Drowning the kidneys: from fluid overload to physiology-guided fluid management in onco-hematology

Abstract Acute kidney injury (AKI) is a frequent complication in patients with cancer. Although AKI in oncology is often multifactorial, it is frequently attributed to nephrotoxicity or intrinsic tubular injury. However, its hemodynamic mechanisms remain underrecognized. Accumulating evidence from critical care and cardiorenal medicine indicates that fluid overload, venous congestion, and increased intra-abdominal pressure are major drivers of kidney dysfunction and adverse outcomes in patients with cancer. These mechanisms are particularly relevant in onco-hematology, where protocol-driven hydration, transfusions, systemic inflammation, and capillary leak are common. This review examines venous congestion as an underrecognized and potentially reversible contributor to AKI in patients with cancer, by integrating epidemiological data, mechanistic insights, and clinical evidence. Particular emphasis is placed on the distinction between fluid responsiveness (FR) and fluid tolerance (FT), with the reviewed studies reporting that many patients with AKI are neither fluid responsive nor fluid tolerant and that these phenotypes evolve dynamically over time. Tumor lysis syndrome is presented as a paradigmatic clinical scenario in which aggressive hydration is widely recommended despite limited high-quality evidence and a substantial risk of fluid intolerance. We further describe the role of point-of-care ultrasound in the bedside assessment of cardiac filling pressures, venous congestion, and stroke volume, and propose a physiology-driven framework for AKI evaluation that prioritizes exclusion of urinary tract obstruction, systematic assessment of FT, and selective evaluation of FR in hypotensive or low-flow states. Adopting this approach may help individualize fluid management, reduce iatrogenic harm, and improve renal outcomes in patients with cancer.