Name: a retrograde implantation approach for peritoneal dialysis catheter placement in mice
Uploaded: 2022-07-20T13:00:00
Description: Watch this Scientific Journal Video about A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice at JoVE.com

This work was supported by NIH 1R01HL132325 and R21 DK119740-01 (VCC) and AHA Cardio-oncology SFRN CAT-HD Center grant 857078 (VCC and SL).

For this study, eight female C57BL/6J mice, 8-12 weeks in age, and an average weight of 20 g were used. The mice were housed under standard conditions and were fed with chow and water ad libitum. This study was performed with the approval of the Institutional Animal Care and Use Committee (IACUC), Boston University Medical Center (AN-1549). The procedures described here were performed under sterile conditions.
1. Anesthetize the mouse in an Isoflurane chamber, and inject the ana...

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I., Sequeira, A., Narayan, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Going+home:+Access+for+home+modalities.">Going home: Access for home modalities.</a> Advances in Chronic Kidney Disease. 27 (3), 253-262 (2020).</li><li>van de Luijtgaarden, M. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trends+in+dialysis+modality+choice+and+related+patient+survival+in+the+ERA-EDTA+Registry+over+a+20-year+period.">Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period.</a> Nephrology Dialysis Transplantation. 31 (1), 120-128 (2016).</li><li>Schaefer, F., Warady, B. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peritoneal+dialysis+in+children+with+end-stage+renal+disease.">Peritoneal dialysis in children with end-stage renal disease.</a> Nature Reviews. Nephrology. 7 (11), 659-668 (2011).</li><li>Gonzalez-Mateo, G. T., Pascual-Anton, L., Sandoval, P., Aguilera Peralta, A., Lopez-Cabrera, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+techniques+for+catheter+placement+and+5/6+nephrectomy+in+murine+Models+of+Peritoneal+Dialysis.">Surgical techniques for catheter placement and 5/6 nephrectomy in murine Models of Peritoneal Dialysis.</a> Journal of Visualized Experiments: JoVE. (137), e56746 (2018).</li><li>Chow, K. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Straight+versus+coiled+peritoneal+dialysis+catheters:+A+randomized+controlled+trial.">Straight versus coiled peritoneal dialysis catheters: A randomized controlled trial.</a> American Journal of Kidney Diseases. 75 (1), 39-44 (2020).</li><li>LaPlant, M. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peritoneal+dialysis+catheter+placement,+outcomes+and+complications.">Peritoneal dialysis catheter placement, outcomes and complications.</a> Pediatric Surgery International. 34 (11), 1239-1244 (2018).</li><li>Al-Hwiesh, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+modified+peritoneal+dialysis+catheter+with+a+new+technique:+Farewell+to+catheter+migration.">A modified peritoneal dialysis catheter with a new technique: Farewell to catheter migration.</a> Saudi Journal of Kidney Diseases and Transplantation. 27 (2), 281-289 (2016).</li><li>Crabtree, J. H., Chow, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peritoneal+dialysis+catheter+insertion.">Peritoneal dialysis catheter insertion.</a> Seminars Nephrology. 37 (1), 17-29 (2017).</li><li>Flessner, M. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peritoneal+changes+after+exposure+to+sterile+solutions+by+catheter.">Peritoneal changes after exposure to sterile solutions by catheter.</a> Journal of the American Society of Nephrology. 18 (8), 2294-2302 (2007).</li><li>Kowalewska, P. M., Margetts, P. J., Fox-Robichaud, A. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peritoneal+dialysis+catheter+increases+leukocyte+recruitment+in+the+mouse+parietal+peritoneum+microcirculation+and+causes+Fibrosis.">Peritoneal dialysis catheter increases leukocyte recruitment in the mouse parietal peritoneum microcirculation and causes Fibrosis.</a> Peritonial Dialysis International: Journal of the International Society for Peritonial Dialysis. 36 (1), 7-15 (2016).</li><li>Kowalewska, P. M., Patrick, A. 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V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tryptophan+metabolites+suppress+Wnt+pathway+and+promote+adverse+limb+events+in+CKD+patients.">Tryptophan metabolites suppress Wnt pathway and promote adverse limb events in CKD patients.</a> The Journal of Clinical Investigation. 132 (1), (2021).</li><li>Belghasem, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metabolites+in+a+mouse+cancer+model+enhance+venous+thrombogenicity+through+the+aryl+hydrocarbon+receptor-tissue+factor+axis.">Metabolites in a mouse cancer model enhance venous thrombogenicity through the aryl hydrocarbon receptor-tissue factor axis.</a> Blood. 134 (26), 2399-2413 (2019).</li><li>Krediet, R. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+peritoneal+membrane+in+chronic+peritoneal+dialysis.">The peritoneal membrane in chronic peritoneal dialysis.</a> Kidney International. 55 (1), 341-356 (1999).</li><li>Gonzalez-Mateo, G. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+exposure+of+mouse+peritoneum+to+peritoneal+dialysis+fluid:+structural+and+functional+alterations+of+the+peritoneal+membrane.">Chronic exposure of mouse peritoneum to peritoneal dialysis fluid: structural and functional alterations of the peritoneal membrane.</a> Peritonial Dialysis International: Journal of the International Society for Peritonial Dialysis. 29 (2), 227-230 (2009).</li><li>Sukul, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-reported+advantages+and+disadvantages+of+peritoneal+dialysis:+results+from+the+PDOPPS.">Patient-reported advantages and disadvantages of peritoneal dialysis: results from the PDOPPS.</a> BMC Nephrology. 20 (1), 116 (2019).</li><li>Lu, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+method+for+islet+transplantation+to+the+omentum+in+mouse.">A method for islet transplantation to the omentum in mouse.</a> Journal of Visualized Experiments: JoVE. (143), e57160 (2019).</li><li>Gotloib, L., Wajsbrot, V., Shostak, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+short+review+of+experimental+peritoneal+sclerosis:+from+mice+to+men.">A short review of experimental peritoneal sclerosis: from mice to men.</a> The International Journal of Artificial Organs. 28 (2), 97-104 (2005).</li><li>Tateda, K., Matsumoto, T., Miyazaki, S., Yamaguchi, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lipopolysaccharide-induced+lethality+and+cytokine+production+in+aged+mice.">Lipopolysaccharide-induced lethality and cytokine production in aged mice.</a> Infection and Immunity. 64 (3), 769-774 (1996).</li><li>Vila Cuenca, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+in+peritoneal+response+after+exposure+to+low-GDP+bicarbonate/lactate-buffered+dialysis+solution+compared+to+conventional+dialysis+solution+in+a+uremic+mouse+model.">Differences in peritoneal response after exposure to low-GDP bicarbonate/lactate-buffered dialysis solution compared to conventional dialysis solution in a uremic mouse model.</a> International Urology and Nephrology. 50 (6), 1151-1161 (2018).</li><li>Penar, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selected+indices+of+peritoneal+fibrosis+in+patients+undergoing+peritoneal+dialysis.">Selected indices of peritoneal fibrosis in patients undergoing peritoneal dialysis.</a> Postepy Higieny Medycyny Doswiadczalnej (Online). 63, 200-204 (2009).</li><li>Yung, S., Chan, T. 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Three murine models of PD are described. This includes a blind puncture of the peritoneal surface, an open-permanent system, and a closed system10. The blind puncture of the peritoneal surface involves direct peritoneal access similar to intraperitoneal injections but does not allow drainage of dialysate. Being a blinded procedure, this method can injure the abdominal visceral organs. The open-permanent system model keeps the dialysis catheter and instillation port outside the body. However, this ...

