Sensitive and Early Markers of Renal Injury: Where Are We and What Is the Way Forward?

Measurement of total urinary protein, glucose, and the appearance of certain enzymes such as N-acetyl-b-(D)glucosaminidase has been used in both animals and man for many years to provide insight into the onset of renal injury. However, it is clear that serum creatinine and such markers are not very sensitive and are generally only raised when acute renal injury or chronic renal injury is well established. With the coming of the ‘‘omics’’ age and the development of transcriptomics, proteomics, and metabonomics, it has become possible to interrogate urine samples to identify new proteins or small organic molecules appearing in urine as the result of a toxic insult or in models of renal disease. This new technology has stimulated considerable interest and effort in trying to identify novel, sensitive, and early urinary biomarkers of renal injury. A sensitive tissue marker of tubular injury, which can be used to identify or confirm the presence of epithelial cell injury even when morphological changes are minimal during the development of a new drug or pesticide or for the evaluation of biopsy material, would be welcomed by all concerned. However, history tells us that it is not one single urinary measurement, but a number of measurements that indicate that renal injury has occurred. Thus, ideally, we are looking for a number of biomarkers that together may inform us not only of the presence of injury but perhaps in which part of the nephron the injury is located.