Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease

Jason Organ, Andrew Srisuwananukorn, Paige Price, Jeffery E. Joll, Kelly C. Biro, Joseph E. Rupert, Xuening (Neal) Chen, Keith G. Avin, Sharon Moe, Matthew Allen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background. The combination of skeletal muscle wasting and compromised function plays a role in the health decline commonly observed in chronic kidney disease (CKD) patients, but the pathophysiology of muscle mass/strength changes remains unclear. The purpose of this study was to characterize muscle properties in the Cy/+ rat model of spontaneously progressive CKD. Methods. Leg muscle function and serumbiochemistry of male Cy/+ (CKD) rats and their nonaffected littermates (NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were assessed ex vivo at the conclusion of the experiment. We tested the hypothesis that animals with CKD have progressive loss of muscle function, and that this functional deficit is associated with loss of muscle mass and quality. Results. Thirty-five-week-old CKD rats produced significantly lower maximum torque in ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion torque (but not plantarflexion torque) in CKD remained steady from 25 to 35 weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL were not different between CKD and NL. However, the EDL of CKD rats showed reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area in the SOL. Conclusions. The results of this study demonstrate that muscle function progressively declines in the Cy/+ rat model of CKD. Because whole muscle mass and architecture do not vary between CKD and NL, but CKD muscles show reduction in individual fiber CSA, our data suggest that the functional decline is related to increased muscle fiber atrophy.

Original languageEnglish (US)
Pages (from-to)223-230
Number of pages8
JournalNephrology Dialysis Transplantation
Volume31
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Kidney Diseases
Chronic Renal Insufficiency
Skeletal Muscle
Torque
Muscles
Muscular Atrophy
Myosin Heavy Chains
Muscle Strength
Ankle
Leg
Histology
Protein Isoforms

Keywords

  • Atrophy
  • Chronic kidney disease
  • Muscle function
  • Muscle quality
  • Rat models

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease. / Organ, Jason; Srisuwananukorn, Andrew; Price, Paige; Joll, Jeffery E.; Biro, Kelly C.; Rupert, Joseph E.; Chen, Xuening (Neal); Avin, Keith G.; Moe, Sharon; Allen, Matthew.

In: Nephrology Dialysis Transplantation, Vol. 31, No. 2, 01.02.2016, p. 223-230.

Research output: Contribution to journalArticle

Organ, Jason ; Srisuwananukorn, Andrew ; Price, Paige ; Joll, Jeffery E. ; Biro, Kelly C. ; Rupert, Joseph E. ; Chen, Xuening (Neal) ; Avin, Keith G. ; Moe, Sharon ; Allen, Matthew. / Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease. In: Nephrology Dialysis Transplantation. 2016 ; Vol. 31, No. 2. pp. 223-230.
@article{8ede867051f04131b030a322f5c9152a,
title = "Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease",
abstract = "Background. The combination of skeletal muscle wasting and compromised function plays a role in the health decline commonly observed in chronic kidney disease (CKD) patients, but the pathophysiology of muscle mass/strength changes remains unclear. The purpose of this study was to characterize muscle properties in the Cy/+ rat model of spontaneously progressive CKD. Methods. Leg muscle function and serumbiochemistry of male Cy/+ (CKD) rats and their nonaffected littermates (NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were assessed ex vivo at the conclusion of the experiment. We tested the hypothesis that animals with CKD have progressive loss of muscle function, and that this functional deficit is associated with loss of muscle mass and quality. Results. Thirty-five-week-old CKD rats produced significantly lower maximum torque in ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion torque (but not plantarflexion torque) in CKD remained steady from 25 to 35 weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL were not different between CKD and NL. However, the EDL of CKD rats showed reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area in the SOL. Conclusions. The results of this study demonstrate that muscle function progressively declines in the Cy/+ rat model of CKD. Because whole muscle mass and architecture do not vary between CKD and NL, but CKD muscles show reduction in individual fiber CSA, our data suggest that the functional decline is related to increased muscle fiber atrophy.",
keywords = "Atrophy, Chronic kidney disease, Muscle function, Muscle quality, Rat models",
author = "Jason Organ and Andrew Srisuwananukorn and Paige Price and Joll, {Jeffery E.} and Biro, {Kelly C.} and Rupert, {Joseph E.} and Chen, {Xuening (Neal)} and Avin, {Keith G.} and Sharon Moe and Matthew Allen",
year = "2016",
month = "2",
day = "1",
doi = "10.1093/ndt/gfv352",
language = "English (US)",
volume = "31",
pages = "223--230",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease

AU - Organ, Jason

AU - Srisuwananukorn, Andrew

AU - Price, Paige

AU - Joll, Jeffery E.

AU - Biro, Kelly C.

AU - Rupert, Joseph E.

AU - Chen, Xuening (Neal)

AU - Avin, Keith G.

AU - Moe, Sharon

AU - Allen, Matthew

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background. The combination of skeletal muscle wasting and compromised function plays a role in the health decline commonly observed in chronic kidney disease (CKD) patients, but the pathophysiology of muscle mass/strength changes remains unclear. The purpose of this study was to characterize muscle properties in the Cy/+ rat model of spontaneously progressive CKD. Methods. Leg muscle function and serumbiochemistry of male Cy/+ (CKD) rats and their nonaffected littermates (NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were assessed ex vivo at the conclusion of the experiment. We tested the hypothesis that animals with CKD have progressive loss of muscle function, and that this functional deficit is associated with loss of muscle mass and quality. Results. Thirty-five-week-old CKD rats produced significantly lower maximum torque in ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion torque (but not plantarflexion torque) in CKD remained steady from 25 to 35 weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL were not different between CKD and NL. However, the EDL of CKD rats showed reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area in the SOL. Conclusions. The results of this study demonstrate that muscle function progressively declines in the Cy/+ rat model of CKD. Because whole muscle mass and architecture do not vary between CKD and NL, but CKD muscles show reduction in individual fiber CSA, our data suggest that the functional decline is related to increased muscle fiber atrophy.

AB - Background. The combination of skeletal muscle wasting and compromised function plays a role in the health decline commonly observed in chronic kidney disease (CKD) patients, but the pathophysiology of muscle mass/strength changes remains unclear. The purpose of this study was to characterize muscle properties in the Cy/+ rat model of spontaneously progressive CKD. Methods. Leg muscle function and serumbiochemistry of male Cy/+ (CKD) rats and their nonaffected littermates (NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were assessed ex vivo at the conclusion of the experiment. We tested the hypothesis that animals with CKD have progressive loss of muscle function, and that this functional deficit is associated with loss of muscle mass and quality. Results. Thirty-five-week-old CKD rats produced significantly lower maximum torque in ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion torque (but not plantarflexion torque) in CKD remained steady from 25 to 35 weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL were not different between CKD and NL. However, the EDL of CKD rats showed reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area in the SOL. Conclusions. The results of this study demonstrate that muscle function progressively declines in the Cy/+ rat model of CKD. Because whole muscle mass and architecture do not vary between CKD and NL, but CKD muscles show reduction in individual fiber CSA, our data suggest that the functional decline is related to increased muscle fiber atrophy.

KW - Atrophy

KW - Chronic kidney disease

KW - Muscle function

KW - Muscle quality

KW - Rat models

UR - http://www.scopus.com/inward/record.url?scp=84964800955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964800955&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfv352

DO - 10.1093/ndt/gfv352

M3 - Article

VL - 31

SP - 223

EP - 230

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 2

ER -