Ureteroscopy and Laser Stone Fragmentation Is Safe and Tends to Improve Renal Function in Patients with Chronic Kidney Disease: Prospective Outcomes with a Minimum Follow-Up of 6 Months

Abstract

Introduction:

The role and long-term follow-up of ureteroscopy and laser stone treatment (URSL) in patients with chronic kidney disease (CKD) is unclear. Given conflicting results and a lack of robust data, we looked at the results of URSL in patients with CKD.

Methods:

Over a 6.5-year period (March 2012–July 2018), prospective outcomes were recorded for consecutive patients who underwent URSL for ureteral or renal stones. The inclusion criteria were all patients with CKD II–V. Renal function was checked preoperatively and at a minimum of 6 months postprocedure. Data were collected and analyzed for patient and stone demographics, procedural and postoperative details, and complications.

Results:

Over the study period, 277 patients with preoperative CKD stage II–V were included with a male:female ratio of 188:89 and a mean age of 66.6 years. The mean preoperative estimated glomerular filtration rate (eGFR) (mL/minute) was 63 (range: 14–89, ±18) with 167 (60.2%) CKD II, 70 (25.2%) CKD IIIa, 27 (9.7%) CKD IIIb, 10 (3.6%) CKD IV, and 3 (1%) CKD V patients. The mean single stone size was 9.6 mm (range: 3–37 mm, ±5.2) and 35.3% had multiple stones. The stone was located in the ureter for 112 patients, kidney for 137 patients, with 28 patients who had stones in both ureter and kidneys. A pre- and postoperative stent was present in 34.3% to 60% and 82.6% to 100% of patients, respectively, with an access sheath used in 103 (37.8%). The mean operative time was 44.5 minutes, with a stone-free rate of 91.6%. Postoperatively the mean eGFR improved to 68 (±20) (p < 0.002). Complications occurred in 22 (7.9%) patients of which 18 were Clavien I/II and 4 were Clavien III/IV complications.

Conclusion:

URSL is safe and effective in patients with CKD with most patients discharged the same day of surgery. For majority of patients with both ureteral and renal stones, the renal function either stayed stable or improved after ureteroscopy on a long-term follow-up irrespective of their underlying CKD status.

Introduction

The incidence of kidney stone disease (KSD) is rising with a lifetime prevalence of 14%.^1,2 Although benign, it can impair renal function as a consequence of obstruction or infection from stones, parenchymal damage from primary condition that led to KSD, or surgical intervention for KSD.³ Surgical treatment of KSD includes extracorporeal shockwave lithotripsy (SWL), percutaneous nephrolithotomy (PCNL), and ureteroscopy (URS).^4,5 The safety and efficacy of ureteroscopy and stone treatment (URSL) is well established in high-risk patients, such as patients with solitary kidneys, pediatric patients, and pregnancy.^4

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It is generally accepted that stone removal will improve renal function, but it is unclear if the surgical procedure required to remove the stone will have a detrimental effect.³ There is a theoretical risk with URSL because of irrigation-related intrarenal pressure, which causes pelvicaliceal dilatation, along with the use of laser energy that can potentially cause heat-related renal tissue damage.^9,10 Although in patients with normal renal function this might not be detrimental, the effect is likely to be more pronounced in patients with pre-existing chronic kidney disease (CKD).¹¹

Removal of stones and the impact of URSL in patients with CKD is largely unknown with only a handful of studies on it.^11

–16 Some of these studies that report on the renal function report conflicting results. Yang and colleagues in their retrospective study suggest a positive effect on renal function for bilateral upper tract calculi.¹² Cho and colleagues report that poor preoperative renal function was predictive of poor postoperative renal function.¹¹ In addition, four studies have shown no statistically significant effect of URS on postoperative renal function.^13

–16 Given conflicting results and a lack of robust data, we looked at the results of ureteroscopy and stone treatment in patients with CKD. We hypothesized that URS and stone removal improves renal function in patients with CKD. Therefore, the objective of this study was to determine the effect of URS and stone removal in patients with pre-existing CKD.

