< em > In Chronic Kidney Disease Altered Cardiac < /em > < em > Metabolism < /em > < em > Precedes Cardiac Hypertrophy < /em >

Am J Physiol Renal Physiol. 2024 Feb 22. doi: 10.1152/ajprenal.00416.2023. Online ahead of print.ABSTRACTConduit arterial disease in CKD is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to human stage 4-5 CKD. PTH and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased and VSMC transdifferentiation was absent. The CKD mice were not hypertensive, and cardiac hypertrophy was absent. Freshly excised cardiac tissue respirometry (Oroboros) showed ADP-stimulated O2 flux was diminished from 52 to 22 pmol/mg (p=0.044). RNAseq of cardiac tissue from CKD mice revealed significantly decreased levels of cardiac mitochondrial oxidative phosphorylation genes. To examine the effect of activin A signaling, some Alport mice were treated with a monoclonal Ab to activin A or an isotype matched IgG beginning at 75 days of life until euthanasia. Treatment with the Activin A Ab did not affect cardiac oxidative phosphorylation. However, the Activin A antibody was active in the skeleton, disrupting the effect of CKD to stimulate osteoclast number, eroded surfaces and the stimulation of osteoclast-driven remodeling. The data reported here show that cardiac mitochondrial respiration is impaired in CKD...

Source: Am J Physiol Renal P... - February 22, 2024 Category: Urology & Nephrology Authors: Matthew J Williams Carmen M Halabi Hiral M Patel Zachary Joseph Kyle McCommis Carla Weinheimer Attila Kovacs Florence Lima Brian Finck Hartmut Malluche Keith A Hruska Source Type: research