A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Summary

This manuscript provides a detailed two-step surgical procedure to perform mouse 5/6^th partial nephrectomy (PNx) with pole ligation. Four weeks after surgery, in comparison with sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.

Abstract

Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy". We describe here an experimental CKD mouse model, named 5/6^th partial nephrectomy (PNx) with pole ligation, which developed uremic cardiomyopathy at four weeks post-surgery. This PNx model was performed by a two-step surgery. In step-one surgery, both poles of the left kidney were ligated. In step-two surgery, which was performed 7 days after the step-one surgery, the right kidney was removed. For the sham surgery, the same surgery procedures were performed but without pole ligation of the left kidney or removal of the right kidney. The surgical procedures are easier and less time-consuming, compared to other methods. However, the remnant functional renal mass is not as easily controlled as the renal artery ligation. Four weeks after surgery, in comparison with the sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.

Introduction

CKD, also known as chronic renal failure, is a progressive loss of kidney function over time that eventually develops into permanent kidney failure. CKD, from early stage renal disease states to end-stage renal disease (ESRD), is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy"^1,2,3. The uremic cardiomyopathy in patients with CKD or ESRD is associated with cardiovascular abnormalities, mainly caused by overload of left ventricular (LV) pressure and/or volume, leadin....

Protocol

All animal care and experiments were approved by the Marshall University Institutional Animal Care and Use Committee (IACUC) in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Male C57BL/6 mice (10-12 weeks old) were housed in a pathogen free animal facility in designated rooms equipped with cages that supply purified air under a 12 h light/dark cycle. Food and water were supplied ad libitum.

1. Surgery Preparation

NOTE: The surgical instruments and materials are obtained from different sources that are not specific to surgery operations. Instrument....

Results

The data indicated that this modified 5/6^th PNx model by pole ligation is a simple and effective model to investigate uremic cardiomyopathy. At four weeks post-surgery, this PNx model presents impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function. The results are summarized below.

At four weeks post-surgery, the PNx mice developed i.......

Discussion

The rat 5/6^th PNx model has been widely used to study CKD. Because of the much smaller kidney size in mouse, the classical artery ligation and pole resection are very challenging in mouse models with possible high mortality rates and unexpected bleeding/blood loss.

We adopted a mouse PNx model with pole ligation to overcome the bleeding/blood loss. This PNx model takes less time with improved survival rate and high reproducibility. This pole ligation model develops the phenotypic ch.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Iris Scissors, 11.5 cm, Straight	World Precision Instruments	501758
WPI Swiss Tweezers #5 11 cm, 0.1x0.06 mm Tips	World Precision Instruments	504506
Jewelers #5 Forceps, 11cm, Straight, Titanium	World Precision Instruments	555227F
Iris Forceps, 10cm, Straight, Serrated	World Precision Instruments	15914
Tweezers #3, 11cm, 0.2x0.4mm Tips	World Precision Instruments	501976
Medesy Iris 4.5" Curved Scissors, Stainless Steel	Net23	3512	www.Net32.com
Dr. Slick Iris Scissors; 3.5"	Avid Max	220-1-965-IrisScsrs-P	www.Avid Max.com
Miltex Iris Scissors 4 1/8" Curved	4mdmedical	V95-306	www.4mdmedical.com
5" Hemostat clap, curved jaw	PJTool	4355	www.pjtool.com
sklar Knapp Iris scissors, straight and sharp/blunt 4"	Medical Device depot	64-3430	www.medicaldevicedepot.com
Kelly Hemostatic Forceps straight 5.5"	Pilgtimmedical	FA710-50	www.pilgtimmedical.com
C57BL/6 mice	Hilltop Lab Animals Inc.
Mouse Handling Table and rectal thermometer	Visualsonics
MicroScan transducer	Vevo 1100	MS400
Vevo 1100 Imaging System	FUJIFILM VisualSonics Inc.
Cystatin C ELISA kit and mouse creatinine kit	Crystal Chem. Inc.
Mouse BUN ELISA kit	MyBioSource Inc