Application of creatinine- and/or cystatin C-based glomerular filtration rate estimation equations in elderly Chinese

Figures & data

Table 1 Equations to estimate glomerular filtration ratea

Name	Year	Sex	scr	cys C	Equation
CKD-EPIscr	2009	Female	≤0.7		144×(scr/0.7)^−0.329×0.993^age(×1.159, if black)
			>0.7		144×(scr/0.7)^−1.209×0.993^age(×1.159, if black)
		Male	≤0.9		141×(scr/0.9)^−0.411×0.993^age(×1.159, if black)
			>0.9		141×(scr/0.9)^−1.209×0.993^age(×1.159, if black)
CKD-EPIcys	2012	Female		≤0.8	133×(cys C/0.8)^−0.499×0.996^age×0.932
				>0.8	133×(cys C/0.8)^−1.328×0.996^age×0.932
		Male		≤0.8	133×(cys C/0.8)^−0.499×0.996^age
				>0.8	133×(cys C/0.8)^−1.328×0.996^age
CKD-EPIscr-cys	2012	Female	≤0.7	≤0.8	130×(scr/0.7)^−0.248×(cys C/0.8)^−0.375×0.995^age(×1.08, if black)
				>0.8	130×(scr/0.7)^−0.248×(cys C/0.8)^−0.711×0.995^age(×1.08, if black)
			>0.7	≤0.8	130×(scr/0.7)^−0.601×(cys C/0.8)^−0.375×0.995^age(×1.08, if black)
				>0.8	130×(scr/0.7)^−0.601×(cys C/0.8)^−0.711×0.995^age(×1.08, if black)
		Male	≤0.9	≤0.8	135×(scr/0.9)^−0.207×(cys C/0.8)^−0.375×0.995^age(×1.08, if black)
				>0.8	135×(scr/0.9)^−0.207×(cys C/0.8)^−0.711×0.995^age(×1.08, if black)
			>0.9	≤0.8	135×(scr/0.9)^−0.601×(cys C/0.8)^−0.375×0.995^age(×1.08, if black)
				>0.8	135×(scr/0.9)^−0.601×(cys C/0.8)^−0.711×0.995^age(×1.08, if black)
Jscr	2009	Female			194×scr^−1.094×age^−0.287×0.739
		Male			194×scr^−1.094×age^−0.287
Jcys	2012	Female			104×cys C^−1.019×0.996^age×0.929–8
		Male			104×cys C^−1.019×0.996^age–8
BISscr	2012	Female			3,736×scr^−0.87×age^−0.95×0.82
		Male			3,736×scr^−0.87×age^−0.95
BISscr-cys	2012	Female			767×scr^−0.40×cys C^−0.61×age^−0.57×0.87
		Male			767×scr^−0.40×cys C^−0.61×age^−0.57
CEscr	2013	Female	≤0.7		140×(scr/0.7)^−0.176×0.993^age
			>0.7		127×(scr/0.7)^−0.616×0.993^age
		Male	≤0.9		128×(scr/0.9)^−0.015×0.993^age
			>0.9		119×(scr/0.9)^−0.688×0.993^age
Ccys	2013				78.64×cys C^−0.964
Cscr-cys	2013	Female			173.9×scr^−0.184×cys C^−0.725×age^−0.193×0.89
		Male			173.9×scr^−0.184×cys C^−0.725×age^−0.193

Note:

a scr was shown as mg/dL, cys C was shown as mg/L, age was shown as years.

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIcys, CKD-EPI equation based on cys C; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; Cscr-cys, Chinese equation based on scr and cys C; Jscr, Japanese equation based on scr; Jcys, Japanese equation based on cys C; scr, serum creatinine; cys C, cystatin C.

