It is well known that ureteral stents can cause problems—namely irritative symptoms to the patient, infection, and encrustation. More than 80% of patients describe difficulties with an indwelling ureteral stent in place and are unable to work, carry out normal daily activities, or have sexual activity impaired by their stent [11]. Up to 35% of stents are colonized with bacteria following insertion and 24% of all stented patients are found to have bacteriuria [12]. Others report 24% of stents have adherent bacteria and of these patients, only 22.5% have bacteria in the urine [13]. Patients with more concomitant comorbidities have higher rates of bacteriuria following stent insertion: healthy patients had a bacteriuria rate of 28%, while patients with chronic renal insufficiency, diabetes, or diabetic nephropathy had bacteriuria rates of 57, 78, and 62%, respectively [14]. Furthermore, these authors also found that bacteria cultured from these stents were more likely to harbor antibiotic resistance, which is likely attributed to the fact that they are more likely to have been prescribed antibiotics for previous infections due to their immune compromised state. In fact, other authors have found immune compromised patients with diabetes, chronic renal insufficiency, or malignancy to be at higher risk for infection associated with ureteral stents [13].

This raises the question as to whether we should be continuously administered pre- and peri-operative antibiotics around ureteroscopy and stent insertion. In the latest best practice policy statement on antimicrobial prophylaxis in urologic surgery, analysis of four pooled studies with 345 patients covering a multitude of transurethral surgeries were summarized and oral fluoroquinolone prophylaxis had equivalent rates of bacteriuria to an intravenous cephalosporin [15]; there was a lower cost of patients taking ciprofloxacin, however, due to its oral administration. There is good level Ib evidence that one dose of oral ciprofloxacin prior to transurethral surgery is sufficient to reduce the postoperative infection rate when placing a stent. For ureteroscopy, the AUA recommends all patients be given prophylaxis with a quinolone or trimethoprim, or alternatively with an aminoglycoside, penicillin, or cephalosporin.

There is very little to no evidence that postoperative antibiotics are necessary in patients who had sterile urine preoperatively and receive a ureteral stent. Preoperative antibiotics do not prevent microbial colonization of the ureteral stent (EAU Guidelines on Urological Infections, 2009, http://www.uroweb.org/gls/pdf/15_Urological_Infections.pdf). In fact the European Association of Urology guidelines do not recommend antibiotic prophylaxis for healthy patients undergoing uncomplicated ureteroscopy for distal ureteral stones. Patients with a preoperative indwelling nephrostomy tube or ureteral stent or those that are immune compromised should receive antibiotic prophylaxis of second or third generation cephalosporin, trimethoprim–sulfamethoxazole, combination of penicillin and beta-lactamase inhibitor, or a fluoroquinolone. Similarly, patients with more proximal ureteral or renal stones, or impacted calculi, should receive antibiotic prophylaxis as mentioned above. Although the antibiotic treatment is recommended to be short term, the ideal length of time has yet to be determined.

It has long been thought that stent encrustation and bacterial biofilm formation occur as a result of a urinary conditioning film that deposits on the stent surface. It has previously been shown that shortly after insertion of a ureteral device, components of the urine begin to deposit and cover its surface. Conditioning film components on the surface of ureteral stents with and without encrustation have been identified after stent removal from patients [16]. Immunoglobulins and Tamm–Horsfall protein were found to bind nonselectively to the stent surface immediately after insertion; it was hypothesized that their positively charged histones and nuclear DNA-condensing proteins promoted encrustation [16]. Similarly, our laboratory has compared urinary conditioning film components on stents between patients as well as between stents made of different materials (manuscript in progress). This study did not find any significant differences in the most common conditioning film components between stents and patients, suggesting that the major components of conditioning films are the same between patients. These conditioning film components included several cytokeratins associated with the urogenital tract, hemoglobin, Tamm–Horsfall protein, fibrinogen, apolipoprotein, serum albumin, and S100A9. Relating the identification of these conditioning film components back to stent-associated complications, bacteria have receptor molecules called adhesins on their surface that are able to interact with the majority of the components facilitating bacterial adhesion, colonization, and biofilm formation. In addition to this, calcium-binding proteins such as Tamm–Horsfall protein, serum albumin, and S100A9 may form a nidus for stent encrustation. Stent surface coatings and drug-eluting stents that are designed to prevent encrustation and infection are likely rendered ineffective by the formation of bacterial biofilms on the stent surface.

