Ureteral stenting is an important procedure in daily clinical practice for urologists as the reasons for ureteral stenting are manifold. Infection, sepsis, stones, strictures, ureteral trauma, external compression of the ureter as well as internal and external tumors and surgical procedures like ureteroscopies make stenting necessary. If untreated, ureteral obstruction can lead to renal failure and eventually death. Ureteral stents represent a simple and effective drainage method to preserve renal function, treat pain caused by ureteral obstruction and avoid external or visible devices such as nephrostomy tubes [1▪▪]. It has been more than 5 decades since the first description of a temporary ureteral stent placed by cystoscopy, and the indications for its use have continued to expand .
The most commonly used stent type is the standard double J stent (DJS), named for its J-shaped curled ends. Manufactured from polyurethane, silicone or various polymers, DJS are changed at 3–6-month intervals, as they are prone to encrustation, obstruction, migration and fracture . In an attempt to avoid the frequent replacement of DJS or the insertion of permanent nephrostomies, self-expanding metallic stents have been proposed in urological practice for patients who require long-term decompression . Alternative options for decompression include tandem ureteral stents and metallic stents, although the preferred method remains controversial.
Deficiencies of the currently used stents like bacterial colonization, encrustation and patients′ discomfort trigger the quest for new developments. In the present review, we focus on the treatment of stent-related symptoms as well as on new materials being used to eventually reduce those symptoms. A recent literature research looking into the new evidence on ureteral stents, metallic stents, biodegradable stents, stent-related symptoms and treatment of symptoms was performed.
STENTS CONSTITUTIVE MATERIALS
Over the last few years, engineers, scientists and clinicians have worked on identifying optimal materials for ureteral stents, focusing specifically on mechanical strength, flexibility, biocompatibility, surface roughness and cost-effectiveness . The stents vary in length, contour, internal and external diameter and drainage issues. An ideal stent should offer simple insertion and removal without discomfort, avoid migration upon deployment and cause minimal urinary symptoms. Furthermore, it should resist biofilm formation or encrustations. A stent with these characteristics would presumably not compromise a patient's quality of life . Table 1 shows a list of the most commonly used ureteral stents in current clinical practice.
Although the vast majority of ureteral stents are placed for a relatively short time, as after ureteroscopies, a number of patients with chronic ureteral obstruction will require long-term ureteral stenting up to several years, elevating the risk of complications . Nowadays, research has focused on the development of ureteral stents with novel materials building biodegradable and drug-eluting stents. These have been investigated to decrease bacterial infection and adhesion, and to improve overall patient comfort .
There are mainly three classes of materials that are employed to fabricate ureteric stents: metals, polymers and biodegradable/bioabsorbable materials . Also, while stent design has established the double-J structure as a default for almost all stents, the main rationale was to avoid migration of these stents once placed successfully. Similar stent modifications have occurred with regard to the stent drainage – such as side holes along the stent and other innovative products such as spiral stents, mesh stents, stents with variations in tail designs and the method of removal of these stents .
Biodegradable ureteral stents
The main advantage of biodegradable ureteral stents (BUS), is that secondary interventions become unnecessary, improving patient morbidity while decreasing the economic burden on the medical system . On the other hand, the controllability of degradation  and migrating fragments from stent degradation still represent an issue that needs to be overcome, which is the main reason why BUS are not available in the market yet even after many years of research [11▪,12]. Nanotechnology and chemical modification of biomaterials may help optimize the properties of degradation . An interesting concept was the development of a biodegradable antireflux ureteral stents (BDG-ARS). Soria et al. examined the effectiveness and biodegradability of the BDG-ARS in a porcine ureter model. According to their results, none of the ureters receiving the BDG-ARS showed any evidence of vesicoureteral reflux. BDG-ARS degradation took place in a controlled and predictable fashion from the third to the sixth weeks without appearance of obstructive fragments [13▪].
Another recent experimental study used a porcine model to evaluate a newly developed BUS produced with natural-based polymers. Barros et al. compared its degradation, mechanical properties, drainage, physiological and histological features with those of a commercially available ureteral stent. In all cases, the BUS was only visible during the first 24 h on radiograph, and in all cases the BUS was completely degraded in urine after 10 days, as confirmed on necropsy. During the degradation process, the mechanical properties of the BUS decreased, while the commercial ureteral stents remained constant. This device presents a homogeneous degradation by surface erosion, good physiological and histopathological response, effective urine drainage, and high biocompatibility [11▪]. Overall, this novel BUS can be regarded as a significant advancement in the field, but further studies are needed to address current limitation of this product and to prove its safety in the clinical setting [11▪].
