The proposed study will define factors which enhance renal regeneration after acute tubular necrosis (ATN) and regulate compensatory kidney growth after uninephrectomy. A recent study in this laboratory has demonstrated that amino acid infusions given to rats with ATN, act directly on the kidney to increase the synthesis of membrane phospholipid in regenerating cells, and also decrease the level of renal functional insufficiency. Experimental ATN is induced by mercuric chloride and the capacity of infused amino acids to enhance recovery is determined by measuring glomerular and tubular function. The biochemical correlates of renal cellular regeneration are assessed in vitro by measuring phospholipid, protein, DNA and RNA synthesis and amino acid transport. Objectives of the proposed investigation are to: A. Use this animal model of ATN to elucidate the biochemical mechanism by which exogenous amino acids stimulate phospholipid biosynthesis in regenerating renal tissue, and determine if amino acids also stimulate protein and nucleic biosynthesis during regeneration. B. Evaluate the efficacy of specific amino acids to enhance recovery from ATN by measuring alterations in renal function and the biochemical correlates of cellular regeneration. C. Isolate and characterize humoral and tissue factors which mediate renal compensatory growth and renal regeneration with an in vitro bioassay which utilizes the rapid increase in renal phospholipid synthesis during compensatory growth as a detector of renal growth promoting activity. D. Define the relationship between phospholipid and protein synthesis during new renal membrane formation. The long-term goals of the proposed study are to provide a biochemical basis for the rational treatment of acute injury of the kidney and of other organs as well.