J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 14, Number 8, August 2022, pages 300-308

U-Shaped Relationship Between Proteinuria and High-Density Lipoprotein Cholesterol: Results of Cross-Sectional and Six Years Cohort Studies (KITCHEN-10)

Figure 1. Percentages of proteinuria according to 10 high-density lipoprotein cholesterol (HDL-C) categories. Open circles indicate mean percentage of proteinuria in each HDL-C category, with proteinuria +1 and no proteinuria 0. Solid and dashed lines express quadratic regression curves and 95% confidence intervals, respectively.

Figure 2. Odds ratios and 95% confidence intervals (CIs) for each category of high-density lipoprotein cholesterol (HDL-C) for proteinuria. Black circles: unadjusted; blue squares: adjusted for age, smoking, pharmacotherapy (hypertension, diabetes, and dyslipidemia), regular exercise, and serum triglyceride level; red triangles: further adjusted for body mass index. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001.

Figure 3. Odds ratios and 95% confidence intervals (CIs) for each category of high-density lipoprotein cholesterol (HDL-C) for proteinuria in participants without regular alcohol consumption. Red diamonds: participants who consumed low amounts of alcohol (< 23 g ethanol per session); green inverted triangles: participants who rarely or never drank alcohol. All odds ratios were adjusted for age, sex, smoking, pharmacotherapy (hypertension, diabetes, and dyslipidemia), regular exercise, serum triglyceride level, and body mass index. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001.

Figure 4. Changes in high-density lipoprotein cholesterol (HDL-C) over 6 years (mg/dL). Open red circles (women) and open blue squares (men) express mean change in HDL-C over 6 years in each baseline HDL-C category. Solid and dashed lines express quadratic regression curves and 95% confidence intervals for the averages, respectively.

Figure 5. Risk ratios and 95% confidence intervals (CIs) for each category of baseline high-density lipoprotein cholesterol (HDL-C) for proteinuria. Black circles: unadjusted; blue squares: adjusted for age, smoking, pharmacotherapy (hypertension, diabetes, and dyslipidemia), regular exercise, and serum triglyceride level; red triangles: further adjusted for body mass index; green inverted triangles: further plus adjusted for HDL-C after 6 years. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001.