Methods

Patients

Over a 6.5-year period between March 2012 and July 2018, prospective outcomes were recorded for consecutive patients who underwent ureteroscopy and lasertripsy for ureteral or renal stones. The study was registered as an “Outcomes of Ureteroscopy” audit with the hospital “Clinical effectiveness and audit office.” The inclusion criteria were all patients with CKD II–V who underwent URSL procedure for ureteral or renal or multiple stones. Pediatric patients and those with normal renal function were excluded. The total number of patients who underwent URS for stone disease (inception cohort) during this time period was 876.

Renal function

Estimated glomerular filtration rate (eGFR) was measured pre- and postoperatively, and derived using the Modification of Diet in Renal Disease study group equation.¹⁷ The National Kidney Foundation classification of CKD was used to classify patients into categories based on eGFR; group II: eGFR 60 to 90 mL/minute, group IIIa: eGFR 45 to 60 mL/minute, group IIIb: eGFR 30 to 45 mL/minute, group IV: eGFR 15 to 30 mL/minute, and group V: eGFR <15 mL/minute.¹⁸ Patients with preoperative group II and above were included in our study. A change in CKD group with improvement or deterioration of renal function was considered a significant change in renal function.

Surgical procedure

All patients had non-contrast computed tomography of kidneys, ureters, and bladder (CTKUB) for diagnosis of stones. Subsequently the decision for URSL was mutually made by the patient and the endourology team in a “Specialist Stone Clinic.” The patients were seen in uro-anesthetist-led preassessment clinic.^19,20 They had their renal function and urine culture along with chest X-ray and other tests as deemed appropriate for a general anesthetic.

Patients were admitted to a dedicated “Surgical day unit” on the day of surgery. They were given oral paracetamol as a premedication and underwent a laryngeal mask airway anesthetic. They received a protocol-based intravenous antibiotic on anesthetic induction based on the urine culture results and their renal function. During the procedure they received 500 mL of intravenous crystalloid and antiemetic. Rescue analgesia was opioid based and titrated to their pain. Patients were discharged with 3 days of regular paracetamol, with tramadol, or dihydrocodeine as rescue analgesia. Unless there were any clinical concerns, the procedures were electively planned as day-case surgeries.

The day of surgery begun with a World Health Organization checklist and all URS procedures followed a standard validated protocol.^19,20 After insertion of safety wire, a rigid URS (4.5F or 6F Wolf or Storz) was performed over an access wire. A ureteral access sheath (9.5F/11.5F or 12F/14F Cook Flexor sheath, Cook Medical) was used for renal stones followed by flexible ureteroscopy with laser fragmentation, basket extraction, or both techniques used in conjunction. A cook Ngage stone extractor (Cook Medical) was used to extract fragments for stone analysis. The intrarenal pressure was kept as low as possible although this was not measured. After the URSL a 6F ureteral stent was placed, which was removed 2 to 4 weeks postprocedure. Renal function was checked at a minimum of 6 months postprocedure and was obtained by the electronic hospital laboratory records. Stone-free rate (SFR) was defined as endoscopically stone free and clinically insignificant fragments ≤2 mm.²¹ Postoperative imaging was using an ultrasonography or CTKUB for radiolucent stone and plain XR for radiopaque stones after 2 to 4 months.

Outcomes

Outcomes were collected for patients who were operated or supervised by a single surgeon (B.K.S.) and data were analyzed by a third party (T.R.) not involved in the original procedure. Patients were divided into five groups based on their renal function (CKD II, CKD IIIa, CKD IIIb, CKD IV, and CKD V). Data were collected and analyzed for patient and stone demographics, pre- and postoperative renal function, procedural details, SFR, and complications. Complications were classified according to the Clavien–Dindo classification.²² The primary outcome measure was the effect of URS on renal function in patients with CKD, and secondary outcomes were SFR and complications related to the procedure.

