Altered systemic bioenergetic reserve in chronic kidney disease predisposes hearts to worse functional outcomes

Area of Science:

• Cardiovascular Biology
• Nephrology
• Metabolic Medicine

Background:

• Chronic kidney disease (CKD) is linked to cardiovascular dysfunction.
• Inter-organ metabolic interactions are crucial in CKD pathophysiology.
• The role of systemic bioenergetic deficits in CKD-associated cardiac dysfunction is not fully understood.

Purpose of the Study:

• To investigate cardiac and systemic metabolic remodeling in rat models of CKD.
• To determine if systemic bioenergetic deficits contribute to cardiac dysfunction in CKD.
• To validate findings in CKD patients.

Main Methods:

• Two rat models of CKD (glomerulosclerosis and interstitial fibrosis) were studied.
• Cardiac function was assessed, including recovery from ischemia.
• ¹H NMR spectroscopy metabolomics and ³¹P NMR spectroscopy were used to analyze metabolic profiles in rats and CKD patients.

Main Results:

• Both CKD models showed comparable cardiac dysfunction and impaired recovery from ischemia.
• Systemic metabolic alterations in skeletal muscle, liver, and kidney were more pronounced than in the heart, indicating reduced bioenergetic reserve.
• CKD patients exhibited impaired phosphocreatine recovery in exercising skeletal muscle, suggesting diminished bioenergetic capacity.

Conclusions:

• Systemic bioenergetic impairment contributes to cardiac dysfunction in chronic kidney disease.
• Targeting systemic metabolic derangements could be a novel strategy for improving cardiac outcomes in CKD.
• Metabolic remodeling plays a significant role in the progression of CKD complications.