**Table 1.** Clinical Characteristics of Participants
HDL-C categories (mg/dL)	30 - 39	40 - 49	50 - 59	60 - 69	70 - 79	80 - 89	90 - 99	100 - 109	110 - 119	≥ 120
Data are presented as mean ± standard deviation, median (interquartile range) for triglycerides, or n (%). ^aAvailable n = 1,179,643.^bAvailable n = 938,010. ^cDrinkers who consume 69 g ethanol or more per session. ^dRegular exercise defined as ≥ 30 min at least twice a week. All continuous and categorical variables showed significant differences with analysis of variance or χ² test, with P < 0.0001 across the 10 categories of HDL-C concentration. S-age: substituted age; BMI: body mass index; SBP: systolic blood pressure; HDL-C: high-density lipoprotein cholesterol; CVD: cardiovascular disease; TG: triglycerides; LDL-C: high-density lipoprotein cholesterol; Hb1Ac: glycated hemoglobin.
N (% of total)	50,786 (4.3)	193,046 (16.2)	284,677 (23.9)	265,804 (22.3)	192,420 (16.2)	112,276 (9.4)	54,760 (4.6)	23,073 (1.9)	8,968 (0.8)	5,599 (0.5)
S-age	52.7 ± 10.1	52.6 ± 9.9	53.1 ± 9.9	53.3 ± 9.9	53.2 ± 9.8	53.2 ± 9.7	53.2 ± 9.5	53.4 ± 9.3	53.5 ± 9.1	53.8 ± 8.9
Women, n (%)	5,743 (11.3)	37,022 (19.2)	90,628 (31.8)	123,705 (46.5)	111,787 (58.1)	73,387 (65.4)	37,530 (68.5)	16,032 (69.5)	6,152 (68.6)	3,568 (63.7)
BMI (kg/m²)	25.3 ± 3.4	24.7 ± 3.3	23.8 ± 3.2	22.8 ± 3.1	21.9 ± 2.9	21.3 ± 2.7	20.9 ± 2.6	20.6 ± 2.5	20.4 ± 2.5	20.5 ± 2.6
SBP (mm Hg)	127 ± 16.8	127 ± 17.0	126 ± 17.2	125 ± 17.6	123 ± 17.8	122 ± 17.9	122 ± 18.0	123 ± 17.9	124 ± 18.4	126 ± 18.3
TG (mg/dL)	191 (134 - 279)	145 (104 - 205)	112 (82 - 155)	90 (67 - 124)	77 (58 - 104)	69 (53 - 92)	65 (50 - 85)	61 (48 - 81)	61 (48 - 79)	60 (47 - 80)
LDL-C (mg/dL)^a	122 ± 32.5	131 ± 31.0	132 ± 31.2	127 ± 31.1	123 ± 30.4	119 ± 29.9	116 ± 29.5	11 3± 30.0	109 ± 30.5	102 ± 32.1
HDL-C (mg/dL)	35.9 ± 3.0	45.1 ± 2.8	54.6 ± 2.8	64.3 ± 2.9	74.1 ± 2.8	84.0 ± 2.8	93.8 ± 2.8	104 ± 2.8	114 ± 2.8	131 ± 14.3
HbA1c (%)^b	5.8 ± 0.9	5.7 ± 0.8	5.6 ± 0.7	5.5 ± 0.6	5.5 ± 0.6	5.5 ± 0.5	5.5 ± 0.5	5.4 ± 0.5	5.4 ± 0.6	5.5 ± 0.6
Proteinuria, n (%)	3,553 (7.0)	10,324 (5.4)	11,759 (4.1)	8,742 (3.3)	5,691 (3.0)	3,069 (2.7)	1,583 (2.9)	702 (3.0)	291 (3.2)	245 (4.4)
Pharmacotherapy
Hypertension, n (%)	11,380 (22.4)	40,148 (20.8)	53,410 (18.8)	44,209 (16.6)	27,191 (14.1)	13,983 (12.5)	6,404 (11.7)	2,575 (11.2)	1,047 (11.7)	774 (13.8)
Diabetes, n (%)	3,262 (6.4)	9,780 (5.1)	11,391 (4.0)	8,153 (3.1)	4,545 (2.4)	2,165 (1.9)	1,077 (2.0)	452 (2.0)	169 (1.9)	157 (2.8)
Dyslipidemia, n (%)	4,756 (9.4)	18,331 (9.5)	28,169 (9.9)	25,569 (9.6)	17,198 (8.9)	9,222 (8.2)	4,451 (8.1)	1,930 (8.4)	733 (8.2)	496 (8.9)
CVD, n (%)	2,511 (6.2)	7,521 (4.9)	9,750 (4.3)	8,231 (3.8)	5,215 (3.3)	2,772 (3.0)	1,251 (2.8)	507 (2.7)	204 (2.8)	135 (2.9)
Current smokers, n (%)	23,766 (46.8)	71,284 (36.9)	81,472 (28.6)	59,418 (22.4)	35,330 (18.4)	18,227 (16.2)	8,562 (15.6)	3,509 (15.2)	14,89 (16.6)	1,128 (20.2)
Heavy alcohol drinkers, n (%)^c	1,730 (3.4)	6,696 (3.5)	9,293 (3.3)	8,062 (3.0)	5,424 (2.8)	3,071 (2.7)	1,589 (2.9)	731 (3.2)	333 (3.7)	302 (5.4)
Daily alcohol drinkers, n (%)	8,339 (16.4)	39,798 (20.6)	66,990 (23.5)	65,497 (24.6)	47,859 (24.9)	29,100 (25.9)	15,331 (28.0)	7,122 (30.9)	3,155 (35.2)	2,184 (39.0)
Regular exercisers, n (%)^d	10,158 (20.0)	42,096 (21.8)	68,417 (24.0)	68,609 (25.8)	51,899 (27.0)	31,696 (28.2)	16,001 (29.2)	7,002 (30.4)	2,811 (31.3)	1,768 (31.6)

Table 1. Clinical Characteristics of Participants

HDL-C categories (mg/dL)

30 - 39

40 - 49

50 - 59

60 - 69

70 - 79

80 - 89

90 - 99

100 - 109

110 - 119

≥ 120

Data are presented as mean ± standard deviation, median (interquartile range) for triglycerides, or n (%). ^aAvailable n = 1,179,643.^bAvailable n = 938,010. ^cDrinkers who consume 69 g ethanol or more per session. ^dRegular exercise defined as ≥ 30 min at least twice a week. All continuous and categorical variables showed significant differences with analysis of variance or χ² test, with P < 0.0001 across the 10 categories of HDL-C concentration. S-age: substituted age; BMI: body mass index; SBP: systolic blood pressure; HDL-C: high-density lipoprotein cholesterol; CVD: cardiovascular disease; TG: triglycerides; LDL-C: high-density lipoprotein cholesterol; Hb1Ac: glycated hemoglobin.

