High-Power Lasers Induce Dose-Dependent Acute Kidney Injury

Abstract

Introduction and Objective:

High-powered lasers have been hypothesized to cause kidney injury; however, no human studies have confirmed or quantified this damage. Our objective was to identify and quantify damage and explore factors affecting degree of injury in patients undergoing retrograde intrarenal surgery (RIRS) with thulium fiber laser (TFL) and Holmium:YAG (Ho:YAG) lasers.

Methods:

Patients undergoing RIRS for unilateral nonobstructing renal stones were randomized to receive lithotripsy with either a 60 W SuperPulse TFL or 120 W pulse-modulated Ho:YAG laser. A control group of patients undergoing RIRS without laser use were used for comparison. Urine samples were collected at 3 time points as follows: preoperative, 1 hour postoperative, and 10 days postoperative. Samples were analyzed using ELISA for key biomarkers—kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin—normalized to urine creatinine. Primary outcome was the extent of renal injury based on biomarker elevation.

Results:

Ninety-one patients with similar baseline patient and stone characteristics were randomized (46 TFL, 45 Ho:YAG). Both lasers led to significant biomarker elevation, which trended toward but did not reach baseline by postoperative day 10. The Ho:YAG laser resulted in a sustained increase in NGAL at 10 days. Multivariate analysis demonstrated that injury is dose dependent on total laser energy used (p < 0.001, p = 0.006) and worse in older patients (p = 0.009) and in those with metabolic syndrome (p = 0.002), with slower recovery in both these groups, but not with the type of laser used. Multiple levels of the nephron are involved.

Conclusions:

There is notable kidney injury induced by both SuperPulse TFL and pulse-modulated Ho:YAG lasers in a dose-dependent manner, but the 2 lasers do not differ in the degree of injury. Injury occurs at multiple levels. Age and metabolic syndrome affect the amount of injury and recovery from injury. Further studies evaluating factors that can mitigate damage from high-energy lasers are needed.

Introduction

Lifetime incidence of kidney stones in the United States approaches 10%.¹ Ideally, treatment would be efficient, efficacious, and minimize renal damage. Shockwave lithotripsy (SWL) procedures, considered less invasive, have decreased as better endoscopes and high-powered lasers (HPLs) have made retrograde intrarenal surgery (RIRS) more efficient. Holmium:YAG (Ho:YAG) lasers have been enhanced with pulse modulation and high-frequency capabilities. The recently introduced SuperPulse thulium fiber laser (TFL) is capable of frequencies as high as 2400 Hz.² HPLs increase the efficiency of stone ablation, but in vitro and human studies show that they increase surrounding fluid temperature, and in vitro studies show histologic evidence of kidney injury. No human studies have measured or compared degree of kidney injury from HPLs.^3

–6 Urine biomarkers noninvasively quantify renal injury in vivo.^7,8 We used urinary biomarkers to quantify renal injury caused by HPLs during RIRS.

Methods

Study design

We conducted an IRB-approved single center, randomized control trial (IRB 21-00084) on patients over 18 years old with renal stones 6 mm to 20 mm undergoing laser RIRS. Eligible patients were consented in the preoperative area by a member of the surgical team. Exclusion criteria included ureteral stones, hydronephrosis, chronic kidney disease (CKD) (eGFR <60), solitary kidney, prestented patients, prior ureteroscopy within 9 weeks, urinary retention, neurogenic bladder, or urinary tract infection within 2 weeks. Intraoperative exclusion criteria included findings of bladder stone(s), urothelial tumor(s), new onset obstruction absent on preoperative imaging, or failure to reach the stone. There were no deviations from the protocol. The study was registered with clinicaltrials.gov (NCT05350423).