Statistical analysis

Data were recorded on an excel spreadsheet (Microsoft) and all statistical analyses were undertaken using SPSS version 25 (IBM, Armonk, NY). Means were compared using t-test. Variables predicting deteriorating renal function were compared using binary logistic regression analysis.

Results

Over a period of 6.5 years, 277 patients with preoperative CKD stage II–V were included with a male:female ratio of 188:89 and a mean age of 66.6 years (range: 27–92 years, ±14.4) (Table 1). The mean preoperative eGFR (mL/minute) was 63 (range: 14–89, ±18) with 167 (60.2%) CKD II, 70 (25.2%) CKD IIIa, 27 (9.7%) CKD IIIb, 10 (3.6%) CKD IV, and 3 (1%) CKD V patients (Table 2).

Table 1.

Baseline Demographics of Whole Cohort

N = 277 (CKD II-167, CKD IIIa-70, CKD IIIb-27, CKD IV-10, and CKD V-3)
Male:female	189:89
Age (years), mean (range, ±SD)	66.6 (29–92, ±14.4)
Mean preoperative eGFR (mL/minute), n (range, SD)	CKD II: 75 (61–89, ±9)
	CKD IIIa: 53 (45–60, ±4)
	CKD IIIb: 37 (30–44, ±4)
	CKD IV: 24 (16–28, ±4)
	CKD V: 14 (14–15, ±1)
Diameter of largest stone (mm), mean (range, ±SD)	9.6 (2–37, ±5.2)
Ureteral: renal stones: both, n, (%)	Ureter: 112 (40.5)
	Renal: 137 (49.5)
	Both: 28 (10.1)
Multiple stones, n, (%)	98 (35.4)
Access sheath use, n, (%)	104 (37.5)
Operative time, mean (range, ±SD) (minutes)	44.5 (9–141, ±25.7)
Stone-free rate, n, (%)	254 (91.7)
Complications, n, (%)	22 (7.9)
Length of stay, mean (range, ±SD) (days)	0.8 (0–29, ±2.3)

CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; SD = standard deviation.

Table 2.

Baseline Characteristics and Operative Detail by Preoperative Chronic Kidney Disease Group

		Age		No. of stones		Stone size		Cumulative stone size		Stone location				Operative time (minutes)		Preoperative stent		Postoperative stent		Access sheath
Preoperative CKD groups	n	Mean (range)	SD	Mean (range)	SD	Mean (range)	SD	Mean (range)	SD	Ureter		Kidney		Mean	SD (range)	% yes	n	% yes	n	% yes	n
Preoperative CKD groups	n	Mean (range)	SD	Mean (range)	SD	Mean (range)	SD	Mean (range)	SD	%	n	%	n	Mean	SD (range)	% yes	n	% yes	n	% yes	n
II	167	66 (91–27)	15	2 (8–0)	1	9 (2–37	5	12 (3–44)	8	51.67	86	48.33	81	44	26 (9–141)	34.34%	57	82.61%	133	38.41%	64
IIIa	70	66 (92–30)	14	2 (7–0)	1	9 (3–37)	6	12 (2–58)	11	57.41	40	42.59	30	43	24 (12–129)	45.71%	32	82.61%	57	38.24%	27
IIIb	27	70 (91–29)	14	1 (4–1)	1	9 (4–16)	4	11 (2–28)	6	70.37	19	29.62	8	50	29 (22–129)	50.00%	13	95.65%	22	29.63%	8
IV	10	76 (86–60)	9	2 (6–1)	2	13 (10–20)	6	20 (4–48)	16	40.00	4	60.00	6	49	29 (19–115)	60.00%	6	100.00%	10	60.00%	6
V	3	82 (86–77)	5	3 (4–0)	2	11 (5–16)	6	26 (5–58)	23	100.00	3	0.00	0	55	43 (10–96)	0.00%	0	100.00%	2	0.00%	0

