Copper toxicosis and tolerance in the rat: IV. Renal tubular excretion of copper.

Male rats were fed a diet containing o.oo3% copper and killed sequentially up to 15 weeks. The kidney cortices were examined analytically and histochemically for copper. Urinary copper output was measured in one group of copper supplemented rats. Kidney copper concentration rose (mean+SEM, microgramCu/g) to 4238.0 +/- 475 at 4 weeks (control 59 +/- IO) and remained unchanged to 15 weeks. Urinary copper output rose (m +/- SEM, microgramCu/h) to 4.3 +/- 0.36 (control 0.3 +/- 0.04) at 4 weeks; it peaked temporarily IO.9 +/- 2.5, P less than o.o5, at 5 weeks and subsequently fell to 4.I +/- o.75 at 6 weeks and thereafter. Histochemically demonstrable copper accumulated in the renal proximal convoluted tubules up to 4 weeks during which it was excreted into the lumen by exocytosis and cellular exfoliation. Widespread sloughing of necrotic copper-containing tubule cells became marked at 5 weeks but declined subsequently as regeneration occurred. Urinary copper output reflects the changes in kidney copper turnover and is apparently derived from this source. Renal tubular excretion of copper probably serves a protective function in the copper-loaded rat.