Influence of renal compensatory hypertrophy on mitochondrial energetics and redox status

Abstract

A reduction in functional renal mass is common in numerous renal diseases and aging. The remaining functional renal tissue undergoes compensatory growth primarily due to hypertrophy. This is associated with a series of physiological, morphological and biochemical changes similar to those observed after uninephrectomy. Previous work showed that compensatory renal cellular hypertrophy resulted in an increase in susceptibility to several drugs and environmental chemicals and appeared to be associated with oxidative stress. Compensatory renal cellular hypertrophy was also associated with increases in mitochondrial metabolic activity, uptake of glutathione (GSH) across renal plasma and mitochondrial inner membranes, and intracellular GSH concentrations. Based on these observations, we hypothesize that the morphological, physiological and biochemical changes in the hypertrophied kidney are associated with marked alterations in renal cellular energetics, redox status and renal function in vivo. In this study, we used a uninephrectomized (NPX) rat model to induce compensatory renal growth. Our results show alterations in renal physiological parameters consistent with modest renal injury, altered renal cellular energetics, upregulation of certain renal plasma membrane transporters, including some that have been observed to transport GSH, and evidence of increased oxidative stress in mitochondria from the remnant kidney of NPX rats. These studies provide additional insight into the molecular changes that occur in compensatory renal hypertrophy and should help in the development of novel therapeutic approaches for patients with reduced renal mass.