Trial Assessing Renal Damage During Ureteroscopy

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

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.

Study Overview

• Status: Completed
• Conditions: Nephrolithiasis
• Intervention / Treatment: Device: Thulium Fibre Laser; Device: Holmium:Yttrium-Aluminum-Garnet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Mount Sinai West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thulium Fibre Laser (TFL); Patients who are randomized to undergo ureteroscopic laser lithotripsy with the Thulium fibre laser (TFL)	Device: Thulium Fibre Laser; 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.; Other Names: TFL
Experimental: Holmium:Yttrium-Aluminum-Garnet (Ho:YAG); Patients who are randomized to undergo ureteroscopic laser lithotripsy with the Holmium:Yttrium-Aluminum-Garnet (Ho:YAG) laser	Device: Holmium:Yttrium-Aluminum-Garnet; 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.; Other Names: Ho:YAG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Mantu Gupta, Department of Urology, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Actual): November 28, 2022
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: STUDY-21-00084; GCO# 21-0054 (Other Grant/Funding Number: New York Academy of Medicine)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be presented/shared as aggregates.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No