Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury.
BACKGROUND
Acute renal failure (ARF) has a high morbidity and mortality. Many therapies have worked in animals but were unsuccessful in clinical trials. The inability to diagnose ARF early may have impaired the success of these trials.


METHODS
We screened a subtraction library to search for potential disease markers that would be induced rapidly after renal injury. Mice and rats were subjected to 30 to 40 minutes of bilateral ischemia.


RESULTS
mRNA for Cyr61, a secreted growth factor-inducible immediate early gene, was markedly up-regulated at two hours in the kidney but not other organs following renal ischemia. In situ hybridization studies suggested Cyr61 was synthesized in the proximal straight tubule. Cyr61 protein was analyzed by capture with heparin beads followed by Western blotting. Induction of Cyr61 protein could be detected in the kidney within one hour, peaked at four to eight hours, and remained elevated for at least 24 hours following ischemia. Cyr61 protein was detected in urine at three to six hours and peaked at six to nine hours after renal injury. Cyr61 was not detected after volume depletion, which is often difficult to differentiate from ARF.


CONCLUSIONS
The secreted, cysteine-rich, heparin binding protein Cyr61 is rapidly induced in proximal straight tubules following renal ischemia, and excreted in the urine where it might serve as an early biomarker of renal injury.
Muramatsu
Yasunari
Y
Renal Diagnostic and Therapeutic Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tsujie
Michiko
M
Kohda
Yukimasa
Y
Pham
Bertha
B
Perantoni
Alan O
AO
Zhao
Hong
H
Jo
Sang-Kyung
SK
Yuen
Peter S T
PS
Craig
Leonard
L
Hu
Xuzhen
X
Star
Robert A
RA
D058186:Acute Kidney Injury / Q000503:physiopathology / Q000652:urine*; D000818:Animals; D015415:Biomarkers; D055515:Cysteine-Rich Protein 61; D015870:Gene Expression; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000652:urine*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000652:urine*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology / Q000652:urine*; D014511:Uremia / Q000503:physiopathology / Q000652:urine
D015415:Biomarkers; C491850:CCN1 protein, mouse; C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger