Renal function assessment in atrial fibrillation: Usefulness of chronic kidney disease epidemiology collaboration vs re-expressed 4 variable modification of diet in renal disease

Table 1 Baseline characteristics n (%)

Age (yr)	73 ± 11
Men	605 (66.4)
Systolic blood pressure at study entry	139 ± 28
Hypertension	678 (74.4)
Current smoking	77 (8.5)
Diabetes mellitus	220 (24.1)
Heart failure	343 (37.7)
Peripheral arterial disease	92 (10.1)
History of stroke or TIA	103 (11.3)
Coronary artery disease	127 (13.9)
COPD	183 (20.1)
CHA2DS2-VASc:
= 0	62 (6.8)
≥ 1	849 (93.2)
≥ 2	772 (84.7)
History of malignancy	135 (14.8)
HAS-BLED
0	47 (5.2)
1	160 (17.6)
2	365 (40.1)
3	261 (28.6)
4	69 (7.6)
5	6 (0.7)
6	3 (0.3)
Alcohol consumption ≥ 40 g/daily	81 (8.9)
Prior bleeding	115 (12.6)
Anemia	178 (19.5)
Abnormal liver function1	9 (1)
PINRR	58% ± 18%

¹Defined as cirrhosis or elevated liver transaminases enzymes > 3 times higher than the upper limit of normal and elevated total billirubin > 2 times higher than the upper limit of normal. CHA2DS2-VASc: Congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, stroke, vascular disease, female sex category; COPD: Chronic obstructive pulmonary disease; HAS-BLED: Uncontrolled Hypertension: systolic > 160 mmHg, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, elderly > 65 years, drugs/alcohol concomitantly; TIA: Transient ischemic attack; PINRR: Percentage of INRs in therapeutic range.

Table 2 Unadjusted and adjusted effect (HR) on outcomes of continuous estimated glomerular filtration determined by the re-expressed Four variables Modification of Diet in Renal Disease and the new Chronic Kidney Disease Epidemiology Collaboration equations

	MDRD-4		CKD-EPI
n (%)	Unadjusted HR (95%CI)	Adjusted HR (95%CI)	Unadjusted HR (95%CI)	Adjusted HR (95%CI)
Composite endpoint, 98 (10.8)	0.97 (0.958-0.977)	0.981 (0.967-0.988)	0.96 (0.955-0.975)	0.971 (0.963-0.987)
P value	< 0.0001	< 0.0001	< 0.0001	< 0.0001
Major bleeding, 30 (3.3)	0.97 (0.951-0.985)	0.982 (0.965-1.000)	0.97 (0.949-0.984)	0.982 (0.965-1.000)
P value	< 0.0001	0.07	< 0.0001	0.07
Thromboembolism, 18 (2)	0.98 (0.959-1.003)	0.983 (0.965-1.000)	0.97 (0.948-0.996)	0.983 (0.965-1.001)
P value	0.09	0.15	< 0.0001	0.22
All-cause mortality, 60 (6.6)	0.96 (0.948-0.973)	0.984 (0.965-0.995)	0.96 (0.947-0.971)	0.984 (0.965-0.995)
P value	< 0.0001	< 0.0001	0.02	0.001

¹Adjusted for age, sex, previous stroke, basal hemoglobin, chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure or left ventricular ejection fraction ≤ 40%, history of malignant disease and coronary artery disease;

²Adjusted for HAS-BLED risk score [Hypertension (uncontrolled: systolic >160 mmHg)], abnormal renal function, abnormal liver function, stroke, bleeding history or predisposition (anemia), labile international normalized ration (INR), elderly > 65 years, and Drugs/alcohol concomitantly);

³Adjusted for CHA2DS2-VAScscore [Cardiac failure or dysfunction, Hypertension, Age ≥ 75 years (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65 to 74 years, and Sex category (female)];

⁴Adjusted for age, sex, diabetes mellitus, history of malignant disease, previous stroke, basal hemoglobin and congestive heart failure or ejection fraction ≤ 40%. CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; MDRD-4: 4-variable Modification of Diet in Renal Disease Study equation.

