A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous Renal Replacement Therapy in Critically Ill Children

ABSTRACT A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous RenalReplacement Therapy in Critically Ill Children(Fast-Track SBIR PA-20-260) Acute kidney injury (AKI) is characterized by a sudden decrease in the ability of the kidneys to adequately maintain electrolyte, acid-base, and fluid balance. Up to 30% of children admitted to intensive care units develop AKI and the presence of AKI is independently associated with increased length of hospitalization and higher rates of mortality. Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill children and is becoming increasingly common for newborns and small children (under 10 kg) with AKI and congenital kidney failure. Frequent monitoring (2-6 times a day) of anticoagulant therapy (heparin, heparinoids, etc.), kidney function (urea), and electrolyte composition (potassium, phosphorus, etc.) is necessary during the course of CRRT. Existing laboratory tests require large blood volumes, and the cumulative blood loss from routine bloodwork contributes to iatrogenic anemia. The majority of critically ill newborns (90% of extremely low birth weight infants and 58% of premature infants) will require red blood cell transfusions during their time in the neonatal intensive care unit (NICU) as a result of frequent blood draws. To meet the critical unmet need for rapid, low volume blood tests for CRRT monitoring in newborns and children, we will develop a panel of four assays on our near-patient digital microfluidic (DMF) platform to provide comprehensive profiling of anticoagulation dosing, kidney function, and phosphorus balance. Our innovative system will simultaneously measure anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT), blood urea nitrogen (BUN), and phosphorus from lt 50 µL of whole blood input. Plasma separation from whole blood (necessary for all four assays) will be automated on the cartridge to facilitate testing near the patient. By combining four technically complex assays (typically sent to different sections in a lab such as hematology and chemistry) into a single automated test, we can reduce sample-to-answer time and personnel time needed to perform each individual assay, and can significantly reduce the cumulative volume of blood required for recurrent monitoring over the full course of CRRT therapy. Our collaborators on this Fast-Track project include pioneers in pediatric acute care nephrology with multiple recent publications describing novel approaches to CRRT in newborns. Phase I of the project will establish feasibility of the proposed testing platform through development of DMF anti-FXa, aPTT, BUN, and phosphorus assays and demonstration of sufficient analytical and clinical performance. Phase II will combine the four assays into a multiplexed reaction with a time-to-result of under 15 minutes, evaluate the analytical performance and clinical concordance of each assay, and conduct onsite lead user testing of the system to establish reliability and usability. Our final product will initially be marketed for use in newborn and pediatric patients undergoing CRRT. Secondary markets will include both pediatric and adult patients undergoing cardiac surgery or other procedures associated with kidney failure, toxin removal, and ultrafiltration of fluid.