Maximal O₂ uptake is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. While determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal constant load exercise. By comparing individuals with ESRD and healthy controls, the aim of this exploratory study was to characterize mechanisms of exercise intolerance in participants with ESRD by assessing cardiopulmonary physiology at rest and during exercise. Resting spirometry and echocardiography were performed in 20 dialysis-dependent participants with ESRD (age: 59 ± 12 yr, 14 men and 6 women) and 20 healthy age- and sex-matched controls. Exercise tolerance was assessed with ventilatory gas exchange and central hemodynamics during a maximal cardiopulmonary exercise test and 30 min of submaximal constant load exercise. Left ventricular mass (292 ± 102 vs. 185 ± 83 g, P = 0.01) and filling pressure (E/e': 6.48 ± 3.57 vs. 12.09 ± 6.50 m/s, P = 0.02) were higher in participants with ESRD; forced vital capacity (3.44 ± 1 vs. 4.29 ± 0.95 L/min, P = 0.03) and peak O₂ uptake (13.3 ± 2.7 vs. 24.6 ± 7.3 mL·kg^-1·min^-1, P < 0.001) were lower. During constant load exercise, the relative increase in the arterial-venous O₂ difference (13 ± 18% vs. 74 ± 18%) and heart rate (32 ± 18 vs. 75 ± 29%) were less in participants with ESRD despite exercise being performed at a higher percentage of maximum minute ventilation (48 ± 3% vs. 39 ± 3%) and heart rate (82 ± 2 vs. 64 ± 2%). Ventilatory and chronotropic incompetence contribute to exercise intolerance in individuals with ESRD. Both are potential targets for medical and lifestyle interventions.

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