Renal Structural and Functional Alterations Following Repeated Ureteroscopic Procedures: An Exploratory Multimodal Imaging Study (BackFlow2)

October 28, 2026 updated by: Emmeli Grøne Lykkegaard, Region of Southern Denmark

Introduction and objectives

Saline irrigation and instrumentation during Retrograde Intrarenal Surgery (RIRS) causes elevation of intrarenal pressure (IRP) inducing intrarenal backflow (IRB). In an experimental study from 2025 Hinojosa-Gonzalez et al. demonstrated an association between elevated IRP and increased risk of bacteremia. The potential of elevated IRP and IRB to breach physiological barriers and facilitate systemic translocation of renal pelvic contents warrants investigation into their effects on parenchymal integrity and function.

Using contrast-enhanced MRI in a porcine model, Lildal et al. (2023) demonstrated segmental IRB with sharply demarcated areas of contrast distribution, predominantly at the renal poles. The preferential involvement of renal poles resembles the distribution of renal scarring observed in reflux nephropathy, raising the hypothesis that repeated pressure-related exposure may contribute to localized parenchymal alterations.

However, whether repeated ureteroscopic procedures are associated with similar persistent regional changes in renal structure and function remains unclear.

We therefore initiated an exploratory clinical study assessing renal structure and function following multiple ureteroscopic procedures using multiparametric MRI, DMSA scintigraphy and ultrasound elastography.

Materials and methods

This exploratory cross-sectional case-control study aims to enroll 10 patients with repeated unilateral ureteroscopic procedures and 10 healthy controls. Eligible patients must have undergone ≥3 ipsilateral procedures (RIRS/URS/URSL) and ≤1 contralateral procedure. Major exclusions include solitary kidney, metabolic or structural renal disorders compromising MRI analysis, chronic UTI, previous multiple PCNL procedures, and MRI contraindications.

All participants undergo serum creatinine measurement and multiparametric renal MRI (1.5T Philips Ingenia), including T1 mapping, heavily T2-weighted 3D imaging, diffusion-weighted imaging, T2* imaging, and renal arterial flow assessment. Renal scintigraphy is performed using ⁹⁹ᵐTc-DMSA, with planar imaging for quantification of split renal function and SPECT for evaluation of cortical scarring. Bilateral renal shear-wave elastography (Mindray Resona I9 ultrasound system) is conducted to quantify regional parenchymal stiffness in five predefined regions per kidney.

Planned analyses will compare regional imaging parameters between patients and controls and between ipsilateral and contralateral kidneys, accounting for within-subject correlation. Segmental imaging parameters will be compared between groups and kidneys using linear mixed-effects models accounting for repeated measurements within subjects.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Background and Rationale

Retrograde intrarenal surgery (RIRS) and ureteroscopy (URS) are widely used minimally invasive procedures for the treatment of upper urinary tract stones. These procedures require continuous irrigation to maintain endoscopic visibility, which may result in substantial elevations in intrarenal pressure (IRP). Elevated IRP can induce intrarenal backflow (IRB), involving the movement of renal pelvic fluid into the renal parenchyma, venous circulation, lymphatic system, and surrounding interstitial tissue.

Experimental studies have demonstrated that elevated IRP may be associated with intrarenal backflow and renal parenchymal alterations. Previous porcine MRI studies have demonstrated regional distribution of intrarenal backflow, suggesting that pressure-related effects may involve specific anatomical regions of the kidney.

Although the relationship between elevated IRP and infectious complications following ureteroscopy has received increasing attention, the potential long-term structural and functional consequences of repeated ureteroscopic procedures remain insufficiently investigated. In particular, it is unknown whether repeated exposure to elevated intrarenal pressure is associated with persistent regional parenchymal alterations, including fibrosis, atrophy, or impaired renal function.

Study Objectives

The primary objective of BackFlow2 is to investigate potential structural and functional renal alterations in patients with a history of repeated unilateral ureteroscopic procedures for urinary stone disease.

The study aims to:

Assess regional renal parenchymal characteristics using multiparametric magnetic resonance imaging (MRI).

Evaluate renal parenchymal stiffness using ultrasound shear-wave elastography as a potential indicator of fibrotic changes.

Assess split renal function and renal scarring using technetium-99m dimercaptosuccinic acid (⁹⁹ᵐTc-DMSA) scintigraphy.

Compare imaging findings between the previously instrumented kidney and the contralateral kidney within individual participants.

Compare renal imaging parameters and inter-renal differences between patients and healthy controls.

Study Design and Population

BackFlow2 is an exploratory, observational, cross-sectional study conducted at Lillebaelt Hospital, Vejle, Denmark.

The study aims to enrol 20 adult participants, comprising 10 patients with a history of repeated unilateral ureteroscopic procedures and 10 healthy controls.

