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Kidney Week

Abstract: TH-PO024

Treatment with Isolated Mitochondria 5 Days After Kidney Ischemia-Reperfusion Injury Reduces Progression to Interstitial Fibrosis and Tubular Atrophy

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Rousselle, Thomas V., UTHSC, Memphis, Tennessee, United States
  • Mas, Valeria, Transplant Research Institute, Memphis, Tennessee, United States
  • Bajwa, Amandeep, UTHSC, Memphis, Tennessee, United States

Ischemia induces altered bioenergetics with increased mitochondrial swelling, reactive oxygen species 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 treatment of disease.


Renal injury was assessed by plasma creatinine (PCr; mg/dl). 8-wk old C57BL/6 mice were i.v. injected with healthy isolated mitochondria (2.5 mcg/g) 1, 3 or 5 days after unilateral IRI. Nephrectomy of contralateral control kidney was done 1 day prior to euthanizing mice. Change in fibrosis genes were measured and histological changes with Masson trichrome. For in vitro studies, TKPTS were treated with mitochondria (10-50 mcg/ml) 1 day prior to analysis that included measurement of ATP levels, mitochondrial functions (Seahorse), cytokines (RTPCR), and IF microscopy.


In vivo studies demonstrated treatment of mice with 2.5 mcg/g of mitochondria at 1, 3 or 5 days after IRI significantly protected the IRI kidney compared to vehicle treated mice [PCr (0.60±0.04 (+1d) vs 0.54±0.18 (+3d) vs 0.46±0.18 (+5d) vs 1.24±0.2), p<0.05]. The mice treated with mitochondria 1d, 3d or 5d after IRI had significantly less MT labeling compared to vehicle treated mice. The injected mitochondria is found in kidney in proximal tubule cells (anti-CD13 labeled) and co-localizes with endogenous mitochondria. The mitochondria treated mice had significantly lower levels of fibrosis genes (Acta and Col3a1) and significantly higher PGC1α compared to vehicle treated mice. The mitochondria treated mice had significantly higher populations of Ki67 positive cells in both IRI and contralateral control kidneys compared to vehicle. Treatment of TKPTS cells with mitochondria have significantly higher levels of ATP, higher basal oxygen consumption rate and spare respiratory capacity. Similar to IRI studies, addition of mitochondria on TKPTS significant increases PGC1α gene expression, mtDNA/nDNA ratio, and induces proliferation.


Transfer of healthy mitochondria help maintain bioenergetics through upregulation of PGC1α and induced regeneration of PT cells to lessen progression to fibrosis after IRI. Treatment with healthy mitochondria could be used as a therapeutic modality to lessen progression to IFTA.


  • NIDDK Support