Cast nephropathy in the ICU: Early recognition and extracorporeal strategies to improve outcomes

Cast-induced acute kidney injury (AKI) is a frequent yet under-recognized cause of kidney dysfunction in the intensive care unit. It arises when filtered proteins or pigments – free light chains (FLCs) in multiple myeloma, myoglobin in rhabdomyolysis, bilirubin in severe cholestasis, or hemoglobin in intravascular hemolysis – precipitate within kidney tubules, forming obstructive casts and triggering oxidative and inflammatory injury. Early recognition is essential because traditional markers (creatinine, urine output) rise late. Emerging biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and the tissue inhibitor of metalloproteinases-2 · insulin-like growth factor binding protein-7 ([TIMP-2]·[IGFBP7]) panel, detect tubular stress earlier and can guide timely intervention. This narrative review summarizes pathophysiology, diagnostic tools, and extracorporeal strategies tailored to the offending molecule and patient stability. For myeloma cast nephropathy, high cut-off membranes provide robust early FLC clearance but require albumin monitoring; medium cut-off and polymethylmethacrylate membranes offer sustained removal with lower albumin loss. In rhabdomyolysis, continuous kidney replacement therapy with high-flux or newer membranes supports hemodynamic stability and myoglobin clearance; hemoadsorption may be considered in severe cases. In bile cast nephropathy, artificial extracorporeal liver support (e.g., molecular adsorbent recirculating system, fractional plasma separation and adsorption), single-pass albumin dialysis, and hemoadsorption reduce bilirubin and bile acids, while plasma exchange remains reserved mainly for hyperviscosity syndromes. Across etiologies, extracorporeal approaches are most effective when combined with disease-specific treatments, such as chemotherapy for myeloma or targeted therapy for hemolysis. Emerging evidence suggests that integrating artificial intelligence-driven diagnostic tools with these therapeutic strategies may further enhance early recognition and individualized management of renal injury. A patient-centered, pathophysiology-driven strategy can shift extracorporeal therapies from rescue measures to proactive tools that improve kidney recovery and survival. Prospective studies should refine timing, modality selection, and biomarker-based algorithms to optimize outcomes in cast-induced AKI.