TUBULOINTERSTITIAL LESIONS IN YOUNG ZUCKER RATS

Zucker(Z) rats spontaneously develop proteinuria and focal glomerulosclerosis (FGS), but little is known about tubulointerstitial (Tl) changes in the early stages of their disease. Thirteen male Z rats (9 obese, 4 lean) were examined at 75 (n = 6) and 120 (n = 7) days of age, Twenty-four-hour urinary protein excretion (UPr), percent of glomeruli with FGS, proportion of cortex and outer stripe occupied by vimentin (V)-positive (+) tubules (a marker of tubular damage) and the number of OX4+ (la+), OX42+(monocyte/macrophage), OX19+(pan T cell), OX8+(T cytotoxic cell), and OX22+(B cell) cells in both normal areas and around V+ tubules were assessed at each age, Mean UPr was 34.2 +/- 18.5 mg/day at 75 days and 183.6 +/- 129.9 mg/day at 120 days, FGS was only observed in 1% to 3% of glomeruli in five 120-day-old obese rats. All rats showed varying degrees of focal Tl injury histologically, V+ tubules were observed in 12 rats, and the proportion of cortex and outer stripe occupied by V+ tubules varied from 0.1% to 7.7%, The extent of Tl damage was greater at 120 days (3.7% +/- 2.9%) than at 75 days (0.5% +/- 0.5%), There was a 2- to 12-fold increase in the number of OX4+, OX42+, OX19+, and OX8+ cells in areas around V+ tubules, with OX4+ and OX42+ cells predominating. UPr and extent of TI injury correlated well with each other (r = 0.726, P = 0.0050), and both correlated strongly with the total number of OX4+, OX42+, OX19+, and OX8+ cells surrounding V+ tubules (r = 0.718 to 0.949, P = 0.0085 to < 0.0001), In this model, TI damage is closely related to UPr, occurs early before FGS, and is possibly mediated by infiltrating monocytes and T cytotoxic lymphocytes. (C) 1995 by the National Kidney Foundation, Inc.