Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice

Summary

The ischemia-reperfusion injury (IRI) model can be used at different stages of acute kidney injury (AKI) development, especially during AKI to chronic kidney disease (CKD) progression. Here, we describe the procedure for IRI model development in mice via a trans-abdominal approach, clamping renal pedicles via a vascular clip to induce ischemic injury.

Abstract

Acute kidney injury (AKI) is defined as a rapid decline in renal function, in which persistent kidney dysfunction gradually progresses to chronic kidney disease (CKD) due to the irreversible loss of nephrons and their maladaptive repair. In recent years, the incidence of AKI has been increasing concerning diverse etiologies, including volume depletion, sepsis, nephrotoxicity, muscle injury, and major trauma, in which ischemia-reperfusion injury (IRI) accounts for most episodes. Development of the IRI model in mice is induced by surgical clamping of the renal pedicles, which provides powerful and controllable tools for preclinical models of AKI. Importantly, the IRI model is deployed at different stages of the AKI development, especially in the processes of AKI to CKD. Despite the IRI model being widely practiced in many laboratories, a series of variables still influence the results of this model. Here, we describe the procedure of IRI model development to provide a repeatable and reliable method for researchers to explore the underlying pathogenesis in the development of AKI and the progression of AKI to CKD.

Introduction

Acute kidney injury (AKI) is a severe clinical syndrome with significant morbidity and mortality, defined as an increase in serum creatinine of ≥ 0.3 mg/dL (26.5 µM/L) within 48 h or an increase in serum creatinine to ≥ 1.5 times baseline within 7 days, or urine volume < 0.5 mL/kg/h for 6 h^1,2,3. Despite decades of research, effective therapy for AKI is lacking to alleviate kidney damage or accelerate kidney recovery, and a considerable proportion of AKI patients progress to chronic kidney disease (CKD)^4,

Protocol

Male C57BL/6J mice at 8 weeks of age and weighing 25 g were used to establish the AKI model by bilateral ischemia-reperfusion. As per previous studies, we maintain the body temperature at around 36.5 °C-37 °C, and the kidney ischemia duration is 30 min in the IRI surgery^12,13. A total of 6 mice were needed for each group, and sham-operated mice served as controls. The animal experiments in this study have been approved by the Institutional Animal Care a.......

Discussion

In this paper, we have provided a detailed procedure on the renal IRI model, subsequently highlighting that it is a robust model for the progression of AKI and AKI to CKD. In addition, we demonstrate the impact of the two main criteria of kidney injury, including kidney histology and function.

Several key points in surgical procedures need to be emphasized for a repeatable and reliable model. For abdominal surgery, a midline incision is recommended to expose the kidney to minimize trauma assoc.......

Materials

Name	Company	Catalog Number	Comments
Animal hair clipper	FEIYUBIO	19-7002
1-ml syringes	Longreen	SR60061
Ethanol	Macklin	E885996
Gauze	FEIYUBIO	19-5022
Homeothermic monitor system	Warmmate	40 x 50
Needle holder	DKBT	CZQ-00160
Spreader	RWD	R22029-03
Sterile saline	Biosharp	BL158A
Tissue scissors	DKBT	DC-YKJ1002
Tissue tweezers	DKBT	DK079904
Vascular clip	Fine Science Tools	18055-02
Vicryl suture	Shanghai Jinhuan	4 -0