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Urolithiasis

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01.12.2024 | Research

Blood metabolites mediate the impact of lifestyle factors on the risk of urolithiasis: a multivariate, mediation Mendelian randomization study

verfasst von: Zhilong Li, Houyi Wei, Xiaoyu Tang, Tongzu Liu, Sheng Li, Xinghuan Wang

Erschienen in: Urolithiasis | Ausgabe 1/2024

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Abstract

Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10^-8). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis.

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Stamatelou KK, Francis ME, Jones CA, Nyberg LM et al (2003) Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney Int. 5:1817–1823. https://doi.org/10.1046/j.1523-1755.2003.00917.xCrossRef

Skolarikos A, Straub M, Knoll T, Sarica K et al (2015) Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines. Eur Urol. 4:750–763. https://doi.org/10.1016/j.eururo.2014.10.029CrossRef

Ruhayel Y, Tepeler A, Dabestani S, MacLennan S et al (2017) Tract sizes in miniaturized percutaneous nephrolithotomy: a systematic review from the European Association of Urology Urolithiasis Guidelines Panel. Eur Urol 2:220–235. https://doi.org/10.1016/j.eururo.2017.01.046CrossRef

Alexander RT (2023) Do thiazides reduce the risk of kidney-stone recurrence? N Engl J Med 9:841–842. https://doi.org/10.1056/NEJMe2300120CrossRef

Peerapen P, Thongboonkerd V (2023) Kidney stone prevention. Adv Nutr 3:555–569. https://doi.org/10.1016/j.advnut.2023.03.002CrossRef

D’Ambrosio V, Ferraro PM, Lombardi G, Friso S et al (2022) Unravelling the complex relationship between diet and nephrolithiasis: the role of nutrigenomics and nutrigenetics. Nutrients. https://doi.org/10.3390/nu14234961CrossRefPubMedPubMedCentral

Yuan S, Larsson SC (2022) Coffee and caffeine consumption and risk of kidney stones: a Mendelian randomization study. Am J Kidney Dis 1:9-14.e11. https://doi.org/10.1053/j.ajkd.2021.04.018CrossRef

Zhang XZ, Lei XX, Jiang YL, Zhao LM et al (2023) Application of metabolomics in urolithiasis: the discovery and usage of succinate. Signal Transduct Target Ther. 1:41. https://doi.org/10.1038/s41392-023-01311-zCrossRef

Khamaysi A, Anbtawee-Jomaa S, Fremder M, Eini-Rider H et al (2019) Systemic succinate homeostasis and local succinate signaling affect blood pressure and modify risks for calcium oxalate lithogenesis. J Am Soc Nephrol. 3:381–392. https://doi.org/10.1681/asn.2018030277CrossRef

10.

Griffin JL, Atherton H, Shockcor J, Atzori L (2011) Metabolomics as a tool for cardiac research. Nat Rev Cardiol 11:630–643. https://doi.org/10.1038/nrcardio.2011.138CrossRef

11.

Onuh JO, Qiu H (2021) Metabolic profiling and metabolites fingerprints in human hypertension: discovery and potential. Metabolites. https://doi.org/10.3390/metabo11100687CrossRefPubMedPubMedCentral

12.

Johnson CH, Ivanisevic J, Siuzdak G (2016) Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol 7:451–459. https://doi.org/10.1038/nrm.2016.25CrossRef

13.

Wang Y, Liu F, Sun L, Jia Y et al (2023) Association between human blood metabolome and the risk of breast cancer. Breast Cancer Res 1:9. https://doi.org/10.1186/s13058-023-01609-4CrossRef

14.

Shin SY, Fauman EB, Petersen AK, Krumsiek J et al (2014) An atlas of genetic influences on human blood metabolites. Nat Genet. 6:543–550. https://doi.org/10.1038/ng.2982CrossRef

15.

Kettunen J, Demirkan A, Würtz P, Draisma HH et al (2016) Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nat Commun. https://doi.org/10.1038/ncomms11122CrossRefPubMedPubMedCentral

16.

Michailidou K, Lindström S, Dennis J, Beesley J et al (2017) Association analysis identifies 65 new breast cancer risk loci. Nature 7678:92–94. https://doi.org/10.1038/nature24284ADSCrossRef

17.

Ebrahim S, Davey Smith G (2008) Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology? Hum Genet 1:15–33. https://doi.org/10.1007/s00439-007-0448-6CrossRef

18.

Sleiman PM, Grant SF (2010) Mendelian randomization in the era of genomewide association studies. Clin Chem 5:723–728. https://doi.org/10.1373/clinchem.2009.141564CrossRef

19.

