| Objective:Glomerular filtration rate(GFR)is the amount of filtrate produced by both kidneys per unit time and is a diagnostic indicator of chronic kidney disease.Blood lipids are closely related to atherosclerotic diseases,and chronic kidney disease is often accompanied by atherosclerosis.In previous studies,the relationship between blood lipids and GFR is unclear.The results of studies are also inconsistent as to whether blood lipids are independent risk factors for GFR decline.Therefore,this study intends to use a cross-sectional study to systematically analyze the relationship between blood lipids,blood lipids ratio and GFR,and then to explore whether there is a causal relationship between blood lipids and GFR through a two-sample bidirectional Mendelian randomization(MR)study,and to further explore the exact relationship between blood lipids and GFR.To provide a basis for clinical prevention and treatment of GFR decline and chronic kidney disease.Methods:The data of this cross-sectional study comes from the extended cohort of the"community population cohort",a key special subject of precision medicine research.This cross-sectional data was selected from the physical examination data of Nanning Second People’s Hospital and Yulin First People’s Hospital of the baseline survey in this cohort.According to the inclusion and exclusion criteria,9856 participants between the ages of 18 and 98 were finally included as research subjects.We conducted questionnaire surveys,anthropometric measurements,and biological sample data collection on the research subjects.The t test,non-parametric test and chi-square test were used to analyze the differences in the distribution of each variable between the GFR normal group and the abnormal group.Linear regression was used to estimate the relationship between TC,TG,HDL-C,LDL-C,Non HDL-C,TC/HDL-C ratio,TG/HDL-C ratio,LDL-C/HDL-C ratio,Non HDL-C/HDL-C ratio and GFR in the overall population.The LDL-C and LDL-C/HDL-C ratio were stratified according to the quartiles and then further analyzed.The relationships between LDL-C,LDL-C/HDL-C ratio and GFR were analyzed using the first quartile as a reference,and the trend test was carried out.Finally,linear regression was used to estimate the relationship between LDL-C,LDL-C/HDL-C ratio and GFR in different gender groups,age groups and BMI groups.Potential confounding factors include gender,age,BMI,ethnicity,education level,occupation,marital status,income status,diet score,systolic blood pressure,diastolic blood pressure,fasting blood sugar,smoking,drinking,tea drinking,sports,high blood pressure,and diabetes.In two-sample bidirectional MR study,SNPs significantly associated with blood lipids and GFR were taken as instrumental variables respectively,and the causality between blood lipids and GFR was evaluated by inverse-variance weighted(IVW),MR-Egger and weighted median(WM).A second MR analysis was performed,using Genetic risk score(GRS)of blood lipids and GFR as instrumental variables respectively,to assess the causal association between blood lipids and GFR.Results:1.The age,height,weight,BMI,systolic blood pressure,diastolic blood pressure and diet scores of the GFR abnormal group are higher than those of the GFR normal group(P<0.005).Gender,ethnicity,occupation type,education level,marital status,income status,smoking,drinking,tea drinking,sports,high blood pressure and diabetes history between the GFR abnormal group and the normal group was statistically significant(P<0.001).There was no significant difference in the fasting blood glucose between the two groups(P=0.385).2.The levels of TC,TG,LDL-C,Non HDL-C,TC/HDL-C,TG/HDL-C,LDL-C/HDL-C and Non HDL-C/HDL-C in the GFR abnormal group were higher than in the normal GFR group(P<0.001),the level of HDL-C was lower than that in the normal GFR group(P<0.001).3.The results of multiple linear regression showed that the LDL-C and LDL-C/HDL-C ratio were associated with GFR in the overall population(P<0.05).For every unit increase in LDL-C and LDL-C/HDL-C,the GFR level decreased by 1.33 and 1.31 m L/min/1.73m~2,respectively.No association was found between TC,TG,HDL-C,Non HDL-C,TC/HDL-C,TG/HDL-C,Non HDL-C/HDL-C and GFR level(P>0.05).Compared