Clinical efficacy and safety of flexible ureteroscopy and percutaneous nephrolithotomy for large kidney stones: A retrospective comparative study

Abstract

BACKGROUND

Renal stones ranging 20–40 mm are very common in China. Although no large-sample clinical studies have confirmed the clinical efficacy and safety of this method, there is also a lack of comparative data with traditional treatment.

AIM

To investigate the clinical efficacy of flexible ureteroscopy (FURS) and percutaneous nephrolithotomy (PCNL) by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1 (sVCAM-1) and kidney injury molecule 1 (KIM-1) levels in patients with large kidney stones (> 2 cm in diameter).

METHODS

This single-center observational study was performed at a Chinese hospital between January 1, 2021, and October 30, 2023. All 250 enrolled patients were diagnosed with large kidney stones (> 2 cm) and divided into a FURS group (n = 145) and a PCNL group (n = 105) by the surgical method. The FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous nephrolithotomy. The operation time, time to palinesthesia, intraoperative blood loss, drop in hemoglobin, length of hospital stay, stone clearance rate, and complications were recorded in the two groups. Preoperative and postoperative serum sVCAM-1 levels, erythrocyte sedimentation rate (ESR), urine KIM-1 levels, preoperative and postoperative pain visual analog scale (VAS) and Wisconsin quality of life questionnaire (WISQOL) scores were also documented.

RESULTS

All 250 eligible patients completed the follow-up. There were no significant differences in baseline characteristics between the two groups (P > 0.05). The operation time in the FURS group was significantly greater than that in the PCNL group. The time to ambulation, intraoperative blood loss, decrease in hemoglobin, and length of hospital stay were significantly lower in the FURS group than in the PCNL group. The FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative complications. There was no significant difference in antibiotic use between the groups. Postoperative serum sVCAM-1 levels, urine KIM-1 levels, and VAS scores were lower in the FURS group than in the PCNL group, but postoperative ESR and WISQOL scores were greater in the FURS group than in the PCNL group.

CONCLUSION

FURS demonstrated superior clinical efficacy in treating large kidney stones (> 2 cm in diameter) compared PCNL. It not only improved the postoperative stone clearance rate and reduced complications and recovery time but also positively affected serum SCM-1, ESR, and urine KIM-1 levels, subsequent improvement of patient quality of life.

Key Words: Kidney stones, Flexible ureteroscopy, Percutaneous nephrolithotomy, Clinical effective, SCM-1, Erythrocyte sedimentation rate, Kidney injury molecule 1

Core Tip: Our large-sample clinical study aimed to explore the clinical effectiveness of flexible ureteroscopy and percutaneous nephrolithotomy for postoperative stone clearance and managing the levels of soluble vascular cell adhesion molecule 1 and kidney injury molecule 1 in patients with large kidney stones exceeding 2 cm in diameter.

INTRODUCTION

Percutaneous nephrolithotomy (PCNL) is the main treatment option and the preferred surgical procedure for the treatment of renal stones from 2–4 cm in diameter, offering an excellent stone-free rate (SFR)[1,2]. Advancements and developments in PCNL surgical methods have made PCNL the preferred treatment for kidney stones according to established guidelines. It is widely used in clinical practice owing to its minimally invasive nature, lower complication rates, better kidney stone clearance[3,4]. However, selecting puncture channels for ectopic stones is challenging, and patients may experience various serious complications after surgery.

Flexible ureteroscopy (FURS), a new endoscopic technique developed in recent years, uses a flexible ureteroscope with both active and passive flexure at its tip. This enables convenient access to various calyces and facilitates examination of the entire renal collection system, thereby minimizing the extensive trauma caused by PCNL. Previous studies have reported SFRs from 73% to 93.2% after FURS[5,6]. However, no large-sample clinical studies have confirmed the clinical efficacy and safety of this method, and there is a lack of comparative data on traditional treatment methods. Huang et al[7] reported that FURS achieved a satisfactory SFR and a relatively low complication rate using the relocation technique. Chen et al[8] also reported that FURS using a novel flexible ureteric access sheath, was a superior alternative to mini-PCNL for treating kidney stones from 2–3 cm in diameter. In addition, although there was no significant difference in the effectiveness of super-mini-PCNL and standard PCNL on renal calculi with a diameter > 3 cm, the length of hospital stay after super-mini-PCNL was markedly shorter[9].

Soluble vascular cell adhesion molecule-l (sVCAM-1) is important for the adhesion of lymphocytes to the inflammatory endothelium. The erythrocyte sedimentation rate (ESR), which is an indicator of red blood cell aggregation, can also be used to monitor early infection. Kidney injury molecule-1 (KIM-1) is known for its marked increase in proximal convoluted tubule epithelial cells after ischemic and toxic renal injury and for the fact that it is not affected by changes in urine physicochemical properties. In this large-scale study, we explored the clinical efficacy, inflammatory endothelium, red blood cell aggregation, early infection signs, and renal ischemic and toxic injury associated with FURS and PCNL by measuring serum sVCAM-1 levels, ESR, and urine KIM-1 levels. The clinical effectiveness of FURS and PCNL for postoperative stone clearance and in managing sVCAM-1 and KIM-1 levels were compared in patients with large kidney stones exceeding 2 cm in diameter.

MATERIALS AND METHODS

Study design and patients

A single-center observational study was conducted at our hospital in China from January 1, 2021, to October 30, 2023. The inclusion criteria were: (1) Preoperative urological imaging (B-ultrasound, plain films, CT, and magnetic resonance urography) confirming the presence of kidney > 2 cm in diameter; (2) unilateral kidney stones and normal blood urea nitrogen and creatinine levels before the operation; (3) able to tolerate surgery and anesthesia, with no dysfunction of important organs (heart, lung, liver, etc) following preoperative examination; (4) provided signed informed consent for the surgery and voluntarily choosing the surgical method; and (5) complete clinical records and follow-up data. The exclusion criteria were: (1) Kidney stones < 20 cm in diameter; (2) a high fever before the operation and a severe urinary tract infection confirmed by laboratory examination; (3) incomplete operative procedure or need of a second operation due to various factors; (4) unable to undergo normal surgical anesthesia for various reasons; (5) kidney malformations, urinary tract stenosis, ureteropelvic junction site stenosis, etc; (6) a history of mental illness, kidney surgery, or malignant tumors, etc; (7) poorly controlled blood sugar and blood pressure; and (8) severe hip and knee deformities, rendering the lithotomy position difficult.

The study collected comprehensive data from current medical records regarding factors that increase the likelihood of harm, such as sex, age, and cause of injury. Follow-ups were conducted via online or telephone communication. The registration number of the study was THH-IPR-2021103 (January 1, 2021).The study protocol was approved by the Clinical Research Ethics Committees of Wuxi Taihu Hospital (Approval Number THH-YXLL-2021-0103).

Method of FURS surgery

Conventional ureteroscopy was performed on the side affected by the kidney stone approximately 2 wk before surgery to facilitate the placement of a double-J (D-J) stent. On the day of the surgery, after the patient was positioned in lithotomy under general anesthesia, the indwelling D-J stent was removed. A ureteral access sheath (Cook Medical, Bloomington, IN, United States; male 14 Fr, 45 cm; female 14 Fr, 35 cm) was used to ensure proper urine flow to the renal pelvis. A flexible ureteroscope was used to explore the location, size, and number of stones. After removal of the zebra guide wire, a titanium laser fiber (230 µm) was inserted into the electronic ureteroscope to directly fragment the stones. Large stones were extracted using a stone basket to ensure that the residual fragments were < 3 mm in diameter. Postoperatively, D-J stents were reinserted and a urinary catheter was placed.

Method of PCNL surgery

The surgical instruments used were a 9.8 F ureteroscope with a power of 30 w, an 8.5 F ureteroscope with a power of 10 W, and a 200 µm soft mirror fiber. The surgical procedure consisted of several steps. The anesthesia options included epidural anesthesia, followed by positioning the patient in the lithotomy position. After dilating the urethra and placing the zebra guide wire, the ureteroscope was inserted into the affected renal pelvis. A sheath tube was inserted after the removal of the hard mirror, and then a soft mirror was inserted into the renal pelvis. This facilitated the determination of the location, size, and shape of the stones. Continuous pulse lithotripsy was the method of choice for stone fragmentation. Stone fragments were extracted using a lithotripsy net basket. An indwelling catheter was inserted after the procedure.

