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In this study, 32,351 subjects were included; 60.74% were men, and the median age was 44 years (range, 30–54 years). The median blood lipid levels of all participants was 4.60 mmol/L (range 4.10–5.20 mmol/L), 1.50 mmol/L (range 1.10–2.30 mmol/L), 1.33 mmol/L (range 1.12–1.57 mmol/L), 3.02 mmol/L (range 2.56–3.51 mmol/L), 3.48 mmol/L (range 2.89–4.17 mmol/L), 1.16 mmol/L (range 0.72–1.91 mmol/L), 2.27 mmol/L (range 1.84–2.77 mmol/L) for TC, TG, HDL-C, LDL-C, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C, respectively. The proportion of participants who were consumming alcohol, following a high-salt diet, and high-fat diet was smaller than 30%. The prevalence of hypertension, CHD, diabetes, and dyslipidemia was 28.42%, 2.69%, 6.96%, and 36.53%, respectively. The prevalence rates of hypertension, CHD, diabetes, and dyslipidemia in the CKD population were 29.63%, 6.94%, 25.46% and 51.39%, respectively. The prevalence of hypertension, CHD, diabetes, and dyslipidemia was significantly higher in the CKD than in the non-CKD population (Table 1).
Table 1. Baseline characteristics
Characteristics CKD (n = 648) NO-CKD (n = 31,703) Total (n = 32,351) Age (years) 59 (45–70) 44 (38–54) 44 (39–54) Sex (Male) 484 (74.69) 19,167 (60.46) 1,9651 (60.74) Occupation Managerial staff 86 (13.27) 4,121 (13.00) 4,207 (13.00) Worker staff 493 (76.08) 24,596 (77.58) 25,089 (77.55) Technical and logistics staff 69 (10.65) 2,986 (9.42) 3,055 (9.44) Education Junior middle school or below 389 (60.03) 11,777 (37.15) 12,166 (37.61) Senior middle school or equivalent 151 (23.30) 8,925 (28.15) 9,076 (28.05) College or above 108 (16.67) 11,001 (34.70) 11,109 (34.34) Income (≥ ¥2,000) 288 (44.44) 15,446 (48.72) 15,734 (48.64) Smoking (Yes) 248 (38.27) 11,629 (36.68) 11,877 (36.71) Alcohol consumption (Yes) 143 (22.07) 6,599 (20.82) 6,742 (20.84) Regular exercise 340 (52.47) 14,558 (45.92) 14,898 (46.05) High-salt diet 164 (25.31) 7,018 (22.14) 7,182 (22.20) High-fat diet 138 (21.30) 6,127 (19.33) 6,265 (19.37) BMI, kg/m2 24.88 (22.76–27.33) 23.34 (21.19–25.59) 23.38 (21.2–25.64) Hypertension 192 (29.63) 4,227 (13.33) 9,193 (28.42) CHD 45 (6.94) 825 (2.60) 870 (2.69) Diabetes 165 (25.46) 2,086 (6.58) 2251 (6.96) Dyslipidemia 333 (51.39) 11,484 (36.22) 11817 (36.53) Family history of kidney disease 1 (0.15) 52 (0.16) 53 (0.16) eGFR- mL/min per 1.73 m² 90.40 (70.41–105.63) 105.46 (95.47–113.02) 105.28 (95.08–112.97) TC, mmol/L 4.80 (4.20–5.40) 4.6 (4.10–5.20) 4.60 (4.10–5.20) TG, mmol/L 1.90 (1.30–2.80) 1.50 (1.10–2.30) 1.50 (1.10–2.30) HDL-C, mmol/L 1.23 (1.04–1.47) 1.33 (1.12–1.57) 1.33 (1.12–1.57) LDL-C, mmol/L 3.15 (2.67–3.67) 3.01 (2.56–3.5) 3.02 (2.56–3.51) TC/HDL-C 3.89 (3.22–4.56) 3.47 (2.89–4.15) 3.48 (2.89–4.17) TG/HDL-C 1.50 (0.98–2.54) 1.15 (0.72–1.90) 1.16 (0.72–1.91) LDL-C/HDL-C 2.55 (2.08–3.1) 2.27 (1.83–2.76) 2.27 (1.84–2.77) Note. Values are expressed as number (percent) or median (interquartile range). BMI, body mass index; CKD, chronic kidney disease; CHD, coronary heart disease; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. -
In this cohort study, the median follow-up time was 2.2 (0.5, 4.2) years, during which 2.00% (n=648) of the participants developed CKD. Figure 1 shows the relationship between lipid profiles and risk of CKD by RCS analysis. After adjusting for confounders in Model 3, there was a positive linear dose-response relationship between TC, TG, TC/HDL-C, and TG/HDL-C levels and the risk of CKD (P for overall < 0.05, P for nonlinear > 0.05). There was a negative linear dose-response relationship between HDL-C levels and CKD risk (P for overall < 0.05, P for nonlinear > 0.05). There was a nonlinear dose-response relationship between LDL-C and LDL-C/HDL-C levels and the risk of CKD (P for overall < 0.05, P for nonlinear < 0.05). The inflection point of LDL-C was 2.82 mmol/L, the HRs left and right the inflection point were 0.37 (0.23, 0.59) and 1.15 (0.92, 1.43), respectively; the inflection point of LDL-C/HDL-C was 2.01 mmol/L, and the HRs left and right the inflection point were 0.51 (0.23, 1.43) and 1.28 (1.05, 1.55).
Table 2 shows the HRs and 95%CI for the associations between the five lipid indicators and CKD in the three models. In Model 3, the HRs for CKD per one SD increase in lipid levels were 1.11 (1.01, 1.22) for TC, 1.10 (1.05, 1.16) for TG, 0.75 (0.58, 0.98) for HDL-C, 1.16 (1.08, 1.24) for TC/HDL-C, and 1.09 (1.05, 1.14) for TG/HDL-C, respectively. Furthermore, Figure 2 shows the risk of CKD at different lipid levels in Model 3. The risk of CKD significantly increased in the highest quartiles (Q4) of TG, TC/HDL-C, and TG/HDL-C compared with the lower quartiles (Q1). In the quartile group, the P trends for TC, TG, TC/HDL-C, and TG/HDL-C were significant; however, reagarding HDL-C there was no particular trend. Compared to participants with normal lipid levels, the risk of CKD was significantly higher in those with abnormal TG levels, whereas participants with lipid levels below the median had a significantly increased risk of CKD compared to participants with lipid levels below the median.
Table 2. Hazard ratios and 95% confidence interval for CKD per one standard deviation increase in lipid profiles
Lipid profiles Model 1 Model 2 Model 3 HRs (95% CI) P HRs (95% CI) P HRs (95% CI) P TC 1.22 (1.11, 1.35) < 0.001 1.18 (1.07, 1.30) 0.001 1.11 (1.01, 1.22) 0.025 TG 1.19 (1.13, 1.24) < 0.001 1.15 (1.10, 1.21) < 0.001 1.10 (1.05, 1.16) < 0.001 HDL-C 0.58 (0.45, 0.75) < 0.001 0.71 (0.55, 0.93) 0.012 0.75 (0.58, 0.98) 0.035 TC/HDL-C 1.26 (1.19, 1.34) < 0.001 1.20 (1.13, 1.29) < 0.001 1.16 (1.08, 1.24) < 0.001 TG/HDL-C 1.15 (1.11, 1.20) < 0.001 1.12 (1.08, 1.17) < 0.001 1.09 (1.05, 1.14) < 0.001 Note. Values are expressed as median (interquartile range). Model 1 was adjusted for age, sex, occupation, education level, and income. Model 2 was additionally adjusted for smoking, alcohol consumption, exercise, high-salt diet, high-fat diet, and BMI, based on Model 1. Model 3 was additionally adjusted for comorbidities (hypertension, CHD, dyslipidemia, and diabetes), family history of kidney disease, and baseline eGFR based on Model 2. HRs, hazard ratios; CI, confidence interval; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol Figure 2. Hazard Ratios and 95% Confidence Interval for Lipid Profiles Grouped by Level. In the Q2, Q3, and Q4, Q1 was used as the reference. In the critical value (or median), except for HDL-C, the reference is smaller than the critical value (or median), and the reference is greater than the critical value in HDL-C. Model was adjusted for age, sex, occupation, education level, income, smoking, alcohol consumption, exercise, high-salt diet, high-fat diet, BMI, hypertension, CHD, diabetes, hyperlipidemia, family history of kidney disease and baseline eGFR (Model 3). HRs, hazard ratios; CI, confidence interval; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; BMI, body mass index; CKD, chronic kidney disease; CHD, coronary heart disease; SD, standard deviation
