title: Changes in Pre- and Post-Exercise Gene Expression among Patients with Chronic Kidney Disease and Kidney Transplant Recipients.
abstract: BACKGROUND
  Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown.
  
  
  METHODS
  Study cohort: non-diabetic male/female 4/1, age 52±2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed.
  
  
  RESULTS
  Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre-and post-transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant.
  
  
  CONCLUSIONS
  Despite an improvement in serum inflammatory markers, no significant differences in glucose disposal were observed post-transplant. The reduced skeletal muscle gene expression, including NFAT/calcineurin gene expression, in response to a single bout of exercise was not improved post-transplant. This study suggests that the improvements in inflammatory mediators post-transplant are unrelated to changes of NFAT/calcineurin gene expression.
authors: School for the Science of Health Care Delivery, Arizona State University, Phoenix, Arizona, United States of America.|Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.|Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, United States of America.
authors: Dawn K
authors: DK
authors: Coletta
authors: School of Life Sciences, Arizona State University, Phoenix, Arizona, United States of America.
authors: Latoya E
authors: LE
authors: Campbell
authors: NIH NIDDK, Phoenix, Arizona, United States of America.
authors: Jennifer
authors: J
authors: Weil
authors: Division of Nephrology and Hypertension, Mayo Clinic, Phoenix, Arizona, United States of America.
authors: Bruce
authors: B
authors: Kaplan
authors: Division of Nephrology and Hypertension, Mayo Clinic, Phoenix, Arizona, United States of America.
authors: Marie
authors: M
authors: Clarkson
authors: School for the Science of Health Care Delivery, Arizona State University, Phoenix, Arizona, United States of America.
authors: Jean
authors: J
authors: Finlayson
authors: School for the Science of Health Care Delivery, Arizona State University, Phoenix, Arizona, United States of America.|Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
authors: Lawrence J
authors: LJ
authors: Mandarino
authors: Division of Nephrology and Hypertension, Mayo Clinic, Phoenix, Arizona, United States of America.
authors: Harini A
authors: HA
authors: Chakkera
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D019703:Calcineurin / Q000235:genetics; D003131:Combined Modality Therapy; D005081:Exercise Therapy; D005260:Female; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000235:genetics; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000628:therapy; D066027:Transplant Recipients
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D019703:Calcineurin; D005947:Glucose