Mitochondrial enzymes infused into the kidney under hydrodynamic pressures significantly improves creatinine and BUN levels at the onset of moderate and severe acute kidney injuries

ABSTRACT

Introduction: The COVID-19 pandemic has highlighted the need to address how renal insults are treated. There is an urgent need to better understand the complex relationship between infections and kidney disease and develop safe and effective approaches that can be translated to the clinic. Hydrodynamic fluid delivery has shown promise in influencing renal function in disease models. This technique previously provided preconditioned protection in acute injury models by upregulating the mitochondrial adaptation, while hydrodynamic injections of saline alone have also improved microvascular perfusion. Accordingly, hydrodynamic mitochondrial gene delivery was applied to investigate its ability to halt renal impairment that may occur following episodes of acute moderate and severe injuries in a rat model. Methods: Transgene infusates were prepared by suspending approximately 2 μg of IDH2 (isocitrate dehydrogenase 2 (NADP+) and mitochondrial) plasmid DNA/g of body weight in 0.5 ml of saline. Animals were subjected to moderate (bilateral pedicle clamp 30 mins) or severe (bilateral pedicle clamp 60 mins) forms of ischemia-reperfusion injury (IRI). Infusates were delivered directly into the left renal vein within 5 seconds, roughly 1 hour after IRI was established. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were monitored for 2 weeks. Results: Significant reductions in the levels of both metabolites (p < 0.05 for both cases) were achieved with single transgene treatments administered at both time points. Specifically, the maximal rises in SCr and BUN levels were reduced by at least 50%, which translated the effects of a severe injury to a moderate injury and a moderate injury to a mild injury. Conclusions: Therefore, this study identifies an approach that boosts recovery and halts the progression of ischemia-reperfusion at its inception and can be vital for high-risk conditions and may help devise translation models to address the rising incidence of acute renal diseases. No conflict of interest