Early Markers of Nephrotoxicity

Abstract:

The kidney is susceptible to a wide range of nephrotoxins which vary in their effect from mild renal dysfunction to severe damage and end-stage renal failure. The identification of the presence of early renal damage, and also of individuals at risk of developing renal dysfunction, is important in order that corrective therapies can be applied at an early stage. However, glomerular filtration rate (GFR) is unlikely to fall until 50% of nephrons have ceased to function. A major challenge is to provide measurements, both qualitative and quantitative, that give an early indication of the initial site of renal damage before gross deterioration in kidney function has occurred. Nephrotoxic exposure results in a cascade of events of gradually increasing severity. Initially, functional changes occur which, if exposure continues, then progress past a point of no return leading ultimately to renal failure. Most biomarkers measure the effect of a toxin on the kidney, but some are insensitive, making it difficult to measure accurately the extent to which the kidney has been exposed. Used selectively, biomarkers are able to give information on the stage and severity of the damage/disease process. To be useful, a biomarker should be easily measured by robust inexpensive procedures, which can be carried out on random or timed urine samples. The effect of nephrotoxic agents is best assessed with a small battery of tests that can be followed by more specialized tests to confirm the severity and type of renal damage that has occurred.