Table 3 Unadjusted and adjusted effect (HR) on outcomes of categorical estimated glomerular filtration rate determined by the re-expressed four variables Modification of Diet in Renal Disease and the new Chronic Kidney Disease Epidemiology Collaboration equations

		MDRD-4		CKD-EPI
n (%)		Unadjusted HR (95%CI)	Adjusted HR (95%CI)	Unadjusted HR (95%CI)	Adjusted HR (95%CI)
Composite endpoint, 98 (10.8)	≥ 60	1.00 (Reference)
	30-59	2.43 (1.592-3.703)	1.71 (1.11-2.78)	2.51 (1.642-3.827)	1.81 (1.1-2.8)
		P < 0.0001	P = 0.02	P < 0.0001	P = 0.02
	< 30	6.99 (3.585-13.649)	3.3 (1.6-6.9)	7.4 (3.871-14.125)	3.6 (1.8-7.4)
		P < 0.0001	P = 0.001	P < 0.0001	P < 0.0001
Major bleeding, 30 (3.3)	≥ 60	1.00 (Reference)
	30-59	1.53 (0.715-3.260)	1.012 (0.46-2.25)	1.87 (0.883-3.948)	1.22 (0.58-2.75)
		P = 0.30	P = 0.95	P = 0.1	P = 0.58
	< 30	3.56 (0.811-15.580)	1.03 (0.22-4.95)	3.65 (0.827-16.074)	1.1 (0.25-5.35)
		P = 0.09	P = 0.93	P = 0.08	P = 0.9
Thromboembolism, 18 (2)	≥ 60	1.00 (Reference)
	30-59	2.04 (0.734-5.649)	1.43 (0.49-4.15)	2.13 (0.767-5.917)	1.43 (0.50-4.25)
		P = 0.17	P = 0.15	P = 0.15	P = 0.50
	< 30	8.01 (1.664-38.555)	5.1 (1.04-25.4)	7.84 (1.625-37.825)	5 (1.0-24.9)
		P = 0.009	P = 0.045	P = 0.01	P = 0.04
All-cause mortality, 60 (6.6)	≥ 60	1.00 (Reference)
	30-59	3.34 (1.909-5.827)	2.64 (1.4-2.7)	3.14 (1.793-5.481)	2.44 (1.3-4.5)
		P < 0.0001	P = 0.002	P < 0.0001	P = 0.005
	< 30	10.64 (4.843-23.359)	4.9 (2.0-11.9)	10.89 (5.122-23.166)	5.2 (2.2-12.3)
		P < 0.0001	P < 0.0001	P < 0.0001	P < 0.0001

¹Adjusted for age, sex, previous stroke, basal hemoglobin, chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure or ejection fraction ≤ 40%, history of malignant disease and coronary artery disease;

²Adjusted for HAS-BLED risk score [Hypertension (uncontrolled: systolic > 160 mmHg)], Abnormal renal function, abnormal liver function, stroke, bleeding history or predisposition (anemia), labile international normalized ration (INR), elderly > 65 years, and drugs/alcohol concomitantly);

³Adjusted for CHA2DS2-VAScscore [Cardiac failure or dysfunction, Hypertension, Age ≥ 75 years (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65 to 74 years, and Sex category (female)];

⁴Adjusted for age, sex, diabetes mellitus, history of malignant disease, previous stroke, basal hemoglobin and congestive heart failure or ejection fraction ≤ 40%. CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; MDRD-4: 4-variable Modification of Diet in Renal Disease Study equation.

Table 4 Calibration and discrimination abilities of the re-expressed four variables Modification of Diet in Renal Disease and the new Chronic Kidney Disease Epidemiology Collaboration equations

			MDRD-4	CKD-EPI	P value
Composite endpoint	Calibration, χ2 (P value)		1.7 (0.79)	3.5 (0.48)
	c-statistic (95%CI)	eGFR continuous	0.683 (0.629-0.737)	0.695 (0.643-0.747)	0.748
		eGFR categorical	0.632 (0.600-0.664)	0.639 (0.607-0.670)	0.452
Major bleeding	Calibration, χ2 (P value)		5.9 (0.20)	5.4 (0.25)
	c-statistic (95%CI)	eGFR continuous	0.666 (0.581-0.751)	0.677 (0.596-0.759)	0.8548
		eGFR categorical	0.550 (0.443-0.658)	0.571 (0.465-0.679)	0.7872
Thromboembolism	Calibration, χ2 (P value)		0.13 (0.99)	1.9 (0.76)
	c-statistic (95%CI)	eGFR continuous	0.616 (0.584-0.648)	0.644 (0.612-0.675)	0.2736
		eGFR categorical	0.617 (0.585-0.649)	0.622 (0.590-0.654)	0.7582
All-cause mortality	Calibration, χ2 (P value)		0.83 (0.94)	1.5 (0.82)
	c-statistic (95%CI)	eGFR continuous	0.715 (0.684-0.744)	0.722 (0.691-0.750)	0.5227
		eGFR categorical	0.679 (0.647-0. 709)	0.678 (0.646-0.708)	0.911

eGFR: Estimated glomerular filtration rate; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; MDRD-4: 4-variable Modification of Diet in Renal Disease Study equation.