Myocardial adaptations in advanced kidney disease

Molecular changes underlying the failing heart in chronic kidney disease (CKD) remains largely undefined. To date, a severe paucity of translational studies investigating these changes utilizing human heart tissues from kidney failure patients exists. Moreover, no studies have examined alterations of the cardiac cytoskeleton in CKD, despite its central role in regulating organelle function, bioenergetics and myocardial remodeling. In this 3-arm cross-sectional controlled cohort study, we compared donor heart tissues from dialysis patients, to patients with hypertension with relatively preserved GFR, and healthy controls. We present evidence for transcriptomic changes in the hearts of dialysis patients, involving cytoskeletal dysregulation and dysfunction of mitochondrial bioenergetics. Overall design: We conducted a 3-arm observational cross-sectional controlled cohort study of explanted human heart tissues. 109 donor hearts were collected, 50 met eligibility criteria for inclusion from hemodialysis-dependent patients (HD), hypertension (HTN) with relatively preserved GFR and healthy controls. Left ventricular tissues were subjected to pathologic examination and RNA-sequencing.