Enhancing Renal Stone Management: Tip-Flexible Ureteral Access Sheath in Cystine Stone Surgery

Introduction

Cystinuria is a genetic disorder characterized by defective dibasic amino acid transporters in the renal proximal tubules and small intestine, leading to impaired reabsorption of cystine, lysine, arginine, and ornithine [1]. Due to the relatively low solubility of cystine, it accumulates in the urine and can eventually form cystine stones [2]. The prevalence of cystinuria varies geographically, affecting approximately 1 in 7000 individuals worldwide. Cystine stones account for 1% to 2% of adult urolithiasis cases and 6% to 8% of all pediatric kidney stones [3]. Diagnosing cystinuria is often challenging due to its rarity, but it should be considered in pediatric patients and young adults under 30 years old who present with recurrent or bilateral kidney stones [4].

Management of cystinuria requires a multimodal approach. A dedicated group of experts has published clinical practice recommendations for cystinuria, emphasizing the importance of individualized treatment plans [5]. Both the American Urological Association (AUA) and the European Association of Urology (EAU) advocate for early surgical intervention in the management of cystine stones [6,7]. The AUA recommends considering surgical removal for stones >10 mm or those that are symptomatic, and suggests earlier intervention even for smaller cystine stones due to their tendency to grow and recur. Similarly, the EAU emphasizes proactive management of cystine stones, highlighting the importance of regular monitoring and timely surgical treatment to prevent complications associated with their genetic basis and recurrent nature.

In this paper, we present the diagnosis and surgical treatment of a patient with multiple bilateral renal stones, including a significantly larger stone in the right kidney that was later found to be composed of L-cystine. We detail the procedure of flexible ureteroscopic lithotripsy using a tip-flexible ureteral access sheath (TF-UAS) to achieve complete stone clearance. At 7-month follow-up, the right kidney remained stone-free, while the left-sided stones had grown significantly despite the use of alkalizing agents. This marked difference in prognosis underscores the importance of early surgical intervention for patients with cystinuria. We further discuss these findings in the context of the relevant literature.

Case Report

A 24-year-old man was referred to the urology outpatient clinic after a routine health check ultrasound detected multiple bilateral renal stones. He was asymptomatic, and his physical examination, vital signs, and routine blood tests were unremarkable. Urinalysis revealed the presence of a few white blood cells and acidic urine (pH 6.5). Computed tomography (CT) identified a large right renal stone measuring 30×25 mm (average CT value: 649 HU; maximum CT value: 738 HU) and 2 smaller, clinically insignificant stones in the left kidney (Figure 1A). Due to the size of the right stone, surgical removal was recommended, while the left stones were managed conservatively given the absence of symptoms.

Under general anesthesia, the patient was positioned in lithotomy. A 6/7.5 Fr rigid ureteroscope was introduced into the bladder under direct vision, followed by the placement of a guidewire into the right renal pelvis to facilitate the insertion of a tip-flexible ureteral access sheath (TF-UAS; 12–14 Fr; 35 cm; Shenzhen Kangyibo Technology Development Co., Ltd., Shenzhen, China). A disposable digital flexible ureteroscope (HU30S; Shenzhen HugeMed Medical Technical Development Co., Ltd., Shenzhen, China) was advanced to the right renal pelvis, where multiple stones, including the large renal stone, were identified. Holmium laser lithotripsy was performed using a Lumenis Pulse™ 100H Holmium Laser System (Boston Scientific, NJ, USA) set to 0.6 J energy and 50 Hz frequency. During lithotripsy, the irrigation flow rate was maintained at 50 ml/min with a pressure of 30 mmHg, increasing to 90 ml/min when flushing the stones. Stone fragments larger than 3 mm were retrieved using a Cook® stone basket (Cook Medical Europe Ltd., Limerick, Ireland). Smaller fragments were aspirated through the TF-UAS under a negative pressure of 150 mmHg. After confirming the absence of residual stones, a 5 Fr double-J stent (Marflow; APR Medtech Ltd., Oxfordshire, UK) was placed. The total operative time was 189 minutes, with minimal blood loss.

The patient recovered uneventfully and was discharged on the second postoperative day, with a total hospital stay of 4 days. At the one-month follow-up, stone composition analysis revealed that the extracted stones were composed of L-cystine (Figure 2). A follow-up CT scan confirmed complete stone clearance (Figure 1B), and the double-J stent was removed without signs of encrustation. He declined genetic testing for cystinuria but was prescribed potassium sodium hydrogen citrate granules (Uralyt-U®; Viatris, Shanghai, China) at a dosage of 2.5 g in the morning and afternoon, and 5 g at night. At the 7-month follow-up, he remained asymptomatic, and his urine pH had increased to 8.0. However, CT imaging revealed significant growth of the left-sided renal stones despite the use of alkalizing agents, while the right kidney remained stone-free (Figure 1C). The patient decided against further surgical intervention for the left stones but agreed to continue with regular outpatient follow-ups.

