Shrunken pore syndrome and mortality: a cohort study of patients with measured GFR and known comorbidities

Figures & data

Table 1. Basic characteristics of the Lund Cystatin C standardization cohort, stratified by the quartiles of the ratio of estimated GFR according to CAPA_CYS and LMR_CR.

	Total	CAPACYS / LMRCR ratio	CAPACYS / LMRCR ratio	CAPACYS / LMRCR ratio	CAPACYS / LMRCR ratio
		<0.70	0.70–0.84	0.85–0.99	≥1.00
N	2781	645	699	728	709
Age, years	63 (20–85)	64 (24–86)	63 (22–87)	62 (20–84)	62 (19–85)
Females, % (n)	48.6 (1 332)	43.4 (280)	47.5 (332)	51.0 (372)	51.9 (368)
BMI, kg/m^2	26 (18–39)	26 (18–40)	27 (19–40)	26 (18–37)	26 (19–36)
Heigth, cm	170 (152–190)	171 (152–190)	170 (152–190)	170 (151–191)	170 (154–190)
Weight, kg	76 (49–115)	77 (46–119)	78 (50–121)	75 (49–112)	74 (50–109)
BSA^a	1.9 (1.5–2.3)	1.9 (1.4–2.4)	1.9 (1.5–2.3)	1.9 (1.4–2.3)	1.9 (1.5–2.3)
LBM^b	53.6 (37.5–75.3)	54.2 (36.2–76.0)	54.3 (38.2–75.5)	53.3 (37.0–74.7)	52.4 (38.9–75.7)
mGFR^c	57 (10–118)	46 (8–106)	56 (10–118)	66 (12–114)	59 (10–123)
Cystatin C, mg/L	1.45 (0.75–4.38)	1.94 (1.07–5.30)	1.41 (0.88–4.33)	1.17 (0.78–3.70)	1.20 (0.67–3.92)
Creatinine, µmol/L	95 (45–427)	98 (43–422)	92 (44–388)	88 (46–356)	109 (47–499)
CAPACYS^c	47 (10–107)	33 (7–71)	49 (10–91)	61 (13–101)	59 (11–124)
LMRCR^c	61 (11–111)	59 (12–116)	63 (12–114)	66 (13–108)	53 (10–106)
CAPACYS / LMRCR ratio	0.86 (0.46–1.29)	0.61 (0.34–0.70)	0.78 (0.70–0.85)	0.92 (0.85–0.99)	1.10 (1.00–1.44)
CKD-EPICYS^c	46 (10–112)	31 (8–74)	48 (10–97)	60 (12–109)	58 (12–119)
CKD-EPICR^c	66 (11–127)	63 (12–129)	68 (12–130)	72 (13–126)	56 (8–125)
CKD-EPICYS / CKD-EPICR ratio	0.78 (0.41–1.26)	0.54 (0.32–0.81)	0.70 (0.58–0.93)	0.84 (0.70–1.00)	1.00 (0.84–1.51)
FASCYS / FASCR ratio	0.84 (0.47–1.34)	0.62 (0.39–0.96)	0.77 (0.59–1.09)	0.89 (0.70–1.21)	1.05 (0.83–1.167)
FASCYS	48 (15–109)	36 (12–79)	49 (15–96)	58 (18–105)	59 (17–128)
FASCR	62 (13–140)	60 (14–147)	64 (14–145)	67 (15–131)	55 (11–128)
Cancer, % (n)	28.6 (794)	28.5 (184)	30.8 (215)	29.3 (213)	25.7 (182)
CVD, % (n)	27.0 (750)	34.1 (220)	28.0 (196)	22.9 (167)	23.6 (167)
Diabetes, % (n)	11.1 (308)	17.8 (115)	12.7 (89)	8.2 (60)	6.2 (44)
CKD, % (n)	14.8 (411)	18.0 (116)	13.7 (96)	10.9 (79)	16.9 (120)

^aBody surface area, calculated using Dubois formula 0.007184 × weight^0.425 × height^0.725.

^bLean body mass, calculated using James formula for women as 1.07 × weight – 148 × (weight/height)² and men as 1.10 × weight – 128 × (weight/height)². Weight in kg and height in cm.

