Evidence of functional deficits at the single muscle fiber level in experimentally-induced renal insufficiency

Chronic kidney disease patients present with metabolic and functional muscle

abnormalities, called uremic myopathy, whose mechanisms have not yet been fully

elucidated. We investigated whether chronic renal insufficiency (CRI) affects skeletal

muscle contractile properties at the cellular level. CRI was induced surgically in New

Zealand rabbits (UREM), with sham-operation for controls (CON), and samples were

collected at 3 months post-surgery, following euthanasia. All protocols had University

Ethics approval following national and European guidelines. Sample treatments and

evaluations were blinded. Maximal isometric force was assessed in 382 permeabilized

psoas fibers (CON, n=142, UREM, n=240) initially at pH7, 10oC (‘standard’

conditions), in subsets of fibers in acidic conditions (pH6.2, 10oC) but also at near

physiological temperature (pH7, 30oC and pH6.2, 30oC). CRI resulted in significant

smaller average CSA (~11%) for UREM muscle fibers (vs CON, P<0.01). At

standard conditions, UREM fibers produced lower absolute and specific forces (i.e.

normalized force per fiber CSA) (vs CON, P<0.01); force increased in 30oC for both

groups (P<0.01), but the disparity between UREM and CON remained significant.

Acidosis significantly reduced force (vs pH7, 10oC P<0.01), similarly in both groups

(in UREM by -48% and in CON by -43%, P>0.05). For the first time, we give

evidence that CRI can induce significant impairments in single psoas muscle fibers

force generation, only partially explained by fiber atrophy, thus affecting muscle

mechanics at the cellular level.