Amino acid and albumin losses during hemodialysis. Protein and calorie malnutrition are prevalent in chronic hemodialysis (HD) patients and has been linked to increased mortality and morbidity in this patient population, Concern has been raised that the open pore structure of high flux membranes may induce the loss of more amino acids (AA) compared to low flux membranes. To address this issue, we prospectively analyzed pre- and post-HD plasma AA profiles with three different membranes in nine patients. Simultaneously, we measured dialysate AA losses during HD. The membranes studied were: cellulosic (cuprophane-CU), low flux polymethylmethacrylate (LF-PMMA), and high flux polysulfone (HF-PS) during their first use. Our results show that pre-HD plasma AA profiles were abnormal compared to controls and decreased significantly during HD with all dialyzers. The use of HF-PS membranes resulted in significantly more AA losses into the dialysate when compared to LF-PMMA membranes (mean ± SD; 8.0 ± 2.8 g/dialysis for HF-PS, 6.1 ± 1.5 g/dialysis for LF-PMMA, p < 0.05, and 7.2 ± 2.6 g/dialysis for CU membranes, P = NS). When adjusted for surface area and blood flow, AA losses were not different between any of the dialyzers. We also measured dialysate AA losses during the sixth reuse of the HF-PS membrane. Losses of total AA increased by 50% during the sixth reuse of HF-PS membrane compared to its first use. In addition, albumin was detected in the dialysate during the sixth reuse of HF-PS membrane. We therefore measured albumin losses in all patients dialyzed with HF-PS membranes as a function of reuse. Albumin losses increased significantly beyond 15 reuses. Average albumin losses were 1.5 ± 1.3 g/dialysis below the 15th reuse, but increased to 9.3 ± 5.5 g/dialysis during the 20th reuse. We conclude that the abnormal plasma AA profile in HD patients is further exacerbated with hemodialysis for most of the individual amino acids, and that dialysate AA losses are modulated by membrane characteristics and reuse. Further, HF-PS membranes with reuse numbers over 15 lose substantial amounts of albumin in the dialysate.