^cmL/min/1.73 m². Unless otherwise noted, continuous characteristics are presented as median (2.5–97.5 percentiles); categorical values are presented as percent (count).

Figure 1. Distribution of the eGFR_CYS/eGFR_CR-ratio, calculated using three pairs of eGFR equations. CAPA_CYS and LMR_CR [19,25]. CKD-EPI_CYS and CKD-EPI_CR [26]. FAS_CYS and FAS_CR [27].

Figure 2. Survival stratified on the quartiles of the ratio of estimated GFR using the CAPA_CYS and LMR_CR equations (<0.70, 0.70–0.84, 0.85–0.99 and ≥ 1.00) for all 1332 female (A) and 1449 male (B) patients.

Table 2. Cox regression for all-cause mortality in the Lund Cystatin C standardization cohort (n = 2781).

	A		B		C
	HR (95 % CI)	p	HR (95 % CI)	p	HR (95 % CI)	p
CAPACYS / LMRCR ratio		<0.001^a		<0.001^a		<0.001^a
<0.70	3.0 (2.5–3.6)		3.2 (2.6–3.8)		3.0 (2.4–3.7)
0.70–0.84	2.2 (1.8–2.7)		2.3 (1.9–2.7)		2.2 (1.8–2.7)
0.85–0.99	1.3 (1.1–1.6)		1.3 (1.1–1.6)		1.3 (1.1–1.6)
≥1.00	1.0 (Ref.)				1.0 (Ref.)
CAPACYS, mL/min/1.73 m^2		<0.001				0.002
< 30	4.1 (3.0–5.7)		–		1.7 (1.0–2.8)
30–59	2.0 (1.5–2.8)		–		1.0 (0.7–1.6)
60–89	1.7 (1.2–2.3)		–		1.1 (0.7–1.6)
≥90	1.0 (Ref.)		–		1.0 (Ref.)
LMRCR, mL/min/1.73 m^2		<0.001				<0.001
<30	2.3 (1.9–2.8)		–		0.7 (0.4–1.1)
30–59	1.2 (1.0–1.5)		–		0.5 (0.4–0.7)
60–89	1.2 (1.0–1.5)		–		0.6 (0.5–0.8)
≥90	1.0 (Ref.)		–		1.0 (Ref.)
mGFR, mL/min/1.73 m^2		<0.001		<0.001		0.43
<30	2.9 (2.4–3.6)		1.2 (0.9–1.5)		1.0 (0.7–1.6)
30–59	1.5 (1.2–1.8)		0.6 (0.5–0.8)		0.9 (0.6–1.2)
60–89	1.5 (1.2–1.9)		0.7 (0.6–0.9)		0.9 (0.7–1.2)
≥90	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
BMI, kg/m^2		0.007		<0.001		<0.001
<20	1.2 (0.9–1.5)		1.2 (1.0–1.6)		1.2 (1.0–1.5)
20–24	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
25–29	0.8 (0.7–1.0)		0.8 (0.7–1.0)		0.8 (0.7–1.0)
≥30	0.9 (0.7–1.0)		0.7 (0.6–0.8)		0.7 (0.6–0.8)
Age, per 10 years	1.65 (1.57–1.73)	<0.001	1.57 (1.48–1.66)	<0.001	1.58 (1.49–1.68)	<0.001
Female	1.2 (1.1–1.4)	0.003	1.1 (1.0–1.3)	0.051	1.1 (1.0–1.3)	0.042
Cancer	2.6 (2.3–2.9)	<0.001	2.4 (2.1–2.7)	<0.001	2.5 (2.2–2.9)	<0.001
CVD	1.4 (1.2–1.6)	<0.001	1.1 (1.0–1.3)	0.087	1.1 (1.0–1.3)	0.076
Diabetes	1.6 (1.3–1.8)	<0.001	1.2 (1.0–1.5)	0.024	1.2 (1.0–1.5)	0.024
CKD	1.3 (1.2–1.6)	<0.001	1.1 (0.9–1.3)	0.28	1.1 (0.9–1.3)	0.50

A: unadjusted (univariate) analysis evaluating each variable at a time.

B: adjusted model including all variables in the table, except CAPA_CYS and LMR_CR.

C: adjusted model including all variables in the table.

^a p-value for trend, from separate analysis using the CAPA_CYS / LMR_CR ratio as a continuous variable rather than as categorical.

Table 3. Cox regression for all-cause mortality in the Lund Cystatin C standardization cohort stratified by sex (males; n = 1429, and females; n = 1352)

	Male		Female
	HR (95 % CI)	p	HR (95 % CI)	p
CAPACYS / LMRCR ratio		<0.001^a		<0.001^a
< 0.70	2.6 (1.9–3.6)		3.2 (2.3–4.4)
0.70–0.84	1.9 (1.4–2.6)		2.5 (1.8–3.3)
0.85–0.99	1.0 (0.7–1.4)		1.5 (1.2–2.0)
≥ 1.00	1.0 (Ref.)		1.0 (Ref.)
CAPACYS, mL/min/1.73 m^2		0.010		0.15
< 30	2.6 (1.1–6.0)		1.3 (0.6–2.7)
30–59	1.5 (0.7–3.3)		0.9 (0.5–1.5)
60–89	1.3 (0.6–2.6)		1.0 (0.6–1.6)
≥90	1.0 (Ref.)		1.0 (Ref.)
LMRCR, mL/min/1.73 m^2		<0.001		0.018
<30	0.4 (0.2–0.9)		1.0 (0.6–2.0)
30–59	0.4 (0.2–0.7)		0.7 (0.4–1.1)
60–89	0.6 (0.4–0.9)		0.7 (0.5–1.0)
≥90	1.0 (Ref.)		1.0 (Ref.)
mGFR, mL/min/1.73 m^2		0.40		0.74
<30	1.0 (0.5–1.9)		1.0 (0.5–1.7)
30–59	0.8 (0.4–1.4)		0.9 (0.5–1.4)
60–89	0.8 (0.5–1.3)		1.0 (0.7–1.5)
≥90	1.0 (Ref.)		1.0 (Ref.)
BMI, kg/m^2		0.002		<0.001
<20	1.1 (0.7–1.7)		1.3 (1.0–1.7)
20–24	1.0 (Ref.)		1.0 (Ref.)
25–29	0.7 (0.6–0.9)		0.9 (0.7–1.1)
≥30	0.7 (0.5–0.9)		0.7 (0.5–0.9)
Age, per 10 years	1.72 (1.57–1.89)	<0.001	1.47 (1.36–1.59)	<0.001
Cancer	2.4 (2.0–2.9)	<0.001	2.6 (2.2–3.2)	<0.001
CVD	1.1 (0.9–1.3)	0.33	1.2 (1.0–1.4)	0.13
Diabetes	1.3 (1.0–1.6)	0.035	1.2 (0.9–1.6)	0.30
CKD	1.1 (0.9–1.4)	0.35	1.0 (0.7–1.3)	0.81

^ap-value for trend, from separate analysis using the CAPA_CYS / LMR_CR ratio as a continuous variable rather than as categorical.

Figure 3. Survival stratified on 6 groups for the ratio of estimated GFR using the CAPA_CYS and LMR_CR equations (six groups; <0.60, 0.60–0.69, 0.70–0.84, 0.85–0.99, 1.00–1.09 and ≥1.10) for all 2781 patients.

Table 4. Cox regression for all-cause mortality in the Lund Cystatin C standardization cohort (n = 2781) using 6 groups for the CAPA_CYS/LMR_CR ratio.

