Project: Research project

Project Details


DESCRIPTION (Adapted from Applicant's Abstract): Remnant nephrons adapt to the loss of renal mass through changes in structure and function. Some of these compensatory adaptations appear to promote injury in these surviving nephrons. Hemodynamic alterations have been especially emphasized as pathways of progression. More recently they and others have focused on several metabolic adjustments of the remnant tubule and have assessed their potential role as mechanisms of progressive renal injury. In particular, increased ammoniagenesis and oxygen consumption per residual nephron have been studied and the possibility raised that complement and free radical mediated injuries accrue to these two tubular adaptations, respectively. Enhanced, cortical ammonia levels can trigger the complement cascade with pro-inflammatory consequents. Increased oxygen consumption can generate increased amounts of reactive oxygen species with cytotoxic effects. However, their most recent studies of a model of dietary induced deficiency of free radical scavengers, suggest that these two adaptations may be linked. That is, augmented oxygen consumption leads to increased generation of ammonia via the intermediary increase free radical production. The proposed studies will provide both quantitative descriptions of this processes at several levels and will test several mechanistic hypotheses. Specifically, they propose to morphometrically quantitate the proximal tubular mitochondrial compartment during adaptive stresses since this organelle is the major site of the renal ammoniagenesis and respiration. Second, they will measure key elements of the biochemical machinery for these two processes in this compartment and will test the hypothesis that ammoniagenesis is tied to respiration at least in part by the action of reactive oxygen metabolites. Finally, they will test the effects of manipulations of ammoniagenesis and free radical accumulation in vivo (on renal growth and injury)."
Effective start/end date8/1/917/31/96


  • National Institute of Diabetes and Digestive and Kidney Diseases


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