Follow-up and outcome evaluation

All patients completed 2 mo of follow-up, and survival data were obtained. The evaluation included clinical outcomes, complications, length of hospital stay, and hospitalization cost.

Perioperative indices: The operation duration, time to ambulation, intraoperative blood loss, decrease in hemoglobin level, and the total length of hospital stay were recorded. Stone clearance rates were evaluated 3 mo after surgery, with successful clearance defined as either no residual stones detectable by ultrasound or any remaining stone fragments being less than 2 cm in diameter. The use of antibiotics and postoperative complications, such as urine leakage of < 12 h and fever, a body temperature of > 38 °C, were recorded.

Biochemical indices: About 3 mL of peripheral blood was drawn from the patients at admission (preoperative level) and at 24 h after the operation (postoperative level) and then centrifuged (3000 rpm, 10 min, centrifugation radius 10 cm) to separate the serum. The serum sVCAM-1 concentration was measured with an enzyme-linked immunosorbent assay (ELISA), and the ESR was determined with a Westergren test tube assay. The concentration of KIM-1 in the urine was measured by ELISA in, 5-mL samples collected from both patient groups before and after surgery.

Questionnaire follow-up: Pain and quality of life were evaluated before and after surgery with the visual analog scale (VAS)[10] and the Wisconsin Quality of Life (WISQOL) scale[11].

Statistical analysis

The unpaired t-test was used to analyze normally distributed continuous data (mean ± SD), and the independent-samples Mann–Whitney U test was used to analyze non-normally distributed data. The χ² test or the χ² test with continuity correction was used to compare categorical data, as appropriate. Statistically significant mean differences or risk ratios were calculated taking into account two-sided 95% confidence intervals and P values < 0.05 were statistically significant. The statistical analysis was performed with SPSS version 24 for Windows (IBM Corp., Armonk, NY, United States). The assessments did not include any interim analyses.

RESULTS

Baseline patient characteristics of the overall population

An extensive evaluation was carried out on 316 individuals who presented with large kidney stones and underwent surgery at our hospital between January 1, 2021, and October 30, 2023. Two-hundred fifty patients met the inclusion criteria and were divided into two groups based on the surgical technique they underwent: the FURS group (n = 145) and the PCNL group (n = 105). No significant differences were observed in the baseline data of the two groups (Table 1). All patients included in the current study were successfully evaluated. The final follow-up for the last patient included in the study was conducted on December 31, 2023.

Table 1 Baseline data at admission.

Features	FURS, n = 145	PCNL, n = 105	P value
Age in years	43.67 ± 5.25	42.91 ± 5.07	0.253
Sex			0.945
Male	89 (61.38)	64 (60.95)
Female	56 (38.62)	41 (39.05)
Diameter of kidney stones in cm	2.83 ± 0.36	2.79 ± 0.32	0.365
Type of kidney stones
Pyelolithiasis	13 (8.97)	10 (9.52)	0.880
Lower calyceal calculi	32 (22.07)	27 (25.71)	0.926
Middle calyceal calculi	49 (33.79)	33 (31.43)	0.694
Upper calyceal calculi	51 (35.17)	35 (33.34)	0.763
Smoking history			0.939
Yes	49 (33.79)	35 (33.33)
No	96 (66.21)	70 (66.67)
Drinking history			0.642
Yes	62 (42.76)	48 (45.71)
No	83 (57.24)	57 (54.29)
Living environment			0.461
Town	99 (68.28)	67 (63.81)
Countryside	46 (31.72)	38 (36.19)
Side of kidney stones			0.860
Left	84 (57.93)	62 (59.05)
Right	61 (42.07)	43 (40.95)

Data are n (%) or mean ± standard deviation. FURS: Flexible ureteroscopy; PCNL: Percutaneous nephrolithotomy.