Randomization and procedure

The purpose was to evaluate noninferiority of two laser modalities with regard to occult kidney damage defined as producing a change in eGFR of 1 mg/mL based on two prior studies by Fahmy and colleagues and van Timmeren and associates.^9,10 Fahmy prospectively compared urinary kidney injury molecule-1 (KIM-1) levels after SWL and laser RIRS. SWL in 50 patients resulted in KIM-1 increasing from 5.78 to 10.14 ng/mL after 2 hours (p < 0.001), but RIRS in 10 patients effected no change (5.78 to 5.49 ng/mL). van Timmeren and coworkers evaluated 11 healthy controls and 53 patients with varying kidney diseases and found a −27.5 correlation (p = 0.016) between KIM-1 and eGFR. That is, a 1 ng/mL rise in KIM-1 correlated to a 27.5 mL/min decline in eGFR. To power our study using an eGFR change of 10 mg/mL with an allocation ratio of 1:1, 99% power, noninferiority limit of 20%, and alpha of 5% using the noninferiority power calculation, we required 49 patients in each study arm. Factoring a 10% dropout rate, we sought to enroll 108 patients. Patients were randomized to Ho:YAG (Lumenis P120 with Moses 2.0) or SuperPulse TFL (Olympus Soltive Premium). Block randomization was performed via sealedenvelope.com with the scheme stored on a password-protected computer. Patients and surgeons were blinded to group allocation by not revealing the treatment until a stone was visualized.

The first sample (preoperative [V1]) was collected after induction of anesthesia and prior to surgical intervention using a Foley catheter. Procedures were conducted by experienced endourologists (M.G. and W.A.) with standardized methodology, including use of a Storz Flex-X2 7.5F flexible ureteroscope, no ureteral access sheaths (UASs), and use of only gravity irrigation at 80 cm H₂O (∼60 mm Hg) with no pressurized, mechanical, or hand irrigation systems. Upon entering the renal pelvis, full pyeloscopy ensured that the stone burden was consistent with preoperative imaging. Treatment allocation was revealed by a research assistant, and the allocated laser was brought into the room. Patients consenting for the study who had ureteroscopy, but did not require laser treatment (stones basket extracted or stone in question submucosal/parenchymal and not amenable to treatment), served as the control group to assure that laser energy itself, not ureteroscopy, was responsible for biomarker elevation.

In standard practice, although not using a UAS or using pressurized irrigation, we do frequently pause and aspirate renal pelvic fluid during treatment to prevent generating high temperatures with high-power settings and to improve observation. Starting settings were 0.5 J and 5 Hz for Ho:YAG and 1 J and 2 Hz for TFL and increased to 0.5 J and 50 Hz (25 watts) in every patient to achieve high-powered dusting with the goal to generate particles smaller than the laser fiber (200 µm). Power is increased to 25 watts only for brief intervals, not exceeding 5 seconds. For duty cycle management, laser activation is limited to 10-second bursts, followed by a mandatory 20-second pause to reduce cumulative heat deposition. In addition, frequent aspiration of the collecting system fluid is performed between laser activations to further mitigate thermal buildup.

Laser settings, total laser energy, laser on/off time, lasing time, and operative time were documented. Visible laser-induced tissue damage was documented and graded as follows:

Level 0:

No visible damage to mucosa; minor erythema because of scope-related trauma. Level 1:

Blanching or fluffing of mucosa after contact with laser; no evidence of mucosal disruption (bleeding should not be present).

Level 2:

Penetration to submucosal tissues; obvious defect in mucosal layer after contact with laser, +/- bleeding, no extravasation of contrast.

Level 3:

Full-thickness perforation of renal pelvis (contrast extravasation) or observation of renal parenchyma or fat.

All procedures (including control patients) concluded with placement of a 6F silicone stent (Black Silicone Filiform Double Pigtail Ureteral Stent, Cook Medical, Indiana, USA) and a 16F Foley catheter as per study protocol.

The second urine sample (1 hour postoperative [V2]) was obtained 1 hour postoperatively in the recovery room via the aspiration side port of the indwelling Foley catheter at catheter removal, and the third sample (10 days postoperative [V3]) 10 days postoperatively via a voided urine sample just prior to stent removal.

