Key result
Chronic kidney disease was associated with a 35% reduction in skeletal muscle phosphocreatine utilisation during exercise compared to healthy controls, reflecting diminished bioenergetic capacity.
Why the study?
The extent to which systemic bioenergetic deficits contribute to cardiac dysfunction in chronic kidney disease remains unclear.
Does chronic kidney disease induce systemic bioenergetic impairment and predispose the heart to worse functional outcomes following ischaemia?
Cross-Sectional (n=15)
No
Does chronic kidney disease induce systemic bioenergetic impairment and predispose the heart to worse functional outcomes following ischaemia?
Effect estimate: 35% lower
p-value: p=<0.05
Systemic bioenergetic impairment in chronic kidney disease, evident in both preclinical models and human patients, significantly increases cardiac susceptibility to ischaemia-reperfusion injury.
Systemic bioenergetic deficits may warrant monitoring in CKD; hypothesis-generating for cardiac outcomes in humans.
Chronic kidney disease (CKD) is characterised by progressive loss of kidney function and structural damage, which contributes to systemic complications, including cardiovascular dysfunction. Inter-organ metabolic interactions are increasingly recognised as important in the pathophysiology of CKD, but the extent to which systemic bioenergetic deficits contribute to cardiac dysfunction remains unclear. We investigated cardiac and systemic metabolic remodeling in two rat models of CKD with distinct aetiologies: glomerulosclerosis induced by partial nephrectomy and interstitial fibrosis induced by an adenine-rich diet. Despite differing renal pathology, both models exhibited comparable cardiac dysfunction, including impaired recovery following 25 min of ischaemia. 1 H NMR spectroscopy metabolomic analysis revealed that systemic metabolic alterations in skeletal muscle, liver, and kidney were more pronounced than those in the heart, indicating reduced systemic bioenergetic reserve. These findings were supported by data from CKD patients, in whom 31 P NMR spectroscopy of exercising skeletal muscle demonstrated impaired phosphocreatine recovery, consistent with diminished bioenergetic capacity and reduced force generation. These results suggest that systemic bioenergetic impairment contributes to CKD-associated cardiac dysfunction. Targeting systemic metabolic derangements may represent a novel strategy to improve cardiac outcomes in CKD.
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Young et al. (2025) conducted a cross-sectional in Chronic kidney disease (n=15). Chronic kidney disease vs. Healthy volunteers with normal renal function was evaluated on Phosphocreatine (PCr) utilisation during exercise (ΔPCr) (35% lower, p=<0.05). Chronic kidney disease was associated with a 35% reduction in skeletal muscle phosphocreatine utilisation during exercise compared to healthy controls, reflecting diminished bioenergetic capacity.
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