Skeletal muscle single fiber force production declines early in juvenile male mice with chronic kidney disease

Abstract Children with chronic kidney disease (CKD) frequently exhibit delayed physical development and reduced physical performance, presumably due to skeletal muscle dysfunction. However, the cellular and molecular basis of skeletal muscle impairment in juvenile CKD remains poorly understood. Cellular (single fiber) and molecular (myosin‐actin interactions and myofilament properties) function was examined ex vivo in slow (soleus) and fast (extensor digitorum longus) contracting muscles of juvenile male (6 weeks old) CKD and control mice. CKD was induced by 0.2% adenine diet for 3 weeks starting at 3 weeks of age. Specific tension (maximal isometric force divided by cross‐sectional area) was reduced in larger myosin heavy chain (MHC) I and IIA fibers and in all IIB fibers in juvenile male mice with CKD due to fewer strongly bound myosin‐actin cross‐bridges. Fiber cross‐sectional area in juvenile CKD mice was unchanged in MHC I and IIB fibers and increased in MHC IIA fibers, compared to controls. CKD slowed cross‐bridge kinetics (slower rate of myosin force production and longer myosin attachment time, ton) in MHC IIA fibers, and accelerated kinetics (shorter ton) in MHC IIB fibers, which may indicate fiber type dependent shifts in contractile velocity in juvenile CKD. Overall, our findings show that single fiber myopathy is an early event during juvenile CKD, manifesting prior to the development of cellular atrophy as reduced force generation due to fewer strongly bound myosin heads. These results warrant clinical translation and call for early interventions to preserve physical function in children with CKD

Intradialytic exercise increases cardiac power index

Introduction: Mortality rates are high in end-stage renal disease due to cardiovascular complications. Perfusion of the myocardium declines during and after hemodialysis sessions with the potential for aerobic exercise to mitigate these during hemodialysis. Objectives: The purpose of this study was to investigate acute changes in hemodynamics in subjects with end-stage renal disease (ESRD) during exercise. Patients and Methods: Subjects (n = 10) were monitored for 1.5 hours during hemodialysis treatment during a control (CON) and an exercise (EX) session. Subjects cycled using an ergometer strapped to the reclining dialysis chair at an RPE of 11-13 for 30 minutes during the EX session beginning at 30 min into dialysis and ending at 60 minutes. Data for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were collected using an automated blood pressure cuff attached to the hemodialysis machine. Data for cardiac output (Q̇ ), cardiac power index (CPI), stroke volume (SV), systemic vascular resistance (SVR), and heart rate (HR) were collected using the NICaS bioelectrical impedance device. Results: During the EX session, CPI, Q̇ , SV, and HR were significantly greater (P<0.05) than the CON session. Additionally, Q̇ was significantly (P< 0.05) greater at 45 minutes and 60 minutes compared to 15 minutes. HR was significantly (P<0.05) greater at 45 minutes compared to 90 minutes. No significant interactions were found for MAP, CPI, Q̇ , HR, SV, SBP, DBP, or SVR. Conclusion: In conclusion, exercise during dialysis may decrease the likelihood of experiencing ischemic or hypotensive events by enhancing myocardial perfusion through increasing CPI and Q̇