During 1946–1974, research reframed acute kidney injury as a systemic, multifactorial syndrome rather than solely a glomerular disorder. The dominant pattern highlighted that severe trauma, shock, circulatory dysfunction, liver disease, medication exposure, and microangiopathy could precipitate renal failure, with emphasis on renal tubular injury and pathophysiology. Methodologically, there was a move toward clinical-pathological correlation and early implementation of aggressive supportive care, including dialysis, to improve outcomes.