Independent variable	HR (95 % CI)	p	Independent variable	HR (95 % CI)	p
CAPACYS / LMRCR ratio		<0.001^a	mGFR, mL/min/1.73 m^2		0.37
<0.60	3.3 (2.5–4.5)		<30	1.0 (0.6–1.5)
0.60–0.69	2.7 (2.0–3.5)		30–59	0.8 (0.6–1.2)
0.70–0.84	2.2 (1.7–2.8)		60–89	0.9 (0.7–1.2)
0.85–0.99	1.3 (1.0–1.6)		≥90	1.0 (Ref.)
1.00–1.09	1.0 (0.7–1.3)		BMI, kg/m^2		<0.001
≥1.10	1.0 (Ref.)		<20	1.2 (0.9–1.5)
CAPACYS, mL/min/1.73 m^2		0.005	20–24	1.0 (Ref.)
<30	1.6 (0.9–2.7)		25–29	0.8 (0.7–1.0)
30–59	1.0 (0.7–1.6)		≥30	0.7 (0.6–0.8)
60–89	1.1 (0.7–1.6)
≥90	1.0 (Ref.)		Age, per 10 years	1.58 (1.49–1.68)	<0.001
LMRCR, mL/min/1.73 m^2		<0.001	Female	1.1 (1.0–1.3)	0.042
<30	0.7 (0.5–1.2)		Cancer	2.5 (2.2–2.9)	<0.001
30–59	0.5 (0.4–0.8)		CVD	1.1 (1.0–1.3)	0.080
60–89	0.7 (0.5–0.9)		Diabetes	1.2 (1.0–1.5)	0.019
≥90	1.0 (Ref.)		CKD	1.1 (0.9–1.3)	0.52

^ap-value for trend, from separate analysis using the CAPA_CYS / LMR_CR ratio as a continuous variable rather than as categorical.

Table 5. Cox regression for all-cause mortality in the Lund Cystatin C standardization cohort (n = 2781) using eGFR_CYS/eGFR_CR-ratio intervals based on the CKD-EPI equations.

Independent variable	HR (95 % CI)	p	Independent variable	HR (95 % CI)	p
CKD-EPICYS/ CKD-EPICR ratio		<0.001^a	mGFR, mL/min/1.73 m^2		0.174
< 0.70	2.4 (1.9–3.1)		<30	1.0 (0.7–1.6)
0.70–0.84	1.5 (1.2–1.9)		30–59	0.8 (0.6–1.2)
0.85–0.99	1.2 (0.9–1.6)		60–89	0.9 (0.7–1.2)
≥ 1.00	1.0 (Ref.)		≥90	1.0 (Ref.)
CKD-EPICYS, mL/min/1.73 m^2		<0.001	BMI, kg/m^2		<0.001
<30	1.5 (1.0–2.4)		<20	1.3 (1.0–1.6)
30–59	2.5 (1.5–4.1)		20–24	1.0 (Ref.)
60–89	1.4 (1.0–2.0)		25–29	0.8 (0.7–1.0)
≥90	1.0 (Ref.)		≥30	0.7 (0.6–0.8)
CKD-EPICR, mL/min/1.73 m^2		<0.001
<30	0.5 (0.4–0.7)		Age, per 10 years	1.50 (1.41–1.59)	<0.001
30–59	0.7 (0.4–1.0)		Female	1.0 (0.9–1.2)	0.67
60–89	0.6 (0.5–0.7)		Cancer	2.5 (2.2–2.8)	<0.001
≥90	1.0 (Ref.)		CVD	1.1 (1.0–1.3)	0.046
			Diabetes	1.3 (1.1–1.5)	0.007
			CKD	1.1 (0.9–1.3)	0.43

^ap-value for trend, from separate analysis using the CKD-EPI_CYS / CKD-EPI_CR ratio as a continuous variable rather than as categorical.

Table 6. Cox regression for all-cause mortality in the Lund Cystatin C standardization cohort (n = 2781) using eGFR_CYS/eGFR_CRc ratio intervals based on the FAS equations.

