Therapeutic Strategies Targeting the Kidney–Liver–Immune–Heart Network: Circadian and Mechanosensory Pathways in CKD-Associated Cardiac Injury

The present review discusses vitamin A/retinoid metabolism as a cross-organ axis in which hepatic clock-dependent retinoid handling may affect immune clock gene expression through the stimulation of retinoic acid 6-Janus kinase 2-signal transducer and activator of transcription 5 signaling, potentially promoting pro-inflammatory monocyte states. We further highlight mechanosensory signaling as a second convergent layer that integrates hemodynamic forces with tissue microenvironmental cues. Among these pathways, G protein-coupled receptor 68, a proton- and flow-sensitive G protein-coupled receptor, is discussed as a representative druggable node linking mechanical and inflammatory signaling in chronic kidney disease-associated cardiac injury. Finally, we outline potential therapeutic directions, including (i) circadian alignment/chronopharmacology, (ii) modulation of retinoid metabolism and signaling, and (iii) targeted inhibition of primary immune and mechanosensory effectors.