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Figure 3 shows the fitted regression curves between the lipid profiles and CKD. With the increase of blood lipid levels, the risk of CKD appears to reach abruptly the cutoff value. TC, TG, TC/HDL-C, and TG/HDL-C presented an upward jump at cutoff value, while the cutoff values were 6.3, 4.3, 5.5, and 3.1 mmol/L, increasing the risk of CKD by 0.90% (P = 0.006), 1.50% (P = 0.016), 2.30% (P = 0.011), and 1.60% (P = 0.018), respectively; whereas HDL-C had a downward jump at the cutoff value (0.8 mmol/L), while the risk was reduced by 1% (P = 0.031) (Figure 3A). Because the relationship between LDL-C, LDL-C/HDL-C, and CKD was nonlinear, a group with statistically significant results was selected for RDD analysis. The cutoff value for LDL-C (< 2.82 mmol/L) was 1.5 mmol/L, and the risk of CKD was reduced by 0.50% (P = 0.018); the cutoff value for LDL-C/HDL-C (≥ 2.82 mmol/L) was 4.9 mmol/L, the risk increased by 1.60% (P = 0.008) (Figure 3B).
Figure 3. Fitted regression curves between lipid profiles and the risk of CKD. (A) Lipid profiles are linearly correlated with CKD. (B) Lipid profiles are nonlinearly associated with CKD, and groups with statistically significant results are grouped by inflection points. The x-axis is the level of lipid profiles, and the y-axis is the hazard function for CKD. TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CKD, chronic kidney disease
Figure 4 shows the results of the validity tests and robustness check for the RDD. In the validity tests, the pseudo-outcome results showed that the LATE estimate of the above covariates was not significant at the cutoff value, satisfying the smoothness assumption. The results of the McCrary’s test showed that the density function estimates were partially overlapping confidence intervals on both sides of the cutoff values. The results showed that the lipid level distribution at the cutoff value was continuous and met the continuous hypothesis. In the robustness check, the results of the pseudo-cutoff point showed that, after changing the cutoff value, the reference interval of the regression coefficient of all models was zero, indicating that the original cutoff value was real, and the regression results were relatively stable. The results of the donut-hole approach showed that after removing samples of 20% and below the cutoff value, the results were still significant, while after removing samples below 30% and 40% of the cutoff value, most of the results obtained were not statistically significant because too many samples were removed; however, the results could still be considered stable. The results of bandwidth selection showed that the majority of results was significant. All of the above test results showed that the cutoff values found in this study were effective and stable with high reliability.
