Acute renal failure: From renal physiology to the renal transcriptome

Acute renal failure: From renal physiology to the renal transcriptome. Acute renal failure (ARF) is defined as an abrupt fall in glomerular filtration rate. Fully 5% of all patients admitted to the hospital undergo ARF with an attendant increase in morbidity and mortality. We have studied murine models of ischemia/reperfusion and cisplatin-induced renal failure in detail to determine the physiologic and molecular events that are responsible for the syndrome. Both forms of treatment induce necrosis of the proximal tubules, as well as more subtle changes in distal nephron viability, including apoptosis. Both forms are characterized by reduced renal blood, reduced glomerular filtration rate, and a urine-concentrating defect. Simultaneous with the onset of these morphologic and functional features is the commitment of cells to DNA synthesis and cell division, which is preceded by activation of signal transduction pathways and gene transcription that presumably underlie the morphologic and functional changes responsible for the syndrome. We describe a functional genomic approach using microarray data and available database searches to attempt to predict new targets for investigation of the pathogenesis and treatment of this disease