Ureteral stents: new ideas, new designs

Abstract

Ureteral stents represent a minimally invasive alternative to preserve urinary drainage whenever ureteral patency is deteriorated or is under a significant risk to be occluded due to extrinsic or intrinsic etiologies. The ideal stent that would combine perfect long-term efficacy with no stent-related morbidity is still lacking and stent usage is associated with several adverse effects that limit its value as a tool for long-term urinary drainage. Several new ideas on stent design, composition material and stent coating currently under evaluation, foreseen to eliminate the aforementioned drawbacks of ureteral stent usage. In this article we review the currently applied novel ideas and new designs of ureteral stents. Moreover, we evaluate potential future prospects of ureteral stent development adopted mostly by the pioneering cardiovascular stent industry, focusing, however, on the differences between ureteral and endothelial tissue.

Introduction

Since 1978, when the double-J stent and the single-pigtail stent were introduced by Finney and Hepperlen and colleagues to the urological society, ureteral stent usage has become a routine practice for every urologist [Finney, 1978, Hepperlen et al. 1978]. Over the course of time, many improvements on ureteral stent design and composition material have taken place in an attempt to improve the efficacy of the stents. Nevertheless, ureteral stent usage is associated with several adverse effects that limit its value as a tool for long-term urinary drainage. Stent infection, encrustation or migration, hyperplastic urothelial reaction and patient’s discomfort are the most common stent-related problems [Dyer et al. 2002]. Consequently, the ideal stent that would combine perfect long-term efficacy with no stent-related morbidity is still under investigation. In this article we review the recent advances in the evolution of the ureteral stent as well as potential future prospects adopted in the rapidly evolving cardiovascular stent development.

Ideal ureteral metal stent

The ideal ureteral stent has not yet been designed. Nevertheless, several authors have outlined its characteristics very well. The perfect ureteral stent should demonstrate optimal flow characteristics and should be well tolerated by the patient. Biocompatibility, radiopacity, visibility on ultrasound, ease of insertion and removal are also important features. Moreover, resistance to infection, corrosion and encrustation are characteristics that are crucial for long-term ureteral patency. A stent providing long-term ureteral patency and combining the above features represents the ultimate goal of urological stent research [Liatsikos et al. 2009; Dyer et al. 2002].

Future trends in ureteral stents

The continuous research for the creation of the ideal stent includes developments in several features such as stent design, composition material and stent coating. Despite the incorporation of several novel developments of these features on the same stent, we describe the evolution of each feature separately for reasons of discrimination.

Stent design

Ureteral metal mesh stents represent a promising application of vascular mesh stents to urology aiming to provide ureteral drainage in challenging cases where the conventional double-pigtail stents have failed (Figure 1). Mesh stents are composed of a very delicate metal mesh structure that supports the integrity of the tubular structure of the stented ureter, while allowing lateral flexibility to permit safe stent placement and some kind of postplacement ureteral movement. Moreover, having numerous holes on their body, mesh stents protect the stented epithelium from strangulation and ischemia and minimize irritative symptoms [Olweny et al. 2000]. Further advances in mesh stent design and construction can give additional favorable characteristics to these stents. Taking examples from the use of mesh stents in the cardiovascular system, the intra-struts wells on the Conor Medsystems stent act as drug reservoirs for the creation of drug-eluting stents (DESs) [Kukreja et al. 2008], while the XTENT custom NX allows in-vivo customization of the stent length [Wilkes Evans et al. 2007].

Figure 1.

Stented ureter with multiple metal mesh stents. The patient was suffering from extensive retroperitoneal metastasis of malignant disease.

Tail stents (Microvasive Urology/Boston Scientific) and dual durometer stents (Sof-Curl/ACMI and the Polaris/Microvasive Urology–Boston Scientific) are stents incorporating other novel design characteristics. In order to decrease ureteral stent-related bladder irritability, the tail stent incorporates a tapered straight distal tail that resides in the bladder. Dual durometer stents incorporate a transition from a firm biomaterial at the renal end to a soft biomaterial or a fine loop at the bladder end, in an attempt to facilitate stent placement, reduce migration and minimize patient discomfort due to bladder irritation. Promising results have been reported for both novel designs [Lingeman et al. 2009; Lam and Gupta, 2004; Liatsikos et al. 2002; Dunn et al. 2000].

Vesicoureteral reflux due to ureteral stent placement is considered to be one of the implicated factors contributing to stent-related patient discomfort. In an attempt to diminish the aforementioned morbidity an antireflux membrane has been incorporated into ureteral stents. In a study enrolling 133 double-J ureteral stents with and without antireflux membrane, antireflux stents demonstrated a lower complication rate and provided higher patient comfort compared with stents without this valve [Ecke et al. 2010].

