Related Experiment Video
Updated: Jun 16, 2026
Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform
Published on: April 12, 2021
Impaired metabolism in donor kidney grafts after steroid pretreatment
Julia Wilflingseder1, Alexander Kainz, Irmgard Mühlberger
1Department of Nephrology KH Elisabethinen, Linz, Austria.
Abstract:
Summary We recently showed in a randomized control trial that steroid pretreatment of the deceased organ donor suppressed inflammation in the transplant organ but did not reduce the rate or duration of delayed graft function (DGF). This study sought to elucidate such of those factors that caused DGF in the steroid-treated subjects. Genome-wide gene expression profiles were used from 20 steroid-pretreated donor-organs and were analyzed on the level of regulatory protein-protein interaction networks. Significance analysis of microarrays (SAM) yielded 63 significantly down-regulated sequences associated with DGF that could be functionally categorized according to Protein ANalysis THrough Evolutionary Relationships ontologies into two main biologic processes: transport (P < 0.001) and metabolism (P < 0.001). The identified genes suggest hypoxia as the cause of DGF, which cannot be counterbalanced by steroid treatment. Our data showed that molecular pathways affected by ischemia such as transport and metabolism are associated with DGF. Potential interventional targeted therapy based on these findings includes peroxisome proliferator-activated receptor agonists or caspase inhibitors.
Insights
Steroid pretreatment of organ donors reduced inflammation but did not prevent delayed graft function (DGF). Gene expression analysis revealed that hypoxia-affected transport and metabolism pathways contribute to DGF, suggesting new therapeutic targets.
Area of Science:
- Transplantation immunology
- Genomics
- Molecular biology
Background:
- Steroid pretreatment of deceased organ donors suppresses inflammation but does not prevent delayed graft function (DGF).
- The underlying mechanisms causing DGF in steroid-treated subjects remain unclear.
Purpose of the Study:
- To identify molecular factors contributing to DGF in steroid-pretreated donor organs.
- To elucidate the pathways affected in DGF despite steroid intervention.
Main Methods:
- Genome-wide gene expression profiling of 20 steroid-pretreated donor organs.
- Analysis of regulatory protein-protein interaction networks.
- Significance analysis of microarrays (SAM) to identify differentially expressed genes.
Main Results:
- 63 significantly down-regulated sequences associated with DGF were identified.
- Affected biological processes included transport and metabolism (P < 0.001).
- Identified genes suggest hypoxia as a primary cause of DGF, unaffected by steroid treatment.
Conclusions:
- Molecular pathways involved in transport and metabolism, affected by ischemia and hypoxia, are associated with DGF.
- Steroid treatment does not counteract the effects of hypoxia on these pathways.
- Potential targeted therapies include peroxisome proliferator-activated receptor agonists or caspase inhibitors.
Related Concept Videos
01:28Kidney Transplant I: Introduction
01:26Kidney Transplant II: Surgical Procedure
01:16Kidney Transplant III: Nursing Management
01:40Cell-mediated Immune Responses
01:29Acute Kidney Injury III: Clinical Manifestations
01:29Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...