High-normal albuminuria is strongly associated with incident chronic kidney disease in a nondiabetic population with normal range of albuminuria and normal kidney function

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Figure legends

Figure 1. Comparison of UACR in the group with and without the onset of CKD after

10 years. UACR urine albumin to urine creatinine ratio.The error bars represent the

interquartile range. P<0.001 versus incident CKD group

Figure 2. Receiver-operating characteristic (ROC) curve of baseline UACR and

incident CKD 10 years later. The area under the curve (95% confidence interval) was

0.83, and optimal cut-off points (sensitivity, specificity) of incident CKD 10 years later

were 7.0 mg/gCr (0.79, 0.81)

Figure 3. Transition of UACR ranges after 10 years. UACR urine albumin to urine

creatinine ratio. Participants ZKRGHYHORSHG8$&5•PJJ&UDIWHU\HDUVDUH

shown as light-gray polka-dot bar, and cases 7.0 ”8$&5 mg/gCr after 10 years

are shown as light-gray bar. Cases with UACR of <7.0 mg/gCr even after 10 years are

shown as dark-gray bar



Table 1. Clinical characteristics of study subjects

Non-Incident CKD

Variables

N=288

eGFR

<60a,

UACR

Incident CKD

<30b

eGFR •60a, UACR •b

N=3

N=26

Age, years

41.8 ± 0.3

45.0 ± 3.2

43.2 ± 1.1*

BMI, kg/m2

22.8 ± 3.7

22.8 ± 4.2

25.6 ± 3.8

Current smoking, n (%)

144 (51.4)

2 (66.7)

16 (61.5)

Systolic BP, mmHg

122.7 ± 16.0

126.0 ± 22.6

137.7 ± 16.7*

Diastolic BP, mmHg

77.2 ± 10.2

83.3 ± 15.3

86.7 ± 11.8*

Hematuria, n (%)

12 (4.2)

0 (0)

1 (3.9)

Urinary acid, mg/dL

5.9 ± 1.3

6.4 ± 0.9

6.2 ± 1.0

UACR, mg/g

5.7 ± 0.2

5.6 ± 2.0

12.8 ± 0.7* †

Hemoglobin, g/dL

14.9 ± 0.8

14.2 ± 0.2

15.3 ± 0.9†

Albumin, g/dL

4.6 ± 0.2

4.5 ± 0.3

4.6 ± 0.2

Total cholesterol, mg/dL

192.5 ± 30.2

199.7 ± 5.1

195.6 ± 30.6

LDL cholesterol, mg/dL

105.5 ± 30.3

103.3 ± 15.5

104.5 ±30.1

HDL cholesterol, mg/dL

59.5 ± 15.5

53.0 ± 19.0

61.2 ± 14.7

137.4 ± 119.1

216.7 ± 126.2

149.1 ± 89.2

12.8 ± 2.8

12.9 ± 1.2

12.7 ± 2.8

0.70 ± 0.003

0.73 ± 0.03

0.68 ± 0.01*

eGFR, mL/min/1.73 m

99.0 ± 0.5

92.6 ± 4.7

101.8 ± 1.6* †

High-sensitivity CRP, mg/dL

0.28 ± 1.22

0.04 ± 0.17

0.10 ± 0.10

5.8 ± 0.8

5.9 ± 0.5

5.8 ± 0.7

Triglycerides, mg/dL

BUN, mg/dL

Creatinine, mg/dL

HbA1c, %

Incident CKD

eGFR (mL/min/1.73 m2), b UACR (mg/gCr)

UACR, urine albumin to urine creatinine ratio; BMI, body mass index; BP, blood pressure;

eGFR, estimated glomerular filtration rate. Data are mean ± SD or median (interquartile range)

for continuous variables. Differences between the groups were analyzed using the MannWhitney U test or chi-square test. * P<0.05 versus Non-Incident CKD.



Table 2. Multivariate logistic regression analysis of parameters related

to incident CKD

Parameters

Odds ratio

95% CI

P value

Age, 1 year

1.01

0.93 – 1.10

0.80

BMI, 1 kg/m²

1.00

0.92 – 1.11

0.91

Current smoker, presence

1.18

0.46 – 2.98

0.73

Hypertension, presence

2.52

0.97 – 6.53

0.045

UACR, 1 mg/gCr

1.24

1.14 – 1.35

<0.001

Dyslipidemia, presence

1.16

0.47 – 2.84

0.74

eGFR, 1 mL/min/1.73 m2

1.00

0.96 – 1.06

0.84

The adjusted r2 of the model was 0.25

CI, confidence interval; BMI, body mass index; UACR, urine albumin to urine creatinine ratio;

eGFR, estimated glomerular filtration rate. Hypertension was defined as systolic blood pressure

%3•PP+J or GLDVWROLF%3•PP+J Dyslipidemia was defined as LDL cholesterol

•PJG/+'/FKROHVWHURO PJG/WULJO\FHULGHV•PJG/, or use of lipid-lowering

drugs.



