An observational study in Urolithiasis, Intrarenal Pressure and MRI Scans, sponsored by Region of Southern Denmark. Enrolling by invitation at 1 site in Denmark. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Region of Southern Denmark · Observational
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.
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.
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.
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.
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.
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.
253 studies on the registry are indexed under Urolithiasis; 67 are open to participants now.
This study's planned enrollment of 20 is below the median of 150 across 65 observational studies indexed under Urolithiasis.
Browse Urolithiasis studies →Region of Southern Denmark is the lead sponsor of 14 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Patiet group:
Inclusion Criteria:
Exclusion Criteria:
Healthy controls:
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Renally healthy individuals.
Renal Parenchymal Structural and Functional Assessment by Multiparametric MRI
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.
Time frame: Baseline (single MRI examination during the study visit).
Regional Renal Parenchymal Stiffness Assessed by Ultrasound Elastography
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.
Time frame: Baseline (single ultrasound examination during the study visit).
Renal Cortical Scarring Assessed by 99mTc-DMSA SPECT
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.
Time frame: Baseline (single scintigraphic examination during the study visit).
Estimated Glomerular Filtration Rate (eGFR)
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.
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)
Plan to share: No — 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.
Started Mar 2025 (actual). Primary completion is estimated for Aug 2027, 28 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Region of Southern Denmark