Pediatric Critical Care Nephrology Across Resource Settings: From the Development of Low-Cost Hemodialysis Devices for Neonates and Children to the Implementation of Precision Medicine for AKI Management in High-Income ICUs

Background: Acute kidney injury (AKI) is a frequent complication of pediatric critical illness, associated with substantial short- and long-term morbidity and mortality. Its burden differs markedly across healthcare contexts: in low-resource regions, mortality remains high due to lack of access to renal replacement therapy (RRT), while in high-resource settings the key challenge is advancing personalization and precision of care. This dissertation had two aims: (1) to design and evaluate ultra-low-cost, electricity-free hemodialysis devices for children and neonates in low-resource settings; and (2) to investigate biomarkers and functional assays for precision AKI management in high-resource pediatric intensive care units (PICUs). Methods and Results: In Part I, a stepwise development pathway led from proof- of-concept prototypes (mSLAMB) to optimized pediatric (Kirpa KitTM) and neonatal (Brophy KitTM) systems. These manual syringe-driven devices minimized extracorporeal volume and achieved reproducible solute clearance and ultrafiltration in vitro. The Kirpa KitTM was then tested in a first-in-human case, demonstrating feasibility, safety, and precise ultrafiltration. In Part II, four clinical studies were conducted. In pediatric septic shock, we observed profound ACE dysfunction, with absent activity and paradoxically elevated concentrations both associated with adverse kidney outcomes. Serum renin improved AKI prediction when integrated with the Renal Angina Index and urinary NGAL, enhancing specificity and positive predictive value. The furosemide stress test reliably predicted AKI progression and RRT initiation, even in children already at stage 3 AKI. Finally, uNGAL measured during RRT predicted both prolonged therapy and successful liberation, suggesting utility as a biomarker of renal recovery. Conclusions: This work addresses the dual global challenge of pediatric AKI by developing novel, accessible RRT solutions for low-resource settings and advancing biomarker- and function-guided precision approaches in high-resource PICUs. These complementary strategies aim to reduce preventable mortality where dialysis is unavailable and to personalize management where advanced support is accessible.