A hemodialysis system is disclosed. The hemodialysis system includes a disposable set including a blood pumping tube, a fresh dialysate pumping tube, and a spent dialysate pumping tube. The hemodialysis system also includes a dialysis instrument including a blood pump head, a fresh dialysate pump head, a spent dialysate pump head, a first motor positioned and arranged to operate the blood pump head, a second motor positioned and arranged to operate the fresh dialysate pump head, and a third motor positioned and arranged to operate the spent dialysate pump head. When the disposable set is loaded into the dialysis instrument, the blood pumping tube comes into registry with the blood pump head, the fresh dialysate pumping tube comes into registry with the fresh dialysate pump head, and spent dialysate pumping tube comes into registry with the spent dialysate pump head.