Associations of Estimated Glomerular Filtration Rate with All-Cause Mortality and Cardiovascular Mortality in Patients with Diabetic Foot Osteomyelitis

Figures & data

Table 1 Baseline Characteristics of the Study Population Based on eGFR (mL/Min/1.73m²)

Characteristics	All (N = 199)	<60 (N=39)	60–89 (N = 48)	≥ 90 (N = 112)	P
Age, years	60.19 ± 12.50	62.62 ± 13.18	62.35 ± 10.86	58.41 ± 12.73	0.075
Sex, n (%)					0.411
Female	74 (37.19%)	11 (28.21%)	18 (37.50%)	45 (40.18%)
Male	125 (62.81%)	28 (71.79%)	30 (62.50%)	67 (59.82%)
Smoke, n (%)					0.373
No	91 (45.73%)	15 (38.46%)	20 (41.67%)	56 (50.00%)
Yes	108 (54.27%)	24 (61.54%)	28 (58.33%)	56 (50.00%)
Duration of diabetes (years)	11.31 ± 6.16	10.38 ± 6.46	11.48 ± 6.15	11.56 ± 6.08	0.578
TEXAS, n (%)					0.787
3B	96 (48.24%)	17 (43.59%)	23 (47.92%)	56 (50.00%)
3D	103 (51.76%)	22 (56.41%)	25 (52.08%)	56 (50.00%)
Laboratory parameters
SCr, umol/L	78.71 ± 38.69	122.40 ± 59.73	83.97 ± 17.82	61.25 ± 18.00	< 0.001
eGFR, mL/min·1.73m^2	92.43 ± 32.03	48.56 ± 7.20	76.27 ± 7.10	114.64 ± 22.46	< 0.001
UACR, mg/g	26.79 (17.56–106.73)	353.26 (26.49–434.93)	28.99 (18.29–109.75)	25.05 (16.69–61.40)	< 0.001
HbA1c, %	8.88 ± 2.05	8.88 ± 1.96	8.41 ± 2.26	9.08 ± 1.97	0.171
WBC, ×10^9/L	11.41 ± 2.84	11.82 ± 2.67	10.79 ± 2.98	11.53 ± 2.83	0.195
Hb, g/L	117.21 ± 20.37	119.63 ± 17.11	117.83 ± 19.56	116.10 ± 21.78	0.631
TC, mmol/L	4.69 ± 1.76	4.57 ± 1.86	4.47 ± 1.90	4.82 ± 1.66	0.451
TG, mmol/L	2.06 ± 0.56	2.22 ± 0.57	2.03 ± 0.50	2.01 ± 0.57	0.119
HDL-C, mmol/L	1.16 ± 0.38	1.19 ± 0.34	1.13 ± 0.41	1.17 ± 0.38	0.780
LDL-C, mmol/L	2.77 ± 0.93	2.77 ± 0.88	2.71 ± 1.01	2.80 ± 0.93	0.859
apoA1, g/L	1.20 ± 0.26	1.17 ± 0.24	1.23 ± 0.28	1.19 ± 0.26	0.606
apoB, g/L	0.96 ± 0.25	1.02 ± 0.22	0.94 ± 0.28	0.94 ± 0.24	0.228
ABI	0.87 ± 0.36	0.80 ± 0.40	0.84 ± 0.31	0.90 ± 0.36	0.244
Comorbidities
T2DM, n (%)					0.561
No	9 (4.52%)	3 (7.69%)	2 (4.17%)	4 (3.57%)
Yes	190 (95.48%)	36 (92.31%)	46 (95.83%)	108 (96.43%)
Hypertension, n (%)					0.746
No	36 (18.09%)	8 (20.51%)	7 (14.58%)	21 (18.75%)
Yes	163 (81.91%)	31 (79.49%)	41 (85.42%)	91 (81.25%)
CHD, n (%)					0.022
No	126 (63.32%)	18 (46.15%)	29 (60.42%)	79 (70.54%)
Yes	73 (36.68%)	21 (53.85%)	19 (39.58%)	33 (29.46%)
CVD, n (%)					0.309
No	152 (76.38%)	32 (82.05%)	33 (68.75%)	87 (77.68%)
Yes	47 (23.62%)	7 (17.95%)	15 (31.25%)	25 (22.32%)
Sepsis, n (%)					0.386
No	171 (85.93%)	32 (82.05%)	44 (91.67%)	95 (84.82%)
Yes	28 (14.07%)	7 (17.95%)	4 (8.33%)	17 (15.18%)
PVD, n (%)					0.646
No	98 (49.25%)	19 (48.72%)	21 (43.75%)	58 (51.79%)
Yes	101 (50.75%)	20 (51.28%)	27 (56.25%)	54 (48.21%)
Neuropathy, n (%)					0.642
No	86 (43.22%)	17 (43.59%)	18 (37.50%)	51 (45.54%)
Yes	113 (56.78%)	22 (56.41%)	30 (62.50%)	61 (54.46%)
Infection, n (%)					0.159
Moderate	118 (59.30%)	20 (51.28%)	25 (52.08%)	73 (65.18%)
Severe	81 (40.70%)	19 (48.72%)	23 (47.92%)	39 (34.82%)
Location
Forefoot, n (%)					0.312
No	19 (9.55%)	6 (15.38%)	5 (10.42%)	8 (7.14%)
Yes	180 (90.45%)	33 (84.62%)	43 (89.58%)	104 (92.86%)
Midfoot, n (%)					0.082
No	184 (92.46%)	33 (84.62%)	44 (91.67%)	107 (95.54%)
Yes	15 (7.54%)	6 (15.38%)	4 (8.33%)	5 (4.46%)
Hindfoot, n (%)					0.792
No	183 (91.96%)	35 (89.74%)	45 (93.75%)	103 (91.96%)
Yes	16 (8.04%)	4 (10.26%)	3 (6.25%)	9 (8.04%)
All-cause mortality n (%)					0.002
Survival	148 (74.37%)	24 (61.54%)	30 (62.50%)	94 (83.93%)
Dead	51 (25.63%)	15 (38.46%)	18 (37.50%)	18 (16.07%)
MACE, n (%)					0.002
No	134(71.28%)	19 (54.29%)	28 (60.87%)	87 (81.31%)
Yes	54 (28.72%)	16 (45.71%)	18 (39.13%)	20 (18.69%)

