Nephrotoxicity of ferric nitrilotriacetate. An electron-microscopic and metabolic study.

Repeated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) induce nephrotoxic features such as proximal tubular necrosis and renal failure, an unexpected phenomenon for a ferric compound. The mechanism of Fe-NTA toxicity was investigated by electron microscopy and respiration studies of renal cortical mitochondria in rats. Four hours after a single intraperitoneal injection of Fe-NTA, 5 mg iron/kg body wt, loss of microvilli, increased number of cytoplasmic vacuoles, electron-dense cytoplasmic deposits, mitochondrial swelling, karyorrhexis, and rupture of cytoplasmic membrane were observed in proximal tubular epithelia. At 24 hours, an increased number of cells had become necrotic. Polarographic studies of mitochondria from renal cortex 4 hours after Fe-NTA treatment showed a significant decrease in State 3 respiration and DNP-uncoupled respiration, whereas little change was observed in State 4 respiration and ADP/O.