Drug-eluting stents and stent coatings
As foreign bodies in the urinary system, the surface of stents creates an environment for bacterial and fungal colonization with the potential of biofilm formation. This complication can lead to recurrent infections or urosepsis episodes and the need for premature removal or relapsing replacement of the ureteral stent . The biofilm makes embedded bacteria less accessible to the human immune system and significantly decreases antibiotic susceptibility, making antibiotics inefficient to the bacteria adherent to the surface. In addition, urine with infectious bacteria accumulated on the surface of implants pose a threat to humans . Furthermore, bacterial colonization is often considered the initial step for encrustation of any urinary drainage device like catheters, stents, nephrostomy tubes .
Surface coatings for ureteral stents aim to prevent infections and encrustation by inhibiting bacterial attachment and survival on the device, as well as resisting urinary crystal formation and adherence . Application of antiadhesive technology by modifying surface charge, hydrophobicity and roughness, and antimicrobial compounds like silver, antibiotics, detergents and so on, are some of the numerous tested strategies.
Although a variety of materials have been designed to prevent bacteria adhesion, they were unable to inhibit bacterial growth and proliferation. Recently, antibiotics have been incorporated into the bio-absorbable polymer coatings, representing one plausible approach to overcome stent-induced infection by its sustained drug release profile with polymer degradation . Due to their capability of local drug delivery, drug-eluting stents with biodegradable polymers as reservoirs have shown great potential in the application of interventional therapy . Ma et al. studied coated ureteral stents of poly L-lactide-co-ε-caprolactone (PLCL) with three different compositions as carriers for ciprofloxacin lactate (CIP), and evaluated the antibacterial profiles of the stents in vitro. In their findings, PLCL5050-CIP coatings significantly inhibited bacterial growth. With the ciprofloxacin eluting design, 99.8% of bacteria were inhibited after 30 h and all the bacteria lost their viability at 54 h. Hence, they suggested that PLCL copolymers with tunable degradation rate as carriers for CIP could be used as a promising long-term antibacterial coating for ureteral stents .
Zhao et al. developed a novel material called Cu-bearing antibacterial stainless steel. In-vitro immersion tests have shown that it not only inhibited proliferation of bacteria and formation of biofilm, but also had less encrustation. Its antibacterial effectiveness against Escherichia coli reached 92.7% in artificial urine for 24 h and 90.3% in human urine for 6 h . However, this approach is limited by high production costs as well as insubstantial clinical benefits in the trials carried out so far [1▪▪].
Coated and drug-eluting stents seem to be promising concepts to prevent stent-related symptoms, but still have to be considered as experimental approaches [1▪▪]. There is no stent coating that can be definitively recommended at the moment [1▪▪].
Different types of metallic stents exist, including the nonexpandable coiled metallic Resonance stent, a nickel–cobalt–chromium–molybdenum alloy DJS (Cook Medical, Bloomington, Indiana, USA), the thermo-expandable metal alloy Memokath 051 stent which is a nickel–titanium alloy that forms a tight spiral structure (PNN Medical, Glostrup, Denmark), and the self-expandable covered metallic Uventa stent that has two layers of a self-expandable nickel–titanium alloy mesh covering a polytetrafluoroethylene layer (Taewoong Medical, Gojeong-ro, Wolgot-myeon, Gimposi, Gyeonggi-do, South Korea) . In a recent systematic review, the most commonly reported metal mesh stents used in the ureter for the management of malignant ureteral obstruction were the Wallstent (Boston Scientific/Microvasive, Natick, Massachusetts, USA), the Memokath 051 (PNN Medical A/S, Kvistgaard, Denmark), the Uventa (Taewoong Medical, Seoul, South Korea), and the Allium (Allium Medical Solutions Ltd, Caesarea, Israel) . Wallstents are not specifically designed for ureteral use and were related to low patency rates (29–100% during a maximum follow-up of 140 months) due to lumen occlusion caused by hyperplasia or tumor expansion. The thermo-expandable Memokath 051 metal mesh stent achieved high patency rates (82–100%), but high migration rates (10.8– 17.4%) were reported. Finally, the Uventa metal mesh stent, has been used in variable sizes with high patency rates (64.8–100%). The Allium covered metal mesh stent had high patency rates (86.9–100%) .
Since standard polymer DJS are unable to provide the long-term drainage seen with metal stents and require recurrent changes every 3–6 months (necessitating a minimum of two to four exchanges per year) the application of a metal stent may result in overall cost savings although the purchase price is higher for each metal stent . This makes metal stents an option for long-term use as they are able to resist lumen occlusion from extrinsic compression, allowing for longer indwelling times .
