Systemic inflammation is known to target tubular epithelial cells (TECs), leading to acute kidney injury. Tubular cells have been implicated in the response to inflammatory mediators in ischaemic and septic renal damage. Moreover, loss of tubular cells by apoptosis or epithelial-to-mesenchymal transition may ingenerate conditions that lead to progression towards chronic kidney disease. On the other hand, TECs may actively contribute to the production of inflammatory mediators that may propagate the injury locally or in distant organs. In the present review, we discuss the tubular cell response and its contribution to systemic inflammation.