Reappraisal of Proteinuria and Estimated GFR to Predict Progression to ESRD or Death for Hospitalized Chronic Kidney Disease Patients

Figures & data

Figure 1. Flow chart of patients in the study.

Table 1. Clinical characteristics of 5122 participants classified according to levels of eGFR and proteinuria

eGFR mL/min/1.73 m^2; Proteinuria	≥ 60			30–59			15–29
	± or less	1+	2+ or more	± or less	1+	2+ or more	± or less	1+	2+ or more
Patients, n (%)	3,630	493	359	283	101	175	21	13	47
	(70.9)	(9.6)	(7.0)	(5.5)	(2.0)	(3.4)	(0.4)	(0.3)	(0.9)
Age, years		54.4 ± 18.3^A			69.6 ± 12.5^B			71.7 ± 13.6^C
	54 ± 18^a	59 ± 17^b	57 ± 18^c	71 ± 12^d	71 ± 12^e	67 ± 13^f	71 ± 16	80 ± 9	70 ± 13
Male, n	1845	290	218	176	66	111	10	6	31
Female, n	1785	203	141	107	35	64	11	7	16
Systolic BP,		125 ± 14^D			132 ± 14^E			135 ± 17^F
mmHg	125 ± 13^g	127 ± 14^h	130 ± 15^i	130 ± 13^j	129 ± 13^k	136 ± 15^l	132 ± 18	129 ± 14	137 ± 16
Diastolic BP,		73 ± 8^G			74 ± 8^H			73 ± 9^I
mmHg	73 ± 8^m	73 ± 8^n	75 ± 8^o	73 ± 7^p	73 ± 7^q	76 ± 9^r	72 ± 8	70 ± 8	74 ± 10
RAAS rate, %	20.4	34.9	47.9	51.6	63.4	74.9	52.9	69.2	78.7
Referral rate, %	0.8	1.4	8.6	6.7	10.9	15.4	28.6	7.7	23.4

Notes: Values are expressed as mean ± SD or percentage. Referral rate; referral rate to nephrologists. Summary of significant differences at p < 0.05: A vs. B, A vs. C in age; D vs. E, D vs. F in systolic BP; G vs. H in diastolic BP; a vs. b, a vs. c, d vs. f in age; g vs. h, g vs. i, h vs. i, j vs. k, k vs. I in systolic BP; m vs. o, n vs. o, p vs. r, q vs. r in diastolic BP.

Table 2. Renal survival rate and mortality of participants classified according to levels of eGFR and proteinuria at 5 years

eGFR, mL/min/1.73 m^2; Proteinuria	Proportion of downward eGFR levels (95% CI) at 5 years	Proportion of patients death (95% CI) at 5 years	Proportion of eGFR <15 (95% CI) at 5 years
≥60; ± or less	18.0% (16.4–19.6%)^a	11.6% (10.3–12.8%)	0.03% (0.00–0.08%)
≥60; 1+	27.1% (22.2–32.0%)^b	26.0% (21.7–30.2%)	0.00% (0.00–0.00%)
≥60; 2+ or more	42.3% (35.5–49.1%)^c	27.8% (22.7–32.8%)	3.1% (0.8–5.5%)
30–59; ± or less	24.3% (17.7–30.9%)^d	21.9% (16.4–27.4%)^j	4.0% (0.8–7.2%)^l
30–59; 1+	17.3% (8.1–26.6%)^e	37.5% (27.1–47.9%)^k	3.2% (0.00–7.6%)^m
30–59; 2+ or more	40.2% (30.9–49.5%)^f	25.8% (18.9–32.8%)	17.0% (9.8–24.2%)^n
15–29 ± or less	4.8% (0.00–13.9%)^g	19.3% (2.3–36.4%)	4.8% (0.00–13.9%)^o
15–29; 1+	42.9% (3.9–81.8%)^h	61.4% (29.5–94.4%)	42.9% (3.9–81.8%)^p
15–29; 2+ or more	72.8% (52.1–93.4%)^i	53.4% (36.8–70.0%)	72.8% (52.1–93.4%)^q
<60 or 2+ or more	34.4% (30.5–38.3%)	28.4% (25.3–31.5%)	9.0% (6.7–11.4%)
<30 or 2+ or more	42.4% (37.1–47.6%)	29.6% (25.6–33.5%)	12.4% (9.0–15.8%)
Overall	22.0% (20.5–23.4%)	16.5% (15.3–17.6%)	1.7% (1.3–2.2%)