Urinary biomarker analysis

Urine samples were analyzed for spot urine creatinine and by ELISA for 3 biomarkers as follows: KIM-1, neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2M)—all normalized to the simultaneously collected urine creatinine levels. Levels of KIM-1, NGAL, and β2M were determined by the commercially available MILLIPLEX® Kidney Injury Magnetic Bead Luminex Assay Panels (EMD Millipore/Millipore Sigma, Billerica, Massachusetts). Urine samples were centrifuged at 13,500 RPM for 10 minutes at 4°C to clear precipitates prior to assay. Samples were diluted 1:2 for KIM-1, 1:100 for NGAL, and 1:500 for β2M with assay buffer and measured in duplicate on 96-well plates. Incubation was done overnight (16–18 hours) with primary capture antibody at 4°C followed by detection antibody at room temperature for 1 hour and then for 30 minutes with streptavidin–phycoerythrin. Plates were read on the Luminex Flexmap 3D System. Data were analyzed using MILLIPLEX Analyst 5.1 software (EMD Millipore/Millipore Sigma, Billerica, Massachusetts).

Outcomes

Primary outcome was extent of renal injury measured by changes in urinary biomarkers from baseline. Secondary outcomes were total laser energy used, lasing time, lithotripsy time, laser ablation efficiency, laser energy consumption, laser ablation speed, laser activity (operator duty cycle), postoperative complications, readmissions, and emergency room visits for 3 months after operation.

Statistics

Baseline characteristics and stone information are shown in Table 1 and operative data in Table 2. Statistical significance was assessed using Mann–Whitney U tests for continuous variables and either Chi-squared or Fisher’s Exact tests for categorical variables. Trends in KIM-1, NGAL, and β2M levels from V1 to V3 were calculated for Ho:YAG, TFL, and control groups (Fig. 2). Paired sample t-tests assessed whether changes in biomarker concentration from V1 to V2, V2 to V3, and V1 to V3 were significant for each group, including controls (Fig. 3). Multivariate linear regression analysis was performed to evaluate laser type as a predictor of percent change of biomarkers from V1 to V2, V2 to V3, and V1 to V3 (Table 3). Variables in the multivariate model were selected a priori or if they demonstrated a p-value less than 0.1 on univariate analysis. Collectively, these included operative group, age, presence of metabolic syndrome, preoperative eGFR, operative time, and total laser energy. All statistical analyses were performed using SPSS Statistics Version 28 (IBM Corp., Armonk, N.Y., USA) with a two-tailed alpha of 0.05 indicating significance.

Table 1.

Demographics and Preoperative Information

	Holmium group (n = 45)	Thulium group (n = 46)
Age [IQR]	56.0 [39.0–67.5]	59.0 [46.5–63.5]
BMI [IQR]	27.4 [23.8–30.4]	25.8 [23.8–29.4]
Gender, n (%)
Male	18 (40.0)	23 (50.0)
Female	27 (60.0)	23 (50.0)
ASA Score, n (%)
1	4 (8.9)	1 (2.2)
2	33 (73.3)	35 (76.1)
3	8 (17.8)	9 (19.6)
4	0 (0.0)	1 (2.2)
Diabetes, n (%)	7 (15.6)	10 (21.7)
Diuretics, n (%)	3 (6.7)	5 (10.9)
ACE Inhibitors, n (%)	6 (13.6)	6 (13.0)
Anticoagulants, n (%)	2 (4.4)	1 (2.2)
Previous Stone Surgery, n (%)	17 (37.8)	24 (52.2)
Laterality, n (%)
Left	24 (53.3)	25 (54.3)
Right	21 (46.7)	21 (45.7)
Total Stone Burden, mm [IQR]	12.0 [9.0–19.0]	13.0 [9.0–19.0]
Stone Volume, mm3 [IQR]	214.0 [82.8–310.6]	176.9 [91.9–292.3]
HU [IQR]	837.5 [473.5–1144.0]	992 [824.8–1194.0]
Preoperative Creatinine [IQR]	0.80 [0.67–0.99]	0.80 [0.71–0.98]
Preoperative eGFR [IQR]	92.0 [76.5–106.0]	92.5 [84.8–103.0]

IQR = interquartile range.

