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Urinary exosomes from a mouse model of chronic tubulointerstitial kidney disease induced by chronic renal ischemia–reperfusion injury and nephrectomy

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Background

Biomarkers for the early diagnosis of chronic kidney disease (CKD) will lead to its better management. Rodent models will be helpful for biomarker discovery. Urinary exosomes, membrane bound vesicles, may contain interesting biomarkers.

Objective

To produce a mouse model of CKD with sufficient urine volume for exosome studies.

Methods

We characterized a mouse models of CKD induced by 55 min ischemia–reperfusion injury and contralateral nephrectomy at 1 wk after the chronic ischemia–reperfusion injury (Chr IR) in 7 mice and other 7 sham-operated control mice. We collected 24 h urine for urine exosome extraction.

Results

Blood urea nitrogen, serum creatinine, and proteinuria increased as early as 2 wk, and reciprocally lower hematocrit. The renal injury, proteinuria, and anemia persisted 12 wk after nephrectomy as consistent with uremic symptoms. The mouse model of CKD showed renal histopathology of interstitial fibrosis with mild glomerular injury, and failure to grow. At 12 wk, the volume of urine collected in 24 h was sufficient for exosome extraction. Urinary exosomes were demonstrated by western blots showing tumor susceptibility gene 101 protein.

Conclusions

Mice with renal injury induced by Chr IR showed renal injury and proteinuria as early as 2 wk with uremic symptoms and tubulointerstitial fibrosis. Most importantly, the 24 h volume of urine at 12 wk was sufficient for exosome extraction.

eISSN:
1875-855X
Langue:
Anglais
Périodicité:
6 fois par an
Sujets de la revue:
Medicine, Assistive Professions, Nursing, Basic Medical Science, other, Clinical Medicine