*Proportion of downward eGFR levels included participants whose eGFR transitioned to downward CKD stage 5 years, proteinuria of 2+ or more and eGFR under 60 (mL/min/1.73 m²) and proteinuria of 2+ or more and eGFR under 30 were categorized to assess efficiently as a screening for risk of progressing to ESRD.

Notes: Summary of significant differences at p < 0.05: a vs. b, a vs. c, b vs. c in eGFR ≥60; d vs. f, e vs. f, j vs. k, l vs. n, m vs. n in eGFR 30–59; g vs. i, o vs. q in eGFR 15–19.

Table 3. Renal survival rate and mortality of participants on prescription of renin–angiotensin–aldsterone system inhibitors at 5 years

eGFR, mL/min/1.73 m^2; Proteinuria	Proportion of downward eGFR levels (95% CI) at 5 years		Proportion of patients death (95% CI) at 5 years		Proportion of eGFR <15 (95% CI) at 5 years
	With RAAS inhibitors	Without RAAS inhibitors	With RAAS inhibitors	Without RAAS inhibitors	With RAAS inhibitors	Without RAAS inhibitors
≥60; ± or less	32.5%^a	13.6%^b	10.60%	11.80%	0.00%	0.10%
	(26.7–36.2%)	(11.9–15.2 %)	(8.2–13.1%)	(10.4–13.3%)	(0.0–0.0%)	(0.0–0.4%)
≥60; 1+	42.8%^c	17.2%^d	29.60%	23.10%	0.00%	0.00%
	(34.2–51.4%)	(118–22.5%)	(22.4–36.8%)	(18.0–28.3%)	(0.0–0.0%)	(0.0–0.0%)
≥60; 2+ or more	56.6%^e	26.7%^f	20.6%^o	34.6%^p	5.00%	0.50%
	(47.5–65.7%)	(17.3–36.1%)	(14.2–27.1%)	(16.2–34.9%)	(1.0–9.0%)	(0.0–1.5%)
30–59: ± or less	31.5%^g	13.1%^h	19.20%	25.50%	6.10%	0.00%
	(26.2–40.4%)	(4.2–21.9%)	(12.4–26.1%)	(16.2–34.9%)	(1.4–10.9%)	(0.0–0.0%)
30–59; 1+	24.6%^i	2.7%^j	26.10%	39.70%	4.70%	0.00%
	(11.5–37.6%)	(0.0–7.9%)	(23.2–49.2%)	(22.5–56.9%)	(0.0–11.1%)	(0.0–0.0%)
30–59; 2+ or more	45.9%^k	10.8%^l	16.9%^q	54.3%^r	18.10%	11.50%
	(35.7–56.2%)	(0.0–22.7%)	(10.0–23.8%)	(37.4–71.2%)	(10.1–26.1%)	(0.0–27.3%)
15–29; ± or less	0.00%	10.00%	9.10%	31.40%	0.00%	10.00%
	(0.0–0.0%)	(0.0–28.6%)	(0.0–26.1%)	(0.0–26.1%)	(0.0–0.0%)	(0.0–28.6%)
15–29; 1+	46.40%	0.00%	54.30%	100%	46.40%	0.00%
	(7.1–85.8%)	(0.0–0.0%)	(17.2–91.3%)	(100–100%)	(7.1–85.8%)	(0.0–0.0%)
15–29; 2+ or more	78.5%^m	0.0%^n	46.7%^s	76.0%^t	78.5%^u	0.0%^v
	(58.9–98.1%)^j	(0.0–0.0%)	(27.9–65.6%)	(47.5–100%)	(58.9–98.1%)	(0.0–0.0%)

*Proportion of downward eGFR levels included participants whose eGFR transitioned to downward CKD stage at 5 years.