N (% of total)

50,786 (4.3)

193,046 (16.2)

284,677 (23.9)

265,804 (22.3)

192,420 (16.2)

112,276 (9.4)

54,760 (4.6)

23,073 (1.9)

8,968 (0.8)

5,599 (0.5)

S-age

52.7 ± 10.1

52.6 ± 9.9

53.1 ± 9.9

53.3 ± 9.9

53.2 ± 9.8

53.2 ± 9.7

53.2 ± 9.5

53.4 ± 9.3

53.5 ± 9.1

53.8 ± 8.9

Women, n (%)

5,743 (11.3)

37,022 (19.2)

90,628 (31.8)

123,705 (46.5)

111,787 (58.1)

73,387 (65.4)

37,530 (68.5)

16,032 (69.5)

6,152 (68.6)

3,568 (63.7)

BMI (kg/m²)

25.3 ± 3.4

24.7 ± 3.3

23.8 ± 3.2

22.8 ± 3.1

21.9 ± 2.9

21.3 ± 2.7

20.9 ± 2.6

20.6 ± 2.5

20.4 ± 2.5

20.5 ± 2.6

SBP (mm Hg)

127 ± 16.8

127 ± 17.0

126 ± 17.2

125 ± 17.6

123 ± 17.8

122 ± 17.9

122 ± 18.0

123 ± 17.9

124 ± 18.4

126 ± 18.3

TG (mg/dL)

191 (134 - 279)

145 (104 - 205)

112 (82 - 155)

90 (67 - 124)

77 (58 - 104)

69 (53 - 92)

65 (50 - 85)

61 (48 - 81)

61 (48 - 79)

60 (47 - 80)

LDL-C (mg/dL)^a

122 ± 32.5

131 ± 31.0

132 ± 31.2

127 ± 31.1

123 ± 30.4

119 ± 29.9

116 ± 29.5

11 3± 30.0

109 ± 30.5

102 ± 32.1

HDL-C (mg/dL)

35.9 ± 3.0

45.1 ± 2.8

54.6 ± 2.8

64.3 ± 2.9

74.1 ± 2.8

84.0 ± 2.8

93.8 ± 2.8

104 ± 2.8

114 ± 2.8

131 ± 14.3

HbA1c (%)^b

5.8 ± 0.9

5.7 ± 0.8

5.6 ± 0.7

5.5 ± 0.6

5.5 ± 0.5

5.4 ± 0.5

5.4 ± 0.6

5.5 ± 0.6

Proteinuria, n (%)

3,553 (7.0)

10,324 (5.4)

11,759 (4.1)

8,742 (3.3)

5,691 (3.0)

3,069 (2.7)

1,583 (2.9)

702 (3.0)

291 (3.2)

245 (4.4)

Pharmacotherapy

Hypertension, n (%)

11,380 (22.4)

40,148 (20.8)

53,410 (18.8)

44,209 (16.6)

27,191 (14.1)

13,983 (12.5)

6,404 (11.7)

2,575 (11.2)

1,047 (11.7)

774 (13.8)

Diabetes, n (%)

3,262 (6.4)

9,780 (5.1)

11,391 (4.0)

8,153 (3.1)

4,545 (2.4)

2,165 (1.9)

1,077 (2.0)

452 (2.0)

169 (1.9)

157 (2.8)

Dyslipidemia, n (%)

4,756 (9.4)

18,331 (9.5)

28,169 (9.9)

25,569 (9.6)

17,198 (8.9)

9,222 (8.2)

4,451 (8.1)

1,930 (8.4)

733 (8.2)

496 (8.9)

CVD, n (%)

2,511 (6.2)

7,521 (4.9)

9,750 (4.3)

8,231 (3.8)

5,215 (3.3)

2,772 (3.0)

1,251 (2.8)

507 (2.7)

204 (2.8)

135 (2.9)

Current smokers, n (%)

23,766 (46.8)

71,284 (36.9)

81,472 (28.6)

59,418 (22.4)

35,330 (18.4)

18,227 (16.2)

8,562 (15.6)

3,509 (15.2)

14,89 (16.6)

1,128 (20.2)

Heavy alcohol drinkers, n (%)^c

1,730 (3.4)

6,696 (3.5)

9,293 (3.3)

8,062 (3.0)

5,424 (2.8)

3,071 (2.7)

1,589 (2.9)

731 (3.2)

333 (3.7)

302 (5.4)

Daily alcohol drinkers, n (%)

8,339 (16.4)

39,798 (20.6)

66,990 (23.5)

65,497 (24.6)

47,859 (24.9)

29,100 (25.9)

15,331 (28.0)

7,122 (30.9)