Dual lumen ureteral stents have been introduced to replace the simultaneous insertion of two ipsilateral stents in cases where a single stent’s ureteral flow is not satisfactory [Hafron et al. 2006]. Clinical evaluation of this novel idea is awaited. In addition, good results have been published with horn-shaped stents used for the stenting of ureteropelvic junction [Talja et al. 2002]. Finally, an old idea from 1989 is being revisited for the possible incorporation in future stent designs: the presence of magnetic materials in ureteral stents. By this approach, stent removal can be performed via minimally invasive techniques using a magnet on a special retrieval catheter. Magnetip (ACMI [Surgitek], Racine, WI) is a magnetic-material-tipped ureteral stent that can be retrieved without the need for cystoscopy using the aforementioned concept [Taylor and McDougall, 2002; Macaluso et al. 1989].

At this point, we have to emphasize that future trends in ureteral stent design do not necessarily involve totally novel ideas. Several currently available stent designs, including the common double-J polymeric stent, the full metal double-J stent (Resonance stent, Cook Ireland, Limerick, Ireland; see Figure 2) or the thermoexpandable shape memory stents (Memokath 051, Engineers & Doctors A/S, Copenhagen, Denmark) have already demonstrated quite promising results [Liatsikos et al. 2010; Agrawal et al. 2009; Kulkarni and Bellamy, 2001]. Their current efficacy is good but not ideal. Combining of their tested effective design with future developments in composition materials and/or stent coatings, as described in the following, can create totally new stents with enhanced long-term efficiency.

Figure 2.

The lower pigtail end of a full metal double-pigtail resonance stent. Note the unique spiral metal structure of the stent which provides adequate resistance to external tension.

Composition materials

The gold standard of composition material in the case of ureteral stents is polymeric compounds, including silicone, polyurethane Siliteck, C-Flex, Percuflex, Tecoflex and others [Venkatesan et al. 2010; Beiko et al. 2003]. The reason for the use of polymeric materials is that, in general, they appear to be more inert in nature than metals or other substances. However, polymeric stents demonstrate certain limits in their ability to resist external compression forces [Christman et al. 2009]. Thus, metallic materials have been introduced to create more resistant stents indicated for diseases such as malignant extrinsic ureteral obstruction where compression forces are expected to be high [Pedro et al. 2007]. Nitinol (nickel/titanium alloy), superalloy titanium, stainless steel and chromium cobalt are the most commonly used materials in metal ureteral stents. There are ongoing attempts to create a combination of a polymeric stent coating developed with a metal skeleton, with the objective of constructing a stent combining both polymeric inertness and metal strength characteristics [Pedro et al. 2007; Trueba Arguinarena and Fernandez del Busto, 2004; Ko et al. 2002; Leveillee et al. 1998].

In an attempt to avoid the repeated cystoscopy during stent removal, several biodegradable–bioabsorbable materials have been introduced in stent composition. Polyglycolide, Poly D, L lactide, Poly L lactide and Uriprene are biodegradable polymeric materials that when used for ureteral stent composition can induce total stent absorption over a varied period [Chew et al. 2010; Talja et al. 2002]. Degradation time depends both on the material used and the amount of substance to be degraded. For example, second-generation stents are degraded from the distal to the proximal end because the coating is thicker on the more proximal portion [Chew et al. 2010]. Current data on biodegradable stent application in the human ureter are limited. Moreover, several problems with this novel idea have already been encountered. Phase II trials of a temporary ureteral drainage stent (Boston Scientific Microvasive, Natick, MA) revealed that in some cases stent fragments did not dissolve properly and required shock-wave lithotripsy and ureteroscopy for removal [Lingeman et al. 2003]. Another stent composed of poly-l-lactide-co-glycolide (PLGA), evaluated for its use after retrograde endopyelotomy in a porcine model, was not pursued clinically due to incompatibility issues [Olweny et al. 2002]. In addition, conditions such as ureteral strictures need a prolonged time of stenting in contrast to other procedures such as after shock-wave lithotripsy when a short-term ureteral drainage is indicated. Consequently, a single biodegradable stent cannot fit all conditions and disease-specific stent development is required. New bioabsorbable stents are already under experimental evaluation demonstrating promising results and clinical trials are expected. Second-generation biodegradable stents such as the Uriprene® stent composed of suture-like material begins degrading at 2 weeks and are completely degraded by 10 weeks after placement. Third-generation biodegradable stents are fully degraded by 4 weeks. Experimental data in pigs confirms the biocompatibility and efficiency of these evolved stents. Nevertheless, clinical data in humans are still lucking [Chew et al. 2010].

Stent coatings

The stent industry quite quickly realized that instead of searching for the ideal composition material for the creation of novel stents, current materials and stent designs could be used as the platforms to be covered with other substances with desirable characteristics. Stent coating is the part of stent evolution with the most significant development and the most promising future prospects.