Clinical outcomes between the two groups

The duration of the operation for the FURS group was significantly longer than that for the PCNL group. The FURS group had a significantly shorter time to ambulation, less intraoperative blood loss and decrease in hemoglobin level, and a shorter hospital stay than the PCNL group (P < 0.05; Table 2). The FURS group had a higher postoperative clearance rate than the PCNL group (P < 0.05; Table 2), and the incidence of complications was lower in the FURS group than in the PCNL group (P < 0.05; Table 2). However, the use of antibiotics in the two groups was not significantly different (P > 0.05; Table 2).

Table 2 Clinical outcomes.

Parameter	FURS, n = 145	PCNL, n = 105	P value
Operative time in minutes	95.37 ± 11.94	67.19 ± 20.55	0.000
Time to bed activity in hours	7.95 ± 2.19	19.67 ± 2.74	0.000
Intraoperative blood loss in mL	15.83 ± 2.57	75.28 ± 19.64	0.000
Hemoglobin decline in g/L	3.19 ± 0.66	11.09 ± 1.84	0.000
Hospital stays in days	5.71 ± 1.37	7.15 ± 1.53	0.000
Postoperative clearance rate	133 (91.72)	78 (74.29)	0.000
Usage rate of antibiotics	11 (7.59)	21 (20.00)	0.004
Complications
Urine leakage	0 (0)	8 (7.62)	0.001
Fever	12 (8.28)	24 (22.86)	0.003

Data are n (%) or mean ± standard deviation. FURS: Flexible ureteroscopy; PCNL: Percutaneous nephrolithotomy.

Comparison of biochemical indices between the groups

The serum sVCAM-1 and urine KIM-18 levels were significantly lower in the FURS group than in the PCNL group. However, the serum ESR was significantly higher in the FURS group than in the PCNL group (P < 0.05; Table 3).

Table 3 Comparison of the biochemical indices.

Index	FURS, n = 145		PCNL, n = 105		P value
	Preoperative	Postoperative	Preoperative	Postoperative
sVCAM-1 in ng/mL	229.04 ± 39.17	531.58 ± 49.26a	234.53 ± 38.72	894.01 ± 52.08a	0.000
KIM-18 in mm/h	72.34 ± 12.29	92.25 ± 17.67a	73.66 ± 12.92	116.42 ± 26.17a	0.000
ESR in ng/mL	16.85 ± 1.41	8.29 ± 0.65a	16.17 ± 1.38	7.18 ± 0.62a	0.000

^aP < 0.05, vs same group preoperative biochemical indices levels.

Data are mean ± standard deviation. Postoperative biochemical indices levels in FURS group vs PCNL group, P < 0.001. ESR: Erythrocyte sedimentation rate; FURS: Flexible ureteroscopy; KIM-18: Kidney injury molecule 1; PCNL: Percutaneous nephrolithotomy; sVCAM-1: Soluble vascular cell adhesion molecule 1.

Comparison of VAS and WISQOL scores between the groups

The VAS score was significantly lower in the FURL group than in the PCNL group, and the WISQOL score was significantly greater in the PCNL group than in the FURL group (P < 0.05; Table 4).

Table 4 Comparison of visual analog scale scores and Wisconsin Quality Of Life Questionnaire scores.

Score	FURS, n = 145		PCNL, n = 105		P value
	Preoperative	Postoperative	Preoperative	Postoperative
VAS	5.61 ± 1.59	2.19 ± 0.75a	5.52 ± 1.53	3.35 ± 1.14a	0.000
WISQOL	109.62 ± 14.97	127.95 ± 10.52a	110.22 ± 15.26	120.74 ± 11.51a	0.000

^aP < 0.05, vs same group preoperative biochemical indices levels.

Data are mean ± standard deviation. Postoperative biochemical indices levels in FURS group vs PCNL group, P < 0.001. FURS: Flexible ureteroscopy; PCNL: Percutaneous nephrolithotomy; VAS: Visual analog scale; WISQOL: Wisconsin quality of life questionnaire.

