Predictors of decline in kidney function in the general population: a decade of follow-up from the Tehran Lipid and Glucose Study

Figures & data

Figure 1. Flow chart of inclusions and exclusions of the study participants. SBP: systolic blood pressure; DBP: diastolic blood pressure; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; FPG: fasting plasma glucose; 2-h PG: 2-hour post-challenge plasma glucose; Scr: serum creatinine; eGFR: estimated glomerular filtration rate.

Table 1. Baseline characteristics of the study participants stratified by gender: Tehran Lipid and Glucose Study.

	Men	Women
Number of participants	3141	4049	p-value
Continuous variables, Mean ± SD
Age (year)	44.55 ± 15.30	42.76 ± 14.05	<.001
BMI (kg/m^2)	26.37 ± 4.16	28.23 ± 4.99	<.001
WC (cm)	93.56 ± 11.01	89.97 ± 12.99	<.001
FPG (mg/dL)	98.06 ± 29.19	98.17 ± 32.45	.881
2-h PG (mg/dL)	113.23 ± 53.50	118.46 ± 50.23	<.001
SBP (mmHg)	119.27 ± 17.41	115.19 ± 19.20	<.001
DBP (mmHg)	75.71 ± 10.70	74.28 ± 10.38	<.001
eGFR at baseline (ml/min/1.73 m^2)	87.83 ± 15.91	84.12 ± 16.03	<.001
TC (mg/dL)	189.28 ± 38.35	195.80 ± 43.46	<.001
HDL-C (mg/dL)	35.48 ± 8.72	41.62 ± 10.62	<.001
TG (mg/dL)	146 (102–211)^a	128 (89–187)^a	<.001
Categorical variables, number (%)
Marital status			<.001
Married	2593 (82.55)	3197 (78.96)
Single	516 (16.43)	415 (10.25)
Widowed/Divorced	32 (1.02)	437 (10.79)
Smoking status			<.001
Never	1783 (56.77)	3843 (94.91)
Former	596 (18.97)	89 (2.20)
Current	762 (24.26)	117 (2.89)
Education level			<.001
>12 years	624 (19.87)	492 (12.15)
6–12 years	1778 (56.61)	2096 (51.77)
<6 years	739 (23.53)	1461 (36.08)
Physical activity			<.001
Inactive	1385 (44.09)	1359 (33.56)
Moderately active	580 (18.47)	1202 (29.69)
Sufficiently active	1176 (37.44)	1488 (36.75)
Prevalent CVD, yes	211 (6.72)	172 (4.25)	<.001
Family history of diabetes, yes	737 (23.46)	650 (16.05)	<.001
Glucose-lowering drug use, yes	133 (4.23)	246 (6.08)	<.001
Antihypertensive drug use, yes	153 (4.87)	427 (10.55)	<.001
Lipid-lowering drug use, yes	77 (2.45)	170 (4.20)	<.001

BMI: body mass index; WC: waist circumference; FPG: fasting plasma glucose; 2-h PG: 2-hour post-challenge plasma glucose; SBP: systolic blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; CVD: cardiovascular disease.

^aData presented as median (IQR) for skewed variables (TG).

Figure 2. The sex-specific crude incidence rate of kidney function decline per 10,000 person-year, stratified by 10-year age group categories. Legend: Due to the small numbers of those aged ≥80 years, all subjects aged ≥70 years were categorized into one age group.

Table 2. Association of risk factors with decline in kidney function in the Tehran Lipid and Glucose Study.

	Cox regression analysis			Competing risk analysis
Characteristics	Model 1	Model 2	Model 3	Model 3
	HR (95%CI)	HR (95%CI)	HR (95%CI)	SHR (95%CI)
Age (years)
20–34	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
35–49	1.06 (0.93–1.22)	1.02 (0.88–1.19)	1.83 (1.56–2.16)	1.84 (1.57–2.17)
50–64	1.52 (1.33–1.75)	1.21 (1.00–1.45)	3.78 (3.05–4.69)	3.77 (3.05–4.66)
≥65	2.08 (1.75–2.47)	1.52 (1.20–1.93)	7.84 (5.93–10.38)	6.95 (5.19–9.31)
Female gender (male reference)	1.19 (1.07–1.32)	1.21 (1.06–1.39)	1.61 (1.40–1.85)	1.65 (1.43–1.90)
Blood pressure categories
Normal	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
Prehypertension	1.23 (1.09–1.39)	1.15 (1.01–1.31)	1.21 (1.06–1.38)	1.21 (1.06–1.38)
Hypertension	1.94 (1.71–2.19)	1.51 (1.30–1.77)	1.73 (1.48–2.01)	1.69 (1.45–1.97)
Glycemic status categories
Normal	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
Prediabetes	1.16 (1.03–1.33)	0.99 (0.86–1.15)	0.97 (0.84–1.11)	0.97 (0.84–1.12)
Diabetes	1.87 (1.62–2.15)	1.40 (1.19–1.65)	1.30 (1.10–1.53)	1.27 (1.07–1.50)
Body mass index categories
Normal	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
Overweight	0.97 (0.86–1.09)	0.86 (0.74–1.01)	0.94 (0.80–1.10)	0.94 (0.81–1.10)
Obese	1.16 (1.02–1.33)	0.90 (0.72–1.13)	0.97 (0.77–1.21)	0.96 (0.77–1.20)
Physical activity
Inactive	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
Moderately active	0.86 (0.75–0.98)	0.83 (0.72–0.95)	0.84 (0.73–0.96)	0.84 (0.73–0.97)
Sufficiently active	1.02 (0.91–1.14)	1.01 (0.90–1.13)	0.95 (0.84–1.07)	0.95 (0.85–1.07)
Marital status
Married	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
Single	0.90 (0.77–1.06)	1.13 (0.93–1.36)	1.00 (0.83–1.22)	1.01 (0.84–1.22)
Widowed/Divorced	1.62 (1.35–1.94)	1.12 (0.92–1.36)	1.23 (1.01v1.49)	1.24 (1.01–1.53)
Education level
>12 years	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
6–12 years	1.05 (0.90–1.23)	1.02 (0.87–1.20)	0.90 (0.77–1.06)	0.89 (0.76–1.04)
<6 years	1.61 (1.37–1.90)	1.12 (0.93–1.36)	0.95 (0.79–1.16)	0.93 (0.77–1.13)
Smoking status
Never	1.00 (reference)	1.00 (reference)	1.00 (reference)	1.00 (reference)
Former	0.91 (0.76–1.10)	0.93 (0.76–1.13)	0.96 (0.79–1.17)	0.96 (0.78–1.17)
Current	0.93 (0.79–1.09)	1.15 (0.97–1.38)	1.09 (0.92–1.31)	1.07 (0.89–1.28)
TC/HDL-C, per 1-SD^b	1.02 (0.97–1.07)	0.94 (0.88–1.01)	0.97 (0.90–1.04)	0.97 (0.90–1.04)
TG, per 1-SD^a, ^b	1.09 (1.04–1.15)	1.05 (0.98–1.14)	1.09 (1.01–1.17)	1.09 (1.01–1.17)
Waist circumference, per 1-SD^b	1.10 (1.05–1.16)	1.01 (0.92–1.11)	1.00 (0.91–1.10)	1.01 (0.92–1.11)
Lipid-lowering drug use, yes	1.30 (1.00–1.68)	0.91 (0.69–1.19)	0.99 (0.76–1.30)	0.98 (0.74–1.29)
Prevalent CVD, yes	1.56 (1.27–1.91)	1.12 (0.90–1.39)	1.36 (1.09–1.68)	1.27 (1.01–1.59)
Family history of diabetes, yes	0.82 (0.71–0.94)	0.85 (0.73–0.97)	0.87 (0.76–1.00)	0.87 (0.75–1.00)
eGFR, per 1 mL/min/1.73 m^2 greater	–	–	1.06 (1.05–1.06)	1.06 (1.05–1.06)

Model 1: Crude model.

Model 2: Adjusted for age, gender, blood pressure, glycemic status, obesity status, physical activity level, marital status, education level, smoking status, TC/HDL-C, TG, waist circumference, lipid-lowering drug use, prevalent CVD, family history of diabetes.

Model 3: Model 2 + baseline eGFR.

TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; SHR: sub-distribution hazard ratio; CI: confidence interval.

^aLog-transformed TG was used.

^b1 SD TC/HDL-C, log-transformed TG, and waist circumference are equal to 1.70 mg/dL, 0.55 mg/dL, and 12.30 cm, respectively.

Table 3. Sub-distribution Hazard ratios and 95% CI of risk factors for the decline in kidney function, stratified by baseline eGFR, in the Tehran Lipid and Glucose Study^a.

Characteristics	eGFR <60 mL/min/1.73 m^2(n = 349) (Events = 69)	eGFR ≥60 mL/min/1.73 m^2(n = 5439) (Events = 1402)	p for interaction
Age, per 1 year greater	0.99 (0.96–1.03)	1.06 (1.05–1.07)	.037
Female gender	0.89 (0.45–1.76)	1.77 (1.53–2.04)	.067
Blood pressure categories
Normal	1.00 (reference)	1.00 (reference)
Prehypertension	2.93 (0.96–6.08)	1.18 (1.03–1.34)	.195
Hypertension	4.97 (1.72–14.41)	1.55 (1.32–1.82)	.069
Glycemic status categories
Normal	1.00 (reference)	1.00 (reference)
Prediabetes	1.11 (0.56–2.21)	0.95 (0.82–1.10)	.907
Diabetes	1.18 (0.59–2.33)	1.23 (1.04–1.47)	.936
Body mass index categories
Normal	1.00 (reference)	1.00 (reference)
Overweight	0.93 (0.46–1.88)	0.96 (0.82–1.12)	.585
Obese	0.82 (0.32–2.13)	1.00 (0.80–1.25)	.827
Physical activity
Inactive	1.00 (reference)	1.00 (reference)
Moderately active	0.97 (0.50–1.88)	0.84 (0.72–0.97)	.659
Sufficiently active	0.79 (0.44–1.45)	0.95 (0.84–1.07)	.814
Marital status
Married	1.00 (reference)	1.00 (reference)
Single/Widowed/Divorced	1.38 (0.71–2.71)	1.20 (1.05–1.38)	.199
Education level
>12 years	1.00 (reference)	1.00 (reference)
6–12 years	0.30 (0.11–0.81)	0.93 (0.79–1.09)	.044
<6 years	0.26 (0.10–0.67)	0.90 (0.74–1.10)	.006
Smoking status
Never	1.00 (reference)	1.00 (reference)
Former	0.94 (0.41–2.13)	0.94 (0.76–1.15)	.586
Current	2.03 (0.56–7.40)	1.06 (0.88–1.27)	.346
TC/HDL-C, per 1-SD	1.04 (0.70–1.53)	0.97 (0.90–1.04)	.098
TG, per 1-SD^b	1.17 (0.81–1.68)	1.09 (1.01–1.17)	.064
Waist circumference, per 1-SD	0.91 (0.59–1.42)	1.00 (0.91–1.10)	.911
Lipid-lowering drug use, yes	1.17 (0.52–2.62)	0.94 (0.70–1.28)	.559
Prevalent CVD, yes	0.73 (0.39–1.39)	1.28 (1.00–1.63)	.366
Family history of diabetes, yes	1.50 (0.75–3.00)	0.86 (0.74–0.99)	.209
eGFR, per 1 mL/min/1.73 m^2 greater	0.96 (0.93–1.00)	1.07 (1.06–1.07)	<.001

Adjusted for age, gender, blood pressure, glycemic status, obesity status, physical activity level, marital status, education level, smoking status, TC/HDL-C, TG, waist circumference, lipid-lowering drug use, prevalent CVD, family history of diabetes, and baseline eGFR.

TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; CI: confidence interval.

^aResults of competing risk analysis.

^bLog-transformed TG was used.

Table 4. Sub-distribution Hazard ratios and 95% CI of risk factors for the decline in kidney function, stratified by gender, in the Tehran Lipid and Glucose Study^a.

Characteristics	Men (n = 3141) (Events = 582)	Women (n = 4049) (Events = 889)	p for interaction
Age (years)
20–34	1.00 (reference)	1.00 (reference)
35–49	1.65 (1.26–2.17)	1.92 (1.56–2.37)	.251
50–64	3.86 (2.75–5.41)	3.65 (2.74–4.85)	.695
≥65	7.29 (4.62–11.50)	6.78 (4.59–10.03)	.611
Blood pressure categories
Normal	1.00 (reference)	1.00 (reference)
Prehypertension	1.04 (0.85–1.26)	1.34 (1.13–1.59)	.061
Hypertension	1.63 (1.28–2.08)	1.73 (1.42–2.12)	.618
Glycemic status categories
Normal	1.00 (reference)	1.00 (reference)
Prediabetes	0.98 (0.79–1.23)	0.95 (0.79–1.15)	.799
Diabetes	1.45 (1.11–1.90)	1.15 (0.93–1.42)	.356
Body mass index categories
Normal	1.00 (reference)	1.00 (reference)
Overweight	0.99 (0.78–1.25)	0.92 (0.75–1.14)	.906
Obese	0.95 (0.65–1.38)	0.97 (0.74–1.28)	.301
Physical activity
Inactive	1.00 (reference)	1.00 (reference)
Moderately active	0.80 (0.63–1.02)	0.86 (0.72–1.02)	.740
Sufficiently active	0.93 (0.78–1.12)	0.96 (0.82–1.12)	.672
Marital status
Married	1.00 (reference)	1.00 (reference)
Single	1.06 (0.79–1.42)	0.96 (0.74–1.24)	.323
Widowed/Divorced	1.00 (0.44–2.27)	1.27 (1.02–1.59)	.646
Education level
>12 years	1.00 (reference)	1.00 (reference)
6–12 years	0.81 (0.65–1.01)	0.99 (0.77–1.26)	.198
<6 years	0.74 (0.55–0.98)	1.12 (0.84–1.48)	.044
Smoking status
Never	1.00 (reference)	1.00 (reference)
Former	0.95 (0.76–1.19)	1.00 (0.61–1.63)	.822
Current	1.09 (0.88–1.34)	1.14 (0.76–1.71)	.762
TC/HDL-C, per 1-SD	0.89 (0.79–1.01)	1.03 (0.94–1.13)	.194
TG, per 1-SD^b	1.17 (1.04–1.31)	1.03 (0.93–1.14)	.827
Waist circumference, per 1-SD	0.97 (0.83–1.13)	1.02 (0.91–1.14)	.278
Lipid-lowering drug use, yes	0.66 (0.35–1.23)	1.13 (0.82–1.57)	.108
Prevalent CVD, yes	0.95 (0.67–1.36)	1.60 (1.20–2.13)	.022
Family history of diabetes, yes	0.94 (0.76–1.15)	0.83 (0.67–1.01)	.331
eGFR, per 1 mL/min/1.73 m^2 greater	1.05 (1.04–1.06)	1.06 (1.05–1.07)	.536

