Mouse Renal Artery Catheterization for Local Delivery of Drugs in Capsulated or Free Forms

Background

Arterial delivery of drugs to the kidneys in free and encapsulated forms has enormous potential to increase local drug concentrations and reduce the side effects of therapy on other organs. The choice of therapy parameters (active substance, pharmaceutical form, dosage regimen, volume, etc.), as well as understanding drug accumulation and retention in the kidneys during arterial delivery, requires a wide range of complex studies on animals. In this regard, small laboratory animals, especially mice, are the most attractive and economical.

The success of the study directly depends on the correctness of the arterial delivery procedure, which is especially difficult for mice due to their small size. Incorrectly performed injections in the renal artery could disrupt the kidney blood supply and lead to tissue damage. The vast majority of drug delivery protocols through the renal artery are based on ligation and direct injection into the abdominal aorta [1]. Chen et al. reported that direct injection of the rAAV2-GFP vector into the rat abdominal aorta using 45 min ligation of renal vein and abdominal aorta led not only to successful transfection of tubular epithelial cells but also to focal areas of chronic interstitial infiltration with mononuclear cells, tubular atrophy, and scar formation [2]. Authors suggested that these changes are most likely the result of ischemic injury inherent in the procedure and not a consequence of recombinant adeno-associated viral vector administration or an adverse immune response to it or the transgene. A similar protocol for mice with short-term occlusion (several minutes) and puncture of the abdominal aorta was presented by Dahlqvist et al. [3]. Zaw Thin et al. developed a percutaneous minimally invasive ultrasound-guided renal artery injection to enhance cell delivery to mice kidneys [4]. This procedure appears to be less invasive (only puncture of muscles and skin with a syringe) than the others but requires a special ultrasound imaging system. In addition, in this protocol, the renal artery wall is punctured with a 29-gauge needle (0.33 mm diameter). Note that the diameter of the mouse renal artery is in the range of 0.3–0.4 mm [5], which determines a high risk of significant blood loss after injection without the ability to stop bleeding. At the same time, the authors reported 70% success.

In our protocol, we describe the catheterization of the mouse renal artery by inserting a thin catheter into a small puncture in the femoral artery and then approaching the left renal artery through the abdominal aorta [6–8]. This protocol is similar to the standard clinical approach [9–11]. It does not require blockade of the target kidney blood flow, disruption of the integrity, and ligation of the renal artery or abdominal aorta, unlike other described methods [1–4, 12, 13]. This protocol requires microsurgery skills but can be extremely useful for studies in which maintaining a normal blood supply to the target kidney as well as vascular integrity is critical.