Table 2.

Operative Information and Outcomes for Holmium Versus Thulium Study Groups

	Holmium group (n = 45)	Thulium group (n = 46)	p-value
Operative Time, mins [IQR]	56.0 [42.0–68.0]	52.5 [42.8–72.3]	0.846
Total Laser Energy, kJ [IQR]	1.7 [1.0–4.8]	1.98 [1.3–4.4]	0.727
Total Laser Time, sec [IQR]	432.5 [197.0–910.5]	469.0 [282.0–1077.0]	0.495
Total Lithotripsy Time, sec [IQR]	2160.0 [1320.0–2880.0]	1950.0 [1365.0–3135.0]	0.846
Laser Efficiency [IQR]
Laser Energy Consumption(J/mm3)	13.4 [4.9–25.4]	12.9 [6.8–35.5]	0.435
Laser Activity (Operator Duty Cycle) (%)	25.2 [10.6–44.0]	33.8 [17.7–49.2]	0.212
Laser Ablation Speed (mm3/s)	0.38 [0.21–1.21]	0.27 [0.17–0.55]	0.264
Visible Damage			0.164
No visible damage	10 (21.7)	8 (17.8)
Mucosa only-blanching	26 (56.5)	33 (73.3)
Penetration into submucosa	10 (21.7)	4 (8.9)
Stone Composition, n (%)			0.299
>50% CaOx	35 (77.8)	36 (78.3)
>50% UA	3 (6.7)	0 (0.0)
>50% HA	3 (6.7)	6 (13.0)
Other / Unknown	4 (8.9)	4 (8.7)
Clavien–Dindo Complications, n (%)			0.677
None	42 (93.3)	41 (89.1)
I	1 (2.2)	4 (8.7)
II	1 (2.2)	1 (2.2)
III	0 (0.0)	0 (0.0)

Continuous variables reported as medians. p-Values derived from Chi-squared tests, Fisher’s exact tests, or Mann–Whitney U tests, with significance set to p < 0.05.

IQR = interquartile range.

Table 3.

Multivariate Linear Regression Analysis for Changes in Biomarkers Across Collection Times

Factor	V1 → V2 Delta (%)		V2 → V3 Delta (%)		V1 → V3 Delta (%)
Factor	Standardized β coefficient	p-value	Standardized β coefficient	p-value	Standardized β coefficient	p-value
KIM-1
Operative Group
Control	Ref	—	Ref	—	Ref	—
Holmium	0.228	0.440	−0.205	0.564	0.086	0.810
Thulium	0.446	0.132	−0.294	0.406	0.061	0.865
Age, years	−0.362	0.005*	0.152	0.280	−0.108	0.416
Metabolic Syndrome	−0.121	0.286	0.087	0.475	−0.059	0.608
eGFR	−0.023	0.856	0.145	0.296	0.115	0.371
Operative Time, mins	0.098	0.420	0.024	0.854	0.084	0.512
Total Laser Energy, kJ	−0.140	0.262	0.387	0.006*	0.319	0.019*
NGAL
Operative Group
Control	Ref	—	Ref	—	Ref	—
Holmium	0.055	0.916	−0.064	0.903	−0.059	0.909
Thulium	0.067	0.897	−0.134	0.798	−0.153	0.768
Age, years	−0.128	0.336	−0.298	0.031*	−0.341	0.009*
Metabolic Syndrome	−0.102	0.377	0.029	0.803	0.026	0.815
eGFR	−0.023	0.860	−0.020	0.880	−0.047	0.709
Operative Time, mins	0.198	0.120	−0.035	0.789	0.014	0.913
Total Laser Energy, kJ	0.137	0.289	0.060	0.645	0.050	0.695
Beta-2
Operative Group
Control	Ref	—	Ref	—	Ref	—
Holmium	0.128	0.728	−0.086	0.794	0.034	0.918
Thulium	0.325	0.379	0.010	0.975	0.110	0.736
Age, years	0.040	0.779	0.068	0.597	0.004	0.976
Metabolic Syndrome	−0.107	0.394	0.300	0.008*	0.328	0.002*
eGFR	−0.217	0.126	0.088	0.492	−0.083	0.473
Operative Time, mins	0.237	0.072	−0.228	0.054	−0.116	0.315
Total Laser Energy, kJ	−0.074	0.583	0.441	<0.001*	0.400	0.001*

Significance set to p < 0.05 (bolded and * for reference).