Figure 4. Validity test and robust check of RDD between lipid profiles and CKD. (A) Lipid profiles are linearly correlated with CKD; (B) lipid profiles are nonlinearly associated with CKD, and groups with statistically significant results are grouped by inflection points. a: Pseudo-outcome test, the x-axis is the variable for the pseudo-outcome, and the y-axis is the local average treatment effect estimate value; b: McCrary's test, the x-axis is the level of lipid profiles, and the y-axis is the density function estimates; c: pseudo-cutoff point, the x-axis is the level of lipid profiles (i.e. the pseudo-cutoff value), and the y-axis is the local average treatment effect estimate value; d: donut-hole approach, the x-axis is the percentage of sample removed, and the y-axis is the local average treatment effect estimate value; e: bandwidth selection, the x-axis is the different bandwidth values, and the y-axis is the local average treatment effect estimate value. TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CKD, chronic kidney disease;
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The dose-response curves for males and females (Supplementary Figure S2, available in www.besjournal.com), non-dyslipidemia, and dyslipidemia (Supplementary Figure S3, available in www.besjournal.com) were plotted separately. In each group, blood lipid levels (TC, TG, HDL-C, TC/HDL-C, and TG/HDL-C) were linearly correlated with CKD, while LDL-C was nonlinearly associated with CKD, except in female. The LDL-C/HDL-C ratio was nonlinearly associated with CKD in male and non-dyslipidemia. Table 3 shows the HRs for CKD associated with lipid profiles stratified by sex and dyslipidemia. These results were similar to those for the total population. In general, the effects of TG, TC/HDL-C, and TG/HDL-C were greater in women and patients with dyslipidemia than in men or patients without dyslipidemia. In the RDD analysis, the TC/HDL-C cutoff values in male, female, non-dyslipidemia, and dyslipidemia were 6.6, 5.5, 5.9, and 5.3, respectively, while the risk of CKD increased by 1.90% (P = 0.003), 1.10% (P = 0.038), 0.90% (P = 0.010), and 1.10% (P = 0.045), respectively. All the indicators passed the validity test (Supplementary Figure S4, available in www.besjournal.com). In addition, the LDL-C cutoff value for dyslipidemia was not statistically significant. In males, with a cutoff value of 1.5 for LDL-C (< 2.77), the risk of CKD was reduced by 0.60% (P = 0.038), while, with a cutoff value of 4.0 for LDL-C (≥ 2.77), this risk was increased by 1.50% (P = 0.024) (Figure 5B). LDL-C levels passed the validity and robustness tests (Figure S5).
Table 3. Hazard Ratios (per 1-SD) for CKD in the Stratified Analysis by Sex and Dyslipidemia
Variables Sex Dyslipidemia Male
HRs (95% CI)Female
HRs (95% CI)NO
HRs (95% CI)YES
HRs (95% CI)TC 1.17 (1.05, 1.31)* 0.94 (0.78, 1.13) 1.09 (0.98, 1.21) 1.15 (0.93, 1.43) TG 1.08 (1.02, 1.14)* 1.18 (1.05, 1.32)* 1.07 (0.99, 1.16) 1.33 (1.01, 1.74)* HDL-C 0.84 (0.71, 0.99)* 0.58 (0.35, 0.95)* 0.70 (0.53, 0.94)* 1.02 (0.51, 2.01) TC/HDL-C 1.15 (1.06, 0.9)* 1.19 (1.01, 1.40)* 1.09 (1.02, 1.17)* 1.17 (1.08, 1.26)* TG/HDL-C 1.08 (1.03, 1.13)* 1.15 (1.06, 1.26)* 1.06 (0.96, 1.17) 1.14 (1.04, 1.25)* LDL-C -§ 0.78 (0.59, 1.02) -§ -§ LDL-C/HDL-C -§ 1.06 (0.76, 1.46) -§ 0.95 (0.65, 1.40) Note. * P < 0.05. § There is a nonlinear correlation between blood lipid levels and CKD. Figure 5. Fitted Regression Curves between Lipid Profiles and the risk of CKD. A: Fitted regression curves between TC/HDL-C and CKD (fitted regression curves in a:male; b: female; c: non-dyslipidemia; d: dyslipidemia. The x-axis is the level of TC/HDL-C, and the y-axis is the hazard function for CKD). B: Fitted regression curves between LDL-C and CKD (fitted regression curves between e: LDL-C (<2.77) and CKD in males; f: LDL-C (≥2.77) and CKD in males; g: LDL-C (<2.85) and CKD in non-dyslipidemia; h: LDL-C (<2.88) and CKD in dyslipidemia. The x-axis is the level of LDL-C, and the y-axis is the hazard function for CKD). TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol
The HRs on either side of the inflection point are shown in Supplementary Figures S1 and S2. The model was adjusted for age, sex, occupation, education level, income, smoking, alcohol consumption, exercise, high-salt and high-fat diets, BMI, hypertension, CHD, diabetes, hyperlipidemia, family history of kidney disease, and baseline eGFR (Model 3). TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol
doi: 10.3967/bes2024.113
The Effect of Blood Lipid Profiles on Chronic Kidney Disease in a Prospective Cohort: Based on a Regression Discontinuity Design
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Abstract:
Objective Previous studies on the association between lipid profiles and chronic kidney disease (CKD) have yielded inconsistent results and no defined thresholds for blood lipids. Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted. Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD. A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD. Results Over a median follow-up time of 2.2 (0.5, 4.2) years, 648 (2.00%) subjects developed CKD. The lipid profiles that were significantly and linearly related to CKD included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, and TG/HDL-C, whereas low-density lipoprotein cholesterol (LDL-C) and LDL-C/HDL-C were nonlinearly correlated with CKD. TC, TG, TC/HDL-C, and TG/HDL-C showed an upward jump at the cutoff value, increasing the risk of CKD by 0.90%, 1.50%, 2.30%, and 1.60%, respectively, whereas HDL-C showed a downward jump at the cutoff value, reducing this risk by 1.0%. Female and participants with dyslipidemia had a higher risk of CKD, while the cutoff values for the different characteristics of the population were different. Conclusions There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China, and TG, TC/HDL-C, while TG/HDL-C showed a stronger risk association. The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk. -
Key words:
- Blood lipid profiles /
- Chronic kidney disease /
- Regression discontinuity design /
- Prospective cohort
&These authors contributed equally to this work.
注释:1) DECLARATION OF INTERESTS: -
Figure 1. Dose-response relationship between lipid profiles and risk of CKD. A: Lipid profiles are linearly correlated with CKD (TC, TG, HDL-C, TC/HDL-C, and TG/HDL-C). B: Lipid profiles are nonlinearly associated with CKD (LDL-C, LDL-C/HDL-C). The solid line indicates the adjusted HR, and the shaded area represents 95%CI for HR. The x-axis represents the level of lipid profiles, and the y-axis the HRs for CKD where the reference value is the clinical cutoff or the 50th percentile of composite indicator (specifically, 6.2 mmol/L for TC, 2.3 mmol/L for TG, 1 mmol/L for HDL-C, 4.1 mmol/L for LDL-C, 3.48 for TC/HDL-C, 1.16 for TG/HDL-C, and 2.27 for LDL-C/HDL-C). Model was adjusted for age, sex, occupation, education level, income, smoking, alcohol consumption, exercise, high-salt diet, high-fat diet, BMI, hypertension, CHD, diabetes, hyperlipidemia, family history of kidney disease and baseline eGFR (Model 3). HRs, hazard ratios; SD, standard deviation; BMI, body mass index; CKD, chronic kidney disease; CHD, coronary heart disease; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol
Figure 2. Hazard Ratios and 95% Confidence Interval for Lipid Profiles Grouped by Level. In the Q2, Q3, and Q4, Q1 was used as the reference. In the critical value (or median), except for HDL-C, the reference is smaller than the critical value (or median), and the reference is greater than the critical value in HDL-C. Model was adjusted for age, sex, occupation, education level, income, smoking, alcohol consumption, exercise, high-salt diet, high-fat diet, BMI, hypertension, CHD, diabetes, hyperlipidemia, family history of kidney disease and baseline eGFR (Model 3). HRs, hazard ratios; CI, confidence interval; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; BMI, body mass index; CKD, chronic kidney disease; CHD, coronary heart disease; SD, standard deviation
Figure 3. Fitted regression curves between lipid profiles and the risk of CKD. (A) Lipid profiles are linearly correlated with CKD. (B) Lipid profiles are nonlinearly associated with CKD, and groups with statistically significant results are grouped by inflection points. The x-axis is the level of lipid profiles, and the y-axis is the hazard function for CKD. TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CKD, chronic kidney disease