with the Q1 group(<2.55 mmol/L)of LDL-C,the GFR level were reduced by 1.09,2.00 and2.53m L/min/1.73m~2in the Q2(2.55-3.11 mmol/L),Q3(3.11-3.69 mmol/L)and Q4(≥3.69 mmol/L)groups,respectively(all P<0.05).Compared with the Q1group(<1.90)of LDL-C/HDL-C,the difference between the Q1 and Q2(1.90-2.51)groups was not statistically significant(P=0.095);GFR level was reduced by 1.77 and 2.91m L/min/1.73m~2 in the Q3(2.51-3.15)and Q4(≥3.15)groups,respectively(all P<0.001).With the increase of LDL-C and LDL-C/HDL-C,the GFR level showed a downward trend(both P<0.001).4.The LDL-C was associated with GFR in people with<40 years old and40-60 years old(P<0.005).For every 1 mmol/L increase in LDL-C,GFR decreased by 1.13 and 1.88 m L/min/1.73m~2,respectively;no association was found between LDL-C level and GFR level in people with≥60 years old(P=0.934).The LDL-C/HDL-C ratio was associated with the GFR in the<40,40-60 and≥60 groups(P<0.05),and the GFR decreased by 0.78,1.75 and 2.15m L/min/1.73m~2 with every unit increase in the LDL-C/HDL-C ratio,respectively.5.In the male population,the LDL-C level was associated with the GFR level(P<0.001).For every 1 mmol/L increase in LDL-C in men,the GFR level decreased by 1.21 m L/min/1.73m~2;LDL-C/HDL-C ratio was associated with GFR level(P<0.001),and GFR level decreased by 1.34 m L/min/1.73m~2 with every unit increase of LDL-C/HDL-C ratio in men.In the female population,no association was found between LDL-C level(P=0.230),LDL-C/HDL-C ratio(P=0.975)and GFR level.The female population was further divided into groups of<49 years old and≥49 years old according to different ages.The results showed that no association was found between LDL-C and GFR in female with<49 years old and≥49 years old(both P>0.05).No association was found between LDL-C/HDL-C ratio and GFR in female with<49 years old(P=0.081).The LDL-C/HDL-C ratio was associated with the GFR in female with≥49 years old(P=0.047),and the GFR decreased by 2.24 m L/min/1.73m~2with every unit increase in the LDL-C/HDL-C ratio.6.In normal body weight,overweight and obese people,LDL-C was associated with GFR(P<0.01).For every 1 mmol/L increase in LDL-C,GFR decreased by 1.72,1.14 and 1.08 m L/min/1.73m~2,respectively;LDL-C/HDL-C ratio was associated with the GFR(P<0.01),and the GFR decreased by 1.71,1.18 and 1.11 m L/min/1.73m~2 with every unit increase in the LDL-C/HDL-C ratio,respectively.7.In the positive MR analysis of TC—GFR and LDL-C—GFR,IVW,MR-egger regression and WM methods all showed that TC and LDL-C had no causal effect on GFR(P>0.05);In the positive MR analysis of TG—GFR and HDL-C—GFR,IVW and MR-egger regression methods showed that TG and HDL-C had no causal effect on GFR(P>0.05),WM method showed that TG and HDL-C had a causal effect on GFR(P<0.05);In the reverse GFR—TG and GFR—HDL-C MR analysis,IVW,MR-egger regression and WM methods all showed that GFR had no causal effect on TC and HDL-C(P>0.05);In the reverse GFR—TG and GFR—HDL-C MR analysis,IVW,MR-egger regression and WM methods all showed that GFR had no causal effect on TG and HDL-C(P>0.05);In reverse MR analysis of GFR—TC and GFR—LDL-C,IVW and WM methods showed no causal effect of GFR on TC and LDL-C(P>0.05),MR-egger regression showed that GFR had a causal effect on TC and LDL-C(P<0.05).The second MR analysis using GRS as an instrumental variable supported no causal relationship between TC,TG,HDL-C,LDL-C and GFR.Conclusions:Both LDL-C and LDL-C/HDL-C ratio are independent risk factors for GFR,and GFR level gradually decreases with the increase of LDL-C and LDL-C/HDL-C.There is a dose-response relationship between LDL-C and LDL-C/HDL-C ratio and GFR.Further subgroup analysis found that GFR level still gradually decreased with the increase of LDL-C and LDL-C/HDL-C in men,people with<40 years old and 40-60 years old,and people with different BMI.It should be noted that there is only a negative association between LDL-C/HDL-C and GFR level in people with≥60 years old and female with≥49 years old.No association was found between TC,TG,HDL-C,Non HDL-C,TC/HDL-C,TG/HDL-C,Non HDL-C/HDL-C and GFR level.MR results showed no causal association between lipids(TC,TG,HDL-C,LDL-C)and GFR. |
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