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

## TL;DR

Chronic kidney disease reduces the body's energy reserves, making the heart more vulnerable to dysfunction.

## Contribution

The study reveals that systemic bioenergetic deficits, not just local heart changes, contribute to cardiac dysfunction in CKD.

## Key findings

- Both rat CKD models showed comparable cardiac dysfunction despite different kidney damage types.
- Systemic metabolic changes in skeletal muscle, liver, and kidney were more severe than in the heart.
- CKD patients had impaired phosphocreatine recovery in skeletal muscle, indicating reduced bioenergetic capacity.

## Abstract

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. 1H 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 31P 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.

The online version contains supplementary material available at 10.1038/s41598-025-25314-8.