Trial Assessing Renal Damage During Ureteroscopy

Study Overview
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Brief Summary
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This is an ongoing randomized controlled trial of patients undergoing URSLL with unilateral non-obstructing renal stones. Patients are randomized to undergo URSLL with either the TFL or Ho:YAG laser. Each patient's urine is collected immediately pre-op (V1), 1 hour post-op (V2), and 10 days post-op (POD#10, V3). Samples are analyzed by enzyme-linked immunosorbent assay (ELISA) for the following biomarkers: Kidney injury molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2M), then normalized to urine creatinine.

Detailed Description
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Patients scheduled for ureteroscopic laser lithotripsy (URSLL) will be screened and if eligible and agreeable, enrolled into the study. Patients will then be randomized preoperatively via block randomization in groups of 5 to receive lithotripsy with either Ho:YAG or TFL laser intraoperatively. All patients enrolled will have a ureteral stent placed at the end of the procedure. After induction of anesthesia but before any surgical intervention, the surgeon will empty the bladder and collect a sample of urine that will serve as the Preoperative Urine Sample. One hour following the end of the procedure, a second sample of urine will be collected from the Foley catheter that will serve as the Immediate Post-Op Urine Sample. A third and final urine sample of urine will be collected approximately 10 days postoperatively just prior to stent removal and serve as the Follow-up urine sample. Patients for whom all three urine specimens are collected will be considered to have completed the study. Immediately after collection, the samples will be stored in a freezer at -80 ºC. All samples will be analyzed for biomarkers of renal parenchymal injury to determine differences between pre- and postoperative concentrations. The biomarkers that will be quantified include Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and Beta-2-microglobulin (B2M). Concentrations of urinary biomarkers are determined in duplicate from urine samples using the multiplex cytokine panel [MILLIPLEX MAP Human Kidney Injury Panel 1 (KIM-1), Panel 2 (N-GAL2) and Panel 3 (B2 microglobulin)- Millipore Corp., Burlington, MA] as per manufacturer's instructions. The urine samples were 1:2 diluted for Panel 1, 1:100 diluted for Panel 2 and 1:500 diluted for Panel 3. The kit provided lyophilized pre-mixed standard was reconstituted and used to generate 6-point serial dilutions and run on assay plate along with the samples. Analyte median fluorescent intensity (MFI) values were obtained. Anticipate enrollment is 108 patients total (54 in each cohort) to adequately power the study based upon an alpha of 0.05 statistical power of 0.80.

Official Title
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Use of Urinary Biomarkers to Quantify Degree of Renal, Parenchymal and Urothelial Damage During Ureteroscopy

Conditions
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Nephrolithiasis

Intervention / Treatment
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* Device: Thulium Fibre Laser
* Device: Holmium:Yttrium-Aluminum-Garnet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years Patients undergoing unilateral ureteroscopic laser lithotripsy for the treatment of non-obstructing renal stones Total stone burden between 5 and 20 mm Exclusion Criteria: Presence of pre-existing indwelling ureteral stent Presence of hydronephrosis preoperatively (on either side) CKD as defined by eGFR < 60 mL/min GU anatomical anomalies (including urinary diversion, solitary kidney, ureteral stricture disease, ureteropelvic junction obstruction)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thulium Fibre Laser (TFL)<br>Patients who are randomized to undergo ureteroscopic laser lithotripsy with the Thulium fibre laser (TFL) | Device: Thulium Fibre Laser<br>* The TFL is a relatively new laser in the field of urology. First introduced on the market in 2017, it offers theoretically superior stone dusting qualities and smaller fiber sizes to allow for better irrigation.<br>* Other names: TFL;|
| Experimental: Holmium:Yttrium-Aluminum-Garnet (Ho:YAG)<br>Patients who are randomized to undergo ureteroscopic laser lithotripsy with the Holmium:Yttrium-Aluminum-Garnet (Ho:YAG) laser | Device: Holmium:Yttrium-Aluminum-Garnet<br>* The Ho:YAG is currently the most commonly used laser in the field of urology and for the better part of the last 3 decades has been considered the gold standard for laser lithotripsy.<br>* Other names: Ho:YAG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Kidney Injury Molecule-1 (KIM-1) | Urinary biomarker - a specific biomarker of renal damage to measure the degree of renal parenchymal damage. | Baseline, 1 hour postoperatively, and 10 days postoperatively | 
| Change in Neutrophil Gelatinase-associated Lipocalin (NGAL) | Urinary biomarker - a specific biomarker of renal damage to measure the degree of renal parenchymal damage. | Baseline, 1 hour postoperatively, and 10 days postoperatively | 
| Change in β2-microglobulin (β2M) | Urinary biomarker - a specific biomarker of renal damage to measure the degree of renal parenchymal damage. | Baseline, 1 hour postoperatively, and 10 days postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operative Time | Operative time (minutes) is calculated from time of procedure start (insertion of endoscope into urethral meatus) to time of removal of endoscope from urethral meatus after procedure completion. | Day 1, Intraoperatively |