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Hypothyroidism and Kidney Function: A Mendelian Randomization Study.

Christina Ellervik1,2,3, Samia Mora4,5,6,7, Paul M Ridker4,5,6,7,8

  • 1Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts.

Thyroid : Official Journal of the American Thyroid Association
|January 9, 2020
PubMed
Summary
This summary is machine-generated.

Bidirectional Mendelian randomization (MR) shows hypothyroidism, elevated TSH, and TPOAb are linked to reduced kidney function (eGFRcrea) and increased CKD risk. Free thyroxine (fT4) showed no consistent association.

Keywords:
creatininecystatin Chypothyroidismkidney function teststhyrotropin

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Area of Science:

  • Endocrinology
  • Nephrology
  • Genetic Epidemiology

Background:

  • Observational studies show associations between thyroid and kidney function, but causality and directionality remain uncertain.
  • Mendelian randomization (MR) offers a genetic approach to infer causal relationships, addressing limitations of observational data.

Purpose of the Study:

  • To investigate the causal relationship between thyroid function (hypothyroidism, TSH, fT4, TPOAb) and kidney function (eGFRcrea, eGFRcys, CKD, UACR) using bidirectional MR.
  • To determine the directionality of associations between thyroid and kidney function.

Main Methods:

  • Utilized individual-level data from the Women's Genome Health Study (WGHS) and summary statistics from the Chronic Kidney Disease Genetics Consortium (CKDGen).
  • Employed genetic variants associated with thyroid function and kidney function as instrumental variables in a bidirectional MR framework.
  • Performed sensitivity analyses to ensure the robustness of MR findings.

Main Results:

  • Bidirectional MR supported a causal link from hypothyroidism to decreased eGFRcrea and increased CKD risk in both WGHS and CKDGen.
  • Elevated TSH within the reference range was associated with decreased eGFRcrea and increased CKD in CKDGen.
  • Thyroid peroxidase antibodies (TPOAb) were robustly associated with decreased eGFRcrea and eGFRcys in CKDGen.

Conclusions:

  • Bidirectional MR provides evidence for a causal effect of hypothyroidism, elevated TSH, and TPOAb on reduced kidney function and increased CKD.
  • Free thyroxine (fT4) did not show consistent associations with kidney function in MR analyses.
  • Reverse MR analyses indicated no consistent association of kidney function with thyroid function.