Independent variable	HR (95 % CI)	p	Independent variable	HR (95 % CI)	p
FASCYS/ FASCR ratio		<0.001^a	mGFR, mL/min/1.73 m^2		0.36
< 0.70	2.7 (2.2–3.5)		<30	1.3 (0.8–1.9)
0.70–0.84	1.9 (1.5–2.3)		30–59	1.0 (0.7–1.5)
0.85–0.99	1.2 (1.0–1.5)		60–89	1.0 (0.8–1.3)
≥ 1.00	1.0 (Ref.)		≥90	1.0 (Ref.)
FASCYS, mL/min/1.73 m^2		<0.001	BMI, kg/m^2		<0.001
<30	2.2 (1.3–3.7)		<20	1.2 (0.9–1.5)
30–59	1.3 (0.8–2.1)		20–24	1.0 (Ref.)
60–89	1.2 (0.8–1.7)		25–29	0.8 (0.7–0.9)
≥90	1.0 (Ref.)		≥30	0.7 (0.6–0.8)
FASCR, mL/min/1.73 m^2		<0.001
<30	0.9 (0.6–1.4)		Age, per 10 years	1.49 (1.40–1.58)	<0.001
30–59	0.6 (0.4–0.9)		Female	1.1 (1.0–1.3)	0.036
60–89	0.7 (0.6–0.9)		Cancer	2.5 (2.1–2.8)	<0.001
≥90	1.0 (Ref.)		CVD	1.2 (1.0–1.3)	0.034
			Diabetes	1.3 (1.1–1.6)	0.003
			CKD	1.1 (0.9–1.3)	0.27

^ap-value for trend, from separate analysis using the FAS_CYS / FAS_CR ratio as a continuous variable rather than as categorical.

Table 7. Cox regression for cause-specific mortality in the Lund Cystatin C standardization cohort (n = 2781).

	Cancer mortality		CVD mortality^b		Diabetes mortality^b		CKD mortality^b
	HR (95 % CI)	p	HR (95 % CI)	p	HR (95 % CI)	p	HR (95 % CI)	p
CAPACYS / LMRCR ratio		<0.001^a		0.001^a		0.087^a		0.10^a
< 0.70	3.3 (2.3–4.9)		2.4 (1.6–3.7)		2.0 (0.8–4.7)		5.1 (0.6–46.0)
0.70–0.84	2.4 (1.7–3.3)		1.7 (1.1–2.5)		1.9 (0.8–4.7)		3.3 (0.3–33.7)
0.85–0.99	1.3 (1.0–1.8)		1.2 (0.7–1.8)		1.2 (0.5–3.3)		2.2 (0.2–25.6)
≥ 1.00	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
CAPACYS, mL/min/1.73 m^2		0.21
<30	1.3 (0.6–2.8)		–		–		–
30–59	1.0 (0.6–1.7)		–		–		–
60–89	1.2 (0.8–1.9)		–		–		–
≥90	1.0 (Ref.)		–		–		–
LMRCR, mL/min/1.73 m^2		0.058
<30	0.7 (0.3–1.4)		–		–		–
30–59	0.6 (0.3–0.9)		–		–		–
60–89	0.7 (0.5–0.9)		–		–		–
≥90	1.0 (Ref.)		–		–		–
mGFR, mL/min/1.73 m^2		0.030
<30	0.4 (0.2–0.8)		–		–		–
30–59	0.8 (0.5–1.3)		–		–		–
60–89	0.9 (0.6–1.2)		–		–		–
≥90	1.0 (Ref.)		–
BMI, kg/m^2		0.001		0.80		0.57		0.48
<20	1.1 (0.8–1.5)		0.8 (0.4–1.7)		1.1 (0.1–9.4)		4.7 (0.4–51.8)
20–24	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
25–29	0.8 (0.7–1.0)		0.9 (0.6–1.2)		1.9 (0.8–4.4)		0.8 (0.2–3.9)
≥30	0.7 (0.5–0.9)		0.9 (0.6–1.2)		1.5 (0.6–3.8)		0.7 (0.1–3.7)
Age, per 10 years	1.42 (1.30–1.55)	<0.001	2.54 (2.21–2.94)	<0.001	2.12 (1.58–2.84)	<0.001	3.78 (1.86–7.71)	<0.001
Female	1.2 (1.0–1.5)	0.042	0.7 (0.5–0.9)	0.007	0.8 (0.4–1.4)	0.42	0.5 (0.1–2.1)	0.35
Cancer	7.8 (6.1–9.8)	<0.001	0.7 (0.4–1.0)	0.035	0.4 (0.1–1.2)	0.10	–^c
CVD	1.1 (0.9–1.3)	0.51	1.3 (1.0–1.7)	0.080	1.1 (0.6–2.0)	0.81	4.2 (1.1–16.7)	0.038
Diabetes	0.9 (0.7–1.3)	0.75	1.3 (0.9–1.9)	0.18	8.1 (4.4–15.1)	<0.001	6.7 (1.7–25.5)	0.006
CKD	0.7 (0.5–1.2)	0.26	1.5 (1.1–2.0)	0.011	2.2 (1.2–4.1)	0.011	1.4 (0.4–5.0)	0.64