Adjusted for age, blood pressure, glycemic status, obesity status, physical activity level, marital status, education level, smoking status, TC/HDL-C, TG, waist circumference, lipid-lowering drug use, prevalent CVD, family history of diabetes, and baseline eGFR.

TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; CI: confidence interval.

^aResults of competing risk analysis.

^bLog-transformed TG was used.

Table 5. Sub-distribution Hazard ratios and 95% CI of risk factors for the decline in kidney function, stratified by menopausal status among women, in the Tehran Lipid and Glucose Study^a.

Characteristics	Premenopausal women (n = 2649) (Events = 506)	Postmenopausal women (n = 1400) (Events = 383)	p for interaction
Age, per 1 year greater	1.07 (1.05–1.09)	1.04 (1.02–1.06)	.750
Blood pressure categories
Normal	1.00 (reference)	1.00 (reference)
Prehypertension	1.35 (1.10–1.67)	1.32 (0.97–1.80)	.950
Hypertension	1.36 (0.93–1.97)	1.84 (1.37–2.46)	.045
Glycemic status categories
Normal	1.00 (reference)	1.00 (reference)
Prediabetes	1.09 (0.83–1.42)	0.87 (0.67–1.14)	.390
Diabetes	0.69 (0.47–1.01)	1.32 (1.01 − 1.73)	<.001
Body mass index categories
Normal	1.00 (reference)	1.00 (reference)
Overweight	0.89 (0.69–1.15)	1.10 (0.74–1.65)	.169
Obese	0.96 (0.67–1.38)	1.15 (0.72–1.84)	.050
Physical activity
Inactive	1.00 (reference)	1.00 (reference)
Moderately active	0.85 (0.67–1.07)	0.89 (0.68–1.16)	.939
Sufficiently active	1.00 (0.81–1.23)	0.95 (0.75–1.21)	.389
Marital status
Married	1.00 (reference)	1.00 (reference)
Single/Widowed/Divorced	1.13 (0.89–1.45)	1.10 (0.86–1.42)	.905
Education level
>12 years	1.00 (reference)	1.00 (reference)
6–12 years	1.00 (0.77–1.30)	1.91 (0.70–5.20)	.198
<6 years	1.03 (0.73–1.46)	1.91 (0.71–5.12)	.225
Smoking status
Never	1.00 (reference)	1.00 (reference)
Former	1.47 (0.81–2.68)	0.78 (0.39–1.56)	.305
Current	0.90 (0.49–1.62)	1.55 (0.89–2.70)	.150
TC/HDL-C, per 1-SD	0.97 (0.84–1.11)	1.10 (0.98–1.24)	.077
TG, per 1-SD^b	1.10 (0.96–1.27)	0.97 (0.82–1.10)	.455
Waist circumference, per 1-SD	0.95 (0.81–1.12)	1.09 (0.92–1.29)	.016
Lipid-lowering drug use, yes	0.17 (0.02–1.25)	1.29 (0.93–1.79)	.026
Prevalent CVD, yes	1.43 (0.68–3.00)	1.31 (0.95–1.80)	.964
Family history of diabetes, yes	0.77 (0.59–1.01)	0.95 (0.69–1.31)	.180
eGFR, per 1 mL/min/1.73 m^2 greater	1.08 (1.07–1.09)	1.04 (1.03–1.06)	<.001

Adjusted for age, blood pressure, glycemic status, obesity status, physical activity level, marital status, education level, smoking status, TC/HDL-C, TG, waist circumference, lipid-lowering drug use, prevalent CVD, family history of diabetes, and baseline eGFR.

TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; CI: confidence interval.

^aResults of competing risk analysis.

^bLog-transformed TG was used.

Data availability statement

The data supporting this study’s findings are available from the corresponding author, F.H., upon reasonable request.