Discussion

This case report highlights the critical importance of early diagnosis and surgical intervention for cystine stones, even in asymptomatic patients. Achieving complete stone clearance is essential to improving short-term stone-free rates (SFR) and reducing complications such as infections and obstructions, which are particularly significant since patients with cystine stones often suffer from impaired health-related quality of life [8]. In our case, complete clearance of the right cystine renal stones, along with urine alkalizing agents, prevented stone recurrence over a seven-month follow-up period. However, despite medical therapy, the left-sided stones grew at an alarming rate, indicating the need for surgical removal.

Cystinuria is frequently overlooked without the aid of stone composition analysis. The global prevalence of urolithiasis ranges from 1% to 19% [9], and incidental findings through abdominopelvic CT scans can be as high as 14.8% [10]. With the increasing prevalence of urolithiasis among younger adults, diagnosing cystinuria has become more challenging [11]. Defining stone composition is crucial for optimizing treatment plans. In this case, neither the patient nor his parents were aware of his cystinuria until the stone composition analysis was reported post-discharge. Since the patient declined further surgical intervention and genetic testing, he is now limited to dietary adjustments and medical therapy. Physicians have cautioned that he may be at an increased risk for significant renal damage and chronic kidney failure in the long term [12].

On average, patients who have formed cystine stones undergo 3.1 to 4.2 surgical interventions during a mean follow-up of 5 to 8 years, despite the use of medications [13,14]. When divided SF and non-SF groups, the latter received a higher average number of procedures (4.0 vs 2.5). The increased number of surgical interventions was also associated with reduced renal function. However, patients in these studies predominantly underwent shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL). SWL is not recommended, as the number of sessions required increases with stone size, and cystine stones are quite resistant to it [15,16]. When comparing SFR between different treatment modalities, flexible ureteroscopic lithotripsy (FURL) showed a significantly higher SFR than SWL and mini PCNL (90.2% vs 61.5% vs 83.8%) for lower pole renal hard stones ≤2 cm [17]. For stones >2 cm, PCNL provided a higher initial SFR [18]. With the supplementary use of TF-UAS, the immediate and 3-month SFR was significantly higher than using conventional UAS for upper urinary tract stones ≤3 cm [19]. Therefore, flexible ureteroscopy with TF-UAS may be an advantageous alternative for cystine stones, especially those ≤3 cm, minimizing the risk of recurrence.

TF-UAS is a relatively novel device often combined with a vacuum system that aids in stone aspiration [20]. The EAU conducted a multicenter prospective study and found that the combination of FURS with flexible and navigable suction UAS could achieve a very high SFR with negligible serious adverse event and reintervention rates for stones in all locations [21]. A statewide collaborative study found that traditional UAS significantly increased the odds of postoperative emergency department visits and hospitalization due to complaints of flank pain, hematuria, urinary tract infections/pyelonephritis, and fever, making the addition of UAS in FURS controversial [22]. It was determined that a safe intrarenal pelvic pressure must be maintained by keeping the ratio of ureteroscope-sheath diameter ≤0.75 for traditional UAS and <0.85 for TF-UAS [23,24]. The flexible tip of TF-UAS allowed for better navigation of the target stone, and the vacuum system combined with irrigation can effectively remove stones, enhancing stone clearance rates, even for stones measuring 20–30 mm [25,26].

Recent prospective clinical trials have demonstrated that the thulium fiber laser provides superior three-month outcomes compared to the holmium laser, including notably higher stone-free rates and fewer intraoperative complications [27]. Notably, Gismondi et al. reported on a case involving bilateral multiple cystine renal calculi managed effectively with the thulium fiber laser [28]. The authors highlighted the efficacy of the popcorn dusting technique, with a total operative time of 120 minutes. The patient had an uneventful postoperative recovery, and follow-up CT scans showed only a 3 mm residual stone. In our study, the operative time exceeded the generally recommended limit of 90 minutes, underscoring the necessity of refining our surgical techniques. The integration of a TF-UAS with the thulium fiber laser might potentially reduce operative times and enhance postoperative outcomes.

The acceptable levels of urinary cystine are 250 mg/L or less at a urinary pH ≥7 [27]. A sustained pH ≥7.5 can be useful for attempting dissolution of existing cystine stones, but such high pH levels can be difficult to maintain clinically and may precipitate calcium phosphate [3]. Serum cystine level testing and urinary cystine excretion measurements are important tools for monitoring a patient’s condition. Unfortunately, these tests were not conducted in this case, as cystinuria was only confirmed after the stone composition analysis results were received and the patient declined excessive tests during follow-up. Although conservative and pharmaceutical therapies can reduce cystine stone formation, most patients will inevitably require surgery [28]. Therefore, minimally-invasive surgical procedures that offer high SFR in the first session are preferred. Nonetheless, urinary alkalinization remains a cornerstone of treatment for cystinuric patients, and strict compliance with treatment is crucial for better long-term prognosis. Long-term medication is also associated with side effects, the need for constant monitoring of renal function, and high costs [29]. Therefore, it is the physician’s duty to adopt a pragmatic and proactive approach to cystine stone management.

Conclusions

Early minimally-invasive management with high SFR is recommended for asymptomatic cystinuria patients, as complete stone clearance offers a better prognosis by preventing recurrence compared to medical therapy alone. Strict follow-up, along with comprehensive monitoring of patient compliance and condition, is also essential for optimal outcomes.