An erratum was issued for:&#160;<a href="https://www.jove.com/t/63689">A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice</a>. The Authors section was updated from:
Saran Lotfollahzadeh1 
Mengwei Zhang1 
Marc Arthur Napoleon1 
Wenqing Yin1 
Josephine Orrick1 
Nagla Elzind1 
Austin Morrissey1 
Isaac E. Sellinger1 
Lauren D. Stern1 
Mostafa Belghasem2 
Jean M. Francis1 
Vipul C. Chitalia1,3,4 
1Renal Section, Department of Medicine, Boston University School of Medicine 
2Department of Biomedical Science, Kaiser Permanente Bernard J. Tyson School of Medicine 
3Veterans Affairs Boston Healthcare System 
4Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology
to:
Saran Lotfollahzadeh1 
Mengwei Zhang1 
Marc Arthur Napoleon1 
Wenqing Yin1 
Josephine Orrick1 
Nagla Elzind1 
Austin Morrissey1 
Isaac E. Sellinger1 
Lauren D. Stern1 
Mostafa Belghasem2 
Jean M. Francis1 
Vipul C. Chitalia1,3,4 
1Renal Section, Department of Medicine, Boston University Aram V. Chobanian &#38; Edward Avedisian School of Medicine 
2Department of Biomedical Science, Kaiser Permanente Bernard J. Tyson School of Medicine 
3Veterans Affairs Boston Healthcare System 
4Institute of Medical Engineering and Sciences, Massachusetts Institute of Technology

An erratum was issued for:&#160;<a href="https://www.jove.com/t/63689">A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice</a>. The Authors section was updated.