^ap-value for trend, from separate analysis using the CAPA_CYS / LMR_CR ratio as a continuous variable rather than as categorical.

^bEstimated without CAPA_CYS, LMR_CR and mGFR due to no deaths in the reference category and few cases in the lower categories. The results for the CAPA_CYS /LMR_CR -ratio are similar to those using an unadjusted model.

^cNot able to estimate since no deaths in CKD had a cancer diagnosis.

Table 8. Cox regression for all-cause mortality in three sub-cohorts, patients with no prior diagnosis (n = 1049), patients with normal measured GFR (≥60 mL/min/1.73m²; n = 1300), and patients with both normal mGFR and no prior diagnosis (n = 567).

	Sub-cohort 1		Sub-cohort 2		Sub-cohort 3
	No prior diagnosis		Normal measured GFR		No prior diagnosis and normal measured GFR
	HR (95 % CI)	p	HR (95 % CI)	p	HR (95 % CI)	p
CAPACYS / LMRCR ratio		<0.001^a		<0.001^a		0.001^a
< 0.70	3.7 (2.2–6.1)		4.1 (2.6–6.5)		7.3 (2.3–23.2)
0.70–0.84	2.5 (1.6–4.0)		2.7 (1.9–4.0)		3.2 (1.3–8.0)
0.85–0.99	1.5 (1.0–2.3)		1.6 (1.2–2.3)		1.8 (0.8–4.0)
≥ 1.00	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
CAPACYS, mL/min/1.73 m^2		0.85		0.69		0.50
<30	0.9 (0.3–3.2)		1.1 (0.4–3.2)		0.4 (0.0–4.4)
30–59	0.8 (0.3–2.3)		0.8 (0.5–1.4)		0.3 (0.1–1.4)
60–89	0.8 (0.3–2.0)		1.0 (0.6–1.5)		0.5 (0.2–1.5)
≥ 90	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
LMRCR, mL/min/1.73 m^2		0.71		0.063		0.50
<30	1.2 (0.4–3.7)		–		–
30–59	1.0 (0.4–2.5)		0.9 (0.5–1.5)		1.8 (0.4–7.1)
60–89	0.8 (0.4–1.7)		0.7 (0.5–1.0)		1.0 (0.4–2.2)
≥ 90	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
mGFR, mL/min/1.73 m^2		0.15		0.99		0.19
<30	1.9 (0.7–5.1)		–		–
30–59	1.1 (0.5–2.9)		–		–
60–89	1.5 (0.7–3.3)		1.0 (0.7–1.3)		1.7 (0.8–4.0)
≥ 90	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
BMI, kg/m^2		0.032		0.019		0.17
<20	1.9 (1.1–3.2)		1.4 (1.0–2.0)		2.5 (1.0–6.0)
20–24	1.0 (Ref.)		1.0 (Ref.)		1.0 (Ref.)
25–29	1.0 (0.7–1.3)		0.9 (0.7–1.1)		0.9 (0.5–1.6)
≥30	0.8 (0.6–1.2)		0.8 (0.6–1.0)		1.2 (0.6–2.5)
Age, per 10 years	1.82 (1.61–2.05)	<0.001	1.45 (1.32–1.60)	<0.001	1.78 (1.42–2.23)	<0.001
Female	1.2 (0.9–1.5)	0.27	1.1 (0.8–1.3)	0.44	1.1 (0.6–1.8)	0.80
Cancer	–		4.3 (3.4–5.5)	<0.001	–
CVD	–		1.0 (0.8–1.3)	0.98	–
Diabetes	–		0.9 (0.5–1.4)	0.58	–
CKD	–		0.6 (0.2–1.8)	0.33	–

^ap-value for trend, from separate analysis using the CAPA_CYS / LMR_CR ratio as a continuous variable rather than as categorical.

