NDT Advance Access published online on December 29, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk009
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1 Department of Medicine #2, Yokohama City University, Yokohama, Japan
* To whom correspondence should be addressed. Background. Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats. Methods. We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method. Results. Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes. Conclusions. Urinary excretions of L-PGDS are likely to reflect the underlying increase in glomerular permeability. This property may be useful to predict forthcoming glomerular damage following diabetes in OLETF rats.
Received November 25, 2004
Accepted November 28, 2005
Original Article
Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats
Momoko Ogawa 1,
Nobuhito Hirawa 1,
Takamasa Tsuchida 2,
Naomi Eguchi 3,
Yukari Kawabata 4,
Atsushi Numabe 5,
Hideyuki Negoro 4,
Rie Hakamada-Taguchi 4,
Kousuke Seiki 2,
Satoshi Umemura 1,
Yoshihiro Urade 3,
and
Yoshio Uehara 4 *
2 Biochemistry Research Laboratory, Central Research Institute, Maruha Corporation, Tsukuba, Japan
3 Core Research for Evolution Science and Technology, Japan Science and Technology Corporation and Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan
4 Health Service Center, University of Tokyo, Tokyo, Japan
5 The Department of Clinical Laboratory Medicine and Institute of Medical Science, Dokkyo University School of Medicine, Mibu, Japan
Yoshio Uehara, E-mail: uehara-2im{at}h.u-tokyo.ac.jp
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  Y. Uehara, H. Makino, K. Seiki, Y. Urade, and on behalf of L-PGDS Clinical Research Group of Kid Urinary excretions of lipocalin-type prostaglandin D synthase predict renal injury in type-2 diabetes: a cross-sectional and prospective multicentre study Nephrol. Dial. Transplant., February 1, 2009; 24(2): 475 - 482. [Abstract] [Full Text] [PDF]
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