3,155 (35.2)

2,184 (39.0)

Regular exercisers, n (%)^d

10,158 (20.0)

42,096 (21.8)

68,417 (24.0)

68,609 (25.8)

51,899 (27.0)

31,696 (28.2)

16,001 (29.2)

7,002 (30.4)

2,811 (31.3)

1,768 (31.6)

**Table 2.** Prevalence of Proteinuria in Participants Without Habitual Alcohol Consumption
HDL-C category (mg/dL)	20 - 39	40 - 49	50 - 59	60 - 69	70 - 79	80 - 89	90 - 99	≥ 100
aLow amount of alcohol consumption (less than 23 g of ethanol per session). ^bLow frequency of alcohol consumption (rarely drinks or cannot drink alcohol). The percentages of proteinuria were decreased across the increasing HDL-C in the both conditions (Cochran-Armitage test, both P < 0.0001). HDL-C: high-density lipoprotein cholesterol.
Subjects who consume low amount of alcohol (n = 460,837)a
Case of proteinuria, n (% in each group)	1,383 (7.4)	3,797 (5.5)	4,299 (4.1)	3,268 (3.1)	2,132(2.7)	1,170 (2.5)	532 (2.4)	372 (2.6)
Subjects who hardly or not drink alcohol (n = 402,180)^b
Case of proteinuria, n (% in each group)	1,467 (7.6)	3,606 (5.5)	3,908 (4.1)	2,828 (3.1)	1,775 (2.7)	978 (2.6)	443 (2.5)	276 (2.7)

Table 2. Prevalence of Proteinuria in Participants Without Habitual Alcohol Consumption

HDL-C category (mg/dL)

20 - 39

40 - 49

50 - 59

60 - 69

70 - 79

80 - 89

90 - 99

≥ 100

aLow amount of alcohol consumption (less than 23 g of ethanol per session). ^bLow frequency of alcohol consumption (rarely drinks or cannot drink alcohol). The percentages of proteinuria were decreased across the increasing HDL-C in the both conditions (Cochran-Armitage test, both P < 0.0001). HDL-C: high-density lipoprotein cholesterol.

Subjects who consume low amount of alcohol (n = 460,837)a

Case of proteinuria, n (% in each group)

1,383 (7.4)

3,797 (5.5)

4,299 (4.1)

3,268 (3.1)

2,132(2.7)

1,170 (2.5)

532 (2.4)

372 (2.6)

Subjects who hardly or not drink alcohol (n = 402,180)^b

Case of proteinuria, n (% in each group)

1,467 (7.6)

3,606 (5.5)

3,908 (4.1)

2,828 (3.1)

1,775 (2.7)

978 (2.6)

443 (2.5)

276 (2.7)

**Table 3.** Incidence of Proteinuria After 6 Years in 451,987 Participants Without Proteinuria at Baseline
HDL-C category (mg/dL)	20 - 39	40 - 49	50 - 59	60 - 69	70 - 79	80 - 89	90 - 99	100 - 109	≥ 110
The incidents of proteinuria were decreased across the increasing HDL-C (Cochran-Armitage test, P < 0.0001). HDL-C: high-density lipoprotein cholesterol.
N (% of total)	18,067 (4.0)	72,657 (16.1)	107,775 (23.8)	101,522 (22.5)	74,201 (16.4)	43,298 (9.6)	20,991 (4.6)	8,587 (1.9)	4,889 (1.1)
Incident of proteinuria, n (% in each group)	751 (4.2)	2,592 (3.6)	2,992 (2.8)	2,218 (2.2)	1,475 (2.0)	819 (1.9)	408 (1.9)	163 (1.9)	79 (1.6)

Table 3. Incidence of Proteinuria After 6 Years in 451,987 Participants Without Proteinuria at Baseline

HDL-C category (mg/dL)

20 - 39

40 - 49

50 - 59

60 - 69

70 - 79

80 - 89

90 - 99

100 - 109

≥ 110

The incidents of proteinuria were decreased across the increasing HDL-C (Cochran-Armitage test, P < 0.0001). HDL-C: high-density lipoprotein cholesterol.

N (% of total)

18,067 (4.0)

72,657 (16.1)

107,775 (23.8)

101,522 (22.5)

74,201 (16.4)

43,298 (9.6)

20,991 (4.6)

8,587 (1.9)

4,889 (1.1)

Incident of proteinuria, n (% in each group)

751 (4.2)

2,592 (3.6)

2,992 (2.8)

2,218 (2.2)

1,475 (2.0)

819 (1.9)

408 (1.9)

163 (1.9)

79 (1.6)