A method of removing unwanted molecules from blood includes (i) directing a flow of blood from a patient through a first hemofilter, (ii) removing a volume of fluid from the blood using the first hemofilter, (iii) combining a volume of first substitution fluid with an outflow from the first hemofilter, the volume of first substitution fluid being substantially equal to the volume of fluid removed from the blood using the first hemofilter, (iv) directing the combined first hemofilter outflow and the first substitution fluid volume from the first hemofilter through a second hemofilter, (v) combining a second substitution fluid with outflow from the second hemofilter, and (vi) returning the combined second hemofilter outflow and the second substitution fluid volume from the second hemofilter to the patient.