Table 9. Total all-cause mortality (%), prevalence (%) of SPS and hazard ratios (HR) for all-cause mortality using different eGFR_CYS/eGFR_CR-ratios for the SPS diagnosis.

	Total cohort		Sub-cohort 1 No prior diagnosis		Sub-cohort 2 Normal measured GFR		Sub-cohort 3 No prior diagnosis and normal measured GFR
CAPACYS / LMRCR ratio	%	HR (95% CI)	%	HR (95% CI)	%	HR (95% CI)	%	HR (95% CI)
<0.70	23.1	3.0 (2.4–3.7)^a	17.1	3.7 (2.2–6.1)^b	17.0	4.1 (2.6–6.5)^b	11.5	7.3 (2.3–23.2)^b
<0.60	11.1	3.3 (2.5–4.5)^c	8.2	4.4 (2.3–8.5)^c	7.4	5.3 (2.8–10.2)^c	5.3	14.2 (2.4–85.2)^c
Total all-cause mortality, %	37.7		21.0		30.2		11.8

Evaluation in the total cohort and in three sub-cohorts, patients with no prior diagnosis (n = 1049), patients with normal measured GFR (≥60 mL/min/1.73m²; n = 1300), and patients with both normal mGFR and no prior diagnosis (n = 567).

^aFully-adjusted model presented in Table 2 (column C).

^bFully-adjusted model presented in Table 8.

^cAdjusted for the same variables as in a and b, respectively, full model not presented.

Table 10. Cox regression for all-cause mortality in the Lund Cystatin C standardization cohort (n = 2781), when excluding CAPA_CYS, LMR_CR and mGFR, both one at a time and simultaneously.

	p	p	p	p	p	p	p	p
	HR (95 % CI)	HR (95 % CI)	HR (95 % CI)	HR (95 % CI)	HR (95 % CI)	HR (95 % CI)	HR (95 % CI)	HR (95 % CI)
	A	B	C	D	E	F	G	H
CAPACYS / LMRCR ratio	<0.001^a	<0.001^a	<0.001^a	<0.001^a	<0.001^a	<0.001^a	<0.001^a	<0.001^a
< 0.70	3.0 (2.4–3.7)	3.3 (2.7–4.0)	3.0 (2.5–3.7)	3.0 (2.4–3.8)	3.2 (2.6–3.8)	3.3 (2.7–4.0)	3.0 (2.5–3.7)	2.9 (2.4–3.5)
0.70–0.84	2.2 (1.8–2.7)	2.3 (1.9–2.8)	2.3 (1.9–2.8)	2.2 (1.8–2.7)	2.3 (1.9–2.7)	2.3 (1.9–2.8)	2.3 (1.9–2.8)	2.1 (1.7–2.5)
0.85–0.99	1.3 (1.1–1.6)	1.4 (1.1–1.7)	1.3 (1.1–1.6)	1.3 (1.1–1.6)	1.3 (1.1–1.6)	1.4 (1.1–1.7)	1.3 (1.1–1.6)	1.3 (1.1–1.6)
≥ 1.00	1.0 (Ref.)	1.0 (Ref.)	1.0 (Ref.)	1.0 (Ref.)	1.0 (Ref.)	1.0 (Ref.)	1.0 (Ref.)	1.0 (Ref.)

A: adjusted for CAPA_CYS, LMR_CR, mGFR, BMI, age, female, cancer, CVD, diabetes and CKD.

B: same as A but excluding CAPA_CYS.

C: same as A but excluding LMR_CR.

D: same as A but excluding mGFR.

E: same as A but excluding CAPA_CYS and LMR_CR.

F: same as A but excluding CAPA_CYS and mGFR.

G: same as A but excluding mGFR and LMR_CR.

H: same as A but excluding CAPA_CYS, LMR_CR and mGFR.

^ap-value for trend, from separate analysis using the CAPA_CYS / LMR_CR ratio as a continuous variable rather than as categorical.

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