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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Homocysteine exchange across skeletal muscle in patients with chronic kidney disease
Giacomo Garibotto1, Daniela Picciotto2, Daniela Verzola1
1Department of Internal Medicine, University of Genova, Genova, Italy.
Insights
Muscle releases homocysteine (Hcy) into circulation, impacting plasma levels in chronic kidney disease (CKD) patients. Folate significantly influences this Hcy release, highlighting its role in managing Hcy levels.
Area of Science:
- Metabolic biochemistry
- Renal medicine
- Human physiology
Background:
- Homocysteine (Hcy) regulation in circulation is poorly understood in humans.
- Elevated Hcy is linked to cardiovascular risks, particularly in chronic kidney disease (CKD).
Purpose of the Study:
- To investigate Hcy exchange across the forearm in CKD patients and hemodialysis (HD) patients compared to controls.
- To identify the role of peripheral tissues, particularly muscle, in regulating plasma Hcy levels.
- To explore factors influencing Hcy release from peripheral tissues.
Main Methods:
- Forearm venous occlusion plethysmography was used to measure Hcy exchange.
- Study included CKD patients (eGFR 20±2 ml/min), HD patients, and healthy controls.
- Arterial and deep forearm venous Hcy levels were measured.
Main Results:
- Arterial Hcy was significantly higher in CKD and HD patients compared to controls.
- Hcy levels in deep forearm veins exceeded arterial levels, indicating muscle release in all groups.
- Forearm Hcy release was similar across groups but inversely related to plasma folate levels.
Conclusions:
- Muscle contributes significantly to circulating Hcy levels in humans, including CKD patients.
- Plasma folate levels are a key determinant of Hcy release from peripheral tissues.
- Understanding Hcy release mechanisms is crucial for managing Hcy levels in CKD.
Abstract:
Sites and mechanisms regulating the supply of homocysteine (Hcy) to the circulation are unexplored in humans. We studied the exchange of Hcy across the forearm in CKD patients (n = 17, eGFR 20 ± 2 ml/min), in hemodialysis (HD)-treated patients (n = 14) and controls (n = 9). Arterial Hcy was ~ 2.5 folds increased in CKD and HD patients (p < 0.05-0.03 vs. controls). Both in controls and in patients Hcy levels in the deep forearm vein were consistently greater (+~7%, p < 0.05-0.01) than the corresponding arterial levels, indicating the occurrence of Hcy release from muscle. The release of Hcy from the forearm was similar among groups. In all groups arterial Hcy varied with its release from muscle (p < 0.03-0.02), suggesting that muscle plays an important role on plasma Hcy levels. Forearm Hcy release was inversely related to folate plasma level in all study groups but neither to vitamin B12 and IL-6 levels nor to muscle protein net balance. These data indicate that the release of Hcy from peripheral tissue metabolism plays a major role in influencing its Hcy plasma levels in humans and patients with CKD, and that folate is a major determinant of Hcy release.
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