Infection can also lead to stent encrustation—particularly with organisms that possess the urea splitting enzyme urease (e.g., Proteus mirabilis) that forms an ammonium ion from ammonia in a process that utilizes free hydrogen atoms and results in the alkalization of urine (increasing pH) [17]. At a higher pH, magnesium, ammonium, and phosphate (i.e., struvite) crystals and calcium apatite crystals can form. Given the interaction of calcium and magnesium with proteins of the conditioning film, encrustation of the indwelling stent can occur. Aside from bacterial-induced urinary alkalization, other conditions that lead to an increase in urinary pH in the absence of bacteria can trigger precipitation of urinary ions that in the presence of the conditioning film will cause encrustation. Prevention of conditioning film deposition and bacterial adhesion are important points to consider for future research of ureteral stents. Although prevention of conditioning film formation will be a big step in preventing encrustation, it may not eliminate bacterial adhesion as they contain several factors on their surface that will allow them to interact with biomaterials in the absence of specific binding partners via ionic and hydrophobic interactions. Finding a biomaterial that resists both encrustation and bacterial adhesion is a great challenge.

The most common complication of indwelling ureteral stents is pain experienced by the patient. Over 80% of patients with a ureteral stent experience pain and discomfort [11]. Much speculation has gone into the cause of the discomfort and the exact causes are unknown, but one theory is uroepithelial irritation during stent movement within the ureter as the patient goes about their day-to-day activities. A previous study showed that the ureteral stent moves within the ureter, kidney, and bladder when the patient moves and may cause discomfort [18]. This movement is likely attributed to the fact that ureteral JJ stents are not anchored in place: the pigtail curls in the bladder and kidney are designed to prevent migration of the stent, but allow the stent to slide and move. Using an in vitro stent-induced injury model, our laboratory has shown that the irritation of urothelial cells by a ureteral stent piece triggers the secretion of vast amounts of pro-inflammatory cytokines [19], which may be a cause of stent-associated pain.

Even though there is no clear data to support the use of one type of stent over another, there is good data that longer stents that protrude into the bladder produce more symptoms. Choosing the correct length stent will significantly help reduce patient stent symptoms. Stents that cross the midline of the bladder result in significantly more dysuria, urgency and irritative voiding symptoms than patients with stents that do not cross the midline. Long stents are associated with excess material in the bladder—and, therefore, presumably with more bladder irritation—but do not result in excess stent length in the kidney [20]. Fluoroscopic studies of stented patients show that, with motion, the stent tends to bow in the mid and proximal ureter and the excess length slides in and out of the bladder at the ureterovesical junction, with relatively little motion seen in the kidney [18]. El Nahes and colleagues have identified additional factors that contribute to stent-associated symptoms that include crossing of the lower coil to the other side of the bladder, calyceal position of the upper coil, stent length, and larger stent diameter [21]. Certainly, stents that have a lot of excess material in the bladder may cause more mucosal irritation of the bladder and have been shown to result in more patient discomfort.

How is the correct stent length chosen? This question has baffled many urologists and many methods have been described including measuring patient height, torso length, intravenous urography, and direct ureteral measurement. One study found that direct intraoperative measurement of ureteral length was better than patient height at correlating with the correct stent length [22]. Another study evaluated several anthropometric factors, including patient height, BMI, and distances from the acromion process (shoulder) to the head of the ulna (wrist), olecranon process (elbow) to the head of the ulna, xiphoid process to pubis, umbilicus to pubis, and anterior iliac spine to anterior iliac spine [23]. They measured ureteral length intraoperatively with a 5 Fr ureteral catheter and found that height, xiphoid process to pubis distance, and the shoulder to wrist distance all correlated with ureteric length. Ho et al. recommend a 22 cm stent for patients 149.5–178.5 cm in height, but did not study patients outside this height range [24]. To date, there is no standard accepted method of determining the most appropriate length of ureteral stent.

Phenazopyridine and oxybutynin have been administered orally in an attempt to relieve stent-related symptoms. In a randomized trial involving 60 patients randomized to phenazopyridine, oxybutynin or placebo, the following measures were recorded: narcotic, use, flank pain, suprapubic pain, urinary frequency, urgency, dysuria, and hematuria [25]. There was a trend, although statistically insignificant due to the small group numbers, for a reduction in narcotic usage in the oxybutynin group. Phenazopyridine significantly reduced the amount of hematuria patients had on postoperative day 1 compared to placebo. Perhaps a larger study would discern if either of these medications would be helpful in relieving stent symptoms.

Patients randomized to alfuzosin following ureteroscopy and stent insertion had significantly less narcotic use, less overall pain in the back and groin area, less flank pain during urination and less urinary frequency compared to patients given placebo [26]. Tamsulosin also produced similar significant results in other placebo-controlled prospective trials of patients undergoing ureteral stent placement following ureteroscopy [27, 28]. There is good data to suggest that alpha blockers are an excellent way to prevent and relieve ureteral stent symptoms [29].

