Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischaemia is a leading cause of AKI, where reduced blood flow to the kidney triggers hypoxia and cell death in the nephron epithelium, impairing essential fluid handling and waste removal functions. While injured tubules have some capacity to recover, severe injury can result in chronic kidney disease (CKD) through a 'maladaptive repair' process characterised by failed epithelial regeneration, inflammation, and metabolic dysregulation. There are no targeted therapies for AKI or the transition to CKD and insight into human disease mechanisms remains limited. To address this gap, we evaluated the capacity of iPSC-derived human kidney organoids to model hypoxic injury. Transcriptional, proteomic, and metabolomic profiling revealed tubular injury, cell death, cell cycle arrest and altered metabolism in kidney organoids cultured in hypoxic conditions. After a recovery period, injured organoids had increased signatures of TNF and NF-κB signalling pathways linked to maladaptive repair. Single cell RNA sequencing localised AKI and maladaptive repair markers such as GDF15, ICAM1, TGFB1, and CCN1 to injured tubules. Metabolic phenotypes linked to CKD were also evident including dysregulated gluconeogenesis, amino acid and lipid metabolism. iPSC-derived macrophages integrated into kidney organoids displayed a robust activation and inflammatory response to hypoxic injury, which is currently being interrogated with high-resolution spatial transcriptomics. Our multi-omic analysis defines the molecular mechanisms of human AKI and maladaptive repair, highlighting new opportunities to test therapeutics and model immune-mediated interactions.