Several substances have been tested as potential coatings for urinary tract stents. Polymeric stents can be coated with a variety of nondissolvable polymers (AQ, Cook Urological; Lse, Cook Urological; SL-6, Applied Medical, CA, USA; HydroPlus, Boston Scientific, MA, USA) which increase biocompatibility and reduce friction between the stent and ureter during placement [Liatsikos et al. 2010]. Enhanced biocompatibility and friction characteristics of ureteral stents are related to a decrease in postplacement urothelial reaction, biofilm formation and, consequently, long-term stent efficiency.

Heparin is very promising ureteral stent coating. Heparin-coated polymeric stents (Endo-Sof Radiance, Cook Urological) provide to the stent an antiadhesive surface that reduces biofilm formation and concomitant stent encrustation. Consequently, this coating can postpone stent replacement providing a useful tool for long-term urinary drainage. When indwelled for 10 and 12 months in two human cases, heparin-coated stents were found to be free of encrustation [Cauda et al. 2008]. Nevertheless, the ability of the heparin coating to demonstrate an inhibitory effect on bacterial adherence was not verified in vitro [Lange et al. 2009]. Coating stents with active enzymes that would degrade surface biomaterial deposits is an alternative idea to reduce stent encrustation. In an in-vivo rabbit bladder implantation model, enzyme-coated (oxalyl-coenzyme A and formyl coenzyme) silicone disks were found to demonstrate a reduction in the amount of encrustation after 30 days of implantation versus control disks [Watterson et al. 2003].

Diamond-like carbon coating is a plasma-deposited diamond-like amorphous carbon material that is characterized by its excellent biocompatibility. A preliminary study in 10 patients using a stent with this coating demonstrated quite promising results. A decrease in stent friction, encrustation tendencies and biofilm formation was reported [Laube et al. 2007]. Further investigation in larger patient groups is necessary to confirm the superiority of this novel coating.

Hydrogel is a coating surface modification method applied mostly in ureteral stents that allows the anchoring of water molecules on the stent’s surface. Hydrogel-coated stents share advantages such as improved material biocompatibility, hydrophilization and lubrication [Chew and Denstedt, 2004]. A combination of the hydrophilic matrix with hydrophobic drugs seems to be especially promising. In an experimental study, John and colleagues dipped hydrogel-coated ureteral stents into solutions of ciprofloxacin, gentamicin and cefazolin, and proved that the created stents demonstrated antimicrobial properties [John et al. 2007]. Polytetrafluoroethylene (PTFE) is another stent coating used in metal stents that increases the stent’s biocompatibility. As a result, the epithelial reaction to the metal stent is limited. Experimental data in canine ureters have demonstrated that PTFE-covered metallic stents effectively prevent the luminal occlusion caused by urothelial hyperplasia [Chung et al. 2008].

An alternative novel tool for the confrontation of urothelial hyperplasia following ureteral stent placement is expected to be provided from the use of DESs. DESs, one of the largest coronary stent categories, have recently been evaluated for use in the urinary tract. Certain DESs can suppress neointimal hyperplasia following vascular stent placement. Experimental data verify that the urothelium responds in the same way. A significant redaction in urethral and ureteral urothelial hyperplasia was demonstrated after pactitaxel DES placement in the pig ureter and canine urethra [Liatsikos et al. 2007; Shin et al. 2005]. Clinical trials are necessary in order to verify the promising experimental results and define the efficacy of the new ureteral stents in the human ureter.

Following the same idea of incorporating drugs onto the stent surface, several other substances have already been used in DESs in an attempt to diminish stent-related adverse effects. Promising results have been demonstrated in the case of ureteral stents loaded with Triclosan and Ketorolac. Triclosan is a broad-spectrum antimicrobial agent incorporated on ureteral stents to prevent stent infection. When Triclosan-eluting stents were indwelled for 3 months in eight patients a decreased antibiotic usage and significantly fewer symptomatic infections were noted. Nevertheless, a clinical benefit in terms of urine and stent cultures or overall subject symptoms was not revealed [Cadieux et al. 2009]. Ketorolac is a nonsteroidal anti-inflammatory drug incorporated onto ureteral stents to minimize stent-related discomfort. In a prospective, multicenter, double-blind study enrolling 276 patients the overall safety of the Ketorolac-loaded stent was confirmed. A trend toward a treatment benefit was noted since patients appeared to require less pain medication [Krambeck et al. 2010]. Future studies with higher drug concentrations or alternative antibiotic agents or painkillers are expected to retrieve superior clinical benefit in both cases of DESs.

The future direction of cardiovascular stent development

The cardiovascular stent industry is a very profitable area. Thus, increased competition between stent manufacturers is present, speeding up the rate of development. During the last few years the particular field of medical device production has seen many advances, including antibody-coated stents, biomimetic, biocovered and bioactive stents. Obviously, urological stent development has much to gain from these advances.