Notes: Summary of significant differences at p < 0.05: a vs. b, c vs. d, e vs. f, o vs. p in eGFR ≥60; g vs. h, i vs. j, k vs. l, q vs. r in eGFR 30–59; m vs. n, s vs. t, u vs. v in eGFR 15–19.

Figure 2. The relationship between classification of BP and levels of eGFR and proteinuria.

Notes: The risk stratification of BP was classified as ‘low: <100’, ‘normal: 100–130 and <80’, ‘high normal: 130–139 or 80–89’, ‘Grade 1: 140–159 or 90–99’, ‘Grade 2: 160–179 or 100–109’, and ‘Grade 3: ≥180 or ≥110 (mmHg).

Table 4. Multivariate associations between baseline factors and risk for annual transition to downward eGFR levels

Variables	Univariable		Age-adjusted variables		Multivariate variables
	HR (95% CI)	p	HR (95% CI)	p	HR (95% CI)	p
eGFR, mL/min/1.73 m^2; Proteinuria
≥ 60; ± or less	1.0 (ref.)		1.0 (ref.)		1.0 (ref.)
≥ 60; 1+	1.63 (1.31–2.03	<0.001	1.42 (1.14–1.77)	0.002	1.32 (1.06–1.64)	0.015
≥ 60; 2+ or more	2.46 (1.98–3.05)	<0.001	2.30 (1.85–2.85)	<0.001	1.95 (1.56–2.44)	<0.001
30–59; ± or less	1.24 (0.91–1.70)	0.173	0.63 (0.46–0.87)	0.005	0.54 (0.39–0.75)	<0.001
30–59; 1+	0.90 (0.51–1.60)	0.721	0.46 (0.28–0.87)	0.015	0.39 (0.22–0.70)	0.002
30–59; 2+ or more	2.54 (1.90–3.40)	<0.001	1.65 (1.23–2.22)	0.001	1.44 (1.03–1.97)	0.011
15–29; ± or less	0.38 (0.05–2.68)	0.329	0.20 (0.03–1.40)	0.104	0.16 (0.02–1.13)	0.067
15–29; 1+	2.05 (0.66–6.38)	0.215	0.73 (0.24–2.30)	0.596	0.55 (0.18–1.74)	0.311
15–29; 2+ or more	3.86 (2.41–6.19)	<0.001	2.19 (1.36–3.51)	0.001	1.68 (1.08–2.66)	0.007
Average BP category
Low	0.56 (0.30–1.05)	0.073	1.18 (0.63–2.24)	0.6	1.21 (0.67–2.17)	0.526
Normal	1.0 (ref.)		1.0 (ref.)		1.0 (ref.)
High normal	1.50 (1.26–1.79)	<0.001	1.13 (0.95–1.35)	0.17	1.01 (0.85–1.21)	0.890
Grade 1	2.18 (1.84–2.60)	<0.001	1.52 (1.27–1.63)	<0.001	1.21 (1.01–1.45)	0.037
Grade 2 and 3	1.69 (1.14–2.50)	0.009	1.40 (0.95–2.07)	0.093	0.99 (0.70–1.44)	0.664
Prescription of RAAS inhibitors	3.14 (2.73–3.62)	<0.001	2.32 (2.01–2.68)	<0.001	1.94 (1.67–2.27)	<0.001
Age, every 10-year increment	1.53 (1.45–1.61)	<0.001			1.46 (1.33–1.48)	<0.001
Gender, compared with female	1.08 (0.93–1.24)	0.340	1.00 (0.86–1.15)	0.964	0.93 (0.81–1.08)	0.354

Notes: The following multivariable categorical variables were created: eGFR and proteinuria; every eGFR and proteinuria categorizes decline and excretion; BP, every hypertension categorizes elevation; age, every 10-years increment; gender, male or female. The reference groups (ref.) are ‘≥60; ± or less’, and ‘normal’, respectively. The risk stratification of BP was classified as ‘low: <100’, ‘normal: 100–130 and <80’, ‘high normal: 130–139 or 80–89’, ‘Grade 1: 140–159 or 90–99’, ‘Grade 2: 160–179 or 100–109’, and ‘Grade 3: ≥180 or ≥110’ (mmHg).