Erratum: A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice

End-stage renal disease burden 
Chronic kidney disease (CKD) is a worldwide health problem1. Current estimates suggest that more than 850 million people worldwide have kidney disease. The prevalence of kidney disease almost doubles the number of people with diabetes (422 million) and is more than 20 times the prevalence of cancer (42 million) or HIV/AIDS (36.7 million) patients worldwide2. Approximately one in seven Americans have CKD, and two in 1,000 Americans have ESKD requiring a kidney transplant or dialysis support3. Considering the escalating burden of ESKD worldwide, optimizing dialysis technology is crucial3.
Peritoneal dialysis 
PD is a significantly underutilized modality for the treatment of ESKD in the United States. According to the United States Renal Data System (USRDS), the percentage of prevalent PD patients was only 11% in 20204,5. PD confers several advantages over in-center hemodialysis (HD), including a better quality of life, fewer clinic visits, and a decrease in Medicare expenditures6,7. Additionally, PD is a home-based therapy and is associated with a much lower risk of severe infections such as bacteremia and endocarditis that are often related to hemodialysis catheters. Furthermore, PD can be initiated rapidly with an urgent start protocol, decreasing the need for dialysis initiation with indwelling vascular catheters8. PD is considered the preferred method of dialysis in the pediatric ESKD population9.
Peritoneal impairment induced by peritoneal dialysis 
PD entails introducing PD fluid (dialysate) into the peritoneum, which results in inflammation and remodeling of the peritoneal membrane over time. Peritoneal inflammation triggers fibrosis, culminating in the potential loss of ultrafiltration capabilities of the membrane over time. Preservation of the peritoneal membrane is a significant challenge in PD, and further research is critically important to ensure that best clinical practices are available to practitioners. There are well-established murine models to help further the understanding of pathophysiological mechanisms of peritoneal infection and inflammation, solute, water transport kinetics, and membrane failure; still, technical issues with the catheter often limit these models10.
Analyzing the peritoneal membrane changes 
In ESKD patients, dialysate is traditionally introduced in the peritoneal cavity through a Tenkhoff catheter with a deep and superficial cuff. The patients can potentially experience catheter-related complications, including catheter migration, infusion pain, and poor drainage of the dialysate11,12,13. Two major types of peritoneal catheters have been introduced for humans, coiled or straight, to minimize these complications12. Several modifications, including an extra cuff to the conventional two-cuffed catheters, have been added to the original catheters to prolong PD catheter survival11. The insertion technique varies according to several factors by preventing catheter migration to be added after survival, including the availability of the resources and the level of expertise14.
In contrast, the murine models of peritoneal dialysis have fundamental differences in techniques and purpose compared to human peritoneal catheters. For example, peritoneal catheters in murine models are used primarily to study membrane alterations and are less intended for bidirectional drainage functions. The current technique suffers from potential port dislodgement and catheter migration due to the handling of the animals. In the conventional murine models, the access ports were not fixed to the skin. This aspect created an unstable access port, which in awake animals might get dislodged, resulting in catheter migration. Given the importance of murine models in peritoneal membrane research, it is imperative to create effective surgical techniques to generate reliable models. Therefore,&#160;we set out to optimize the conventional model of PD catheter placement. It is important to note that the catheter itself causes histopathologic alterations in the peritoneal membrane, and, thus, any conclusions regarding the effect of PD solutions in animal studies must be interpreted in the context of the PD catheter as a foreign body15,16,17.
Peritoneal membrane histopathology 
PD failure is mainly related to fibrosis and excess angiogenesis resulting in the loss of an osmolar concentration gradient. In addition, the peritoneal membrane filtration capacity might be affected by peritonitis. In addition, infectious peritonitis is a well-established cause for change in the dialysis modality from peritoneal dialysis to hemodialysis.18.

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			<td>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Isoflurane, USP</td>
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			<td>&#160;&#160;&#160;&#160;&#160;&#160; Lipopolysaccharide from E.coli</td>
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			<td>Vicryl Suture</td>
			<td>AD-Surgical</td>
			<td>#L-G330R24</td>
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a retrograde implantation approach for peritoneal dialysis catheter placement in mice

Murine models are employed to probe various aspects of peritoneal dialysis (PD), such as peritoneal inflammation and fibrosis. These events drive peritoneal membrane failure in humans, which remains an area of intense investigation due to its profound clinical implications in managing patients with end-stage kidney disease (ESKD). Despite the clinical importance of PD and its related complications, current experimental murine models suffer from key technical challenges that compromise the models&#39; performance. These include PD catheter migration and kinking and usually warrant earlier catheter removal. These limitations also drive the need for a greater number of animals to complete a study. Addressing these drawbacks, this study introduces technical improvements and surgical nuances to prevent commonly observed PD catheter complications in a murine model. Moreover, this modified model is validated by inducing peritoneal inflammation and fibrosis using lipopolysaccharide injections. In essence, this paper describes an improved method to create an experimental model of PD.