Notes: Mean ± standard deviation (SD) and Median (Inter Quartile Range) for continuous variables. Percentage (%) for categorical variables.

Abbreviations: SCr, serum creatinine; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio; HbA1c, glycosylated hemoglobin; WBC, white blood cells; Hb, hemoglobin; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; apoA1, apolipoprotein A1; apoB, apolipoprotein B; ABI, ankle brachial index; T2DM, type 2 diabetes mellitus; CHD, coronary heart disease; CVD, cardiovascular diseases; PVD, peripheral arterial diseases; MACE, major cardiovascular adverse events.

Table 2 Univariate Cox Proportional Hazard Model of eGFR Levels for All-Cause Mortality (n = 199)

Characteristics	HR	95% CI	-P-value
Sex
Female	1.00	—	—
Male	1.36	(0.75–2.46)	0.3090
Age	1.05	(1.03–1.07)	< 0.0001
BMI	0.95	(0.88–1.02)	0.1253
Duration of diabetes	0.97	(0.93–1.02)	0.2483
Smoke
No	1.00	—	—
Yes	1.25	(0.71–2.18)	0.4393
Hypertension
No	1.00	—	—
Yes	1.29	(0.61–2.75)	0.5049
CHD
No	1.00	—	—
Yes	2.07	(1.20–3.59)	0.0095
CVD
No	1.00	—	—
Yes	1.31	(0.72–2.39)	0.3838
Sepsis
No	1.00	—	—
Yes	2.49	(1.32–4.67)	0.0046
Infection
Moderate	1.00	—	—
Severe	3.26	(1.83–5.79)	< 0.0001
Neuropathy
No	1.00	—	—
Yes	1.61	(0.90–2.88)	0.1091
TEXAS
3B	1.00	—	—
3D	1.16	(0.67–2.02)	0.5964
Forefoot
No	1.00	—	—
Yes	1.33	(0.48–3.69)	0.5831
Midfoot
No	1.00	—	—
Yes	1.69	(0.72–3.97)	0.2268
Hindfoot
No	1.00	—	—
Yes	4.92	(2.56–9.48)	< 0.0001
HbA1c	0.95	(0.83–1.08)	0.45570
WBC	1.02	(0.92–1.12)	0.7133
Hb	1.01	(0.99–1.02)	0.3347
TC	1.08	(0.92–1.27)	0.3317
TG	1.34	(0.83–2.18)	0.2310
HDL	0.59	(0.28–1.21)	0.1505
LDL	1.05	(0.78–1.41)	0.7378
apoA1	1.07	(0.38–2.99)	0.8941
apoB	1.02	(0.34–3.11)	0.9678
SCr	1.01	(1.00–1.01)	0.0037
ABI	0.36	(0.16–0.81)	0.0133

Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; CHD, coronary heart disease; CVD, cardiovascular diseases; MACE, major cardiovascular adverse events; HbA1c, glycosylated hemoglobin; WBC, white blood cells; Hb, hemoglobin; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; apoA1, apolipoprotein A1; apoB, apolipoprotein B; SCr, serum creatinine; ABI, ankle brachial index.