SIDE EFFECTS ASSOCIATED WITH URETERAL STENTING AND THEIR TREATMENT
Flank or abdominal pain and urinary symptoms are the most common stent-related symptoms, especially triggered by activity and urination, in patients requiring short-term stenting. Pain is typically managed using oral analgesic medications like NSAIDs or other opioid-based medications, but what often bothers stented patients more than pain are storage symptoms such as frequency, urgency, dysuria and incontinence . Stent-related infections are also a significant source of patient morbidity. NSAIDs have been shown to reduce ureteral contractility and inflammation by cyclooxygenase inhibition therefore decreasing renal colic in further consequence. In addition, renal prostaglandin synthesis is decreased by NSAIDs resulting in decreased renal blood flow as well as lowering renal and ureteral pressures. The beneficial role of NSAIDs while stents are in place still must be assessed in larger studies .
The pathophysiology of stent-related symptoms has not been fully elucidated but most believe that the flank pain, deteriorating renal function and worsening hydronephrosis despite stent insertion are considered manifestations of stent failure . Flank pain and lower urinary tract symptoms (LUTS) caused by stent placement are attributed to the pressure transmitted to the renal pelvis during urination and lower ureteric and bladder spasms due to local irritation . Multiple efforts have been made to find either novel stent designs that result in less urinary tract irritation or a pharmacological management option to reduce these symptoms. Symptoms associated with stents are widely variable and subjective, making it difficult to capture precisely and in a quantifiable format. The ureteral stent symptom questionnaire (USSQ) introduced by Joshi et al. is a reliable, validated and comprehensive instrument for evaluating stent-related symptoms and their impact on health-related quality of life due to ureteral stents. The USSQ is an important measurement tool used in ureteral stent-related research .
Studies have also examined the role of α-blockers and antimuscarinics, which seem effective in improving stent-related symptoms in some patients. These medications may decrease irritative spasms and reduce reflux of urine back to the kidney, which could explain the ability to relieve flank pain . Also because α-blockers cause relaxation of the prostatic smooth muscle, the bladder neck and the distal ureter smooth muscle to decrease bladder outlet resistance and voiding pressure may decrease, thus explaining the beneficial effects on stent-related LUTS. Antimuscarinics are thought to reduce the involuntary bladder contractions caused by trigone irritation by blocking muscarinic receptors in the detrusor muscle, alleviating the stent-induced urinary storage symptoms [21,22].
The results from randomized control trial data support the hypothesis that α1-blockers not only beneficially influence pain but also urinary symptoms and the quality of life of patients with an indwelling ureteral stent . Pooled data showed significant benefits of α1-blockers in the USSQ subscores for urinary symptoms, pain and general health, as well as the complete USSQ and international prostate symptom score. The predominant side effects of treatment with α1-blockers exhibited in the trials were dizziness, headaches and hypotension; however, these adverse events were rare . There are no clear differences between α1-blockers . The most recent meta-analysis, by Yan et al., evaluated the efficacy of a combination therapy of α-blockers and antimuscarinics versus antimuscarinics alone for relieving stent-related symptoms. Seven publications including 710 patients were used in the meta-analysis, suggesting that α-blockers and antimuscarinics are superior to antimuscarinics alone for the treatment of ureteral stent-related symptoms . Recently, Wang et al., evaluated the efficacy and safety of solifenacin as monotherapy, solifenacin combined therapy with tamsulosin, tamsulosin monotherapy in stent-related symptoms. There were 10 studies involving 1786 participants included in the meta-analysis. Solifenacin monotherapy significantly reduced the total score of USSQ [mean difference −14.90; 95% confidence interval (−25.19, −4.60); P = 0.005], as well as indexes of urinary symptoms, body pain, general health, sexual performance and hematuria, but the differences were not-significant when compared with tamsulosin (except improved sexual performance). Combined therapy of solifenacin and tamsulosin showed no beneficial effects in all indexes of USSQ over solifenacin monotherapy. Only slightly higher incidence of dry mouth was found with solifenacin versus control [25▪].
Ureteral stents are invaluable devices for clinical practice nowadays. The ideal stent has not been designed yet and multiple lines of research are being developed to improve tolerance, design and materials. DJS are still the best option for most patients requiring short-term and long-term usage. Biodegradable stents should be considered for patients with short-term indwelling period, while metallic stents are an alternative option for long-term usage. Current options should be considered individually with simultaneous consideration of cost effectiveness based on the indication, the presenting symptoms and general conditions of each patient, as the mechanisms causing stent-related symptoms are not yet fully understood.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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