Despite the device demonstrating no serious adverse events (SAEs) in a preliminary safety study, researchers believe further enhancements are needed to improve the outcomes associated with the automated wearable artificial kidney (AWAK)-PD system (AWAK Technologies) for peritoneal dialysis patients. Writing in Peritoneal Dialysis International (PDI), the researchers report that 60% of participants developed abdominal pain or discomfort—but a “significant reduction” in serum small and middle molecules with AWAK therapy compared to conventional peritoneal dialysis therapy was also observed.
“This study has also demonstrated improvement in serum urea, creatinine, phosphate and β2-microglobulin clearance with AWAK therapy compared with conventional therapy,” Marjorie W Y Foo (Department of Renal Medicine, Singapore General Hospital, Singapore) et al write in their report. “However, ultrafiltration should be further optimised in future studies. All the clinical observations and findings of the study have provided valuable insights into the technical challenges and limitations that need to be addressed before proceeding to a larger-scale clinical study. Future studies should examine patient-reported outcome measures.”
Due to its early survival advantage over haemodialysis, cost-effectiveness for healthcare providers and policymakers, and improved quality of life including greater patient satisfaction, there is growing interest in peritoneal dialysis as an initial modality of kidney replacement therapy, the study’s authors state. However, while regeneration of peritoneal dialysis fluid using sorbent technology can provide flexibility and improve quality of life further, there are currently no commercially available sorbent-based devices on the market.
Foo et al set out to examine the safety and efficacy of one such device—the tidal technique-based AWAK-PD system—via a single-arm, pilot cohort study, which was conducted at Singapore General Hospital from March 2016 to October 2018. The study included adult patients aged 21–80 years with kidney failure who had been stable on peritoneal dialysis for at least three months. Participants underwent up to nine AWAK therapies over a 72-hour period and were followed up for one month. Primary outcomes in the study were SAEs and completion of nine therapies without device deficiency, while secondary outcomes were weekly peritoneal Kt/V urea, solutes clearance, and adverse events.
In total, 21 patients were screened prior to the study, 17 were enrolled, and 15 were ultimately included in the analysis. “In the early phase of the study, clogging of the device was observed and device design alterations including a change in sorbent composition, mechanical pressure settings and fill volumes were done to rectify these issues, resulting in three configurations of the device and the corresponding patient cohorts,” Foo et al also note. They report that no SAEs were observed in the participants during the study, or at follow-up, while the most common adverse event was abdominal pain/discomfort (n=nine, 60%)—although the majority of these episodes were resolved spontaneously without requiring additional intervention.
Another common adverse event was a feeling of bloatedness during therapy (n=seven, 47%), while four participants (27%) also experienced high blood pressure. The authors note that three of these patients achieved baseline blood pressure upon completion of the study, and one achieved baseline blood pressure at one week following the study—adding that their elevated blood pressure could have been related to abdominal pain/discomfort, anxiety due to frequent interruptions for blood sample collection, or reduced ultrafiltration with AWAK therapy.
Regarding completion of AWAK therapy without interruption, 15 participants underwent 131 AWAK therapies, with 95 (72.5%) of these being “valid” therapies. The AWAK device’s third and final configuration, and the resulting patient cohort—which included 11 patients—saw the majority of participants (n=seven, 64%) complete all nine therapies. Two participants from this third cohort did not complete all nine therapies due to reasons not related to the safety or efficacy of the therapy, while post-study analyses of the device showed that protein was the likely cause of device clogging, resulting in premature termination of the therapy. “Moving forward, the technology still needs further refinement to ensure all intended or prescribed therapies can be carried out without device-related issues,” Foo et al add.
In terms of solute clearance, there were “significant reductions” in serum urea, creatinine, phosphate and serum β2-microglobulin levels following AWAK therapy, compared with pre-AWAK therapy levels, while serum potassium and sodium were comparable before and after therapy. Regarding fluid balance—one of the indicators of the efficacy of AWAK therapy—the study’s results show the median body weights of participants pre- and post-AWAK therapy “were not significantly different”. Fluid reabsorption occurred among patients with residual kidney function, the authors add.
“This was the first AWAK-PD study conducted in humans,” Foo and colleagues state. “There were some limitations of the study including modifications of the device and study protocol due to unexpected challenges. The peritoneal Kt/V urea was estimated given the regenerating nature of the therapy, thus the traditional way of measuring urea clearance was not applicable. Therefore, the result of Kt/V urea from this study may not be directly comparable to that of conventional peritoneal dialysis therapy. The study did not collect strict fluid input/output data, making it difficult to interpret the total ultrafiltration and, therefore, the fluid balance of participants.”