Evaluation of Pain Before and After Removal of Non-obstructive Kidney Stones (ENORC)

Pain associated with renal stone disease is typically caused by an obstructing stone that obstructs the flow of urine, which results in renal collecting system dilatation. Non-obstructing renal calculi that do not cause renal collecting system dilatation are thought to be painless. The objective of this study is to prospectively determine if the removal of non-obstructing renal calculi can reduce or eliminate participant's pain and/or improve their quality of life.

Study Overview

• Status: Completed
• Conditions: Kidney Stone
• Intervention / Treatment: Procedure: Ureteroscopy

Detailed Description

Research Protocol

• Title of research project: Evaluation of pain before and after removal of non-obstructing renal calculi.
• Identification of Principal Investigator: Dr. Naeem Bhojani
• Multicentric study

Rationale & background information Renal stone disease is a common condition representing a lifetime occurrence risk of 10% in men and 7% in women. Renal stone disease is a chronic condition with a high recurrence rate. Additionally, renal stone disease is associated with considerable morbidity including pain. Pain associated with renal stone disease is typically caused by an obstructing stone that obstructs the flow of urine, which results in renal collecting system dilatation. This increases the intraluminal pressure of the urinary collecting system and stretches nerve ending in the ureteral mucosa and renal capsule. Non-obstructing renal calculi that do not cause renal collecting system dilatation are thought to be painless. There is however, some evidence that non-obstructing renal calculi located within the renal calyces actually do cause pain. In a small (n=13) retrospective study, it was found that ureteroscopic removal of non-obstructing renal calyceal stones achieved complete or partial resolution of pain in all patients. The reason for this pain is unknown.

Objective and hypothesis Objective To prospectively determine if the removal of non-obstructing renal calculi can reduce or eliminate participant's pain and/or improve their quality of life.

Hypothesis We hypothesize that the removal of non-obstructing renal calculi will decrease or eliminate the participant's pain and will improve their quality of life.

Design and methodology

Study type:

o Prospective multicentric study

Study population:

o Patients with non-obstructing renal calculi

Inclusion criteria:

• Patients with renal colic and non-obstructing renal calculi. No stone greater than 10 mm in longest diameter
• All other causes of pain have been eliminated (by clinical judgment; if the cause of pain is in doubt: assessment by a family doctor or medical specialist will be obtained)
• Patients older than 18 years old
• Moderate to severe pain (> or = 5 on BPI pain scale: pain at its worst in the last 24hrs)

Exclusion criteria:

• Patient's with anatomic abnormalities (calyceal diverticulum)
• Ureteral calculi
• Nephrocalcinosis
• Renal Tubular Acidosis (RTA), medullary sponge kidney, sarcoidosis
• Hydronephrosis or hydrocalycosis
• Minimal pain (<5 on BPI pain scale: pain at its worst in the last 24 hrs)

Methodology Our experimental plan begins with the identification of patients with non-obstructing kidney stones (< =10 mm (maximum length; measured via CT) with associated flank pain. Once all other causes of the pain have been eliminated, these patients will undergo ureteroscopy (URS) (standard treatment) to remove the offending kidney stones.

URS will be performed in the standard fashion including the use of a guide wire +/- a ureteral access sheath. Laser lithotripsy will be performed if necessary and all fragments will be extracted with the use of a basket and will be sent for stone analysis. Once the offending stone(s) has/have been removed a double J ureteral stent will be placed if deemed necessary by the surgeon. The duration of the double J ureteral stent will be determined by the surgeon.

All consented patients will undergo 3 evaluations preoperatively; The Brief Pain Inventory (BPI) (short version)[3], the Patient-Reported Outcomes Measurement Information System (PROMIS)-Pain inference/form 6b and the Wisconsin stone quality of life questionnaire (WSQOL). After removal of the renal calculi, these 3 forms will be completed by the participant at the time of stent removal or if no stent was placed, at 2 weeks post-operatively. Thereafter, the forms will be completed again at 6-8 weeks (+/- 1 week) after the initial procedure or 4 weeks (+/- 1 week) after the removal of their double J stent. Finally, the evaluations will be repeated at 12 weeks. Additionally, as with standard care at 6-8 weeks each patient will undergo post-operative imaging to determine if any renal calculi remain.

Analysis of Data With regards to the BPI, if removal of the offending kidney stone(s) is the cause of the patient's pain we expect a decrease in pain ("pain at its worst in the last 24 hours") of at least 20%. Patients included in this study should experience moderate to elevated flank pain in order to be able to detect a decrease of 20% of this pain post-intervention. This decrease will be considered clinically significant. In order to test our hypothesis, we plan to recruit a minimum of 53 patients to achieve a power of 80%. Patients will be their own control.