Eligible patients are aged 18-75 years and must have undergone at least three ureteroscopic procedures (RIRS/URS/URSL) involving the same kidney, with no more than one previous ureteroscopic procedure involving the contralateral kidney. More than one month must have elapsed since the most recent procedure before study examinations.

Healthy controls are aged 35-75 years, have serum creatinine levels within the normal reference range, and have no history of ureteroscopy or known renal disease.

Participants with conditions potentially affecting renal structure or function, or interfering with imaging interpretation, are excluded according to predefined eligibility criteria.

Patients are recruited from the Department of Urology through clinical screening and review of previous ureteroscopic procedures and medical records. Healthy controls are recruited through voluntary participation.

All participants provide written informed consent before undergoing study-specific examinations.

Study Procedures

All participants undergo a multimodal assessment of renal structure and function, comprising serum creatinine measurement, multiparametric MRI, bilateral renal ultrasound elastography, and ⁹⁹ᵐTc-DMSA scintigraphy.

  1. Renal Function Assessment

    Serum creatinine is measured before the imaging examinations to assess overall renal function. In healthy controls, serum creatinine within the normal reference range is required to confirm eligibility.

  2. Multiparametric Renal MRI

    Renal MRI is performed using a 1.5T Philips Ingenia MRI system without intravenous contrast administration.

    The imaging protocol includes:

    T1 mapping using a gradient-echo turbo field echo (GRE TFE) sequence.

    Heavily T2-weighted three-dimensional coronal imaging using a turbo spin-echo (TSE) sequence.

    Diffusion-weighted imaging (DWI) using single-shot echo-planar imaging (EPI) with 14 b-values.

    T2*-weighted imaging using a gradient-echo (GRE) sequence.

    Renal arterial flow imaging using a gradient-echo (GRE) sequence.

    Both kidneys are examined to assess regional differences in renal parenchymal structure and functional imaging characteristics.

    Regions of interest are defined in selected anatomical regions of both kidneys to facilitate intraindividual and between-group comparisons.

  3. Renal Ultrasound Elastography

    Bilateral renal ultrasound shear-wave elastography is performed using a Mindray Resona I9 diagnostic ultrasound system (Mindray, Shenzhen, China) to assess regional renal parenchymal stiffness.

    Three repeated measurements are obtained in each of five predefined anatomical regions per kidney: apical, lateroapical, lateral, lateroinferior, and inferior.

    Regional stiffness measurements are compared between the previously instrumented and contralateral kidneys and between patients and healthy controls.

    Ultrasound elastography is used as a complementary imaging method to investigate potential regional parenchymal alterations associated with fibrosis.

  4. Renal DMSA Scintigraphy

Renal scintigraphy is performed approximately two hours after intravenous administration of 100 MBq ⁹⁹ᵐTc-DMSA.

Imaging is acquired using a Siemens Symbia Intevo SPECT system equipped with low-energy high-resolution collimators.

Static anterior and posterior renal images are obtained to quantify split renal function using the geometric mean of tracer uptake.

Additional single-photon emission computed tomography (SPECT) imaging is performed to assess the presence and anatomical distribution of renal cortical defects consistent with scarring.

Scintigraphic findings are compared between kidneys and between study groups and evaluated in relation to regional MRI and ultrasound elastography findings.

Statistical Analysis

Statistical analyses will focus on intraindividual and between-group differences in renal structure and function.

Linear mixed-effects models (LMMs) will be used in the statistical analysis, accounting for the correlation between repeated regional measurements obtained from kidneys within the same participant.

The models will assess differences between the previously instrumented and contralateral kidneys in patients and compare imaging parameters between patients and healthy controls.

Regional findings from MRI, ultrasound elastography, and DMSA scintigraphy will be evaluated for anatomical correspondence.

The study is exploratory, with a limited sample size. Statistical findings will be interpreted with consideration of effect estimates, uncertainty, and the potential for confounding. Observed associations will not be considered evidence of causality.

Ethical Considerations

The study was approved by the Regional Committee on Health Research Ethics, Southern Denmark (approval number S-20240065).

All participants provide written informed consent before undergoing study-specific examinations.

MRI and ultrasound examinations are non-invasive, and MRI is performed without intravenous contrast administration. DMSA scintigraphy involves exposure to a low dose of ionising radiation.

Study data are handled in accordance with applicable data protection regulations.

The study is intended to provide preliminary clinical evidence regarding potential long-term renal structural and functional alterations following repeated ureteroscopic procedures and to inform the design of future investigations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Vejle, Denmark, 7100
        • Urological Research Unit, Lillebaelt Hospital, Vejle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population comprises 20 adults: 10 patients aged 18-75 years with a history of at least three unilateral ureteroscopic procedures (RIRS/URSL/URS), and 10 healthy controls aged 35-75 years with normal renal function and no history of ureteroscopy. Patients are recruited from the urological department at Lillebaelt Hospital, Vejle, while healthy controls are recruited through voluntary participation.

