Tubular cell lesion, albuminuria, and renal albumin handling in rats treated with adriamycin

Several lines of evidence have suggested that renal handling of proteins in rats with several nephropathies may contribute to the tubulointerstitial d amage observed in these animals. It has been suggested that proteins filter ed by the glomeruli may be toxic for tubule cells. The aim of this study wa s to investigate the relationship between albuminuria and tubular lesions o bserved in rats during the first two weeks after treatment with adriamycin (AD). Thirty female Wistar rats were injected intravenously with adriamycin at the dose of 3.5 (17 rats) or 5 mg/kg body weight (13 rats), and 7 were injected with 0.15 M NaCl (control group). Seven days later, we replaced dr inking water with a 0.10 M sodium bicarbonate solution for 6 of the animals injected with 5 mg/kg adriamycin (group ADB). Urine samples were collected before and 7 and 15 days after treatment to quantify albumin. The rats wer e killed 7 and IS days after the injections, and the kidneys removed for im munohistochemical study. We observed a significant increase in urinary albu min excretion 15 days after AD injection (3.5 mg/kg), but not 7 days after AD. However, in the animals injected with 5.0 mg/kg AD (group AD-5) the inc rease in albuminuria was observed as early as on day 7. The immunohistochem ical studies showed increased vimentin and albumin immunoreaction in the tu bular cells of the renal cortex from the kidneys of rats injected with 3.5 mg/kg (group AD-3) only 18 days after treatment (p < 0.05), whereas in the animals treated with 5 mg/kg AD these immunohistochemical alterations were more intense. However, treatment with sodium bicarbonate attenuated the tub ular lesions and reduced albumin reabsorption in adriamycin-treated rats. I n conclusion, these experiments showed a relationship between albuminuria a nd tubular lesions in adriamycin-treated rats.