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Updated: Oct 9, 2025

White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice
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Obesity and Kidney Function: A Two-Sample Mendelian Randomization Study.

Alisa D Kjaergaard1, Alexander Teumer2,3, Daniel R Witte1,4

  • 1Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.

Clinical Chemistry
|December 18, 2021
PubMed
Summary
This summary is machine-generated.

Genetically high body mass index (BMI) is linked to poorer kidney function, particularly in individuals with type 2 diabetes (T2D). Adverse obesity significantly impacts kidney health, with T2D also contributing to albuminuria.

Keywords:
albuminuriablood urea nitrogenbody mass indexchronicdiabetes mellitusglomerular filtration ratekidney function testsmendelian randomization analysisobesityrenal insufficiencytype 2waist-hip ratio

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Area of Science:

  • Genetics and Public Health
  • Nephrology and Endocrinology

Background:

  • Obesity and type 2 diabetes (T2D) are established risk factors for chronic kidney disease (CKD).
  • Understanding the causal relationship between obesity metrics and kidney function is crucial for public health interventions.

Purpose of the Study:

  • To investigate the causal effects of obesity indicators, specifically body mass index (BMI) and waist-to-hip ratio (WHR), on kidney function using Mendelian randomization (MR).
  • To determine the directionality of the association between obesity and kidney function, and to explore the role of T2D in this relationship.

Main Methods:

  • Utilized bidirectional 2-sample Mendelian randomization (MR) with summary data from large consortia (GIANT, DIAGRAM, CKDGen).
  • Assessed total and direct causal effects of genetically predicted BMI and WHR on estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and urinary albumin-to-creatinine ratio (UACR).
  • Employed multivariable MR and stratified analyses to examine adverse obesity and T2D effects, primarily focusing on European populations with sensitivity analyses.

Main Results:

  • Genetically higher BMI was significantly associated with decreased eGFR, increased BUN, and increased UACR, particularly in individuals with diabetes.
  • Higher BMI also correlated with an increased risk of microalbuminuria and CKD.
  • While genetically high BMI directly impacted eGFR, BUN, and CKD, the pathway to albuminuria was partly mediated by T2D. Kidney function did not causally influence BMI or WHR.

Conclusions:

  • Genetically elevated BMI is causally associated with impaired kidney function, driven by adverse obesity.
  • Type 2 diabetes plays a significant role in the association between obesity and albuminuria.
  • These findings underscore the importance of weight management in preventing and managing chronic kidney disease.