Association between monocyte-lymphocyte ratio and all-cause and cardiovascular mortality in patients with chronic kidney diseases: A data analysis from national health and nutrition examination survey (NHANES) 2003-2010

Figures & data

Figure 1. Flow diagram of the selection of eligible participants.

Table 1. Clinical features of the participants with or without CKD.

Characteristic	Overall (n = 11262)	Non-CKD (n = 8247)	CKD (n = 3015)	P Value
Age (years)	51 (40, 64)	49 (37, 60)	66 (53, 77)	<0.001
Gender (male, %)	5,379 (47%)	3,856 (47%)	1,523 (46%)	0.7
Race				0.4
Mexican American	1,920 (7.0%)	1,424 (7.0%)	496 (6.9%)
Non-Hispanic Black	2,097 (10%)	1,543 (10.0%)	554 (11%)
Non-Hispanic White	5,716 (74%)	4,072 (73%)	1,644 (75%)
Other Race	1,529 (9.4%)	1,208 (NA%)	321 (NA%)
Education level				<0.001
College or above	5,111 (55%)	4,053 (59%)	1,058 (42%)
High School	2,749 (26%)	1,968 (25%)	781 (31%)
Less than high school	3,402 (19%)	2,226 (17%)	1,176 (27%)
Smoking status (%)				0.4
Current smoker	2,195 (20%)	1,723 (21%)	472 (17%)
Former smoker	3,226 (28%)	2,198 (28%)	1,028 (30%)
Never smoker	5,841 (52%)	4,326 (52%)	1,515 (52%)
Comorbidity
Hypertension, n (%)	6,187 (48%)	3,789 (41%)	2,398 (77%)	<0.001
Diabetes, n (%)	3,366 (23%)	1,753 (17%)	1,613 (45%)	<0.001
CVD, n (%)	2,143 (15%)	1,067 (9.9%)	1,076 (32%)	<0.001
Heart failure, n (%)	617 (3.9%)	237 (2.0%)	380 (11%)	<0.001
CHD, n (%)	888 (6.4%)	466 (4.5%)	422 (14%)	<0.001
Dialysis	69 (8.4%)	8 (5.5%)	61 (9.5%)	0.6
Medication history
Statin	750 (6.3%)	496 (5.8%)	254 (8.2%)	<0.001
Aspirin	157 (1.0%)	89 (0.8%)	68 (2.0%)	<0.001
ACEI	620 (4.9%)	415 (4.5%)	205 (6.5%)	<0.001
ACR (mg/g)				<0.001
< =30	9,255 (87%)	8,247 (100%)	1,008 (35%)
30-300	1,841 (12%)	0 (0%)	1,841 (60%)
> =300	166 (1.0%)	0 (0%)	166 (4.6%)
eGFR (ml/min/1.73 m2)				<0.001
G1 (>90)	5,805 (53%)	5,048 (59%)	757 (28%)
G2 (60-90)	3,804 (36%)	3,199 (41%)	605 (19%)
G3a (45-59)	1,026 (7.3%)	0 (0%)	1,026 (35%)
G3b (30-44)	372 (2.2%)	0 (0%)	372 (11%)
G4 (15-30)	211 (1.4%)	0 (0%)	211 (6.5%)
G5 (<15)	44 (0.2%)	0 (0%)	44 (0.8%)
eGFR (ml/min/1.73 m2)	92 (75, 108)	95 (82, 109)	59 (51, 92)	<0.001
Body mass index (kg/m^2)	28 (25, 33)	28 (25, 33)	30 (26, 35)	<0.001
Systolic blood pressure (mmHg)	120 (110, 132)	119 (109, 129)	130 (116, 144)	<0.001
Red blood cell (10^9/L)	4.65 (4.32, 5.02)	4.69 (4.39, 5.03)	4.51 (4.07, 4.98)	<0.001
hemoglobin (g/dL)	14.30 (13.30, 15.30)	14.40 (13.40, 15.40)	13.90 (12.60, 15.00)	<0.001
Platelet (10^9/L)	250 (209, 297)	252 (213, 298)	242 (201, 287)	0.001
ALT (U/L)	22 (17, 29)	22 (17, 29)	21 (17, 27)	0.005
Serum creatine (umol/L)	0.89 (0.74, 1.00)	0.83 (0.72, 0.97)	1.06 (0.86, 1.32)	<0.001
Blood urea nitrogen (mmol/L)	4.64 (3.57, 5.71)	4.28 (3.57, 5.36)	6.07 (4.28, 8.21)	<0.001
TC (mg/dL)	189 (165, 218)	192 (167, 221)	180 (153, 206)	<0.001
TG (mg/dL)	115 (81, 171)	112 (78, 165)	127 (92, 197)	<0.001
Non-HDL-C	135 (110, 164)	137 (113, 165)	126 (100, 157)	<0.001
Glucoses (mmol/l)	5.61 (5.16, 6.27)	5.55 (5.16, 6.05)	6.11 (5.50, 7.49)	<0.001
HbA1c (%)	5.50 (5.20, 5.90)	5.50 (5.20, 5.80)	5.90 (5.40, 6.60)	<0.001
MLR	0.27 (0.21, 0.35)	0.26 (0.21, 0.33)	0.30 (0.23, 0.38)	0.002
NLR	1.96 (1.50, 2.65)	1.94 (1.48, 2.59)	2.19 (1.56, 3.09)	0.003
Albumin (g/L)	42.0 (40.0, 44.0)	42.0 (40.0, 44.0)	41.0 (39.0, 44.0)	<0.001
C-reactive protein(mg/dL)	0.20 (0.08, 0.46)	0.18 (0.08, 0.42)	0.25 (0.10, 0.57)	<0.001
CVD mortality, n (%)	903 (6.4%)	377 (3.7%)	526 (16%)	<0.001
All-cause mortality, n (%)	2,519 (18%)	1,121 (11%)	1,398 (43%)	<0.001

Continuous data were presented as median (interquartile range), categorical data were presented as frequencies (percentages). All estimates include a complex survey design.