The mean single stone size was 9.6 mm (range: 3–37 mm, ±5.2) and 35.3% had multiple stones. The stone location was in the ureter for 112 patients (51.6% CKD II, 57.4% CKD IIIa, 70% CKD IIIb, 42.8% CKD IV, and 100% CKD V) and kidney for 137 patients (48.3% CKD II, 42.5% CKD IIIa, 30% CKD IIIb, and 57.1% CKD IV), with 28 patients who had stones in both ureter and kidneys. A preoperative stent was present in 34.3% to 60% of patients with CKD II–IV and a postoperative stent was placed in 82.6% to 100% of patients with CKD II–V patients. An access sheath was used in 103 (37.8%) patients. The mean operative time was 44.5 minutes (range: 9–141 minutes, ±25.7) and 254 patients (91.6%) were stone free.

Postoperative complications occurred in 22 (7.9%) patients (Tables 3 and 4). This included 11 urinary tract infection/urosepsis (2 Clavien I, 7 Clavien II, and 2 Clavien IVa), 3 postoperative urinary retention (Clavien I), 2 postoperative delirium (Clavien I), 2 pneumonia (1 Clavien I and 1 Clavien II), 1 hematuria requiring catheterization (Clavien I), 1 slipped stent requiring removal and replacement (Clavien IIIb), 1 type 2 respiratory failure requiring noninvasive ventilation (Clavien IVb), and 1 postoperative pain requiring readmission (Clavien I) (Table 4). There was a trend of higher complications for patients with higher CKD stage although this was not statistically significant. The mean SFR was 91.6% and was similar across groups (Table 3). Overall, 81.9% (227/277) went home the same day (day-case procedures). The overall mean length of stay was 0.8 days (range: 0–29, ±2.32).

Table 3.

Preoperative Renal Function and Postoperative Outcomes

		eGFR preoperative		eGFR postoperative		Significant change	Deteriorated function	Improved function	Stone free	Completed as day-case		Complications		Clavien–Dindo complications
Preoperative CKD groups	No. of patients	Mean (range)	SD	Mean (range)	SD		%	%	% yes	% yes	n	% yes	n	1	2	3b	4a	4b
II	167	75 (61–89)	9	78 (39 to >90)	11	CI: 0.8, 3.88 p < 0.002	9.58	29.34	91.72%	82.63%	138	4.7%	8	6	2	0	0	0
IIIa	70	53 (45–60)	4	63 (21 to >90)	17	CI: 5.97, 14.02 p < 0.0001	10.00	20.00	90.00%	81.43%	57	8.5%	6	1	4	0	0	1
IIIb	27	37 (30–44)	4	45 (23 to >90)	18	CI: 1.97, 15.48 p < 0.014	0.00	66.67	100.00%	77.78%	21	11.1%	3	0	1	0	2	0
IV	10	24 (16–28)	4	27 (12–44)	12	NS	5.71	42.86	92.75%	80.00%	8	3/10	3	1	1	1	0	0
V	3	14 (14–15)	1	15 (6–20)	8	NS	18.52	22.22	88.00%	66.67%	2	1/3	1	1	0	0	0	0

CI = confidence interval; NS = not significant.

Table 4.

Complications According to Clavien–Dindo Grade

Clavien–Dindo grade	Complication (no.)
1	Urinary retention (3); UTI (2); delirium (2); hematuria (1); Pneumonia (1); Pain (1)
2	UTI/urosepsis (7); pneumonia (1)
3a	None
3b	Slipped stent requiring removal and replacement (1)
4a	Urosepsis requiring ionotropic support (2)
4b	Type 2 respiratory failure (1)
5	None

UTI = urinary tract infection.