Table 3. Comparison of clinical characteristics according to

albuminuria levels

Age, years

UACR <7.0 mg/gCr

N=240

41.2 ± 5.7

8$&5•PJJCr

N=77

44.0 ± 4.8

BMI, kg/m2

22.6 ± 2.8

24.2 ± 5.7

0.053

Current smoker, n (%)

113 (48.1)

50 (66.7)

0.005

Systolic BP, mmHg

122.1 ± 15.5

129.9 ± 18.5

0.002

Diastolic BP, mmHg

76.6 ± 9.9

82.5 ± 11.9

<0.001

8 (3.3)

5 (6.5)

0.22

Urinary acid, mg/dL

5.9 ± 1.2

6.0 ± 1.3

0.37

UACR, mg/gCr

4.6 ± 1.0

11.5 ± 5.3

<0.001

Hemoglobin, g/dL

14.9 ± 0.8

15.0 ± 0.8

0.76

Albumin, g/dL

4.6 ± 0.2

4.6 ± 0.3

0.60

Total cholesterol, mg/dL

193.4 ± 30.0

191.2 ± 30.5

0.73

LDL cholesterol, mg/dL

107.6 ± 29.5

98.7 ± 31.3

0.02

HDL cholesterol, mg/dL

59.4 ± 15.6

60.2 ± 15.1

0.33

132.0 ± 100.6

161.5 ± 156.1

0.09

12.9 ± 2.6

12.5 ± 3.0

0.50

0.71 ± 0.05

0.68 ± 0.06

<0.001

eGFR, mL/min/1.73 m

98.6 ± 7.4

101.0 ± 9.7

0.08

High-sensitivity CRP, mg/dL

0.3 ± 1.3

0.1 ± 0.1

0.44

HbA1c, %

5.7 ± 0.7

5.7 ± 0.8

0.49

Variables

Hematuria, n (%)

Triglycerides, mg/dL

BUN, mg/dL

Creatinine, mg/dL

P value

<0.001

BMI, body mass index; BP, blood pressure; UACR, urine albumin to urine creatinine ratio;

eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen; HbA1c, hemoglobin

A1c; CRP, C-reactive protein. Data are mean ± SD or median (interquartile range) for

continuous variables. Differences between the groups were analyzed using the Mann-Whitney U

test or Chi-squared test.



Table 4. Multivariable odds ratios for incident CKD according to the

value of UACR

Parameters

Odds ratio

95% CI

P value

UACR •PJJ&U

17.36

6.16 – 48.93

<0.001

Age, 1 year

1.00

0.91 – 1.09

0.95

BMI, 1 kg/m²

0.99

0.90 – 1.08

0.78

Current smoker, presence

1.01

0.41 – 2.52

0.97

Hypertension, presence

2.71

1.05 – 6.98

0.04

Dyslipidemia, presence

1.41

0.59 – 3.39

0.45

eGFR, 1 mL/min/1.73 m2

1.00

0.95 – 1.05

0.91

The adjusted r2 of the model was 0.26

UACR, urine albumin to urine creatinine ratio; BMI, body mass index; eGFR, estimated

glomerular filtration rate. Hypertension was defined as V\VWROLF%3•PP+J or diastolic BP

•PP+J'\VOLSLGHPLDZDVGHILQHGDV/'/FKROHVWHURO•PJG/+'/FKROHVWHURO 

PJG/WULJO\FHULGHV•PJG/or use of lipid-lowering drugs.



mg/gCr

Prevalence of UACR

Figure 1

Figure 2

Parcentage of participants

0%

20%

40%

60%

80%

100%

EDVHOLQH8$&5•PJJ&U

Figure 3

baseline UACR<7.0 mg/gCr

UACR < 7.0 mg/gCr

”8$&5 PJJ&U

8$&5•PJJ&U

Supplemental Table 1. Multivariate logistic analysis of parameters related to incident

