A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous Renal Replacement 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 adequatelymaintain electrolyte, acid-base, and fluid balance. Up to 30% of children admitted to intensive care units developAKI and the presence of AKI is independently associated with increased length of hospitalization and higherrates of mortality. Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modalityfor critically ill children and is becoming increasingly common for newborns and small children (under 10 kg) withAKI 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 necessaryduring the course of CRRT. Existing laboratory tests require large blood volumes, and the cumulative blood lossfrom routine bloodwork contributes to iatrogenic anemia. The majority of critically ill newborns (90% of extremelylow birth weight infants and 58% of premature infants) will require red blood cell transfusions during their time inthe 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 providecomprehensive profiling of anticoagulation dosing, kidney function, and phosphorus balance. Our innovativesystem will simultaneously measure anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT), bloodurea nitrogen (BUN), and phosphorus from < 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. Bycombining four technically complex assays (typically sent to different sections in a lab such as hematology andchemistry) into a single automated test, we can reduce sample-to-answer time and personnel time needed toperform each individual assay, and can significantly reduce the cumulative volume of blood required for recurrentmonitoring over the full course of CRRT therapy.Our collaborators on this Fast-Track project include pioneers in pediatric acute care nephrology with multiplerecent publications describing novel approaches to CRRT in newborns. Phase I of the project will establishfeasibility of the proposed testing platform through development of DMF anti-FXa, aPTT, BUN, and phosphorusassays and demonstration of sufficient analytical and clinical performance. Phase II will combine the four assaysinto a multiplexed reaction with a time-to-result of under 15 minutes, evaluate the analytical performance andclinical concordance of each assay, and conduct onsite lead user testing of the system to establish reliability andusability. 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 proceduresassociated with kidney failure, toxin removal, and ultrafiltration of fluid.
Public Health Relevance Statement: PROJECT NARRATIVE 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. Continuous renal replacement therapy (CRRT) has recently 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. While frequent monitoring of anticoagulant therapy, kidney function, and electrolyte composition is necessary during the course of CRRT, existing laboratory tests require large blood volumes, contributing to iatrogenic anemia and subsequent blood transfusions. 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 platform to provide comprehensive profiling of anticoagulation dosing, kidney function, and phosphorus balance.
Project Terms: <21+ years old><0-11 years old><0-4 weeks old>
