categorical variable)	2.295 (1.008–5.225)	0.048	2.37 (1.062–5.293)	0.035	2.335 (1.040–5.242)	0.040
CK-MB			1.216 (0.995–1.486)	0.056
Albumin					0.990 (0.918–1.067)	0.787

CK-MB: creatine kinase isoenzyme; HR: hazard ratio.