DISCUSSION

PCNL is the preferred treatment for kidney stones with a diameter of > 2 cm, but postoperative complications can be severe[12,13]. In patients with a history of open surgery or secondary surgery, repeated PCNL may cause serious kidney damage[4,14,15]. FURS is also widely used to treat kidney stones owing to its advantages of having a slender and soft lens[16]. However, it is generally not used alone for the treatment of kidney stones with a diameter exceeding 2 cm[17,18]. With advances in medical technology and accumulation of clinical experience, the efficacy of FURS for the treatment of kidney stones of 2–3 cm in diameter has become increasingly recognized[17,19,20].

The study compared and analyzed the therapeutic efficacy of FURS and PCNL in treating kidney stones > 2 cm in diameter. Despite the longer duration of the FURS procedures, it was found to reduce intraoperative blood loss and postoperative drop in hemoglobin level, and had shorter of postoperative bed and hospital stays than PCNL, which was consistent with the results of previous studies[20]. Large stones may require multiple FURS treatment. During FURS, a titanium laser fiber (230 µm) is inserted into the electronic ureteroscope to directly fragment the stones, which may extend the operative time of the procedure compared to PCNL.

FURS can be performed on areas inaccessible to conventional ureteroscopy while avoiding the need for cutaneous and renal channels required during PCNL surgery, which reduces trauma to the surrounding tissue and organs. Compared to hard endoscopic procedures, soft-lens procedures, such as FURS, cause less damage to the ureteral wall, and promote the postoperative recovery of patients to a certain extent. In the absence of postoperative complications, the indwelling catheter could be removed the day after surgery in the FURS group. In the PCNL group, owing to the need to establish a puncture channel during the procedure, absolute postoperative bed rest was required to avoid active bleeding of the kidney caused by exercise. FURS was thus more conducive to postoperative recovery. This study also found that the FURS group had a relatively high stone clearance rate and a lower incidence of complications, which may have been associated with the flexible nature of the FURS devices, which facilitates removal of kidney stones and complex stones with less surgical trauma and a relatively low incidence of complications[21].

Recent studies have shown that Sun’s tip-flexible semirigid ureterorenoscopy was advantageous in terms of operation time, cost, and level of comfort, but that it was associated with a higher incidence of postoperative fever[22]. Extracorporeal shock wave lithotripsy is highly successful and safe for treating kidney stones but is generally used for stones smaller than 2 cm in diameter[23]. Zhu et al[24] reported that multisession FURS was a safe and effective alternative to PCNL for the treatment of intermediate-size renal stones (2–3 cm). To further explore the efficacy of FURS and PCNL for the treatment of kidney stones exceeding 2 cm in diameter, this study evaluated several biochemical indicators. The sVCAM-1 concentration reflects body injury, and the ESR mainly reflects the correlation between the aggregation of blood fibrinogen and immunoglobulin and the rate of erythrocyte decline. After FURS surgery, both serum sVCAM-1 concentration and ESR decreased, indicating that the operation was less invasive and that the risk of infection was also relatively lower.

Urinary KIM-1 level effectively reflects kidney injury, and the decrease in the level in the urine of patients treated with FURS indicated that this procedure caused less damage to renal function compared to other methods. This study also included a comparative analysis of patient feelings. The results of self-assessment scales revealed that the VAS scores of patients treated with FURS were lower and their WISQOL scores were higher than those of the PCNL patients, indicating a high acceptance of the operation.

This study has several limitations. Firstly, the sample size was relatively small and included relatively few patients in each group, which reduced the statistical power of the analysis. Secondly, as this was a single-center study with a cross-sectional and retrospective design, it was not possible to establish a causal relationship based on the data obtained. Thirdly, some baseline data were missing. We recommend that a similar but better controlled, larger, multicenter study be conducted to confirm the promising findings of our study. In the future, more treatment options and individualized treatment need to be explored.

CONCLUSION

In summary, FURS was effective in treating kidney stones with a diameter > 2 cm, significantly reducing the duration of postoperative rehabilitation. Moreover, the procedure had little influence on serum sVCAM-1 concentration, ESR, and urinary KIM-1 levels, suggesting that FURS benefits included not only surgical outcomes but also postoperative quality of life.