THE ROLE OF TUBULAR IRON ACCUMULATION IN THE REMNANT KIDNEY

Iron has been implicated in the pathophysiology of several models of a cute and chronic renal disease. In this study, energy-dispersive x-ray spectrometry was used to quantify and localize iron in rat remnant ki dneys (RK) and normal kidneys (NK) and to determine its pathophysiolog ic significance. Substantial iron accumulation occurred in proximal tu bular cell secondary lysosomes of RK (P < 0.001 versus NK) and reached a plateau at 8 wk after partial nephrectomy. In NK, minor increases o f iron also occurred with aging (P < 0.02). Proximal tubular iron accu mulation correlated independently with protein excretion (r = 0.90) an d impairment of GFR (r = 0.70) and was associated with tubular damage and phosphate accumulation (both P < 0.001). Iron nitrilotriacetate (1 mg/kg ip) increased tubular lysosomal iron accumulation and tubular d amage (P < 0.001 versus nitrilotriacetate) in NK, comparable to levels seen in untreated RK, and increased cortical cytosolic malondialdehyd e, consistent with reactive oxygen species generation. The iron chelat or deferoxamine (30 mg/kg per day ip) significantly reduced iron accum ulation and tubular damage in RK at 4 wk, compared with deferoxamine c helated to iron and untreated RK. These results suggest that filtered iron enters the remnant tubular lysosomes across the brush border memb rane by endocytosis and may produce tubular damage in chronic renal di sease by the generation of reactive oxygen species.