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. Author manuscript; available in PMC: 2018 Oct 1.
Published in final edited form as: Nat Rev Nephrol. 2017 Aug 14;13(10):629–646. doi: 10.1038/nrneph.2017.107

Table 1.

Approaches to correct abnormal mitochondrial function in AKI and diabetic nephropathy

Agent Mechanism of action In vivo and clinical studies*
Acute kidney injury
AICAR (an AMPK activator)

  • Increases AMPK activation

  • Increases crosstalk between SIRT3 and AMPK

  • AICAR administration attenuated decreased serum creatinine and urea levels in Sprague–Dawley rats with IRI (2012)200

  • AICAR attenuated BUN and serum creatinine levels in cisplatin-treated mice (2015)206
Formoterol (a β2AR agonist) Binds to β2AR and induces mitochondrial biogenesis Formoterol restored mitochondrial and renal function in mice with IRI within 6 days (2014)174
LY344864 (a 5-HT1F receptor agonist) Binds to 5-HT1F and induces mitochondrial biogenesis LY344864 restores renal function in mice with IRI within 6 days (2014)175
Elamipretide (a Szeto–Schiller peptide (specifically SS-31)) Prevents the peroxidation of cardiolipin by cytochrome c

  • Enhances efficiency of the ETC and prevents mitochondrial swelling in rats (2014)218

  • Phase I study (NCT02436447) in patients with impaired renal function (2015)221
Diabetic nephropathy
AICAR (an AMPK activator) Increases glucose utilization AICAR decreased blood glucose levels in db/db diabetic mice and ob/ob obese mice (2002)228
Fenofibrate (a PPARα agonist)

  • Decreases hyperglycaemia

  • Increases free fatty acids by targeting lipase

  • Decreases dyslipidaemia and albuminuria

  • Corrected glucose homeostasis in db/db diabetic mice (2006)213

  • Decreased serum creatinine levels and had a renoprotective role for diabetic nephropathy in diabetic rats (2016)215

  • Administrating fenofibrate to patients with type 2 diabetes mellitus decreased cardiovascular disease events (2005)229

5-HT1F, 5-hydroxytryptamine receptor 1F; β2AR, β2 adrenergic receptor; AICAR, 5-aminoimidazole-4-carboxamide-1-β-D-riboside; AKI, acute kidney injury; AMPK, AMP-activated protein kinase; BUN, blood urea nitrogen; ETC, electron transport chain; IRI, ischaemia–reperfusion injury; PPARα, peroxisome proliferator-activated receptor-α; SIRT3, sirtuin 3.

*

The year of the clinical study is given in parentheses.