CKD with UACR •mg/gCr

Parameters

Odds ratio

95% CI

P value

Age, 1 year

1.00

0.91 – 1.09

0.95

BMI, 1 kg/m²

1.01

0.91 – 1.11

0.88

Current smoker, presence

1.11

0.41 – 3.05

0.84

Hypertension, presence

2.96

1.04 – 8.37

0.04

UACR, 1 mg/gCr

1.26

1.15 – 1.38

<0.001

Dyslipidemia, presence

1.01

0.38 – 2.65

0.98

eGFR, 1 mL/min/1.73m2

1.02

0.97 – 1.07

0.48

The adjusted r2 of the model was 0.25

CI, confidence interval; BMI, body mass index; UACR, urine albumin to urine creatinine ratio;

eGFR, estimated glomerular filtration rate. Hypertension was defined as systolic blood pressure

%3•PP+J or GLDVWROLF%3•PP+J Dyslipidemia was defined as LDL cholesterol

•PJG/+'/FKROHVWHURO PJG/WULJO\FHULGHV•PJG/RUXVHRIOLSLG-lowering

drugs.

Supplemental Table 2. Multivariate logistic analysis of parameters related to incident

CKD

Odds ratio

95% CI

P value

Age, 1 year

1.05

0.98 – 1.14

0.18

BMI, 1 kg/m²

1.05

0.96 – 1.14

0.30

Current smoker, presence

1.67

0.74 – 3.76

0.21

Hypertension, presence

2.56

1.12 – 5.89

0.03

Hematuria, presence

0.77

0.09 – 6.58

0.80

Dyslipidemia, presence

1.14

0.51 – 2.52

0.75

The adjusted r2 of the model was 0.07

CI, confidence interval; BMI, body mass index. Hypertension was defined as systolic blood

SUHVVXUH%3•PP+J or GLDVWROLF%3•PP+J Dyslipidemia was defined as LDL

cholesterol •PJG/+'/FKROHVWHURO PJG/WULJO\FHULGHV•PJG/RUXVHRIOLSLGlowering drugs.

Supplemental Table 3. Multivariate logistic regression analysis of parameters related to

incident CKD

Parameters

Odds ratio

95% CI

P value

Age, 1 year

1.01

0.93 – 1.11

0.77

BMI, 1 kg/m²

0.98

0.88 – 1.06

0.68

Current smoker, presence

1.18

0.46 – 3.01

0.74

Systolic BP, 1 mmHg

1.05

1.01 – 1.08

0.004

UACR, 1 mg/gCr

1.22

1.12 – 1.33

<0.001

Dyslipidemia, presence

1.06

0.43 – 2.63

0.90

eGFR, 1 mL/min/1.73m2

1.01

0.96 – 1.06

0.77

The adjusted r2 of the model was 0.26

BMI, body mass index; UACR, urine albumin to urine creatinine ratio; eGFR, estimated

glomerular filtration rate. '\VOLSLGHPLDZDVGHILQHGDV/'/FKROHVWHURO•PJG/+'/

cholesterol <40 mg/dL, WULJO\FHULGHV•PJG/RUXVHRIOLSLG-lowering drugs.

Supplemental Table 4. Multivariable odds ratios for incident CKD according to the value

of UACR

Parameters

Odds ratio

95% CI

P value

U$&5•PJJ&U

15.37

5.34 – 43.73

<0.001

Age, 1 year

0.99

0.91 – 1.09

0.89

BMI, 1 kg/m²

0.96

0.86 – 1.06

0.34

Current smoker, presence

1.06

0.42 – 2.68

0.90

Systolic BP, 1 mmHg

1.05

1.02 – 1.08

0.002

Dyslipidemia, presence

1.25

0.50 – 3.10

0.63

eGFR, 1 mL/min/1.73m2

1.00

0.95 – 1.05

0.97

The adjusted r2 of the model was 0.26

BMI, body mass index; UACR, urine albumin to urine creatinine ratio; eGFR, estimated

glomerular filtration rate. '\VOLSLGHPLDZDVGHILQHGDV/'/FKROHVWHURO•PJG/+'/

FKROHVWHURO PJG/WULJO\FHULGHV•PJG/RUXVHRIlipid-lowering drugs.

Supplemental Table 5. Baseline characteristics according to combination of eGFR and

UACR

Variables

Number

G2

G3

G4

eGFR • 0a

H*)5• a

60 䍸eGFR <90a

60 䍸eGFR <90a

UACR <7.0b

UACR •b

UACR <7.0b

UACR •b

240

75

898

165

UACR, mg/gCr

4.6 ± 0.1

11.3 ± 0.3

4.2 ± 0.1

11.4 ± 0.2†§

Age, years

41.2 ± 5.7

44.0 ± 4.8†

44.9 ± 5.1†

46.4 ± 4.9†‡§

BMI, kg/m2

22.6 ± 2.8

24.1 ± 5.7†

23.2 ± 2.7†

24.3 ± 2.7†§

Current smoker, n (%)