All the implanted catheters were functional till the end of the study, and catheter dislodgement or kinking did not complicate any of the implanted catheters. The current, modified technique was further validated with a peritonitis-induced model using LPS. The control mice received 200 &#181;L of daily normal saline injections, while the experimental mice were injected with 200 &#181;L of LPS, as discussed in protocol step 11, for a total of 7 days following catheter implantation.
The peritone...

Watch this Scientific Journal Video about A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice at JoVE.com

A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice

This article describes modifications of a procedure to implant a peritoneal dialysis catheter in a murine model to avoid major technical issues observed with the conventional techniques.

Murine models are employed to probe various aspects of peritoneal dialysis (PD), such as peritoneal inflammation and fibrosis. These events drive ...

The previous protocols for mouse models of peritoneal dialysis suffer from limitations precluding their long-term use. These limitations, such as catheter coiling and dislodgement, are addressed in this study. This technique prevents PD catheter malfunction for mechanical reasons, allowing their use for a longer time to study pathologies, such as peritoneal fibrosis.This technique will provide a better mouse model to probe molecular pathogenesis and novel therapeutics of peritoneal fibrosis. A key limitation of PD in humans. PD is the mainstay of renal replacement therapy in pediatric patients with ESKD.This optimized model will provide a better test bed to investigate all the issues with PD in humans. Generation of an animal model has a learning curve. This step-by-step video will assist an individual in implementing this technique to generate a durable model for peritoneal dialysis successfully.To begin place the fully anesthetized eight to 12 weeks old C57 black/6J mouse in a left lateral position. After shaving the mouse as specified in the manuscript, disinfect the surgical area by exposing the right flank of the mouse to the heating blanket. Then place the sterile surgical drape over the mouse.Assign the access port pocket one centimeter above the mouse tail. Hold the installation segment with the non-dominant index and thumb finger over the assigned area near the tail. Place the catheter above the skin, and estimate the place for the catheter's tube insertion within the abdominal cavity.Then mark the assigned place for tube insertion, respecting the minimal bending of the tube near the anterior midline. Punch a side hole over the frame of the reservoir section with the mouse ear tagger. Make a horizontal one centimeter wide skin incision one centimeter above the tail.Then bluntly dissect the subcutaneous plane from the underlying muscular layer to make a pouch for the catheter placement to ensure the installation port freely resides in the ideal port pocket. Past the 3-0 suture from the customized side hole. Fix the access port to the muscular bed by tightening the passed suture, keeping the tubing course cephalad.Make a one centimeter incision over the formally marked area near the midline. Place a loose purse string suture with 4-0 round absorbable suture around the incised abdominal wall muscle. Make a one centimeter incision over the muscular layer close to the right midline and pass the proximal felt of the catheter inside the incision.Pass the catheter tube through the prepared tract. Tighten the prepared purse string suture around the tube, while keeping the second felt outside the purse string over the muscular layer, and close the skin with 3-0 absorbable sutures. Ensure that the placed catheter is functional.Check the function with a one milliliter syringe attached to the specific Huber needle for the port. Inject normal saline into the installation port. After confirming a smooth flow with a zero tolerance for resistance, close the skin incisions around the port reservoir with 3-0 absorbable sutures.Enter the port with the Huber needle and inject 100 microliters of normal saline into the port to confirm the patent course. Then inject 200 microliters of lipopolysaccharide, followed by 100 microliters of saline for tube irrigation and ensure that there is no resistance. After seven days of LPS injections and two weeks of catheter implantation, plan for the peritoneal biopsy.After confirming successful anesthesia, make a midline skin incision from bladder to sub xiphoid. Then perfuse the subfascial plane with cold PBS. Make sure the plane is completely dissected without disturbing the integrity of the peritoneum.Analysis of the hematoxylin and eosin stained sections showed a substantial increase in the extracellular matrix, or ECM, in the subperitoneal space. The average ECM in the sub peritoneal space of the control mice was half of that in the LPS exposed mice. The Masson's Trichrome staining detects fibrosis, measured as intensity density normalized to the surface area.Altered vascularity and widening of the subperitoneal space were analyzed using endothelial cell marker CD31, and measured as integrated density in randomly selected high-power field images. Compared to the control, LPS-induced mice showed a threefold increase in subperitoneal fibrosis, approximately eight to ninefold increase in the vascularity, and a twofold increase in the subperitoneal space, marked as SP, were observed. Place the catheter above the skin and mark the point for the catheter insertion, while avoiding the bending of the tube.The insertion should be near the interior midline. Providing the more durable murine PD catheter placement method will allow the researchers to design and execute longer term experiments to probe and target peritoneal membrane failure.

Research

JoVE Journal

Medicine

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