Epidemiologic research shows a strong link between acute or chronic kidney injury and kidney tumors. However, it is unclear whether these associations are causally linked and in which direction. Data from basic and clinical research are now shedding light on this issue, prompting us to propose a new pathophysiological concept with immediate implications for the management of patients with kidney disease and kidney tumors. As a central paradigm, this review proposes kidney damage and repair mechanisms that are active not only during acute kidney injury but also during chronic kidney disease as triggers of DNA damage, promoting the expansion of (pre-) malignant cell clones. We discuss how the different types of kidney tumors relate to renal progenitors at specific sites of injury and to germline or somatic mutations in distinct signaling pathways, as renal progenitors have been identified as the cell of origin for several benign and malignant kidney tumors by different studies. We show how known risk factors for kidney cancer are actually risk factors for kidney injury, which is an upstream cause of cancer. Finally, we propose a new role for nephrologists in the treatment of kidney cancer (i.e., the primary and secondary prevention and treatment of kidney injury to reduce incidence, prevalence, and recurrence of kidney cancer).
