Metabolic and morphometric profile of muscle fibers in chronic hemodialysis patients

Abstract

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.

Fig. 1.

Proportions of types I, IIA, and IIX muscle fibers (top) in the vastus lateralis of control subjects (open bars) and maintenance hemodialysis (MHD) patients (hatched bars). There was a small (2%), but significantly greater, proportion of type I fibers and lower proportion of type IIX fibers in MHD patients (P < 0.05). Mean cross-sectional areas (CSA) from individual type I, IIA, and IIX muscle fibers (bottom) were significantly larger by 33% (P < 0.001), 26% (P < 0.01), and 28% (P < 0.05), respectively, in MHD patients. Values are means ± SE. *Significantly different from control group.

Fig. 2.

Mean succinate dehydrogenase (SDH) activity from individual type I, IIA, and IIX muscle fibers in the vastus lateralis of MHD patients (hatched bars) were lower by 29% (P < 0.0001), 40% (P < 0.0001), and 47% (P < 0.0001), respectively, compared with control subjects (open bars). Values are means ± SE. *Significantly different from control group.

Fig. 3.

Mean number of capillaries per individual type I, IIA, and IIX muscle fibers in the vastus lateralis of MHD patients (hatched bars) were significantly greater by 9% (P < 0.001), 10% (P < 0.001), and 23% (P < 0.001), respectively, compared with control subjects (open bars). Values are means ± SE. *Significantly different from control group.

Fig. 4.

Representative ultrastructure of the vastus lateralis muscle from a healthy control subject (top) and from a MHD patient (bottom). Note a cluster of swollen mitochondria (arrows) and an area of Z-band disruption (*) with hemodialysis. Note difference in scale bars between control and MHD. Mitochondria (arrows) in controls are clearly seen at ×3 the magnification of MHD, and their average size is still smaller than or comparable with MHD.