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Citations to this article

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.
R M Marrades, … , R Rodríguez-Roisin, P D Wagner
R M Marrades, … , R Rodríguez-Roisin, P D Wagner
Published May 1, 1996
Citation Information: J Clin Invest. 1996;97(9):2101-2110. https://doi.org/10.1172/JCI118647.
View: Text | PDF
Research Article

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

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Abstract

After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much as expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by the concurrent effects of fall in muscle blood flow after rHuEPO and abnormal capillary O2 conductance observed in CRF patients. The latter is likely associated with a poor muscle microcirculatory network and capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics and its relationships with muscle O2 transport, before and after rHuEPO therapy, were examined in eight CRF patients (27 +/- 7.3 [SD] yr) studied pre- and post-rHuEPO ([Hb] = 7.8 +/- 0.7 vs. 11.7 +/- 0.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 +/- 3.1 yr) served as controls. We hypothesize that uremic myopathy provokes a cytosolic dysfunction but mitochondrial oxidative capacity is not abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) from the vastus medialis were obtained throughout the exercise protocol consisting of periods of 2 min exercise (at 1.67 Hz) at increasing work-loads interspersed by resting periods of 2.5 min. On a different day, after an identical exercise protocol, arterial and femoral venous blood gas data were obtained together with simultaneous measurements of femoral venous blood flow (Qleg) to calculate O2 delivery (QO2leg) and O2 uptake (VO2leg). Baseline resting [phosphocreatine] to [inorganic phosphate] ratio ([PCr]/[Pi]) did not change after rHuEPO (8.9 +/- 1.2 vs. 8.8 +/- 1.2, respectively), but it was significantly lower than in controls (10.9 +/- 1.5) (P = 0.01 each). At a given submaximal or peak VO2leg, no effects of rHuEPO were seen on cellular bioenergetics ([PCr]/[Pi] ratio, %[PCr] consumption halftime of [PCr] recovery after exercise), nor in intracellular pH (pHi). The post-rHuEPO bioenergetic status and pHi, at a given VO2leg, were below those observed in the control group. However, at a given pHi, no differences in 31P-MRS data were detected between post-rHuEPO and controls. After rHuEPO, at peak VO2, Qleg fell 20% (P < 0.04), limiting the change in QO2leg to 17%, a value that did not reach statistical significance. The corresponding O2 extraction ratio decreased from 73 +/- 4% to 68 +/- 8.2% (P < 0.03). These changes indicate that maximal O2 flow from microcirculation to mitochondria did not increase despite the 50% increase in [Hb] and explain how peak VO2leg and cellular bioenergetics (31P-MRS) did not change after rHuEPO. Differences in pHi, possibly due to lactate differences, between post-rHeEPO and controls appear to be a key factor in the abnormal muscle cell bioenergetics during exercise observed in CRF patients.

Authors

R M Marrades, J Alonso, J Roca, J M González de Suso, J M Campistol, J A Barberá, O Diaz, J V Torregrosa, J R Masclans, R Rodríguez-Roisin, P D Wagner

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Total citations by year

Year: 2024 2022 2020 2018 2014 2012 2009 2008 2007 2005 2004 2003 2002 2001 1999 1997 Total
Citations: 1 1 3 2 1 4 1 1 1 3 1 1 3 1 1 1 26
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Citations to this article (26)

