Acute kidney injury and renal replacement therapy: a critical synthesis of metabolic derangements and nutritional implications

Abstract

Acute kidney injury (AKI) affects up to 50% of critically ill patients and is frequently complicated by severe metabolic derangements, requiring the initiation of replacement therapy (RRT) in 10–15% of cases. Despite substantial progress in the diagnosis of AKI and optimisation of RRT delivery, the nutritional management of these patients remains an underexplored area. AKI is increasingly recognised as a systemic metabolic disorder extending beyond impaired renal clearance. Key metabolic alterations include mitochondrial dysfunction, dysregulated gluconeogenesis, increased proteolysis and altered amino acid metabolism, with accelerated nitrogen wasting. These abnormalities are further amplified by acute systemic stress states, including sepsis, systemic inflammation, trauma, burns, liver dysfunction and multiorgan failure. RRT introduces additional metabolic consequences through extracorporeal losses of amino acids and micronutrients. Conversely, citrate anticoagulation, glucose-containing dialysate, and lactate-buffered solutions represent sources of clinically relevant calories. Current nutritional recommendations are largely extrapolated from heterogeneous intensive care populations. Available evidence suggests that AKI primarily influences energy balance rather than energy expenditure, which appears broadly comparable to that of other critically ill populations. While evidence specific to AKI is limited, protein provision of approximately 1.2-1.3 g/kg/day is generally recommended during critical illness. However, higher intakes of up to 1.7–2.5 g/kg/day may be considered in patients receiving RRT to offset extracorporeal amino acid losses and increased protein catabolism. In this setting, emerging concepts such as metabolic tolerance and biomarker-guided metabolic phenotyping may facilitate individualised nutritional strategies. AKI, particularly when requiring RRT, is associated with profound and dynamic metabolic disturbances that substantially influence energy and protein requirements, thereby making nutrition an integral component of organ support therapies. Future research should evaluate precision nutrition strategies that tailor nutritional support to the phase of critical illness, measured energy expenditure, metabolic tolerance, and RRT-related nutrient losses and gains. Such studies should prioritise patient-centred outcomes, including physical function and recovery, in addition to nutritional and metabolic endpoints.