Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity.
Cadmium (Cd) exposure results in injury to the proximal tubule characterized by polyuria and proteinuria. Kidney injury molecule-1 (Kim-1) is a transmembrane glycoprotein not normally detected in the mature kidney, but is upregulated and shed into the urine following nephrotoxic injury. In this study, we determine if Kim-1 might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. Weekly urine samples were analyzed for Kim-1, protein, creatinine, metallothionein, and Clara cell protein CC-16. Significant levels of Kim-1 were detected in the urine by 6 weeks and continued to increase throughout the treatment period. This appearance of Kim-1 occurred 4-5 weeks before the onset of proteinuria, and 1-3 weeks before the appearance of metallothionein and CC-16. Higher doses of Cd gave rise to higher Kim-1 excretion. Reverse transcriptase-polymerase chain reaction (RT-PCR) expression analysis showed that Kim-1 transcript levels were increased after 6 weeks at the low dose of Cd. Immunohistochemical analysis showed that Kim-1 was present in proximal tubule cells of the Cd-treated rats. Our results suggest that Kim-1 may be a useful biomarker of early stages of Cd-induced proximal tubule injury.
Department of Pharmacology, Midwestern University, Downers Grove, Illinois 60515, USA. wprozi@midwestern.edu
W C
WC
Prozialeck
V S
VS
Vaidya
J
J
Liu
M P
MP
Waalkes
J R
JR
Edwards
P C
PC
Lamar
A M
AM
Bernard
X
X
Dumont
J V
JV
Bonventre
D000818:Animals; D015415:Biomarkers / Q000652:urine*; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000009:adverse effects* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000652:urine*; D008668:Metallothionein / Q000652:urine; D011507:Proteinuria / Q000139:chemically induced* / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014598:Uteroglobin / Q000652:urine
D015415:Biomarkers; D002104:Cadmium; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D008668:Metallothionein; D014598:Uteroglobin; C110936:Havcr1 protein, rat; C556391:Scgb1a1 protein, rat