Table 2 Baseline characteristics of enrolled elderly subjectsa

	All subjects	rGFR <60 mL/min/1.73 m^2	rGFR ≥60 mL/min/1.73 m^2
Age (years)	68 (63–74)	69 (64–75)	68 (63–74)
Age category
60–69	234 (55.9)	67 (52.0)	167 (57.6)
70–79	144 (34.4)	47 (36.4)	97 (33.5)
>80	41 (9.8)	15 (11.6)	26 (9.0)
BUN (mmol/L)	5.86 (4.73–7.67)	8.20 (6.15–12.24)	5.37 (4.27–6.62)
scr (mg/L)	0.93 (0.77–1.20)	1.46 (1.10–1.90)	0.84 (0.68–0.98)
cys C (mg/L)	1.13 (0.96–1.43)	1.72 (1.33–2.48)	1.02 (0.90–1.17)
rGFR (mL/min/1.73 m^2)	74.2 (54.40–88.20)	44.6 (33.25–52.75)	81.3 (73.45–95.73)
rGFR category
≥60	290 (69.2)	/	/
<60	129 (30.8)	/	/
eGFR (mL/min/1.73 m^2)
CKD-EPIscr	75.3 (55.1–90.52)	47.0 (32.96–53.4)	85.1 (72.4–92.3)
CKD-EPIcys	63.1 (45.1–79.6)	35.7 (22.6–50.3)	72.2 (60.2–84.5)
CKD-EPIscr-cys	70.0 (50.3–83.9)	39.2 (27.3–53.8)	77.3 (67.9–89.5)
Jscr	56.2 (42.8–68.3)	36.5 (25.1–47.3)	64.2 (53.4–75.1)
Jcys	61.0 (45.0–73.8)	35.9 (23.1–50.0)	68.2 (58.0–77.8)
BISscr	67.1 (51.9–80.1)	46.4 (35.6–57.5)	74.4 (64.3–83.7)
BISscr-cys	64.4 (49.0–74.9)	40.5 (30.3–52.3)	69.5 (61.6–80.7)
CEscr	69.6 (57.7–81.7)	52.8 (43.1–62.1)	74.8 (67.0–83.5)
Ccys	69.9 (55.7–81.8)	46.6 (32.8–59.7)	77.5 (67.6–87.3)
Cscr-cys	70.0 (55.2–80.3)	45.9 (34.7–59.3)	75.4 (67.8–85.3)
Primary disease or comorbid conditions
Nephritis	45 (10.7)	19 (14.7)	26 (9.0)
Kidney neoplasm	130 (31.0)	51 (39.5)	79 (27.2)
Hematological disease	16 (3.8)	7 (5.4)	9 (3.1)
Hypertension	139 (33.2)	59 (45.7)	80 (27.6)
Coronary heart disease	38 (9.1)	16 (12.4)	22 (7.6)
Diabetes mellitus	85 (20.3)	31 (24.0)	54 (18.6)

Notes:

a Values for continuous variables expressed as median (25th to 75th percentile); values for categorical values expressed as number (percentage). Conversion factors for units: scr in mg/L to μmol/L ×88.4.

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; BUN, blood urea nitrogen; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; CKD-EPIcys, CKD-EPI equation based on cys C; Cscr-cys, Chinese equation based on scr and cys C; eGFR, estimated glomerular filtration rate; Jcys, Japanese equation based on cys C; Jscr, Japanese equation based on scr; rGFR, reference glomerular filtration rate (using the ^99mTc-DTPA renal dynamic imaging method); scr, serum creatinine; cys C, cystatin C.

Table 3 Overall performance of the equationsa

	Bias		Precision	Accuracy
	Median difference	Median absolute difference	IQR of the median difference	P15	P30	P50	RMSE
CKD-EPIscr	−1.47	10.77	21.49	48.45	79.00	92.84	15.70
CKD-EPIcys	−9.05*	12.13*	19.61	41.05**	71.84*	93.32	18.50
CKD-EPIscr-cys	−5.09**	10.21	18.74	51.55	78.76	95.23**	15.30
Jscr	−15.67*	16.32*	20.21	29.36*	62.29*	93.56	22.45
Jcys	−11.26*	13.27*	18.36	39.62**	68.97*	92.84	20.00
BISscr	−5.20**	10.70	21.58	47.26	79.71	95.70*	17.20
BISscr-cys	−8.65**	10.70	16.31	48.93	79.71	96.90*	16.94
CEscr	−3.66	9.92	19.75	52.51	83.05**	94.03	15.74
Ccys	−1.74	9.53	19.14	51.31	82.10	95.47	16.24
Cscr-cys	−3.20	8.81*	17.62	55.13**	85.44*	95.94**	14.87