KIM-1 = kidney injury molecule-1; NGAL = neutrophil gelatinase-associated lipocalin; V1 = preoperative; V2 = 1 hour postoperative; V3 = 10 days postoperative.

Results

Between October 2021 and July 2023, 108 patients meeting inclusion criteria were enrolled (Fig. 1). Patients were randomized to the HPL groups equally, 54 in each arm. Ultimately, there were 46 TFL patients, 45 Ho:YAG, and 5 controls.

FIG. 1.

Flow Diagram.

Demographics and baseline characteristics were comparable (Table 1). Total energy used was similar between HPL groups (1.7 kJ interquartile range [IQR]:1.0–4.8 vs 1.98 kJ IQR:1.31–4.43, p = 0.727). Calculated laser efficiency metrics (laser ablation efficiency, energy consumption, operator duty cycle/activity, and ablation speed) did not differ. Evidence of visible kidney damage did not differ (p = 0.164). Grade 3 injury did not occur. Grade 2 injury (penetration into submucosa) was higher for Ho:YAG than TFL (21.7% vs 8.9%). Stone composition was most commonly calcium oxalate (77.8% vs 78.3%, p = 0.299). Complications were similar (6.7% vs 10.9%, p = 0.677).

Both lasers caused drastic and statistically significant increases in biomarkers (median values in ng/mL TFL: 0.011 to 00.025 KIM-1, 0.526 to 2.518 NGAL, 2.126 to 25.623 β2M; HoYAG: 0.012 to 0.024 KIM-1, 0.572 to 2.448 NGAL, 2.775 to 17.147 β2M), which trended toward, but did not always reach, baseline at day 10 (Figs. 2 and 3). In clear contradistinction, controls had relatively little increase and normalization by day 10. Persistent elevation of biomarkers was both laser and biomarker dependent. Baseline levels of all 3 biomarkers were low and equal between groups (Fig. 2). Elevation of NGAL and KIM-1 was marked, but virtually identical regardless of laser type. Elevation of β2M was also marked; although greater for TFL than holmium, this did not reach statistical significance. By day 10, decreasing values indicated tissue recovery, but in most cases were still statistically significantly higher than baseline (Fig. 3). The decrease in KIM-1 from V2 to V3 was significant for TFL but not holmium. The values of NGAL, in particular, did not substantially decrease by day 10 especially for Ho:YAG patients.

FIG. 2.

Linear representation of Biomarker Collection by Time across all Study Groups.

FIG. 3.

Bar graph representation of Biomarker Collection by Time across all Study Groups.

Multivariate analysis to define factors affecting kidney injury focused on clinical conditions, as well as treatment parameters (Table 3). Age and metabolic syndrome influenced kidney injury. Older patients had a greater elevation in KIM-1 (p = 0.005), slower recovery in NGAL (p = 0.031), and were more likely to have persistent elevation in NGAL from baseline (p = 0.009). Age did not independently influence levels of β2M. Patients with metabolic syndrome had a significantly slower recovery in β2M from V2 to V3 and were more likely to have persistent elevation in β2M (p = 0.008, p = 0.002). Metabolic syndrome did not similarly influence NGAL or KIM-1 levels. The more total laser energy used, the slower the recovery of elevated KIM-1 and β2M levels from V2 to V3 and the more likely there would be persistent elevation at V3 (p = 0.006, p = 0.019, p < 0.001, p = 0.001). This effect was not seen with NGAL, but laser-treated patients in general had slower recovery in NGAL and persistent elevation in NGAL, regardless of total energy used. Operating room time did not independently correlate with biomarker elevation. In addition, type of laser used was not independently associated with biomarker level changes.