*Multivariate variables were calculated after adjustment for each of the other variables.

Table 5. Multivariate associations between baseline factors and risk for death

Variables	Univariable		Age-adjusted variables		Multivariate variables
	HR (95% CI)	p	HR (95% CI)	p	HR (95% CI)	p
eGFR, mL/min/1.73 m^2; Proteinuria
≥60; ± or less	1.0 (ref.)		1.0 (ref.)		1.0 (ref.)
≥60; 1+	2.61 (2.10–3.24)	<0.001	2.28 (1.84–2.83)	<0.001	2.31 (1.86–2.88)	<0.001
≥60; 2+ or more	2.94 (2.32–3.71)	<0.001	2.71 (2.14–3.43)	<0.001	3.04 (2.39–3.87)	<0.001
30–59; ± or less	2.12 (1.58–2.85)	<0.001	1.24 (0.91–1.68)	0.171	1.31 (0.96–1.79)	0.085
30–59; 1+	3.72 (2.60–5.32)	<0.001	2.32 (1.61–3.34)	<0.001	2.65 (1.82–3.86)	<0.001
30–59; 2+ or more	2.75 (1.98–3.80)	<0.001	1.94 (1.40–2.70)	<0.001	2.77 (1.95–3.94)	<0.001
15–29; ± or less	2.32 (0.86–6.22)	0.095	1.38 (0.51–3.71)	0.524	1.60 (0.59–4.31)	0.353
15–29; 1+	6.02 (2.69–13.52)	<0.001	2.63 (1.16–5.96)	0.02	3.19 (1.40–7.27)	0.006
15–29; 2+ or more	5.79 (3.72–9.61)	<0.001	3.61 (2.31–5.65)	<0.001	5.03 (3.16–8.02)	<0.001
Average BP category
Low	0.88 (0.56–1.38)	0.581	1.66 (1.05–2.62)	0.03	1.76 (1.12–2.79)	0.015
Normal	1.0 (ref.)		1.0 (ref.)		1.0 (ref.)
High normal	0.90 (0.75–1.08)	0.266	0.70 (0.58–0.84)	<0.001	0.68 (0.56–0.82)	<0.001
Grade 1	0.80 (0.64–1.00)	0.048	0.56 (0.45–0.70)	<0.001	0.54 (0.43–0.67)	<0.001
Grade 2 and 3	0.51 (0.27–0.95)	0.034	0.42 (0.22–0.79)	0.007	0.34 (0.18–0.65)	<0.001
Prescription of RAAS inhibitors	1.12 (0.94–1.30)	0.218	0.79 (0.67–0.93)	0.005	0.71 (0.60–0.93)	<0.001
Age, every 10-year increment	1.49 (1.41–1.57)	<0.001			1.53 (1.45–1.62)	<0.001
Gender, compared with female	1.43 (1.22–1.67)	<0.001	1.31 (1.12–1.53)	0.001	1.28 (1.10–1.50)	0.002

Notes: The following multivariable categorical variables were created: eGFR and proteinuria; every eGFR and proteinuria categorizes decline and excretion; BP, every hypertension categorizes elevation; age, every 10-years increment; gender, male or female. The reference groups (ref.) are ‘≥60; ± or less’, and ‘normal’, respectively. The risk stratification of BP was classified as ‘low: <100’, ‘normal: 100–130 and <80’, ‘high normal: 130–139 or 80–89’, ‘Grade 1: 140–159 or 90–99’, ‘Grade 2: 160–179 or 100–109’ and ‘Grade 3: ≥180 or ≥110’ (mmHg).

*Multivariate variables were calculated after adjustment for each of the variables.