Intratubular calcium phosphate deposition in acute analgesic nephropathy in rabbits

Earlier chronic studies using both animal and human autopsy material have suggested that the initial lesion of analgesic nephropathy is papillary necrosis with secondary cortical interstitial nephritis. The present study was designed to define ultrastructural changes in renal tubules exposed to high levels of analgesics. Female New Zealand White rabbits were given 5-7 g APC and sacrificed after periods of 6 to 36 hours. As early as 6 hours after treatment, hydroxyapatite crystallite aggregates were seen impacted in Segment III (straight segment) of the proximal tubule at the cortico-medullary junction. Ultrastructural changes included selective calcification of the brush border, mitochondrial calcification, and peroxisomal changes. It was concluded, on the basis of ultrastructural changes, that calcification of altered tubular cells may be an initial event in analgesic nephropathy.