Discussion

HPLs have been engineered to make RIRS more efficient and improve stone-free rates. The Ho:YAG laser, introduced in 1993, has evolved with pulse modulation and high-frequency capabilities, enhancing energy delivery and reducing operative times via improved dusting capability.^11
–13 SuperPulse TFL has come into common use with advantages of less retropulsion and better dusting capabilities than older Ho:YAG systems.² There is no consensus on which technology is superior or induces less damage. In vitro studies have raised concern that HPLs can cause temperature-induced renal injury. However, there is a paucity of clinical data evaluating injury. We quantified urinary biomarkers specific for kidney and urothelial injury before and after RIRS and correlated these markers to different intraoperative variables.

Kidney injury can be evaluated by serum creatinine and eGFR derived from serum creatinine, but these levels do not demonstrate a linear relationship with kidney injury. A patient with two normal kidneys can have one removed without affecting serum creatinine or eGFR. In a study of 120 patients undergoing RIRS, there was no significant decrease in eGFR; however, older age, longer ureteroscopy, thinner renal parenchyma, and ureteral stones were risk factors for renal function deterioration.¹⁴ Another study found that only 4.9% of 163 patients had a significant decrease in GFR after RIRS.¹⁵ Our data also showed no significant change in eGFR 10 days postoperatively. Serum creatinine is affected by factors unrelated to kidney function (e.g., diet, hydration status, and muscle mass). More importantly, serum creatinine and eGFR have poor sensitivity for detecting early or small insults to renal tubular cells and are better for long term and sustained kidney damage. Several urinary protein biomarkers are markers of renal cellular injury. Compared with eGFR, these markers detect renal insult earlier and have significantly higher sensitivity. However, their specificity can be limited; elevations may occur because of nonrenal factors such as systemic inflammation, dehydration, or other organ injuries, which do not necessarily indicate renal damage. Biomarkers can provide insight into the nature of the damage, as some studies suggest that specific patterns of elevation may correlate with reparable vs nonreparable damage. The kinetics of these biomarkers can differ; we chose two markers of acute kidney injury, NGAL and KIM-1, that peak rapidly after injury and return to baseline quickly, and one (β2M) that is a better measure of chronic injury. β2M has been validated as a measure of glomerular and proximal tubular damage.¹⁶ We noted that β2M did not return to baseline after 10 days. In addition, β2M elevation was influenced by metabolic syndrome (p = 0.008), whereas NGAL and KIM-1 were not. The effect of metabolic syndrome on both the persistent elevation of β2M and slow recovery of elevated β2M is consistent with decreased renal reserve. Previous studies have supported that β2M is associated with metabolic disease, early diabetic nephropathy, and early CKD.¹⁷ Patients with metabolic syndrome have a higher likelihood of having poor renal reserve. Even subtle kidney injury could be more difficult to recover from in this subset of patients.

Total laser energy correlated with both slower recovery and persistent elevation of KIM-1 and β2M levels at 10 days. This is direct evidence that laser energy not only causes renal injury but also is dose dependent, with more energy causing more damage and slower recovery. The effect on KIM-1 and β2M raises concern for tubular and glomerular injury. Our findings suggest that providers should be mindful of total energy used by HPLs during RIRS, especially in patients with preexisting kidney disease.

Although β2M reflects glomerular and proximal tubular damage, NGAL is produced in the distal nephron and is synthesized in response to kidney injury.¹⁸ Albert and colleagues found that urinary and plasma NGAL indicate early tubular injury before declining filtration function.¹⁹ Memmos and associates, comparing low-power Ho:YAG RIRS with mini-PCNL and standard PCNL, found that KIM-1 and NGAL levels rose continuously from 2 to 24 to 48 hours, but no difference between treatment arms.¹⁷ Our study similarly found that NGAL rises for both HPLs as early as 1 hour postoperatively. Levels stay elevated on day 10. Persistent elevation of NGAL is concerning, indicating that injury is profound and long-lasting. How long-lasting is yet to be determined, as we did not go beyond 10 days. The slow recovery of injury and persistent elevation of NGAL above baseline were independently influenced by age (p = 0.031 and p = 0.009, respectively), the implication being that older patients recover more slowly from kidney damage and NGAL can detect this. Our data suggest that providers should be particularly careful when treating older patients with HPLs.

