Abstract

Objective: Loss of renal function is often associated with the progressive renal fibrosis in chronic kidney disease; however, there is no mouse model reproducing renal fibrosis in clinical setting. In the present study, we aimed to develop a high survival rate murine renal fibrosis model after an ischemic insult. Design and Method: C57bl/6 mice (6–8 weeks old, male) were divided into four groups: sham (n = 3), nephrectomy only (UNX), n = 3), ischemia/reperfusion (I/R) 35-min (n = 6), and I/R 45-min group (n = 6). Mice were subjected to unilateral ischemia for 35 or 45 min followed by reperfusion. After a 1-week recovery, the right kidney was removed, so that mice lived with one kidney that had received I/R injury. Results: No death due to AKI was observed up to 8 weeks after UNX. I/R followed by UNX increased the urine volume significantly and decreased hematocrit and hemoglobin levels compared with sham and UNX group. The picrosirius red staining analysis showed that I/R followed by UNX showed the significant fibrosis in both perivascular and interstitial area at week 8. Conclusions: These data suggest that this model which induced by I/R injury with UNX afterward showed a high survival rate, progressive fibrosis, anemia, polyuria, which are relevant to the kidney disease in the clinical setting, such as chronic tubulointerstitial nephritis.

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