Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide

Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide. Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO 2 ) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO 2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 ± 9% in the GeO 2 group, 3 ± 1% in the Ge-132 group and 1 ± 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO 2 group. Although systemic toxicities were reduced after GeO 2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge ·Kα X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO 2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO 2 group. From these results, it is concluded that GeO 2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO 2 remains for a considerably long time even after the cessation of GeO 2 intake.