RENAL11: Novel Clog-Based Switch to Surveille Peritoneal Dialysate for Peritonitis

Abstract

Background: Quickly triaging patients on Peritoneal Dialysis (PD) for infection is critical for patient-health outcomes. The best methods of detection, such as blood panels or sample culture, are not suited for quick point-of-care applications. The current detection method is by visual inspection of the fluid by the patient who looks for ‘cloudiness’ in the spent dialysate. Peritoneal dialysis, a type of renal replacement therapy for patients with end-stage renal disease (ESRD), has a survival advantage for the first two years of use over hemodialysis (HD). Other advantages of PD over HD include higher patient satisfaction and lower costs. The main shortcoming of PD is the patients’ increased susceptibility to peritonitis due to the permanent catheter that provides access to the peritoneal cavity for fluid exchanges. The infection can create life-threatening situations for patients. Importantly, for most patients using PD, repeated peritonitis can result in peritoneal membrane failure, necessitating a switch to HD with its associated disadvantages. Preemptive monitoring is currently not available in clinical practice of PD. The current detection method is by visual inspection of the fluid by the patient who looks for ‘cloudiness’ in the spent dialysate. Progress has been made to reduce the incidence of peritonitis, but detection remains problematic. Methods: To achieve this goal, we have developed a novel switch to detect the presence of dangerous levels of WBC in spent peritoneal dialysate (see Figure 1). Since the sensitivity of a clog-based sensor is dependent on the permeability of its membranes, incorporating highly permeable silicon nanomembranes into a white blood cell detector will produce a highly sensitive WBC detector. Spent Dialysate from peritoneal dialysis fluid exchanges (spike the dialysate with varying amounts of WBCs) is pushed at 200 µL/min into the top channel with the top outlet open to the atmosphere. The inlet of the bottom channel is closed, and the outlet pulls at 100 µL/min through the membrane. If the membrane is clogged the transmembrane pressure (recorded for the duration of the experiment at ~0.5-second intervals) will increase. Results: We have preliminary data demonstrating that membranes with 4-µm wide microslit pores block the passage of WBCs while allowing all other cells and proteins in whole blood to pass. Figure 2 shows the pressure increase across the membrane when subjected to varying concentrations of white blood cells in spent dialysate. The slope of the pressure indicates the WBC count. The primary innovation comes from the use of microporous membranes as a fouling-based sensor; using membranes with pores tuned to be just slightly smaller than the size of leukocytes, we will see a change in the transmembrane pressure (under a steady flow rate) as the WBCs block pores which correlates to the WBC concentration.Figure 1. a: Schematic showing WBC-detection switch. Pressure transducers report pressure increase as cells clog the membrane. b: WBCs are drawn to the micropores by transmembrane flow.Figure 2. Transmembrane pressure slope correlates with the white blood cell concentration in the dialysate.