Antibody-coated stents

Recently, techniques allowing the creation of antibody-coated stents have been introduced. The created stents should allow adhesion and proliferation of the surrounding mature endothelial cells and circulating endothelial progenitor cells, which is of primary importance for the in-situ rapid re-endothelialization of cardiovascular stents [Yin et al. 2009]. The particular adhesion ability appears to be of low importance for future application in ureteral stents given that normally no endothelial cells are present in the urinary tract. However, the prospect of antibody-coated stents might allow in the near future the targeted attraction and anchoring of particular elements flowing in the urine that might interfere positively with stent epithelization, urothelial hyperplastic reaction, biofilm formation and stent encrustation.

Biomimetic coatings and biocovered stents

Another very promising advance in stent technology is the creation of a phospholipid copolymer that mimics biological membranes. The creation of biomimetic stents is expected to increase the biocompatibility of future stents [Fan et al. 2007]. Nakayama and colleagues and Fu and coworkers recently developed methods for the creation of in-vivo tissue-engineered autologous tissue-covered stents. This novel insight opens the era of ‘biocovered’ stents that would be recognized as self by the hosting organism. Further, data on the subject are expected [Fu et al. 2009; Nakayama et al. 2007]. Based on the same idea that the use of a natural stent made of autologous tissue would be advantageous due to its biocompatibility, ongoing attempts for the development of tissue-engineered stents from chondrocytes are present. The feasibility of creating cartilaginous stents in vitro and in vivo using chondrocytes-seeded polymer matrices has already been demonstrated [Amiel et al. 2001].

Finally, Fine and colleagues demonstrated that rosette nanotube-coated titanium vascular stents can evoke an enhanced endothelial cell adhesion on the metal stent. The rosette nanotubes is a biomimetic nanostructured coating that mimics the dimensions of natural components of tissues, such as collagen fibrils. Consequently, endothelial cells passing through the stented vessel can easily attach to the particular coating creating a uniform healthy endothelium masking the underlying foreign metal [Fine et al. 2009].

Titanium nitride-oxide coating

A titanium nitride-oxide coating has also been developed. Titanium appears to render the stent surface biologically inert. Consequently, in a potential appliance of this technology in ureteral stents, biofilm formation and stent-induced urothelial hyperplasia are expected to be decreased [Windecker et al. 2001].

Bioactive stents

Sargeant and colleagues recently described a technique of altering the surface chemistry of nickel–titanium (NiTi) shape memory alloy in order to covalently attach self-assembled nanofibers with bioactive functions. These can promote specific biological responses from host tissues such as immobilization of certain proteins and peptides for directed cellular responses, immobilization of gene vectors and immobilization of antibodies for cellular adhesion [Sargeant et al. 2008]. In other words future NiTi ureteral stents can be modified by this technique and create a bioactive surface interfering positively with the underlying urothelium.

Radioactive stents

Radioactive stents have been tested in cardiovascular research and have been almost abandoned due to high rate of restenosis outside the stent edges (a phenomenon called the ‘edge effect’) [Arab et al. 2001]. Nevertheless, ureteral tissue shares few common characteristics with coronary vessels, so future testing might reveal a promising new field for radioactive stents. Stent occlusion due to urothelial and granulation tissue hyperplasia might be prevented with an inhibitor of cell growth, such as ionizing radiation. Selective ion implantation of β-particle-emitting radioisotopes such as phosphorus-32 into the surface of stents is proven to be technically possible and cost effective. Stents wearing gamma-emitting isotopes have also been developed. A future evaluation of this already established technology in urology appears promising.

Novel stents

In matters of novel composition materials, fully biodegradable/bioabsorbable metal mesh stents have recently been introduced. AMS (Biotronik) is an absorbable magnesium metal stent that combines radiopaque, high accuracy in positioning and a high revascularization rate [Erbel et al. 2007].

Conclusion

Ureteral stent development is currently focusing on the enhancement and evolution of stent design, composition material and stent coating. Several novel ideas currently under evaluation have demonstrated quite promising results, raising hopes that ureteral stents will improve their current efficiency and become a tool for the management of a growing variety of new indications in the near future. Cardiovascular stent research is leading the way, introducing new ideas with possible promising implication in urinary tract stenting. Nevertheless, the ureter has different structural and histological characteristics as well as pathophysiological mechanisms implicated in the failure of long-term stenting. Consequently, cardiovascular stent developments would probably require further refinement for ureteral application. Research and development of ureteral stents requires an extensive understanding of the mechanisms involved in ureteral stent failure. Urothelial hyperplasia, stent biofilm formation and encrustation, ureteral mobility and response to ureteral intraluminal foreign-body stimuli are only few of the implicated mechanisms that are not fully understood. Thus, further investigation is deemed necessary.

Conflict of interest statement

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.