Notes:

a Median absolute difference = median value of absolute difference (|eGFR–rGFR|)

* P<0.01

** P<0.05.

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIcys, CKD-EPI equation based on cys C; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; Cscr-cys, Chinese equation based on scr and cys C; eGFR, estimated glomerular filtration rate; IQR, the interquartile range of difference; Jcys, Japanese equation based on cys C; Jscr, Japanese equation based on scr; P₁₅, the proportion of eGFR within 15% of rGFR; P₃₀, the proportion of eGFR within 30% of rGFR; P₅₀, the proportion of eGFR within 50% of rGFR; rGFR, reference glomerular filtration rate; RMSE, root mean square error; scr, serum creatinine; cys C, cystatin C.

Figure 1 Bland–Altman analysis measured and plotted to intuitively compare eGFR with rGFR. Horizontal solid lines represent the mean difference between methods. Horizontal dashed lines represent 95% limits of agreement. GFR was measured in mL/min/1.73 m². (A) CKD-EPIscr, (B) CKD-EPIcys, (C) CKD-EPIscr-cys, (D) Jscr, (E) Jcys, (F) BISscr, (G) BISscr-cys, (H) CEscr, (I) Ccys, and (J) Cscr-cys.

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIcys, CKD-EPI equation based on cys C; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; Cscr-cys, Chinese equation based on scr and cys C; eGFR, estimated glomerular filtration rate; Jcys, Japanese equation based on cys C; Jscr, Japanese equation based on scr; rGFR, reference glomerular filtration rate; scr, serum creatinine; cys C, cystatin C; SD, standard deviation.

Table 4 Diagnosis consistency and misclassification rate of the equationsa

	Threshold 60 mL/min/1.73 m^2		Threshold 45 mL/min/1.73 m^2
	Kappa	Misclassification rate	Kappa	Misclassification rate
CKD-EPIscr	0.632	15.5%	0.638	9.8%
CKD-EPIcys	0.599	19.3%	0.607	12.9%
CKD-EPIscr-cys	0.662	15.0%	0.705	8.6%
Jscr	0.406	31.5%	0.574	14.8%
Jcys	0.569	18.1%	0.601	13.1%
BISscr	0.594	18.1%	0.662	9.1%
BISscr-cys	0.614	18.1%	0.680	9.6%
CEscr	0.654	14.3%	0.529	10.5%
Ccys	0.651	14.8%	0.687	8.1%
Cscr-cys	0.643	15.3%	0.716	7.4%

Note:

a eGFR and rGFR were given in mL/min/1.73 m².

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIcys, CKD-EPI equation based on cys C; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; Cscr-cys, Chinese equation based on scr and cys C; eGFR, estimated glomerular filtration rate; Jcys, Japanese equation based on cys C; Jscr, Japanese equation based on scr; rGFR, reference glomerular filtration rate; scr, serum creatinine; cys C, cystatin C.

Table 5 GFR-specific performance of the equationsa

	rGFR <60 mL/min/1.73 m^2				rGFR ≥60 mL/min/1.73 m^2
	Bias	Precision	Accuracy		Bias	Precision	Accuracy
	Median absolute difference	IQR of the median difference	P30	RMSE	Median absolute difference	IQR of the median difference	P30	RMSE
CKD-EPIscr	11.71	24.15	55.04	16.67	10.31	21.91	89.66	15.27
CKD-EPIcys	9.91	15.02	55.81	14.94	13.18*	20.93	78.97*	19.88
CKD-EPIscr-cys	10.86	17.29	54.26	14.31	9.95	19.79	89.66	15.73
Jscr	9.87	13.54	57.36	13.56	20.16*	22.48	64.48*	25.42
Jcys	9.66	13.86	55.81	14.62	15.61*	19.87	74.83*	21.98
BISscr	8.86*	17.79	72.09*	12.59	12.08*	22.52	83.10*	18.90
BISscr-cys	8.04*	13.00	71.32*	11.60	12.20*	17.45	83.45*	18.83
CEscr	9.83*	14.72	63.57	13.94	9.93	18.04	91.72	17.50
Ccys	7.71*	15.39	70.54*	13.00	10.50	19.30	87.24	17.49
Cscr-cys	6.72*	14.69	73.64*	12.20	9.74	18.39	90.69	15.92

Notes:

a Median absolute difference = median value of absolute difference (|eGFR–rGFR|);

* P<0.01.

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIcys, CKD-EPI equation based on cys C; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; Cscr-cys, Chinese equation based on scr and cys C; eGFR, estimated glomerular filtration rate; IQR, the interquartile range of difference; Jcys, Japanese equation based on cys C; Jscr, Japanese equation based on scr; P₃₀, the proportion of eGFR within 30% of rGFR; rGFR, reference glomerular filtration rate; RMSE, root mean square error; scr, serum creatinine; cys C, cystatin C.

Table 6 Age-specific performance of the equations

	Bias	Precision	Accuracy		Bias	Precision	Accuracy		Bias	Precision	Accuracy
	Median absolute difference	IQR of the median difference	P30	RMSE	Median absolute difference	IQR of the median difference	P30	RMSE	Median absolute difference	IQR of the median difference	P30	RMSE
	Age 60–69 years				Age 70–79 years				Age 80+ years
Cscr-cys	9.06	17.13	86.75*	14.91	7.91**	16.60	85.42	14.54	10.53	24.04	78.05	15.80
Ccys	9.54	17.32	83.33	15.98	9.33	18.70	81.25	15.40	9.97	23.13	78.05	20.10
CEscr	9.71	19.99	8r5.90**	15.93	10.10	20.73	82.64	15.23	10.71	23.12	68.29	16.44
BISscr-cys	10.94	16.54	83.76**	16.46	10.53	15.91	77.78	16.93	12.42**	24.44	63.41	19.47
BISscr	10.13	20.69	83.76**	16.28	12.16**	19.15	77.78	17.58	10.88	27.12	63.41	20.66
Jcys	14.00*	18.11	70.51**	20.28	12.04**	10.43	69.44**	18.75	14.90*	25.13	58.54	22.54
Jscr	16.14*	20.26	64.96*	22.49	17.57*	19.28	60.42*	22.34	13.44*	27.27	53.66**	22.57
CKD-EPIscr-cys	10.21	18.38	79.91	15.08	9.55	20.21	79.17	15.03	12.13	22.53	70.73	17.34
CKD-EPIcys	12.13**	18.85	72.22	18.90	10.90	19.92	72.92	17.41	14.32**	23.41	65.85	19.91
CKD-EPIscr	11.21	22.48	79.06	15.57	9.58	19.16	80.56	15.64	10.23	25.84	73.17	16.69

Notes:

a Median absolute difference = median value of absolute difference (|eGFR–rGFR|)

* P<0.01

** P<0.05.

Abbreviations: BISscr, Berlin equation based on scr; BISscr-cys, Berlin equation based on scr and cys C; Ccys, Chinese equation based on cys C; CEscr, Chinese elderly equation based on scr; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CKD-EPIcys, CKD-EPI equation based on cys C; CKD-EPIscr, CKD-EPI equation based on scr; CKD-EPIscr-cys, CKD-EPI equation based on scr and cys C; Cscr-cys, Chinese equation based on scr and cys C; eGFR, estimated glomerular filtration rate; IQR, the interquartile range of difference; Jcys, Japanese equation based on cys C; Jscr, Japanese equation based on scr; P₃₀, the proportion of eGFR within 30% of rGFR; rGFR, reference glomerular filtration rate; RMSE, root mean square error; scr, serum creatinine; cys C, cystatin C.