Figure 4. Validity test and robust check of RDD between lipid profiles and CKD. (A) Lipid profiles are linearly correlated with CKD; (B) lipid profiles are nonlinearly associated with CKD, and groups with statistically significant results are grouped by inflection points. a: Pseudo-outcome test, the x-axis is the variable for the pseudo-outcome, and the y-axis is the local average treatment effect estimate value; b: McCrary's test, the x-axis is the level of lipid profiles, and the y-axis is the density function estimates; c: pseudo-cutoff point, the x-axis is the level of lipid profiles (i.e. the pseudo-cutoff value), and the y-axis is the local average treatment effect estimate value; d: donut-hole approach, the x-axis is the percentage of sample removed, and the y-axis is the local average treatment effect estimate value; e: bandwidth selection, the x-axis is the different bandwidth values, and the y-axis is the local average treatment effect estimate value. TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CKD, chronic kidney disease;
Figure 5. Fitted Regression Curves between Lipid Profiles and the risk of CKD. A: Fitted regression curves between TC/HDL-C and CKD (fitted regression curves in a:male; b: female; c: non-dyslipidemia; d: dyslipidemia. The x-axis is the level of TC/HDL-C, and the y-axis is the hazard function for CKD). B: Fitted regression curves between LDL-C and CKD (fitted regression curves between e: LDL-C (<2.77) and CKD in males; f: LDL-C (≥2.77) and CKD in males; g: LDL-C (<2.85) and CKD in non-dyslipidemia; h: LDL-C (<2.88) and CKD in dyslipidemia. The x-axis is the level of LDL-C, and the y-axis is the hazard function for CKD). TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol
S2. Dose-response Relationship between lipid profiles and risk of CKD in male and female. A: Lipid profiles are linearly correlated with CKD in male. B: Lipid profiles are nonlinearly associated with CKD in male. C and D: Lipid profiles are linearly correlated with CKD in female. The solid line indicates the adjusted HR, and the shaded area represents 95%CI for HR. The x-axes is the level of lipid profiles, and the y-axes is the HR for CKD. The reference point (HR=1) was the critical value (for TC, TG, HDL-C and LDL-C) or median (for TC/HDL-C, TG/HDL-C and LDL-C/HDL-C). Model was adjusted for age, sex, occupation, education, income, smoking, drinking, exercise, high-salt diet, high-fat diet, BMI, hypertension, coronary heart disease, diabetes, hyperlipidemia, family history of kidney disease and baseline eGFR (Model 3). Abbreviation: HR, Hazard ratios; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
S3. Dose-response relationship between lipid profiles and risk of CKD in stratified analysis by dyslipidemia. A: Lipid profiles are linearly correlated with CKD in non-dyslipidemia. B: Lipid profiles are nonlinearly associated with CKD in non-dyslipidemia. C: Lipid profiles are linearly correlated with CKD in dyslipidemia. D: Linearly (LDL-C/HDL-C) and non-linearly (LDL-C) correlated with CKD in dyslipidemia. The solid line indicates the adjusted HR, and the shaded area represents 95%CI for HR. The x-axes is the level of lipid profiles, and the y-axes is the HR for CKD. The reference point (HR=1) was the critical value (for TC, TG, HDL-C and LDL-C) or median (for TC/HDL-C, TG/HDL-C and LDL-C/HDL-C). Model was adjusted for age, sex, occupation, education, income, smoking, drinking, exercise, high-salt diet, high-fat diet, BMI, hypertension, coronary heart disease, diabetes, hyperlipidemia, family history of kidney disease and baseline eGFR (Model 3). Abbreviation: HR, Hazard ratios; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
S4. Validity test and robust check of RDD between TC/HDL-C and CKD. (1) A: validity test and robust check in male; B: validity test and robust check in female. C: validity test and robust check in non-dyslipidemia; D: validity test and robust check in dyslipidemia. (2) a: pseudo outcome test, the x-axes is the variable for the pseudo outcome, and the y-axes is the local average treatment effect estimate value; b: McCrary's test, the x-axes is the level of lipid profiles, and the y-axes is the density function estimates; c: pseudo cutoff point, the x-axes is the level of lipid profiles (i.e. the pseudo cutoff value), and the y-axes is the local average treatment effect estimate value; d: donut hole approach, the x-axes is the percent of sample removed, and the y-axes is the local average treatment effect estimate value; e: bandwidth selection, the x-axes is the different bandwidth values, and the y-axes is the local average treatment effect estimate value. Abbreviation: TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol.