Description

Patiet group:

Inclusion Criteria:

  • Age 18-75 years.
  • History of ≥3 retrograde intrarenal surgery (RIRS) or ureteroscopy (URS/URSL) procedures on the affected kidney.
  • At least one month since the most recent RIRS/URS procedure at the time of examination.
  • Legally competent and able to understand the study information and provide informed consent.

Exclusion Criteria:

  • Bilateral stone disease with more than one previous ureteroscopic procedure on the contralateral kidney.
  • Known acute or chronic urinary tract infection (UTI).
  • History of multiple percutaneous nephrolithotomy (PCNL) procedures.
  • Known medical renal disease, including metabolic stone disorders such as renal tubular acidosis, primary hyperoxaluria, nephrocalcinosis, or medullary sponge kidney.
  • Solitary kidney
  • Contraindications to MRI, including MRI-incompatible implants or foreign bodies, or claustrophobia preventing examination.
  • Renal anatomical variants or focal abnormalities that may interfere with imaging analysis, including horseshoe kidney, large or multiple renal cysts, or focal renal lesions.
  • Pregnancy.

Healthy controls:

Inclusion Criteria:

  • Age 35-75 years.
  • Serum creatinine within the normal reference range.
  • Legally competent and able to understand the study information and provide informed consent

Exclusion Criteria:

  • Known renal disease, diabetes mellitus, or untreated hypertension.
  • History of ureteroscopy.
  • Active urinary tract infection (UTI) or history of upper urinary tract infections.
  • Contraindications to MRI, including MRI-incompatible implants or foreign bodies, or claustrophobia preventing examination.
  • Known renal anatomical variants or focal abnormalities that may interfere with imaging analysis, including horseshoe kidney, large or multiple renal cysts, or focal renal lesions.
  • Pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: CASE_CONTROL
  • Time Perspectives: CROSS_SECTIONAL

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Patients with repeated unilateral ureteroscopic procedures
Healthy controls

Renally healthy individuals.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Renal Parenchymal Structural and Functional Assessment by Multiparametric MRI
Time Frame: Baseline (single MRI examination during the study visit).

Renal structure and function are assessed using multiparametric 1.5T MRI, including T1 mapping (GRE TFE), heavily T2-weighted 3D imaging (TSE), diffusion-weighted imaging (DWI; 14 b-values), T2*-weighted imaging (GRE), and renal arterial flow imaging (GRE). Quantitative measurements include renal parenchymal T1 relaxation times (ms). Regional renal imaging parameters are compared between kidneys within each participant and between patients with repeated unilateral ureteroscopic procedures and healthy controls.
Baseline (single MRI examination during the study visit).
Regional Renal Parenchymal Stiffness Assessed by Ultrasound Elastography
Time Frame: Baseline (single ultrasound examination during the study visit).

Renal parenchymal stiffness is assessed bilaterally using ultrasound elastography, with three repeated measurements obtained in five predefined regions of each kidney. Regional stiffness values are compared between kidneys within each participant and between patients with repeated unilateral ureteroscopic procedures and healthy controls.
Baseline (single ultrasound examination during the study visit).
Renal Cortical Scarring Assessed by 99mTc-DMSA SPECT
Time Frame: Baseline (single scintigraphic examination during the study visit).

Renal cortical abnormalities consistent with scarring are assessed using 99mTc-DMSA single-photon emission computed tomography (SPECT). The presence and anatomical distribution of cortical defects are evaluated in both kidneys and compared between patients with repeated unilateral ureteroscopic procedures and healthy controls.
Baseline (single scintigraphic examination during the study visit).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Estimated Glomerular Filtration Rate (eGFR)
Time Frame: Baseline (blood sampling within 30 days before the imaging examination for the healthy controls and on the day of examination for the patients)

Estimated glomerular filtration rate is calculated from serum creatinine to assess global renal function and compare renal function between patients with repeated unilateral ureteroscopic procedures and healthy controls. It alse serves as an eligible criteria for the healthy controls.
Baseline (blood sampling within 30 days before the imaging examination for the healthy controls and on the day of examination for the patients)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Region of Southern Denmark

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Emmeli G Lykkegaard, MD, Urological Research Unit, Lillebealt Hospital, Vejle

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 31, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 28, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BackFlow2-S-20240065

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

All participant data are handled in accordance with the EU General Data Protection Regulation (GDPR) and applicable Danish data protection legislation. Study data are securely stored, and access to individual participant data is restricted to authorised members of the research team. Identifiable participant data will not be shared with external parties.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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