*Purpose: Ischemia induces altered bioenergetics with increased mitochondrial swelling and reactive oxygen species (ROS) and ultimately degradation of cellular function. Therapeutic interventions that target to improve mitochondrial health to repair, reprogram or replace mitochondria to restore respiratory functions are beneficial for prevention and treatment of disease.

*Methods: Renal injury was assessed by plasma creatinine (PCr; mg/dl). 8-wk old C57BL/6 mice were i.v. injected with isolated mitochondria (50 mcg, from healthy non-ischemic mouse liver). 1d, 3d or 5d after unilateral IRI. Nephrectomy of contra-lateral control kidney was done on day 13. Change in fibrosis genes were measured by RTPCR and histology changes with Masson trichrome (MT) and picrosirius red were done on day 14.

*Results: In vivo studies demonstrated treatment of mice with 50 mcg of mitochondria at 1d, 3d or 5d after IRI significantly protected compared to vehicle treated mice after IRI [Day 14 PCr (0.6±0.04 (+1d) vs 0.68±0.18 (+3d) vs 0.57±0.18 (+5d) vs 1.54±0.16), p=0.01]. The mice treated with mitochondria 1d, 3d or even 5d after IRI had significantly less MT labeling compared to vehicle treated mice. The +1d or +3d mitochondria treated mice had significantly lower levels of kidney gene expression of Acta and Col3a1 and significantly higher PGC1α gene expression compared to vehicle treated mice at day 14.Transfer of labeled isolated mitochondria (mitotracker dye) signal was found in spleen (in macrophages) and kidney (in PT, identified with anti-CD13 antibody [labels brush border]).

*Conclusions: Our current study demonstrates that up take of healthy mitochondria by PT helps maintain bioenergetics through up-regulation of mitochondria biogenesis gene, PGC1α. Treatment to mice with established kidney injury with healthy mitochondria attenuates progression to fibrosis. Mitochondria could be used as a therapeutic modality to lessen progression to IFTA.

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