S5. Validity test and robust check of RDD between LDL-C and CKD. (1) A: validity test and robust check of RDD between LDL-C (< 2.77) and CKD in male; B: validity test and robust check of RDD between LDL-C (≥ 2.77) and CKD in male; C: validity test and robust check of RDD between LDL-C (< 2.85) and CKD in non-dyslipidemia; D: validity test and robust check of RDD between LDL-C (< 2.88) and CKD in dyslipidemia. (2) a: pseudo outcome test, the x-axes is the variable for the pseudo outcome, and the y-axes is the local average treatment effect estimate value; b: McCrary's test, the x-axes is the level of lipid profiles, and the y-axes is the density function estimates; c: pseudo cutoff point, the x-axes is the level of lipid profiles (i.e. the pseudo cutoff value), and the y-axes is the local average treatment effect estimate value; d: donut hole approach, the x-axes is the percent of sample removed, and the y-axes is the local average treatment effect estimate value; e: bandwidth selection, the x-axes is the different bandwidth values, and the y-axes is the local average treatment effect estimate value. Abbreviation: LDL-C, low-density lipoprotein cholesterol.
Table 1. Baseline characteristics
Characteristics CKD (n = 648) NO-CKD (n = 31,703) Total (n = 32,351) Age (years) 59 (45–70) 44 (38–54) 44 (39–54) Sex (Male) 484 (74.69) 19,167 (60.46) 1,9651 (60.74) Occupation Managerial staff 86 (13.27) 4,121 (13.00) 4,207 (13.00) Worker staff 493 (76.08) 24,596 (77.58) 25,089 (77.55) Technical and logistics staff 69 (10.65) 2,986 (9.42) 3,055 (9.44) Education Junior middle school or below 389 (60.03) 11,777 (37.15) 12,166 (37.61) Senior middle school or equivalent 151 (23.30) 8,925 (28.15) 9,076 (28.05) College or above 108 (16.67) 11,001 (34.70) 11,109 (34.34) Income (≥ ¥2,000) 288 (44.44) 15,446 (48.72) 15,734 (48.64) Smoking (Yes) 248 (38.27) 11,629 (36.68) 11,877 (36.71) Alcohol consumption (Yes) 143 (22.07) 6,599 (20.82) 6,742 (20.84) Regular exercise 340 (52.47) 14,558 (45.92) 14,898 (46.05) High-salt diet 164 (25.31) 7,018 (22.14) 7,182 (22.20) High-fat diet 138 (21.30) 6,127 (19.33) 6,265 (19.37) BMI, kg/m2 24.88 (22.76–27.33) 23.34 (21.19–25.59) 23.38 (21.2–25.64) Hypertension 192 (29.63) 4,227 (13.33) 9,193 (28.42) CHD 45 (6.94) 825 (2.60) 870 (2.69) Diabetes 165 (25.46) 2,086 (6.58) 2251 (6.96) Dyslipidemia 333 (51.39) 11,484 (36.22) 11817 (36.53) Family history of kidney disease 1 (0.15) 52 (0.16) 53 (0.16) eGFR- mL/min per 1.73 m² 90.40 (70.41–105.63) 105.46 (95.47–113.02) 105.28 (95.08–112.97) TC, mmol/L 4.80 (4.20–5.40) 4.6 (4.10–5.20) 