Sample size calculation Sample size calculation was performed using GPower software, version 3.1. Considering a baseline means Visual Analog Scale (VAS) of 7, we conservatively supposed a correlation of 0 and a standard deviation of 2.5. The standard deviation was estimated with the range (i.e. σ ≈ range/4), assuming the VAS to be normally distributed. Thus, a sample size of n = 53 is required to ensure at least 80% power to detect a clinically significant difference of 20 % (post-mean = 5.6), at a significance level of 5 %.

Impact of the Proposed Research The results of this study will conceivably provide significant evidence on whether small non-obstructing renal calculi can cause flank pain.

Ethical considerations

• All personal identifiers, such as patients' names, will be removed and replaced with a unique numerical code.
• Only the principal investigator and approved study staff will be able to identify the patients and have access to the study files.
• The consent will be kept in a locked office at the Research Center of the University of Montéral Hospital Center (CRCHUM).
• The data collected will be protected in files with a password on secure servers (computers).
• The data will be kept during a period of 10 years on secured computers with passwords by the principal investigator of this research project at the CRCHUM. After that, they will be destroyed.
• The combined results from this study may be used to prepare reports and summaries for scientific publications and presentations at scientific meetings. If they are, identity of the patients will remain confidential.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Naeem Bhojani, MD; Phone Number: 14069 514-890-8000; Email: naeem.bhojani@gmail.com
• Study Contact Backup: Name: Kahina Bensaadi, DESS; Phone Number: 30824 514-890-8000; Email: kahina.bensaadi.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2X0A9
      • Centre Hospitalier de l'Université de Montréal (CHUM)
• United States
  • California
    • Davis, California, United States, 95616
      • University of California, Davis
    • San Diego, California, United States, 92093
      • University of California, San Diego
  • Indiana
    • Bloomington, Indiana, United States, 47405
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Milton S. Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Health

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with renal colic and non-obstructing renal calculi. No stone greater than 10 mm in longest diameter
• All other causes of pain have been eliminated (by clinical judgment; if the cause of pain is in doubt: assessment by a family doctor or medical specialist will be obtained)
• Patients older than 18 years old
• Moderate to severe pain (> or = 5 on BPI pain scale: pain at its worst in the last 24hrs)

Exclusion Criteria:

• Patient's with anatomic abnormalities (calyceal diverticulum)
• Ureteral calculi
• Nephrocalcinosis
• RTA, medullary sponge kidney, sarcoidosis
• Hydronephrosis or hydrocalycosis
• Minimal pain (<5 on BPI pain scale: pain at its worst in the last 24 hrs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Ureteroscopy (URS) (standard treatment); Endoscopic procedure used to remove kidney stones	Procedure: Ureteroscopy; Endoscopic removal of kidney stones

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of pain	evaluated using The Brief Pain Inventory; scale from 0-10; worst pain is 10	12 weeks

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Mayo Clinic; University of California, San Diego; University of California, Los Angeles; Brigham and Women's Hospital; Milton S. Hershey Medical Center; University of California, Davis; Vanderbilt University Medical Center; University of Minnesota; Henry Ford Health System; Indiana University; Baylor Scott and White Health
• Investigators: Principal Investigator: Naeem Bhojani, MD, Centre Hospitalier de l'Université de Montréal (CHUM)

Publications and helpful links

General Publications

• Travaglini F, Bartoletti R, Gacci M, Rizzo M. Pathophysiology of reno-ureteral colic. Urol Int. 2004;72 Suppl 1:20-3. doi: 10.1159/000076586.
• Jura YH, Lahey S, Eisner BH, Dretler SP. Ureteroscopic treatment of patients with small, painful, non-obstructing renal stones: the small stone syndrome. Clin Nephrol. 2013 Jan;79(1):45-9. doi: 10.5414/CN107637.
• Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.
• Penniston KL, Antonelli JA, Viprakasit DP, Averch TD, Sivalingam S, Sur RL, Pais VM Jr, Chew BH, Bird VG, Nakada SY. Validation and Reliability of the Wisconsin Stone Quality of Life Questionnaire. J Urol. 2017 May;197(5):1280-1288. doi: 10.1016/j.juro.2016.11.097. Epub 2016 Nov 23.
• Haefeli M, Elfering A. Pain assessment. Eur Spine J. 2006 Jan;15 Suppl 1(Suppl 1):S17-24. doi: 10.1007/s00586-005-1044-x. Epub 2005 Dec 1.
• Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain. 2000 Dec 1;88(3):287-294. doi: 10.1016/S0304-3959(00)00339-0.
• Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.
• Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005 Apr 20;5:13. doi: 10.1186/1471-2288-5-13.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2018
• Primary Completion (Actual): October 6, 2022
• Study Completion (Actual): March 9, 2023

Study Registration Dates

• First Submitted: August 30, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Nephrolithiasis; Renal Stone; Painful stone in kidney; Kidney stone pain
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: 17.314

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No