Title and authors Publication Year
Review of Exercise Interventions to Improve Clinical Outcomes in Nondialysis CKD
Hayden CM, Begue G, Gamboa JL, Baar K, Roshanravan B
Kidney International Reports 2024
Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease
Serrano E, Whitaker-Menezes D, Lin Z, Roche M, Martinez Cantarin MP
International journal of molecular sciences 2022
Impaired skeletal muscle mitochondrial bioenergetics and physical performance in chronic kidney disease
Bryan Kestenbaum, Jorge Gamboa, Sophia Liu, Amir Ali, Eric Shankland, Thomas Jue, Cecilia Giulivi, Lucas Smith, Jonathan Himmelfarb, Ian H. de Boer, Kevin E. Conley, Baback Roshanravan
JCI Insight 2020
The mitochondrial-targeted peptide SBT-20 ameliorates inflammation and oxidative stress in chronic renal failure
L Sun, H Xu, Y Wang, X Ma, Y Xu, F Sun
Aging 2020
Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis
JL Gamboa, B Roshanravan, T Towse, CA Keller, AM Falck, C Yu, WR Frontera, NJ Brown, TA Ikizler
Clinical journal of the American Society of Nephrology : CJASN 2020
Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
HU Prommer, J Maurer, K Websky, C Freise, K Sommer, H Nasser, R Samapati, B Reglin, P Guimarães, AR Pries, U Querfeld
Scientific Reports 2018
Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants
Y Will, JA Dykens
2018
Quantification of skeletal muscle mitochondrial function by 31 P magnetic resonance spectroscopy techniques: a quantitative review
GJ Kemp, RE Ahmad, K Nicolay, JJ Prompers
Acta physiologica (Oxford, England) 2014
Mechanical properties of the upper airway
KP Strohl, JP Butler, A Malhotra
Comprehensive Physiology 2012
Mechanical properties of the upper airway
KP Strohl, JP Butler, A Malhotra
Comprehensive Physiology 2012
Mechanical properties of the upper airway
KP Strohl, JP Butler, A Malhotra
Comprehensive Physiology 2012
Decreased Hypoxia-Inducible Factor-1a in Gastrocnemius Muscle in Rats with Chronic Kidney Disease
M Flisinski, A Brymora, I Bartlomiejczyk, E Wisniewska, R Golda, A Stefanska, L Paczek, J Manitius
Kidney and Blood Pressure Research 2012
Clinical Assessment of Peripheral Muscle Function in Patients with Chronic Obstructive Pulmonary Disease
J Vilaro, R Rabinovich, JM Gonzalez-deSuso, T Troosters, D Rodríguez, JA Barberà, J Roca
American Journal of Physical Medicine & Rehabilitation 2009
Influence of Different Stages of Experimental Chronic Kidney Disease on Rats Locomotor and Postural Skeletal Muscles Microcirculation
M Flisiński, A Brymora, G Elminowska-Wenda, J Bogucka, K Walasik, A Stefańska, G Odrowąż;-Sypniewska, J Manitius
Renal Failure 2008
Physiological Basis of Fatigue
WJ Evans, CP Lambert
American Journal of Physical Medicine & Rehabilitation 2007
Pharmacotherapy of Cachexia
W Doehner
Pharmacotherapy of Cachexia 2005
Chronic Kidney Disease: A Risk Factor for Cardiovascular Disease
RK Wali, WL Henrich
Cardiology Clinics 2005
Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients
KL Johansen, J Doyle, GK Sakkas, JA Kent-Braun
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2005
Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo
GJ Kemp, AV Crowe, HK Anijeet, QY Gong, WE Bimson, SP Frostick, JM Bone, GM Bell, JN Roberts
Nephrology Dialysis Transplantation 2004
ATP synthesis and proton handling in muscle during short periods of exercise and subsequent recovery
D Bendahan, GJ Kemp, M Roussel, YL Fur, PJ Cozzone
Journal of applied physiology 2003
Uremic myopathy
JM Campistol
Kidney International 2002
Skeletal muscle mitochondrial function is preserved in young patients with chronic renal failure
Ò Miró, RM Marrades, J Roca, E Sala, F Masanés, JM Campistol, JV Torregrosa, J Casademont, PD Wagner, F Cardellach
American Journal of Kidney Diseases 2002
Recombinant Human Erythropoietin (rhEPO) in Clinical Oncology
MR Nowrousian
2002
Intravenous l-carnitine increases plasma carnitine, reducesfatigue, and may preserve exercise capacity in hemodialysis patients
EP Brass, S Adler, KE Sietsema, WR Hiatt, AM Orlando, A Amato, CH Investigators
American Journal of Kidney Diseases 2001
Effects of Endurance Training on Skeletal Muscle Bioenergetics in Chronic Obstructive Pulmonary Disease
E Sala, J Roca, RM Marrades, J Alonso, JO de SUSO, A Moreno, JA Barberá, J Nadal, LL JOVER, R Rodriguez-Roisin, PD Wagner
American journal of respiratory and critical care medicine 1999
Physical benefits and challenges of exercise for people with chronic renal disease
SS Fitts
Journal of Renal Nutrition 1997

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