4.60 (4.10–5.20) TG, mmol/L 1.90 (1.30–2.80) 1.50 (1.10–2.30) 1.50 (1.10–2.30) HDL-C, mmol/L 1.23 (1.04–1.47) 1.33 (1.12–1.57) 1.33 (1.12–1.57) LDL-C, mmol/L 3.15 (2.67–3.67) 3.01 (2.56–3.5) 3.02 (2.56–3.51) TC/HDL-C 3.89 (3.22–4.56) 3.47 (2.89–4.15) 3.48 (2.89–4.17) TG/HDL-C 1.50 (0.98–2.54) 1.15 (0.72–1.90) 1.16 (0.72–1.91) LDL-C/HDL-C 2.55 (2.08–3.1) 2.27 (1.83–2.76) 2.27 (1.84–2.77) Note. Values are expressed as number (percent) or median (interquartile range). BMI, body mass index; CKD, chronic kidney disease; CHD, coronary heart disease; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. Table 2. Hazard ratios and 95% confidence interval for CKD per one standard deviation increase in lipid profiles
Lipid profiles Model 1 Model 2 Model 3 HRs (95% CI) P HRs (95% CI) P HRs (95% CI) P TC 1.22 (1.11, 1.35) < 0.001 1.18 (1.07, 1.30) 0.001 1.11 (1.01, 1.22) 0.025 TG 1.19 (1.13, 1.24) < 0.001 1.15 (1.10, 1.21) < 0.001 1.10 (1.05, 1.16) < 0.001 HDL-C 0.58 (0.45, 0.75) < 0.001 0.71 (0.55, 0.93) 0.012 0.75 (0.58, 0.98) 0.035 TC/HDL-C 1.26 (1.19, 1.34) < 0.001 1.20 (1.13, 1.29) < 0.001 1.16 (1.08, 1.24) < 0.001 TG/HDL-C 1.15 (1.11, 1.20) < 0.001 1.12 (1.08, 1.17) < 0.001 1.09 (1.05, 1.14) < 0.001 Note. Values are expressed as median (interquartile range). Model 1 was adjusted for age, sex, occupation, education level, and income. Model 2 was additionally adjusted for smoking, alcohol consumption, exercise, high-salt diet, high-fat diet, and BMI, based on Model 1. Model 3 was additionally adjusted for comorbidities (hypertension, CHD, dyslipidemia, and diabetes), family history of kidney disease, and baseline eGFR based on Model 2. HRs, hazard ratios; CI, confidence interval; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol Table 3. Hazard Ratios (per 1-SD) for CKD in the Stratified Analysis by Sex and Dyslipidemia
Variables Sex Dyslipidemia Male
HRs (95% CI)Female
HRs (95% CI)NO
HRs (95% CI)YES
HRs (95% CI)TC 1.17 (1.05, 1.31)* 0.94 (0.78, 1.13) 1.09 (0.98, 1.21) 1.15 (0.93, 1.43) TG 1.08 (1.02, 1.14)* 1.18 (1.05, 1.32)* 1.07 (0.99, 1.16) 1.33 (1.01, 1.74)* HDL-C 0.84 (0.71, 0.99)* 0.58 (0.35, 0.95)* 0.70 (0.53, 0.94)* 1.02 (0.51, 2.01) TC/HDL-C 1.15 (1.06, 0.9)* 1.19 (1.01, 1.40)* 1.09 (1.02, 1.17)* 1.17 (1.08, 1.26)* TG/HDL-C 1.08 (1.03, 1.13)* 1.15 (1.06, 1.26)* 1.06 (0.96, 1.17) 1.14 (1.04, 1.25)* LDL-C -§ 0.78 (0.59, 1.02) -§ -§ LDL-C/HDL-C -§ 1.06 (0.76, 1.46) -§ 0.95 (0.65, 1.40) Note. * P < 0.05. § There is a nonlinear correlation between blood lipid levels and CKD. -
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