After mean follow-up of 112 weeks (range: 26–260 weeks) the mean eGFR was 68 (±20), which was a significant improvement from baseline (p < 0.002, confidence interval [CI]: 8.05, 1.79). This trend was noted across all preoperative CKD stages and was statistically significant for groups II, IIIa, and IIIb (Table 3). The renal function for most CKD patient groups remained stable. However, a shift in the group and improvement was seen in 29.3% CKD II patients, 20% CKD IIIa patients, 67% CKD IIIb patients, 42.8% CKD IV patients, and 22.2% CKD V patients. A similar shift and deterioration of CKD group was seen in 9.5% CKD II patients, 10% CKD IIIa patients, 5.7% CKD IV patients, and 18.5% CKD V patients.

In addition, patients with both ureteral and renal stones had improved renal function. For ureteral stones, the mean preoperative eGFR was 62 (range: 14–89, ±17), which improved postprocedure to 69 (range: 6–90, ±20) (p < 0.001; CI: 4.63, 9.62). For renal stones, the mean preoperative eGFR was 65 (range: 14–89, ±18) and which improved postprocedure to 67 (range: 12–90, ±20) (p < 0.017; CI: 0.51, 4.97).

Regression analysis was applied to test for association between patient variables and postoperative renal function. Age, preoperative eGFR, stone size, and operative time were all tested, and none was found to be significant predictors of postoperative renal function decline.

Discussion

Meaning of the study

Our study represents one of the largest prospective series of patients with CKD who underwent URSL. The minimum and mean follow-up are 6 months and 2 years, respectively, and this reflects an overall improvement of renal function for both ureteral and renal stones. This was seen for all patients with CKD II–V, although because of small number of CKD IV and V patients it was not statistically significant. Patients who have acute kidney injury are likely to improve more than patients who have CKD. Similarly, patients with obstructive ureteral or renal stone are more likely to see improved renal function after surgical removal. The overall SFR across the groups varied from 88% to 100% and majority of patients went home the same day. The complication rates were slightly higher for patients with worsening renal function, but these were mostly Clavien I or II complication.

Role of ureteroscopy and stone treatment in patients with chronic kidney disease or solitary kidney

Any endourologic intervention for patients with CKD should aim to preserve or improve renal function and to achieve maximal stone clearance with minimal morbidity. Although URS offers good SFR, it is less morbid than PCNL.²³ The safety of URSL in solitary kidneys has been shown recently with a substantial rise in these procedures worldwide.^4,24 This must, however, take into account the intrarenal pressure used, avoidance of drugs that can aggravate CKD, and minimizing complications related to extravasation, ureteral injury, or renal hematoma. CKD is also associated with other comorbidities that affect long-term renal function. Resolution of stone-related obstruction or infections in these patients not only helps in preservation but also avoids further long-term deterioration of renal function. Stone-free status and minimizing repeated procedures is likely to help this. Previous studies have also shown a slight improvement in renal function of patients with CKD, but they were either retrospective or had a short-term follow-up.^11

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Strengths, limitations, and areas of future research

This is a large study on CKD II–V patients, including consecutive patients for a long-time period with a minimum follow-up of 6 months. Data on renal function, SFR, complications were all collected in a standardized manner and analyzed independently. Although deterioration in renal function was seen in a small proportion of patients with CKD, for vast majority the renal function either stayed stable or improved significantly. However, we did not have complete data on elective or emergency URS, presenting symptoms, patient comorbidities, and intrarenal pressure was not measured. Similarly, as majority of patients were discharged the same day, the immediate post-URSL renal function was not captured uniformly although we did capture the long-term renal function.

Future research should include data from multiple centers with patient comorbidities and perhaps randomize and compare other treatment options such as minimally invasive PCNL or SWL for these stones. It is vital to understand the effect of intrarenal pressure, access sheath, and the temperature variation that happens with lasers. These need to be addressed, so we can understand the overall effect on renal function during URSL.

Conclusion

URS and laser stone fragmentation are safe and effective in patients with CKD with most patients discharged the same day of surgery. For majority of patients with both ureteral and renal stones, the renal function either stays stable or improves after the URS on a long-term follow-up irrespective of their CKD status. Several patient and operative factors may play a role in determining this and further study is required in order for these factors to be identified.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

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