Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics

Acute renal failure (ARF) represents a common and serious problem in clinical medicine. Renal ischemia-reperfusion injury (IRI) is the major cause of ARF in the native and transplanted kidney. Several decades of research have provided successful therapeutic approaches in animal models, but translational efforts in humans have yielded disappointing results. The major reasons for this include a lack of early markers for ARF (and hence a delay in initiating therapy), and the multi-factorial nature of the disease. This review focuses on the use of cDNA microarrays to elucidate the molecular genetic mechanisms underlying tubule cell apoptosis, and to identify novel biomarkers for early renal IRI. Also presented is a comparative temporal analysis of cDNA microarray results from mature kidneys following IRI and during normal nephrogenesis. Molecular genetic evidence for the notion that regeneration recapitulates development in the kidney, and that injured tubule cells possess the capacity to de-differentiate to the earliest stages of development, is presented. The implications of these findings to the ability of the kidney to repair itself and potential strategies for accelerating recovery are briefly discussed. (C) 2003 Elsevier Inc. All rights reserved.