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Updated: Sep 5, 2025

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
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ACLY and CKD: A Mendelian Randomization Analysis

Pedrum Mohammadi-Shemirani1,2,3, Michael Chong1,2,3, Nicolas Perrot1

  • 1Department of Biomarkers and Genetics, Population Health Research Institute, Hamilton, Ontario, Canada.

Kidney International Reports
|July 11, 2022
PubMed
Abstract

Insights

Adenosine triphosphate-citrate lyase (ACLY) inhibition may reduce chronic kidney disease (CKD) risk. Genetically reduced ACLY expression was linked to a lower CKD risk, but not estimated glomerular filtration rate or albumin-to-creatinine ratio.

Area of Science:

  • Biochemistry
  • Genetics
  • Nephrology

Background:

  • Adenosine triphosphate-citrate lyase (ACLY) is a therapeutic target for metabolic diseases.
  • ACLY inhibition shows potential in reducing inflammation and kidney fibrosis in mouse models.
  • Genetic analysis of ACLY in chronic kidney disease (CKD) has been lacking.

Purpose of the Study:

  • To investigate the effect of genetically predicted Adenosine triphosphate-citrate lyase (ACLY) expression on the risk of chronic kidney disease (CKD).
  • To evaluate the association between ACLY expression and kidney function markers, including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR).

Main Methods:

  • Constructed a genetic instrument for ACLY expression using 13 variants from the eQTLGen consortium.
  • Performed a 2-sample Mendelian randomization analysis using data from CKDGen, UK Biobank, and FinnGen.
  • Evaluated the effect of genetically predicted ACLY expression on CKD risk, eGFR, and ACR in 66,396 CKD cases and 958,517 controls.

Main Results:

  • Genetically reduced ACLY expression was associated with a 9% reduced risk of CKD.
  • A 34% reduction in ACLY expression score correlated with lower LDL cholesterol.
  • No significant association was found between genetically reduced ACLY expression and eGFR or ACR.

Conclusions:

  • Genetically reduced Adenosine triphosphate-citrate lyase (ACLY) expression is associated with a decreased risk of chronic kidney disease (CKD).
  • ACLY does not appear to influence estimated glomerular filtration rate (eGFR) or albumin-to-creatinine ratio (ACR).
  • Further research into ACLY's role in kidney disease is warranted.
Keywords:
Mendelian randomizationchronic kidney diseasecitratefibrosisgenomics

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