Smith GD, Ebrahim S (2003) ’Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 1:1–22. https://doi.org/10.1093/ije/dyg070CrossRef

20.

Wang H, Fan J, Yu C, Guo Y et al (2021) Consumption of tea, alcohol, and fruits and risk of kidney stones: a prospective cohort study in 0.5 million Chinese adults. Nutrients. https://doi.org/10.3390/nu13041119CrossRefPubMedPubMedCentral

21.

Liu CC, Huang SP, Wu WJ, Chou YH et al (2009) The impact of cigarette smoking, alcohol drinking and betel quid chewing on the risk of calcium urolithiasis. Ann Epidemiol. 8:539–545. https://doi.org/10.1016/j.annepidem.2009.02.006CrossRef

22.

Aizezi X, Xie L, Xie H, Li J et al (2022) Epidemiological and clinical characteristics of stone composition: a single-center retrospective study. Urolithiasis. 1:37–46. https://doi.org/10.1007/s00240-021-01274-2CrossRef

23.

Turney BW, Appleby PN, Reynard JM, Noble JG et al (2014) Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Epidemiol 5:363–369. https://doi.org/10.1007/s10654-014-9904-5CrossRef

24.

Littlejohns TJ, Neal NL, Bradbury KE, Heers H et al (2020) Fluid intake and dietary factors and the risk of incident kidney stones in UK biobank: a population-based prospective cohort study. Eur Urol Focus. 4:752–761. https://doi.org/10.1016/j.euf.2019.05.002CrossRef

25.

Emdin CA, Khera AV, Kathiresan S (2017) Mendelian randomization. JAMA. 19:1925–1926. https://doi.org/10.1001/jama.2017.17219CrossRef

26.

Abecasis GR, Altshuler D, Auton A, Brooks LD et al (2010) A map of human genome variation from population-scale sequencing. Nature. 7319:1061–1073. https://doi.org/10.1038/nature09534CrossRef

27.

Staley JR, Blackshaw J, Kamat MA, Ellis S et al (2016) PhenoScanner: a database of human genotype-phenotype associations. Bioinformatics. 20:3207–3209. https://doi.org/10.1093/bioinformatics/btw373CrossRef

28.

Kamat MA, Blackshaw JA, Young R, Surendran P et al (2019) PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics. 22:4851–4853. https://doi.org/10.1093/bioinformatics/btz469CrossRef

29.

Verbanck M, Chen CY, Neale B, Do R (2018) Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 5:693–698. https://doi.org/10.1038/s41588-018-0099-7CrossRef

30.

Liu M, Jiang Y, Wedow R, Li Y et al (2019) Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet 2:237–244. https://doi.org/10.1038/s41588-018-0307-5CrossRef

31.

Sudlow C, Gallacher J, Allen N, Beral V et al (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 3:e1001779. https://doi.org/10.1371/journal.pmed.1001779CrossRef

32.

Julkunen H, Cichońska A, Tiainen M, Koskela H et al (2023) Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank. Nat Commun. 1:604. https://doi.org/10.1038/s41467-023-36231-7ADSCrossRef

33.

Kurki MI, Karjalainen J, Palta P, Sipilä TP et al (2023) FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 7944:508–518. https://doi.org/10.1038/s41586-022-05473-8ADSCrossRef

34.

Cai J, Wei Z, Chen M, He L et al (2022) Socioeconomic status, individual behaviors and risk for mental disorders: a Mendelian randomization study. Eur Psychiatry 1:e28. https://doi.org/10.1192/j.eurpsy.2022.18CrossRef

35.

Liu N, Tan JS, Liu L, Li H et al (2023) Roles of obesity in mediating the causal effect of attention-deficit/hyperactivity disorder on diabetes. Epidemiol Psychiatr Sci. https://doi.org/10.1017/s2045796023000173CrossRefPubMedPubMedCentral

36.

Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 5:377–389. https://doi.org/10.1007/s10654-017-0255-xCrossRef

37.

VanderWeele TJ (2016) Mediation analysis: a practitioner’s guide. Annu Rev Public Health. https://doi.org/10.1146/annurev-publhealth-032315-021402CrossRefPubMed

38.

Relton CL, Davey Smith G (2012) Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol 1:161–176. https://doi.org/10.1093/ije/dyr233CrossRef

39.

Carter AR, Sanderson E, Hammerton G, Richmond RC et al (2021) Mendelian randomisation for mediation analysis: current methods and challenges for implementation. Eur J Epidemiol 5:465–478. https://doi.org/10.1007/s10654-021-00757-1CrossRef

40.

MacKinnon DP, Fairchild AJ, Fritz MS (2007) Mediation analysis. Annu Rev Psychol. https://doi.org/10.1146/annurev.psych.58.110405.085542CrossRefPubMedPubMedCentral

41.

Wang Y, Ye C, Kong L, Zheng J et al (2023) Independent associations of education, intelligence, and cognition with hypertension and the mediating effects of cardiometabolic risk factors: a Mendelian randomization study. Hypertension 1:192–203. https://doi.org/10.1161/hypertensionaha.122.20286CrossRef

42.

Lee YH, Huang WC, Lu CM, Tsai JY et al (2003) Stone recurrence predictive score (SRPS) for patients with calcium oxalate stones. J Urol 2(Pt 1):404–407. https://doi.org/10.1097/01.ju.0000072365.22948.30CrossRef

43.

Słojewski M, Czerny B, Safranow K, Droździk M et al (2009) Does smoking have any effect on urinary stone composition and the distribution of trace elements in urine and stones? Urol Res 6:317–322. https://doi.org/10.1007/s00240-009-0221-5CrossRef

44.

Marić I, Kizivat T, Smolić M, Smolić R et al (2019) Lifestyle risk factors and bone mass in recurrent stone-forming patients: a cross-sectional study in 144 subjects. Acta Clin Croat. 3:439–445. https://doi.org/10.20471/acc.2019.58.03.06CrossRef

45.

Hamano S, Nakatsu H, Suzuki N, Tomioka S et al (2005) Kidney stone disease and risk factors for coronary heart disease. Int J Urol 10:859–863. https://doi.org/10.1111/j.1442-2042.2005.01160.xCrossRef

46.

Soueidan M, Bartlett SJ, Noureldin YA, Andersen RE et al (2015) Leisure time physical activity, smoking and risk of recent symptomatic urolithiasis: survey of stone clinic patients. Can Urol Assoc J 7–8:257–262. https://doi.org/10.5489/cuaj.2879CrossRef

47.

Prié D, Huart V, Bakouh N, Planelles G et al (2002) Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 13:983–991. https://doi.org/10.1056/NEJMoa020028CrossRef

48.

Hou JW, Wang TR (1995) Methylmalonic aciduria and urolithiasis in a Chinese boy with untreated phenylketonuria. J Inherit Metab Dis 1:79–80. https://doi.org/10.1007/bf00711379CrossRef

49.

Goldfarb DS, Fischer ME, Keich Y, Goldberg J (2005) A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int. 3:1053–1061. https://doi.org/10.1111/j.1523-1755.2005.00170.xCrossRef

50.

Haghighatdoost F, Sadeghian R, Abbasi B (2021) The associations between tea and coffee drinking and risk of calcium-oxalate renal stones. Plant Foods Hum Nutr 4:516–522. https://doi.org/10.1007/s11130-021-00933-4CrossRef

51.

Liu D, Wang J, Chen Y, Liu F et al (2023) Tea intake and risk of kidney stones: a mendelian randomization study. Nutrition. https://doi.org/10.1016/j.nut.2022.111919CrossRefPubMed

52.

Ferraro PM, Taylor EN, Gambaro G, Curhan GC (2013) Soda and other beverages and the risk of kidney stones. Clin J Am Soc Nephrol 8:1389–1395. https://doi.org/10.2215/cjn.11661112CrossRefPubMedPubMedCentral

53.

Kim SY, Yoo DM, Bang WJ, Choi HG (2022) Obesity is positively associated and alcohol intake is negatively associated with nephrolithiasis. Nutrients. https://doi.org/10.3390/nu14194122CrossRefPubMedPubMedCentral

54.

Yang S, Tan W, Wei B, Gu C et al (2023) Association between alcohol and urolithiasis: a mendelian randomization study. Urolithiasis 1:103. https://doi.org/10.1007/s00240-023-01472-0CrossRef

Titel: Blood metabolites mediate the impact of lifestyle factors on the risk of urolithiasis: a multivariate, mediation Mendelian randomization study
verfasst von: Zhilong Li
Houyi Wei
Xiaoyu Tang
Tongzu Liu
Sheng Li
Xinghuan Wang
Publikationsdatum: 01.12.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Urolithiasis / Ausgabe 1/2024
Print ISSN: 2194-7228
Elektronische ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-024-01545-8

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Blood metabolites mediate the impact of lifestyle factors on the risk of urolithiasis: a multivariate, mediation Mendelian randomization study

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