113 (48.1)

48 (65.5)†

382 (43.5)‡

74 (44.9)‡

Systolic BP, mmHg

122.1 ± 15.5

129.1 ± 18.1†

122.6 ± 15.6‡

129.6 ± 18.7†§

Diastolic BP, mmHg

76.6 ± 9.9

82.0 ± 11.7†

76.2 ± 10.0‡

82.7 ± 12.4†§

Hematuria, n (%)

8 (3.3)

5 (6.7)

35 (3.9)

15 (9.1) †§

Hemoglobin, g/dL

14.9 ± 0.8

15.0 ± 0.8

15.0 ± 0.8

15.2 ± 0.9†‡§

HbA1c, %

5.8 ± 0.4

5.8 ± 0.3

5.8 ± 0.8

5.8 ± 0.4

Total cholesterol, mg/dL

193.4 ± 30.0

191.9 ± 30.6

198.1 ± 31.7†

207.8 ± 33.4†‡§

LDL cholesterol, mg/dL

107.6 ± 29.5

98.7 ± 31.7†

111.8 ± 29.6†‡

120.7 ± 30.2†‡§

HDL cholesterol, mg/dL

59.4 ± 15.6

60.5 ± 15.2

58.2 ± 14.8

57.4 ± 19.5‡

131.6 ± 100.6

163.9 ± 157.4

135.4 ± 936

148.2 ± 82.9†§

BUN, mg/dL

12.9 ± 2.8

12.6 ± 3.0

14.5 ± 3.0†‡

15.0 ± 3.5†‡

Creatinine, mg/dL

0.71 ± 0.05

0.68 ± 0.06

0.86 ± 0.08†‡

0.86 ± 0.08†‡

eGFR, mL/min/1.73m2

98.6 ± 7.4

101.0 ± 9.8

77.3 ± 7.3†‡

77.2 ± 7.2†‡

Total protein, g/dL

7.3 ± 0.4

7.3 ± 0.4

7.3 ± 0.4

7.4 ± 0.4

Albumin, g/dL

4.6 ± 0.2

4.6 ± 0.3

4.6 ± 0.2

4.6 ± 0.3

5.9 ± 1.2

6.0 ± 1.2

6.2 ± 1.2

6.2 ± 1.2†

0.31 ± 1.33

0.10 ± 0.10

0.07 ± 0.15

0.10 ± 0.13§

Triglycerides, mg/dL

Urinary acid, mg/dL

High-sensitivity CRP, mg/dL

G1

†‡

eGFR (mL/min/1.73 m2), b UACR (mg/gCr)

UACR, urine albumin to urine creatinine ratio; BMI, body mass index; BP, blood pressure; eGFR,

estimated glomerular filtration rate. Data are mean ± SD or median (interquartile range) for

continuous variables. Differences between the groups were analyzed using the Mann-Whitney U

test or chi-square test. †P<0.05 versus G1. ‡P<0.05 versus G2. §P<0.05 versus G3.

Supplemental Table 6. Multivariate logistic regression analysis of parameters related to

incident CKD, which divided into groups by combining eGFR and UACR

G1

G2

G3

G4

eGFR • 0a

H*)5• a

60 䍸eGFR <90a

60 䍸eGFR <90a

UACR <7.0b

UACR •b

UACR <7.0b

UACR •b

Model 1c

1 (reference)

16.19 (6.26 – 41.88)g

5.39 (2.34 – 12.41)g

16.00 (6.65 – 38.47)g

Model 2d

1 (reference)

13.77 (5.28 – 35.94)g

4.46 (1.92 – 10.37)g

12.20 (5.00 – 29.80)g

Model 3e

1 (reference)

14.26 (5.44 – 37.34)g

4.54 (1.95 – 10.57)g

12.08 (4.94 – 29.57)g

Model 4f

1 (reference)

20.93 (7.84 – 55.86)g

0.56 (0.216 – 1.51)

1.65 (0.60 – 4.58)

eGFR (mL/min/1.73 m2), b UACR (mg/gCr)

Values are expressed as odds ratio (95% confidence interval). Hypertension was defined as

systolic BP • mmHg or diastolic BP • mmHg. Dyslipidemia was defined as LDL

cholesterol •mg/dL, HDL cholesterol <40 mg/dL, triglycerides •mg/dL, or use of lipidlowering drugs.

Model 1 were unadjusted.

Model 2 were adjusted for age, BMI.

Model 3 were adjusted for age, BMI, current smoker, hypertension, dyslipidemia

Model 4 were adjusted for age, BMI, current smoker, hypertension, dyslipidemia, eGFR.

P<0.001 versus reference group.

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