Correlation Study Between Blood Lipid Levels And The Risk Of Kidney Stones And Its Primary Exploration Of Pathogenesis

Part One.Single-centre investigation of blood lipid levels in inpatients with kidney stonesBackground and Purpose: Kidney stones are a common and frequently occurring disease worldwide.In recent years,the prevalence of kidney stones has been increasing.If not effectively controlled,kidney stones can lead to damage to multiple organ systems,seriously affect the daily work and life of patients,and impose a heavy economic burden on patients and their families.Dyslipidaemia is a common metabolic disease in clinical practice,and its complications include renal dysfunction,cardiovascular and cerebrovascular events and even the occurrence of malignant tumours.One survey showed that the prevalence of dyslipidaemia in Chinese adults is as high as 34%.This portion of the study investigated the blood lipid levels of hospitalized patients with kidney stones in our centre from 2018 to 2022 to understand dyslipidaemia in kidney stone patients and to provide more comprehensive treatment for these patients.Methods: Patients with kidney stones who were hospitalized in the Department of Nephrology and the Department of Urology of our hospital from January 1,2018,to December 31,2022,were selected.The research subjects were screened according to the inclusion and exclusion criteria.Total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)levels were collected during hospitalization.The abnormal proportions of TC,TG,LDL-C and HDL-C levels in the overall population and the prevalence of dyslipidaemia were calculated.Then,the whole population was divided into two groups according to sex,and the abnormal proportions of TC,TG,LDL-C and HDL-C levels in each group and the prevalence of dyslipidaemia in the two groups were calculated.The differences in these indicators between the two groups were compared using chi-square test.Results: A total of 1046 eligible subjects were included in this portion of the study,including 687 male patients and 359 female patients,with an average age of 56±13 years.In the overall population,30.4% had abnormal TC,40.34% had abnormal TG,25.53% had abnormal LDL-C,and 25.62% had abnormal HDL-C levels.A total of 64.63% of patients with kidney stones met the diagnostic criteria for dyslipidaemia.The proportion of male patients with abnormal TG and HDL-C levels was significantly higher than that of female patients,and the proportion of male patients with an abnormal TC level was significantly lower than that of female patients(TG,P=0.006;HDL-C,P < 0.001;TC,P=0.003).There was no significant difference in the proportion of abnormal LDL-C levels between the two groups(P=0.09).In addition,the prevalence of dyslipidemia was significantly higher in male patients with kidney stones than in female patients,and the difference was statistically significant(P=0.006).Conclusion: More than 60% of inpatients with kidney stones in our centre from 2018 to 2022 had dyslipidaemia at different levels and degrees.The proportion of abnormal TG,HDL-C and the prevalence of dyslipidemia in male patients were significantly higher than in female patients,the proportion of abnormal TC was significantly lower than in female patients.Part Two.The correlation between blood lipid levels and risk of kidney stones: Data analysis of National Health And Nutrition Examination Survey 2007-2016Background and Purpose: The occurrence and development of kidney stones is a complex multifactorial process that is affected by age,sex,genetics,geography,climate,diet,drugs,metabolism and other factors.Previous studies have investigated the association between dyslipidaemia and the risk of kidney stones,but due to small sample sizes,sampling bias,limited data access and other shortcomings,these results show great differences.The National Health And Nutrition Examination Survey(NHANES)is a large cross-sectional survey that assesses the health and nutritional status of adults and children in the United States.This portion of the work is based on NHANES data from 2007 to 2016 and explores the effect of body lipid levels on the risk of kidney stones.Methods: Participants in the NHANES from 2007 to 2016 were selected and screened according to certain criteria and then divided into a kidney stone group and a non-kidney stone group.Blood lipid,demographic,disease history-related and laboratory examination data were collected from the two groups.The weighted Mann-Whitney U nonparametric test,chi-square test,and univariate and multivariate logistic regression analyses were used to explore the relationships between TC,TG,LDL-C,HDL-C and the risk of kidney stones.Subgroup analysis was performed based on age,sex and body mass index(BMI).Results: The TG level and the rates of abnormal TG and HDL-C in the kidney stone group were significantly higher than those in the normal group,and the HDL-C level was significantly lower than that in the normal group(TG level,P=0.001;TG abnormal rate,P <0.001;HDL-C abnormal rate,P=0.003;HDL-C level,P < 0.001).Univariate weighted logistic regression analysis and multivariate weighted logistic regression analysis in model1 showed that abnormal TG and HDL-C were associated with a higher risk of kidney stones[(TG abnormal)univariate OR=1.461,P < 0.001;model 1 OR=1.253,P=0.027;(HDL-C abnormal)univariate OR=1.443,P = 0.004;model 1 OR=1.371,P=0.019].Multivariate