Table 3 Univariate Cox Proportional Hazard Model of eGFR Levels for MACE (n = 188)

Characteristics	HR	95% CI	P-value
Sex
Female	1.00	—	—
Male	0.98	(0.57–1.70)	0.9477
Age	1.05	(1.03–1.08)	< 0.0001
BMI	0.95	(0.89–1.02)	0.1674
Duration of diabetes	0.98	(0.94–1.03)	0.5070
Smoke
No	1.00	—	—
Yes	1.74	(0.99–3.07)	0.0539
Hypertension
No	1.00	—	—
Yes	1.48	(0.70–3.14)	0.3059
CHD
No	1.00	—	—
Yes	3.3	(1.90–5.74)	< 0.0001
CVD
No	1.00	—	—
Yes	1.31	(0.73–2.35)	0.3665
Sepsis
No	1.00	—	—
Yes	0.7	(0.25–1.95)	0.5006
Infection
Moderate	1.00	—	—
Severe	2.52	(1.47–4.31)	0.0008
Neuropathy
No	1.00	—	—
Yes	1.24	(0.71–2.14)	0.4489
TEXAS
3B	1.00	—	—
3D	0.97	(0.57–1.65)	0.9015
Forefoot
No	1.00	—	—
Yes	1.5	(0.54–4.15)	0.4349
Midfoot
No	1.00	—	—
Yes	1.51	(0.64–3.52)	0.3435
Hindfoot
No	1.00	—	—
Yes	4.48	(2.34–8.57)	< 0.0001
HbA1c	0.97	(0.86–1.10)	0.6341
WBC	1.06	(0.96–1.16)	0.2595
Hb	0.99	(0.98–1.01)	0.3766
TC	1.12	(0.96–1.30)	0.1669
TG	1.15	(0.72–1.82)	0.5683
HDL	0.73	(0.36–1.47)	0.3720
LDL	1.02	(0.76–1.35)	0.9176
apoA1	1.17	(0.43–3.18)	0.7529
apoB	1.41	(0.48–4.15)	0.5334
SCR	1.01	(1.00–1.01)	0.0046
ABI	0.38	(0.17–0.84)	0.0162

Abbreviations: MACE, major cardiovascular adverse events; HR, hazard ratio; CI, confidence interval; BMI, body mass index; CHD, coronary heart disease; CVD, cardiovascular diseases; MACE, major cardiovascular adverse events; HbA1c, glycosylated hemoglobin; WBC, white blood cells; Hb, hemoglobin; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; apoA1, apolipoprotein A1; apoB, apolipoprotein B; SCr, serum creatinine; ABI, ankle brachial index.

Table 4 Multivariate Cox Proportional Hazard Model of Association of eGFR Levels with All-Cause Mortality and MACE

Clinical Outcome	eGFR Category	HR	95% CI	P-value
All-cause mortality
Crude model	eGFR < 90	1.00	—	—
	eGFR ≥ 90	0.36	(0.20–0.64)	0.001
Model I	eGFR < 90	1.00	—	—
	eGFR ≥ 90	0.42	(0.24–0.75)	0.004
Model II	eGFR < 90	1.00	—	—
	eGFR ≥ 90	0.43	(0.22–0.85)	0.015
MACE
Crude model	eGFR < 90	1.00	—	—
	eGFR ≥ 90	0.37	(0.22–0.65)	0.001
Model I	eGFR < 90	1.00	—	—
	eGFR ≥ 90	0.43	(0.33–0.75)	0.003
Model II	eGFR < 90	1.00	—	—
	eGFR ≥ 90	0.51	(0.27–0.96)	0.038

Notes: Crude model adjust for none. Model I: adjust for age, sex, smoke, duration of diabetes. Model II: adjust for age, sex, smoke, duration of diabetes, SCR, CHD, hindfoot, infection, sepsis and ABI. Models for all-cause mortality (n = 199); models for MACE (n = 188).

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 1 Kaplan-Meier curves of the cumulative incidence of all-cause mortality (A) and MACE (B) stratified by eGFR groups.

Table 5 Stratified Analysis by Sex of eGFR Levels with All-Cause Mortality and MACE by Sex

Sex	Clinical Outcome	eGFR Category	HR	95% CI	P-value
Female	All-cause mortality
	Crude model	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.56	(0.22–1.55)	0.276
	Model I	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.72	(0.26–2.02)	0.532
	Model II	eGFR <90	1.00	—	—
		eGFR ≥ 90	0.35	(0.09–1.40)	0.136
	MACE
	Crude model	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.57	(0.24–1.33)	0.192
	Model I	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.78	(0.32–1.93)	0.59
	Model II	eGFR < 90	1.00	—	—
		eGFR ≥ 90	1.27	(0.33–4.87)	0.727
Male	All-cause mortality
	Crude model	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.29	(0.14–0.60)	0.001
	Model I	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.29	(0.14–0.61)	0.001
	Model II	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.33	(0.14–0.76)	0.010
	MACE
	Crude model	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.28	(0.13–0.60)	0.001
	Model I	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.25	(0.12–0.56)	0.001
	Model II	eGFR < 90	1.00	—	—
		eGFR ≥ 90	0.27	(0.11–0.65)	0.004

Notes: Crude model adjust for none. Model I: adjust for age, smoke, duration of diabetes. Model II: adjust for age, smoke, duration, SCR, CHD, hindfoot, infection, sepsis and ABI. Models for all-cause mortality (n = 199); models for MACE (n = 188).

Abbreviations: HR, hazard ratio; CI, confidence interval.