Nephrotoxicity--what do we know and what don't we know?

Nephrotoxicity is the development of functional or structural kidney damage after exposure to one or more of a wide variety of drugs, other treatments or exogenous toxins, and may lead to a variety of functional consequences and structural lesions. Nephrotoxicity is important as it may occur in a substantial proportion of children treated with certain drugs and occasionally lead to severe renal impairment that may prevent the delivery of optimal anticancer treatment and/or reduce the quality of life of long-term survivors. This article describes what is currently known about nephrotoxicity occurring in children treated for malignancy by summarizing published information about the clinical characteristics and long-term outcome of, and the risk factors for the development of, ifosfamide and platinum-induced renal toxicity. Published guidelines for the evaluation and surveillance of nephrotoxicity, and the still incomplete understanding of its pathogenesis, are also outlined. Many gaps in our knowledge of nephrotoxicity are highlighted, including the lack of detailed knowledge about its overall incidence and very long-term impact, the nephrotoxic potential of new drugs, the efficacy of surveillance protocols, the relevance of proteinuria as a component of nephrotoxicity, and our current inability to reliably predict or prevent many episodes of nephrotoxicity.