Lipocalin-type prostaglandin D synthase in urine in adriamycin-induced nephropathy of mice.
OBJECTIVE
Lipocalin-type prostaglandin D synthase (L-PGDS), an enzyme converting prostaglandin H(2) to prostaglandin D(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.


CONCLUSIONS
Urinary L-PGDS excretion is increased in Adriamycin-induced nephropathy, and this precedes overt albuminuria.
Biochemistry Research Laboratory, Central Research Institute, Maruha Corporation, Tsukuba, Japan.
Takamasa
T
Tsuchida
Naomi
N
Eguchi
Yutaka
Y
Eguchi
Atsushi
A
Numabe
Hiroshi
H
Nakajima
Hiroshi
H
Oda
Kousuke
K
Seiki
Rie
R
Hakamada-Taguchi
Yoshihiro
Y
Urade
Yoshio
Y
Uehara
D000818:Animals; D001835:Body Weight; D004317:Doxorubicin; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000473:pathology / Q000652:urine*; D019746:Intramolecular Oxidoreductases / Q000097:blood / Q000378:metabolism / Q000652:urine*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D054834:Lipocalins; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism
D054834:Lipocalins; D012333:RNA, Messenger; D004317:Doxorubicin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase