Automated control mechanisms and methods for controlling fluid flow in a hemodialysis apparatus are described. The methods can involve a controller receiving information from a pressure sensor in a control chamber of a reciprocating diaphragm-based blood pump and causing the application of a time-varying pressure waveform on a diaphragm of the blood pump during a fill-stroke of the blood pump. The controller can be configured and programmed to monitor a pressure variation in the control chamber measured by the pressure sensor and to compare the measured pressure variation to a pre-determined value. Based on such comparison, the controller can initiate a procedure to pause or stop a dialysate pump of the hemodialysis apparatus if the magnitude of the measured pressure variation deviates from the pre-determined value.