weighted logistic regression analysis in model 2 showed that abnormal TG was associated with a higher risk of kidney stones(OR=1.241,P=0.040).Subgroup analysis showed that abnormal TG was significantly associated with an increased risk of kidney stones in the subgroup of 20-40 age group and the subgroup of abnormal BMI [(20-40 age subgroup)univariate OR=1.994,P < 0.001;model 1 OR=1.976,P < 0.001;model 2: OR=1.808,P=0.002;(BMI abnormal subgroup)univariate OR=1.379,P=0.005;model 1: OR=1.295,P=0.022;model 2 OR=1.278,P=0.038].HDL-C abnormality was significantly associated with an increased risk of kidney stones in the subgroup of 20-40 years old(univariate OR=1.757,P=0.005;model 1 OR=1.805,P=0.007;model 2 OR=1.681,P=0.018).Conclusion: Abnormal TG and HDL-C may increase the risk of kidney stones.The effect of abnormal TG on the risk of kidney stones is most significant in the group of 20-40 age and abnormal BMI,and the effect of abnormal HDL-C on the risk of kidney stones is correspondingly seen in the 20 to 40 age group.Part Three.Bioinformatics-based screening of differentially expressed genes in the kidney after high-fat diet stimulationBackground and Purpose: The mechanism by which dyslipidaemia leads to an increased risk of kidney stones is unclear.With the development of second-generation sequencing technology,bioinformatics technology has played an important role in predicting disease targets and exploring pathogenesis.To explore the related mechanism of lipid factors in the pathogenesis of kidney stones,this portion of the study explored the Gene Expression Omnibus(GEO)database and then screened differentially expressed genes in kidneys stimulated by a high-fat diet and analysed the changes in the gene expression levels.This information will provide a basis for the subsequent study of relevant action pathways and their functions.Methods: GSE158197 series files in the GEO database were selected for differential expression analysis to obtain genes with upregulated and downregulated expression levels.Results: In GSE158197 series files,P < 0.05,false discovery rate(FDR)< 0.05 and fold change(FC)≥2 were used as screening conditions,and 308 differentially expressed genes were obtained.The expression levels of 195 genes were upregulated,and 113 genes were downregulated.Conclusion: Based on the differentially expressed genes screened in this part of the study,to further clarify their role in the process of lipid stimulation of the kidney,we will continue to explore the biological functions and metabolic pathways contained in these differentially expressed genes to provide relevant targets for the prevention of kidney stones.Part Four.Bioinformatics analysis of the functional characteristics of differentially expressed genes in kidneys stimulated by a high-fat dietBackground and Purpose: Bioinformatics technology was applied to conduct functional studies on the differentially expressed genes of GSE158197 to further explore the related renal molecular mechanisms and targets of high lipid influence on the occurrence of kidney stones and provide a bioinformatics reference for effective intervention and prevention of kidney stones.Methods: Bioinformatics technology was used to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,gene set enrichment analysis(GSEA),protein-protein interaction(PPI)network construction and hub gene screening.Results: In GO analysis,the top five biological processes(BP)were "fatty acid metabolism","olefin compound metabolism","eicosanoid acid metabolism","unsaturated fatty acid metabolism" and "carboxylic acid biosynthesis".The top five cellular components(CCs)were "collagen-containing extracellular matrix","serine peptidase complex","serine endopeptidase complex" and "platelet α-granule".The top five molecular functions(MF)were monooxygenase activity,oxidoreductase activity on paired donors,oxidoreductase activity on CH-OH donors,carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.KEGG was mainly enriched in "complement and coagulation cascade pathway","steroid hormone biosynthesis","retinol metabolism","chemical carcinogenesis","arachidonic acid metabolism" and other pathways.The top 10 core genes selected by the PPI network were Cyp2b10,Cyp2c38,Cyp2c55,Cyp4a14,Cyp4a12 a,Ugt2b34,Ugt1a10,Ugt1a2,Aldh1a7 and Aldh1a1.GSEA showed that "complement and coagulation cascade pathway","retinol metabolism" and "arachidonic acid metabolism" were significantly upregulated in the high-fat group.The Cyp4a14,Cyp2c38,and Cyp2c55 genes were enriched in the "arachidonic acid metabolism" pathway,and the Cyp4a14,Cyp2c38,Cyp2c55,Ugt2b34,Ugt1a10,Ugt1a2,Aldh1a7,and Aldh1a1 genes were enriched in the "retinol metabolism" pathway.Conclusion: The differentially expressed genes in the kidney after high-fat stimulation may exist in the extracellular matrix and serine protease and promote the occurrence and development of kidney stones by affecting fatty acid metabolism,regulating oxidoreductase and organic acid transmembrane transporter activity,and participating in the complement and coagulation cascade,retinol metabolism pathway and arachidonic acid metabolism pathway.In addition,the cytochrome P450(CYP450)family Cyp4a14,Cyp2c38,Cyp2c55,UDP-glucuronosyltransferases(UGTs),Ugt2b34,Ugt1a10,and Ugt1a2 of the UGT family and Aldh1a7 and Aldh1a1 of the aldehyde dehydrogenase(ALDH)family may play an important role in this process.