Related Experiment Video

Updated: Jun 17, 2026

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
07:35

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Published on: June 23, 2015

Thyroid Hormones Exhibit Promising Prognostic and Therapeutic Potential in Autosomal Dominant Polycystic Kidney

Angelo Michele Lavecchia1, Laura Locatelli1, Matias Trillini1

  • 1Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Italy.

Thyroid : Official Journal of the American Thyroid Association
|June 15, 2026
PubMed
Abstract

Insights

Thyroid hormones (THs) play a role in autosomal dominant polycystic kidney disease (ADPKD) progression. Modulating THs, like thyroxine (T4), may offer a novel therapeutic strategy to reduce cyst growth and preserve kidney function in ADPKD patients.

Area of Science:

  • Nephrology
  • Endocrinology
  • Genetics

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disorder marked by cyst development and declining renal function.
  • The role of thyroid hormones (THs) in ADPKD pathogenesis and their therapeutic potential are currently unknown.
  • This study investigates the involvement of THs in ADPKD and explores their potential as a therapeutic target.

Purpose of the Study:

  • To elucidate the role of thyroid hormones (THs) in the progression of autosomal dominant polycystic kidney disease (ADPKD).
  • To evaluate the therapeutic potential of modulating THs, specifically thyroxine (T4), for treating ADPKD.
  • To explore the clinical relevance of serum TH levels in ADPKD patients.

Main Methods:

  • Engineered 3D polycystic kidney tubules from patient-derived cells to test anti-cystogenic effects of THs.
  • Assessed the in vivo therapeutic efficacy of thyroxine (T4) in PCK rats, an ADPKD animal model.
  • Measured serum TH levels in 90 ADPKD patients and correlated them with renal function (eGFR) in the REORIENTED clinical study.

Main Results:

  • Thyroxine (T4) inhibits cyst growth by modulating proliferative, metabolic, and ferroptotic pathways via αvβ3 integrin binding.
  • T4 administration in PCK rats significantly reduced kidney weight and macrocystic area compared to vehicle control.
  • In ADPKD patients, altered serum TH levels correlate with disease severity: reverse triiodothyronine (rT3) inversely correlates with renal function, while free triiodothyronine (fT3) positively correlates.

Conclusions:

  • Thyroid hormones (THs) contribute to ADPKD progression, indicating their potential as prognostic and therapeutic agents.
  • Modulating THs offers a novel, multi-targeted approach to reduce cyst growth and preserve renal function in ADPKD.
  • These findings support personalized, hormone-based treatments and refined clinical stratification for ADPKD management.
Keywords:
ERK signalingautosomal polycystic kidney diseaseclinical studyferroptosisthyroid hormone signalingαvβ3 integrin

More Related Videos

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Related Concept Videos

Chronic Kidney Disease I: Introduction01:25

Chronic Kidney Disease I: Introduction

Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
Chronic Kidney Disease III: Interprofessional Care01:28

Chronic Kidney Disease III: Interprofessional Care

Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
Hyperthyroidism II: Pathophysiology01:27

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Graves Disease II: Pathophysiology01:24

Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...