Kidney injury is one of the most common complications of extracorporeal cardiopulmonary resuscitation (ECPR), yet the renoprotective effects of temperature management during ECPR remain inconclusive. This study aimed to explore whether therapeutic hypothermia alleviates kidney injury during ECPR and its potential mechanisms.

Eighteen male Sprague-Dawley (SD) rats were randomly allocated to three groups via a computer-generated random number sequence: Sham, ECPR (temperature maintained at 36 ± 0.5°C), and T-ECPR groups (maintained at 32 ± 0.5°C). A cardiac arrest model was established via 6 min of asphyxia, followed by 180 min of Extracorporeal membrane oxygenation (ECMO) support. Kidney injury markers in serum and histopathological changes in the kidneys were evaluated. Additionally, transcriptomic analysis was performed on three kidney tissue samples from both the ECPR and T-ECPR groups, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Eventually we evaluated the differentially expressed inflammation-related genes.

Both the histopathological Paller scores and the serum levels of kidney injury markers were significantly higher in the T-ECPR group than in the ECPR group. Furthermore, transcriptomic and enrichment analyses revealed that inflammation-related pathways were prominently enriched, and the highly expressed genes involved in the inflammatory response were clustered in T-ECPR group.

Compared with normothermia, the application of systemic hypothermia during ECPR is associated with exacerbated kidney injury and upregulated inflammatory genes, potentially correlating with a more severe inflammatory response.