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March 18, 2015PLoS ONEOpen Access

Short-Term Treatment with Diminazene Aceturate Ameliorates the Reduction in Kidney ACE2 Activity in Rats with Subtotal Nephrectomy

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Key result

In rats with subtotal nephrectomy, 2 weeks of diminazene aceturate treatment significantly increased cortical ACE2 mRNA and activity (P<0.05) but did not improve blood pressure or kidney function.

Why the study?

Does diminazene aceturate improve kidney ACE2 activity in rats with subtotal nephrectomy?

Population

Sprague Dawley rats with kidney injury due to subtotal nephrectomy (STNx) and Control rats

Comparison

Diminazene aceturate subcutaneous 15 mg/kg/day… vs Vehicle

Design

Preclinical

Follow-up

2 weeks

Authors

EVElena VelkoskaCSL (Australia)SPSheila K. PatelThe University of MelbourneKGKaren GriggsLa Trobe University

Discussion

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Implication

DIZE effects on renal ACE2 in STNx rats remain hypothesis-generating; human studies needed before any translational consideration.

Structured PICO

Does diminazene aceturate improve kidney ACE2 activity in rats with subtotal nephrectomy?

P
Population
38 female Sprague Dawley rats subjected to subtotal nephrectomy or sham operation, treated with diminazene aceturate or vehicle for 2 weeks.
I
Intervention
Diminazene aceturate (DIZE) subcutaneous 15 mg/kg/day for 2 weeks
C
Comparator
Vehicle
O
Outcome
Kidney ACE2 mRNA and activitysurrogate

Main Result

Absolute Event Rate: 1% vs 0.4%

p-value: p=<0.05

In a rat model of subtotal nephrectomy, short-term diminazene aceturate treatment restored kidney ACE2 activity and mRNA levels but did not improve blood pressure or renal function.

Limitations

  • The precise in vivo mechanism of action of DIZE is not clear, as ex vivo studies showed no direct increase in ACE2 activity.
  • It is not yet known if chronic administration of DIZE has long-term benefits to slow the progression of kidney disease.
  • Animal model findings may not directly translate to human clinical outcomes.
  • Precise in vivo mechanism of action is not clear
  • Unknown if chronic administration has long-term benefits to slow progression of kidney disease

Cite This Study

Velkoska et al. (2015) studied Subtotal nephrectomy (kidney injury) (n=38). Diminazene aceturate (DIZE) vs. Vehicle was evaluated on Cortical ACE2 mRNA (AU) (p=<0.05). In rats with subtotal nephrectomy, 2 weeks of diminazene aceturate treatment significantly increased cortical ACE2 mRNA and activity (P<0.05) but did not improve blood pressure or kidney function.

synapsesocial.com/papers/6a5bbc8e9b5d0f06daf79c70https://doi.org/10.1371/journal.pone.0118758
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Also Consider

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