Related Experiment Video
Updated: Aug 26, 2025
Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation
Published on: May 2, 2013
Role of TGF-β1 +869T>C polymorphism in renal dysfunction one year after heart transplantation
Jorge V López-Ibor1, María J Citores2, Jose Portoles3
1Department of Cardiology, Advanced Heart Failure and Heart Transplantation Unit, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Background:
Chronic kidney disease is a major complication after heart transplantation with wide inter-individual variability. Calcineurin inhibitor nephrotoxicity, mediated by transforming growth factor-beta1 (TGF-β1), is an important contributing factor. Our objective was to evaluate the association between TGF-β1 polymorphisms and renal dysfunction 1-year after heart transplantation.
Methods:
Single-center observational study that included patients who received a first heart transplant between 1990-2013. According to the 1-year eGFR decline, patients were classified as "Stable" (decrease in eGFR<10% or eGFR>60 ml/min/1.73m2) or "Progressors" (decrease in eGFR>10% and eGFR<60 ml/min/1.73m2). "Progressors" were then subdivided by the degree of eGFR decrease in "Mild progressors" (10-30%) or "Rapid progressors" (>30%). The association between TGF-β1 +869T>C polymorphism and other risk factors with the eGFR outcome was analysed.
Results:
A total of 355 patients (78% male; 50.7 ± 11.8 years) were included. According to the 1-year eGFR decline, 220 patients (62%) were classified as "Stable" and 135 (38%) as "Progressors". TGF-β1+869CC genotype was more prevalent in "Stable" vs "Progressors" group (20% vs 8%, p = 0.009). In the multivariate analysis, female sex (p 0.02) and eGFR<60 ml/min/1.73 m2 at first month post-heart transplant (p = 0.004) remained as risk factors of eGFR decline, and TGF-β1 + 869CC genotype (p = 0.001) and renal dysfunction pre-heart transplant (p = 0.04) as protective factors. TGF-β1 + 869CC genotype was less frequently found in "Mild progressors" compared to "Rapid progressors" [p = 0.019; OR (95%CI) = 0.19 (.05-.76)].
Conclusions:
The TGF-β1 +869CC genotype is associated with a lower risk of calcineurin inhibitor nephrotoxicity after heart transplant. This genetic susceptibility could enable a more personalized patient treatment.
Insights
The TGF-β1 +869CC genotype may protect against kidney damage after heart transplants. This finding could lead to personalized treatments for transplant patients to reduce the risk of calcineurin inhibitor nephrotoxicity.
Area of Science:
- Nephrology
- Immunology
- Genetics
Background:
- Chronic kidney disease (CKD) is a common complication following heart transplantation.
- Calcineurin inhibitor (CNI) nephrotoxicity, driven by transforming growth factor-beta1 (TGF-β1), contributes significantly to post-transplant renal dysfunction.
- Significant variability exists in the development of CKD among heart transplant recipients.
Purpose of the Study:
- To investigate the association between specific TGF-β1 gene polymorphisms and the development of renal dysfunction one year after heart transplantation.
- To identify genetic factors that may predict or protect against CNI-induced nephrotoxicity.
Main Methods:
- A single-center observational study included 355 heart transplant recipients (1990-2013).
- Patients were categorized based on 1-year estimated glomerular filtration rate (eGFR) decline as 'Stable' or 'Progressors' (further divided into 'Mild' and 'Rapid').
- The association of TGF-β1 +869T>C polymorphism with eGFR outcomes and other risk factors was analyzed using multivariate analysis.
Main Results:
- The TGF-β1 +869CC genotype was more prevalent in the 'Stable' group (20%) compared to the 'Progressors' group (8%, p=0.009).
- Multivariate analysis identified female sex and early post-transplant renal dysfunction as risk factors for eGFR decline.
- Conversely, the TGF-β1 +869CC genotype and pre-transplant renal dysfunction were found to be protective factors against eGFR decline (p=0.001 and p=0.04, respectively).
Conclusions:
- The TGF-β1 +869CC genotype is associated with a reduced risk of CNI nephrotoxicity after heart transplantation.
- This genetic marker may offer a pathway for personalized patient management to mitigate renal complications.
- Understanding genetic susceptibility can guide tailored therapeutic strategies in heart transplant recipients.
Related Concept Videos
01:16TGF - β Signaling Pathway
01:28Kidney Transplant I: Introduction
01:26Kidney Transplant II: Surgical Procedure
01:24Tissue Transplantation
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...