Tsuchida, Takamasa, Eguchi, Naomi, Eguchi, Yutaka, Numab, Atsushi, Nakajima, Hiroshi, Oda, Hiroshi, Seiki, Kousuke, Hakamada-Taguchi, Rie, Urad, Yoshihiro, and Uehara, Yoshio
Background/Aims: Lipocalin-type prostaglandin D synthase (L-PGDS), an enzyme converting prostaglandin H[sub 2] to prostaglandin D[sub 2] , occurs particularly in the cardiovascular system. Urinary L-PGDS excretion is increased in diabetes prior to overt proteinuria, suggesting that it is a predictor of renal injury. In this study, we tested the hypothesis that L-PGDS excretion reflects renal injury in primary glomerular diseases using Adriamycin-induced nephropathy in mice. Methods: Twenty 6-week-old ICR female mice were intravenously given a dose of 25 mg Adriamycin/kg body weight through the tail vein. 24-hour urine was collected every day, and blood samples were obtained. Results: The mice developed significant albuminuria from day 3 onward (p < 0.05), which was followed by overt proteinuria from day 4 (p < 0.05). Histological examination revealed focal mesangial expansion with partial tubular atrophy. Urinary L-PGDS excretion significantly increased from day 1 onward (p < 0.05), and apparently preceded the increase in urinary albumin excretions. Either serum L-PGDS or creatinine levels were not changed by administration of Adriamycin. However, serum creatinine levels were inversely correlated to urinary L-PGDS excretions (r = –0.88, p < 0.05). Immunohistochemistry showed that L-PGDS occurred in the tubules, but not in the glomeruli in Adriamycin mice and L-PGDS mRNA paralleled urinary L-PGDS excretion. Conclusion: Urinary L-PGDS excretion is increased in Adriamycin-induced nephropathy, and this precedes overt albuminuria. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]