It is unknown exactly from where stent symptoms originate. There is evidence that the junction of the ureter and bladder play a role. In patients who had a ureteral stent post-ureteroscopy, a trial randomized patients to three injections of botulinum toxin A into the bladder around the ureteral orifice or no injection. Stented patients with botulinum toxin A experienced significantly less pain than controls and required less narcotic usage [30]. This lends evidence to the theory that detrusor muscle spasm around the intramural ureter is a cause of ureteral stent pain. Most interestingly, the stent used in this study was a multi-length ureteral stent [30]. There is a belief that more significant material in the bladder leads to more significant symptoms, but there is no randomized clinical data to support this anecdotal belief.

This question is asked often, but there is no conclusive data as to which commercially available stent is the most comfortable for patients. There are a variety of factors that are taken into consideration including the softness (durometer) of the stent, its design, and its size both in length and in diameter. Intuitively, one would think that softer stents would be more comfortable than harder stents; however, randomized trials have shown no difference between soft and hard stents in terms of urinary symptoms, pain, time away from work or sexual dysfunction utilizing the Ureteral Stent Symptom Questionnaire (USSQ) [31]—the only validated tool for evaluating ureteral stent symptoms [32]. In one trial, patients randomized to a “stiffer” stent that was greater than 64A durometer in stiffness (Percuflex^® stent; Boston Scientific, Natick, MA, USA) were compared to patients who received a softer stent (Contour™ stent, Boston Scientific; less than 64A) [32]. No differences between groups were seen at 1 and 4 weeks in terms of urinary symptoms, overall body pain, work performance, or general health index. Lennon et al. randomized patients to firm polyurethane stents or a softer Sof-Flex™ stent [33]. Patients with firmer stents did have a higher rate of dysuria, renal, and suprapubic pain; however, there was no significant difference in the degree of bladder inflammation, stent encrustation, urgency, frequency, nocturia or hematuria and patients in this study were not evaluated using the only validated stent symptom questionnaire, the USSQ. Dual durometer stents have a different firmness in the stent coil—typically the renal coil is firmer to maintain the curl and thus its position while the bladder curl is a softer durometer in an attempt to reduce bladder symptoms. The research group in Bristol, UK randomized 159 patients to receive a firm, single durometer stent (InLay stent, Bard) or a dual durometer stent (Polaris, Boston Scientific) [34]. There were no differences in stent symptoms between groups of patients: 91 and 94% of the Inlay and Polaris stented patients, respectively, still complained of stent symptoms. This study further outlines our poor understanding of why stents cause so much discomfort. Even with a softer bladder coil, patients still complained of symptoms.

In addition to irritating the uroepithelium, indwelling ureteral stents have been shown to affect the rate of ureteral peristalsis, which is the contraction of muscles surrounding the ureter that facilitate and drive urinary flow. This loss of ureteral peristalsis is also hypothesized to cause stent symptoms for patients. Several studies have shown that ureteral stents prevent ureteral peristalsis, which causes backpressure on the kidney due to decreased urinary flow down the ureter [35–37]. This backpressure may be an additional cause for patient discomfort. The decrease and disruption of ureteral peristalsis can also be attributed to the shape and location of the ureteral stent—the renal curl sits in the renal pelvis and may disrupt the pacemaker of ureteral peristalsis which are located in the renal pelvis [38–41]. Contact between the stent and the renal pelvis is believed to throw off the pacemaker, disrupting the rhythmic muscular contractions responsible for driving urinary flow into the bladder. Without these contractions, the renal pelvis becomes swollen or hydronephrotic and is thought to cause significant patient symptoms. Similarly, the diameter of the stent has also been shown to affect peristalsis, as smaller diameter stents have less contact with the ureteral wall compared to larger diameter stents [35, 42]. The prevention of stent symptoms needs to address the overall structure of the stent, minimize the degree of urothelial irritation and disruption of peristaltic activity.

There are a variety of different biomaterials used in stent design with the most popular being a variation or combination involving polyurethane. Most are proprietary polymers based on this technology. Polyethylene stents originally used in stents are no longer used today due to their stiffness and brittleness which has a tendency to fracture when left indwelling for long periods of time. Newer blends of polyethylene and other polymers, such as polyurethane, have been developed to withstand the conditions of the urinary environment such as fracturing, encrusting, and causing infection [43]. Silicone is one of the most currently biocompatible materials used in the urinary tract today in terms of avoiding infection, encrustation, and biofilm production [44–46]. It is also very lubricious which makes insertion easier and may potentially help with patient comfort; however, silicone’s flexibility and elasticity—two favorable properties—are also the cause of the problems with silicone. Namely, negotiating silicone ureteral stents through narrow or tortuous is very difficult since it is too flexible and elastic in these conditions and can often not be inserted under these situations. The development from brittle and firm polyethylene and soft silicone led to polyurethane—a compromise between these two extremes—and the most common biomaterial used in ureteral stents today. Although it is most commonly used, it is also fairly firm and is prone to causing significant discomfort in patients. Newer materials are constantly being developed and include many proprietary-based polymers from various companies.