In the past few decades, accumulating evidence has been generated on the central role of the proximal tubular cell in renal injury and dysfunction, such as can be found in some patients with glomerular proteinuria and in chronic renal rejection or following ischaemic insult. Following initial injury or stimulation of the proximal tubular cells, various cascades of mediator systems can be activated leading, for example, to enhanced local production of complement, chemokines, cytokines and matrix components. The locally produced mediators subsequently can lead to amplification of injury either directly or indirectly by enhancement of influx of proinflammatory cells such as macrophages, polymorphonuclear leukocytes and T cells. The concerted production of cytokines and chemokines may tip the balance to a more proinflammatory pathway leading to irreversible interstitial injury of the kidney and loss of renal function.