Abbreviations: CKD, chronic kidney disease; MLR, monocyte-to-lymphocyte ratio; CVD, cardiovascular disease; CHD, coronary heart disease; ACEI, angiotensin-converting enzyme inhibitors; eGFR, estimated glomerular filtration rate; BMI, body mass index; SBP, systolic blood pressure; ALT, Alanine aminotransferase; BUN, blood urea nitrogen; TC, total cholesterol; TG, triglyceride; Non-HDL-C, non-high density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; NLR, neutrophil to lymphocyte ratio.

Table 2. The partial correlations of MLR and clinical characteristics.

Variables	MLR
	r (95% CI)	P-value
Serum creatine	0.088 (0.043, 0.140)	<0.001
eGFR	−0.063 (-0.096, −0.034)	<0.001
BUN	0.061 (0.024, 0.101)	0.001
HbA1c	−0.159 (-0.187, −0.135)	<0.001
Glucose	−0.145 (-0.173, −0.123)	<0.001
TG	−0.148 (-0.172, −0.126)	<0.001
TC	−0.052 (-0.080, −0.028)	0.004
Red blood cell	−0.140 (-0.171, −0.107)	<0.001
Hemoglobin	−0.087 (-0.114, −0.054)	<0.001

The partial correlation analysis adjusted for age, gender, and race.

Abbreviations: MLR, monocyte-to-lymphocyte ratio; eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen; HbA1c, glycosylated hemoglobin; TC, total cholesterol; TG, triglyceride.

Figure 2. Kaplan-Meier survival curve for mortality by MLR quartiles.

Kaplan-Meier survival curve for all-cause mortality (A) and CVD mortality (B) by MLR.

Table 3. Weighted association between MLR and mortality.

	MLR					p for trend
	Overall	Q1	Q2	Q3	Q4
All-cause mortality
Unadjusted	6.96 (4.24, 11.4)	1.00	1.53 (0.79, 2.93)	2.21 (1.26, 3.87)	3.21 (1.93, 5.33)	<0.001
Model 1	4.26 (2.26, 8.02)	1.00	1.32 (0.78, 2.22)	1.90 (1.13, 3.17)	1.96 (1.16, 3.31)	0.006
Model 2	2.72 (1.22, 6.06)	1.00	1.54 (0.84, 2.82)	2.16 (1.26, 3.70)	1.92 (1.10, 3.35)	0.012
CVD mortality
Unadjusted	9.24 (5.86, 14.6)	1.00	1.46 (0.43, 4.91)	2.71 (0.94, 7.81)	4.34 (1.69, 11.2)	0.001
Model 1	5.21 (2.21, 12.3)	1.00	1.15 (0.35, 3.77)	2.21 (0.78, 6.28)	2.45 (0.87, 6.92)	0.044
Model 2	4.19 (1.02, 17.3)	1.00	1.34 (0.32, 5.71)	2.33 (0.70, 7.80)	2.17 (0.71, 6.59)	0.093

Data are presented as HR (95% CI).

Model 1: adjust for age, sex, race, education level, smoking status, hypertension, diabetes, CVD, history of ACEI and stain.

Model 2: adjust for age, sex, race, education level, smoking status, hypertension, diabetes, CVD, history of ACEI and stain, BMI, SBP, TC, HbA1c, BUN, eGFR, CRP, albumin.

Abbreviations: MLR, monocyte-to-lymphocyte ratio; CVD, cardiovascular disease; ACEI, angiotensin-converting enzyme inhibitors; eGFR, estimated glomerular filtration rate; BMI, body mass index; SBP, systolic blood pressure; ALT, Alanine aminotransferase; BUN, blood urea nitrogen; TC, total cholesterol; HbA1c, glycosylated hemoglobin.

Figure 3. Restricted cubic spline fitting for the association between MLR with mortality.

The association of MLR levels with the all-cause (A) and CVD (B) mortality.

Figure 4. ROC curves of the MLR for predicting mortality.

ROC curves and AUC values of the MLR for predicting all-cause mortality (A) and cardiovascular mortality (B)

Table 4. The efficacy of MLR in predicting all-cause mortality and CVD mortality.

Variables	AUC	95%CI	cutoff value	Sensitivity	Specificity
All-cause mortality
MLR	65.158	63.194-67.122	0.327	53.29	70.996
NLR	60.566	58.529-62.604	2.416	53.577	65.801
eGFR	66.546	64.626-68.467	58.076	62.303	63.946
CRP	51.004	48.925-53.082	0.715	0.715	0.715
CVD mortality
MLR	64.796	62.286-67.305	0.309	63.878	59.663
NLR	54.791	51.958-57.624	1.811	74.715	36.44
eGFR	59.399	56.792-62.006	57.828	65.399	56.489
CRP	51.762	49.009-54.515	0.165	0.165	0.165

Abbreviation: AUC = areas under the curve; CI = confidence interval, CVD, cardiovascular disease; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; eGFR, estimated glomerular filtration rate; CRP; C-reactive protein.

Data availability statement

All analyses during the current study are available in the National Health and Nutrition Examination Survey. This project was supported by the National Natural Science Foundation of China (No. 81870336).