Age was also the only parameter independently associated with degree of injury at 1 hour postoperatively, and the best marker for this was KIM-1. KIM-1, expressed during acute tubular necrosis and produced by the proximal convoluted tubule, is higher in ischemic ATN than chronic renal failure.¹⁸ In addition, UASs have been found to reduce KIM-1 elevation after RIRS.¹⁹ In our study, KIM-1 trended downward, but did not reach baseline by day 10. KIM-1, similar to B2M, was influenced by total laser energy (p < 0.006), with more laser energy used associated with a steeper rise from V1 to V2 and slower recovery from V2 to V3. These findings suggest that HPLs induce ATN, that degree of injury is higher in older patients, and that recovery is slower in patients who receive more laser energy in a dose-dependent manner.

The study by Memmos and colleagues did not check levels beyond 48 hours.¹⁷ We did not check levels between 1 hour and 10 days postprocedure, but noted that by 10 days levels had decreased for most biomarkers. Combining our findings with theirs, it is likely that values peak a few days postoperation and by 10 days are already on the decline. These assumptions are in line with a prospective study evaluating KIM-1 after PCNL and RIRS, in which KIM-1 levels were found to decrease to baseline between 4 hours and 14 days postoperatively.²⁰ Further studies are needed to evaluate long-term values of biomarkers and to correlate biomarkers with other measures of kidney injury such as nuclear renal scans.

Our findings indicate that renal cellular damage occurs, but not how. Laser energy produces thermal damage to surrounding tissues directly and by heating irrigation fluid, resulting in damage by coagulation, carbonization, and denaturation in a dose-dependent manner. In vivo porcine studies show that 40 W can increase temperatures to concerning levels if irrigation is low.³ In our study, total laser energies of 3.14 kJ (TFL) and 3.36 kJ (Ho:YAG) resulted in evidence of cellular damage by biomarker elevation. The direct relationship between temperature increases secondary to HPLs and thermal injury is currently being studied at our institution.

This study had several limitations. We only analyzed urinary biomarkers from a single kidney, and the exact cause of injury, potentially temperature or intrarenal pressure (IRP), remained unclear. Although we attempted to minimize IRP using gravity irrigation (<60 mm Hg) and frequent aspiration of the renal pelvis, we could not definitively confirm consistently low IRP or intrarenal temperature. Furthermore, despite using similar settings for both lasers, subtle differences in their parameters existed. We also did not investigate the impact of lower or higher energy settings (above 25 W) on kidney damage. Future research could explore alternative laser settings and assess whether UASs and increased irrigation flow can mitigate the observed damage.

Conclusions

There is notable dose-dependent laser-induced renal parenchymal damage for both TFL and Ho:YAG lasers. Older age and metabolic syndrome predispose to greater injury and slower recovery. Damage occurs at multiple levels of the nephron. Although the safety profiles of both lasers are similar, there are notable differences in recovery from injury. Further studies evaluating factors that can ameliorate kidney injury caused by HPLs are needed.

Footnotes

Authors’ Contributions

Conception and design: A.J.Y., K.G., M.G., N.K., and D.L. Data analysis and interpretation: B.G., C.C., K.G., M.G., R.K., W.A., D.L., and A.R. Data acquisition: R.S., C.C., B.G., K.G., W.A., A.R. M.P., and S.K.-S. and Drafting the article: K.G., M.G., and A.J.Y. Critical revision of the article for scientific and factual content: K.G., M.G., R.K., W.A., and A.J.Y. Statistical analysis: D.L., C.C., and K.G. Supervision: K.G., M.G., W.A., M.P., and S.K.-S.

Author Disclosure Statement

There are no competing financial interests for all authors.

Funding Information

Valentine Fellow Scholarship Grant from the New York Academy of Medicine and Lumenis.

Abbreviations Used

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