Metabolic and morphometric profile of muscle fibers in chronic hemodialysis patients.
Muscle weakness and effort intolerance are common in maintenance hemodialysis (MHD) patients. This study characterized morphometric, histochemical, and biochemical properties of limb muscle in MHD patients compared with controls (CTL) with similar age, gender, and ethnicity. Vastus lateralis muscle biopsies were obtained from 60 MHD patients, 1 day after dialysis, and from 21 CTL. Muscle fiber types and capillaries were identified immunohistochemically. Individual muscle fiber cross-sectional areas (CSA) were quantified. Individual fiber oxidative capacities were determined (microdensitometric assay) to measure succinate dehydrogenase (SDH) activity. Mean CSAs of type I, IIA, and IIX fibers were 33, 26, and 28% larger in MHD patients compared with CTL. SDH activities for type I, IIA, and IIX fibers were reduced by 29, 40, and 47%, respectively, in MHD. Capillary to fiber ratio was increased by 11% in MHD. The number of capillaries surrounding individual fiber types were also increased (type I: 9%; IIA: 10%; IIX: 23%) in MHD patients. However, capillary density (capillaries per unit muscle fiber area) was reduced by 34% in MHD patients, compared with CTL. Ultrastuctural analysis revealed swollen mitochondria with dense matrix in MHD patients. These results highlight impaired oxidative capacity and capillarity in MHD patients. This would be expected to impair energy production as well as substrate and oxygen delivery and exchange and contribute to exercise intolerance. The enlarged CSA of muscle fibers may, in part, be accounted for by edema. We speculate that these changes contribute to reduce limb strength in MHD patients by reducing specific force.
Division of Pulmonary/Critical Care Medicine, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. michael.lewis@cshs.org
Michael I
MI
Lewis
Mario
M
Fournier
Huiyuan
H
Wang
Thomas W
TW
Storer
Richard
R
Casaburi
Arthur H
AH
Cohen
Joel D
JD
Kopple
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D010101:Oxygen Consumption / Q000502:physiology; D006435:Renal Dialysis / Q000009:adverse effects; D055815:Young Adult