Lysosomal iron accumulation and tubular damage in rat puromycin nephrosis and ageing.
1. Energy dispersive X-ray spectrometry was used to examine the relationship between proteinuria and increased urinary iron excretion, and structural and functional damage in puromycin nephrosis. 2. After 11-12 days rats treated with puromycin (10 mg/100 g, i.v.i.) had greater proteinuria (211.6 +/- 35.7 mg/day, mean +/- s.e.m.) and urinary iron excretion (15.4 +/- 2.2 micrograms/day) than saline-treated controls (14.5 +/- 1.4 mg/day and 1.1 +/- 0.2 micrograms/day, respectively, both P < 0.001). 3. On day 13, mean lysosomal iron concentration of proximal tubular cells (306.6 +/- 64.5 vs 11.9 +/- 8.6 mg%, P < 0.001), and proximal tubular cell damage assessed semi-quantitatively (1.17 +/- 0.10 vs 0.62 +/- 0.10, P < 0.001) were higher and creatinine clearance (0.15 +/- 0.01 vs 0.29 +/- 0.02 mL/min per g kidney weight, P < 0.001) lower than in control rats. 4. At days 35, 60 and 360 there were no differences in any of the measured parameters between rats treated with puromycin or saline, and in both groups proteinuria, tissue damage and lysosomal iron concentration increased with time. 5. Lysosomal iron accumulation was the only independent predictor of both functional and structural damage. 6. In conclusion, the apparent association between proteinuria and tubulo-interstitial damage in puromycin nephrosis, and with ageing, is best explained by factors associated with accumulation of iron within lysosomes of proximal tubule cells.
Department of Renal Medicine, Westmead Hospital, Sydney, NSW, Australia.
D C
DC
Harris
C
C
Tay
B J
BJ
Nankivell
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D005919:Glomerular Filtration Rate / Q000502:physiology; D007501:Iron / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000652:urine; D011691:Puromycin / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013052:Spectrometry, X-Ray Emission; D014168:Transferrin / Q000378:metabolism
D014168:Transferrin; D011691:Puromycin; D008315:Malondialdehyde; D007501:Iron