Abstract: TH-PO0810
Cachexia Accelerates CKD-Induced Cardiomyopathy Through Maladaptive Muscle-Kidney Crosstalk
Session Information
- CKM Axis: Vascular Dysfunction, Atherosclerosis, and Heart Failure in Kidney Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Wu, Jiao, Baylor College of Medicine, Houston, Texas, United States
- Hu, Zhaoyong, Baylor College of Medicine, Houston, Texas, United States
- Thomas, Sandhya S., Baylor College of Medicine, Houston, Texas, United States
Background
Loss of skeletal muscle and adipose tissue causes cachexia in chronic kidney disease (CKD) with worsening morbidity and mortality. Previous reports suggest that parathyroid hormones via the PKA signaling cascade exacerbates worsening browning of white adipose tissue stimulating skeletal muscle atrophy. PKA contains two regulatory (R) subunits. In PKA beta subunit KO mice (RIIβ−/−) mice there is a compensatory increase in adipose tissue subunit RIα entirely replacing lost RIIβ, generating an isoform switch which leads to a lean phenotype with induction of thermogenin gene uncoupling protein 1 (UCP1). This study examines the effects of PKA pathways on CKD-induced cachexia and its role in cardiomyopathy.
Methods
To elucidate the impact of PKA and the lean phenotype in a model of CKD, wild type (WT) vs. PKA beta subunit KO mice (RIIβ−/−) mice were subjected to subtotal nephrectomy. Methods include harvest weights, blood pressure measurements, serum cystatin C and blood urea nitrogen (BUN), and finally cardiac ultrasound.
Results
Our results indicate that in PKA beta subunit KO mice (RIIβ−/−) mice vs. control mice with CKD displayed worsening hyperparathyroidism, skeletal muscle losses, white adipose tissue (WAT) harvest weights and cardiovascular mortality. Additionally, RIIβ−/− mice with CKD displayed worsening systolic blood pressure, skeletal muscle loss, BUN, and importantly kidney function (i.e. cystatin C). Finally, in RIIβ−/− mice with CKD, PKA activation was increased in cardiac muscle with a reduction in insulin/IGF1 receptor signaling in RIIβ−/− with CKD plus an enlarged heart with evidence of systolic dysfunction and reduction in cardiac output.
Conclusion
Our results demonstrate that PKA-mediated muscle wasting in CKD may be related to WAT quantity, therefore higher amounts of WAT may be protective in reducing cardiovascular mortality associated with CKD-induced cardiomyopathy. An unexpected crosstalk exists between the adipose tissue and muscle metabolism. In conclusion, cachexia accelerates CKD-induced cardiomyopathy through maladaptive muscle–kidney crosstalk. Targeting PKA pathways may have therapeutic uses in preventing CKD-induced cardiomyopathy and worsening cardiovascular mortality.
Acknowledgment
VA Merit Award 1I01BX005792 to SST from the United States Department of Veterans Affairs, Biomedical Laboratory Research and Development Program.
Funding
- Veterans Affairs Support