PURPOSE: Hemodialysis (HD) is a life-saving treatment for end-stage renal disease (ESRD) patients. However, it removes amino acids (AAs) from the circulation, thereby lowering plasma AA concentrations and stimulating muscle catabolism. To prevent deterioration in the nutritional status of HD patients, protein ingestion and exercise during HD are increasingly implemented in clinical practice. Nevertheless, it is not known whether these interventions modulate the removal of AAs from the circulation. METHODS: Therefore, we recruited ten ESRD patients (age: 65±16 y, BMI: 24.2±4.8 kg•m -2 ) undergoing HD to participate in this double-blind, crossover trial. During four 4-h HD sessions each patient ingested, in a randomized order, 40 g protein (PRO) or a placebo (PLA) both at rest, as well as following 30 min of intradialytic exercise (PRO+EX and PLA+EX, respectively). Blood and spent dialysate samples were collected every 30 min throughout HD to assess AA concentrations and, as such, to quantify plasma AA availability and AA removal. RESULTS: Baseline plasma AA concentrations averaged 2.93±0.40 mmol•L -1 , with no differences between interventions (P=0.66). During PLA and PLA+EX interventions, subsequent plasma AA concentrations decreased over time to 1.84±0.18 and 1.83±0.16 mmol•L -1 , respectively (time effect P<0.001), with no differences between interventions (P=0.94). Plasma AA concentrations increased following protein ingestion up to peak values of 4.40±0.45 and 4.37±0.73 mmol•L -1 during PRO and PRO+EX interventions, respectively (time effect P<0.001), with no differences between interventions (P=0.18). Accordingly, a significant effect of protein ingestion (P<0.001), but no effect of intradialytic exercise (P=0.22) was observed in AA availability during PLA, PLA+EX, PRO, and PRO+EX interventions (incremental AUC: -227±54, -208±68, 49±87, and 70±34 mmol•L -1 •240 min -1 , respectively). AA removal was greater during PRO and PRO+EX interventions (16.6±2.2 and 17.3±2.3 g, respectively) when compared to PLA and PLA+EX interventions (9.8±2.0 and 10.2±1.6 g, respectively; protein effect P<0.001; intradialytic exercise effect P=0.32). CONCLUSIONS: Removal of AAs during HD can be compensated for by protein ingestion and is not compromised by intradialytic exercise in ESRD patients.