Non-invasive Evaluation of Graft Condition in Adult Patients With Kidney Transplant Using Ultrasound Localization Microscopy and Multispectral Optoacoustic Tomography (ESTIMATOR)

In this study, the condition of the kidney transplant in adults is to be assessed non-invasively using Multispectral Optoacoustic Tomography and Ultrasound Localization Microscopy (ULM). ULM imaging can be performed in a 2-dimensional and a 3-dimensional way (2D and 3D ULM). Therefore, "ULM" in the following texts and measures will refer to 2D and 3D ULM.

New, non-invasive markers that allow conclusions to be drawn about the condition of the transplant should reduce the need for invasive diagnostic procedures in the future.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant; Kidney Biopsy
• Intervention / Treatment: Device: ULM and MSOT

Detailed Description

In this study, the condition of the kidney transplant in adults is to be assessed non-invasively using multispectral multispectral optoacoustic tomography and ultrasound localization microscopy. Associated with common diseases such as arterial hypertension, diabetes mellitus and cardiovascular diseases, chronic renal failure is now a leading cause of death worldwide.

Around 10% of adults in Germany, but children are also affected. The terminal stage of renal insufficiency is defined by a glomerular filtration rate (GFR) which is only 15% of the normal rate and the need for renal replacement therapy in the form of dialysis or transplantation.

Not only the higher quality of life, but also the mortality rate make kidney transplantation the procedure of choice whenever possible.

After successful kidney transplantation, regular monitoring and evaluation of the organ transplant is of great importance to detect a rejection reaction as early as possible.

Among other things, this is done during an extensive annual examination. Not infrequently, and especially in the case of abnormalities in the laboratory diagnosis of blood and urine, a kidney biopsy is also necessary in order to assess the condition of the transplant in the best possible way.

As an invasive diagnostic procedure, the biopsy necessitates a stay in hospital, may result in side effects such as postoperative bleeding and represents a risk and an additional bruden for the patient.

MSOT has already been used to measure renal clearance and the biodistribution of fluorescent substances within the kidney, but new biomarkers have also been established in muscle and intestinal diseases and correlated with clinical scores. ULM has made the visualization of glomeruli, the smallest functional unit of the kidney, in living rats and humans and visualization of cerebral microvasculature in the human brain possible. In this study, the renal function in transplant patients will be evaluated as part of the annual examination and results from histology (biopsy), laboratory and ultrasound diagnostics will be correlated with data from MSOT and 2D and 3D ULM imaging.

The investigators believe that MSOT can be used to gain important molecular insights into the condition of the transplant. With ULM the investigators want to analyze the microvascular architecture within glomerular renal corpuscles and identify changes in perfusion dynamics as morphological signs for transplant evaluation.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Ferdinand Hannah Knieling, PD Dr. Dr.; Phone Number: 0049 9131 85 33118; Email: ferdinand.knieling@uk-erlangen.de
• Study Contact Backup: Name: Adrian Regensburger, PD Dr. Dr.; Phone Number: 0049 9131 33118; Email: adrian.regensburger@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Department of Pediatrics and Adolescent Medicine
      • Principal Investigator: Ferdinand Knieling, MD
      • Contact: Ferdinand Knieling, MD; Phone Number: 0913185 33118; Email: ferdinand.knieling@uk-erlangen.de
      • Contact: Adrian Regensburger, MD; Phone Number: +49 9131 8533118; Email: adrian.regensburger@uk-erlangen.de
      • Principal Investigator: Adrian Regensburger, MD
      • Sub-Investigator: Henriette H Mandelbaum, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

10 patients with kidney transplant and indication for kidney biopsy

Description

Inclusion Criteria:

• kidney transplant
• indication for biopsy set in clinical routine
• minimum 18 years of age
• written consent

Exclusion Criteria:

• allergy against contrast agents/ SonoVue
• tatoos in examined areas
• contraindication against SonoVue
• pregnant women
• breast feeding women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient with kidney transplant; Included are adult (> 18 years) patients with kidney transplant where the indication for a kidney biopsy has been set during clinical routine	Device: ULM and MSOT; transplanted kidney will be examined non-invasively with ULM and MSOT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visualization of microvascular architecture in the transplant kidney	Using Ultrasound Localization Microscopy (ULM) for the non invasive visualization of microvasculature	Day1
Quantification of microvascular dynamics in the transplanted kidney	Using Ultrasound Localization Microscopy (ULM) for the non invasive quantification of microvascular dynamics	Day1
MSOT in human kidney transplant	Measuring MSOT signals (Signals for total/oxygenated/deoxygenated hemoglobin, lipid and collagen) in the human kidney transplant	Day1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ULM visuals and histology	ULM: Correlation of the vascular architecture of the transplant kidney visualized by ULM (e.g. number of segmented glomeruli) with histological parameters (e.g. Banff classification)	Day1
ULM visuals and laboratory results	- ULM: Correlation of the vascular architecture of the transplant kidney visualized by ULM (e.g. number of segmented glomeruli) with laboratory chemical parameters (e.g. renal function parameters, inflammation parameters, immunological parameters)	Day1
ULM visuals and standard sonography	- ULM: Correlation of the vascular architecture of the transplant kidney visualized by ULM (e.g. number of segmented glomeruli) with sonographic parameters (e.g. resistance index (RI), flow velocity)	Day1
ULM quantification and histology	ULM: Correlation of parameters of quantified microvascular perfusion dynamics in the transplant kidney with histological parameters (e.g. Banff classification)	Day1
ULM quantification and laboratory results	- ULM: Correlation of parameters of the quantified microvascular perfusion dynamics in the transplant kidney with laboratory chemical parameters (including renal function parameters, inflammation parameters)	Day1
MSOT: Hb and histology	MSOT: Correlation of the signal determined with MSOT for total/oxygenated/deoxygenated	Day1
MSOT: hb and laboratory results	- MSOT: Correlation of the signal for total/oxygenated/deoxygenated hemoglobin with laboratory chemical parameters	Day1
MSOT hb and sonography	- MSOT: Correlation of the signal for total/oxygenated/deoxygenated hemoglobin determined with MSOT with sonographic parameters	Day1
MSOT hb and histology	- MSOT: Correlation of the signal for total/oxygenated/deoxygenated hemoglobin with with histological parameters	Day1
MSOT Lipid and laboratory results	- MSOT: Correlation of the signal for lipid determined with MSOT with laboratory chemical parameters	Day1
MSOT Lipid and sonographic results	MSOT: Correlation of the signal for lipid determined with MSOT with sonographic parameters parameters	Day1
MSOT lipid and histology	MSOT: Correlation of the signal for lipid determined with MSOT with histological parameters	Day1
MSOT collagen and sonography	- MSOT: Correlation of the signal for collagen determined with MSOT with sonographic parameters	Day1
MSOT collagen and histology	MSOT: Correlation of the signal for collagen determined with MSOT with histological parameters	Day1
MSOT collagen and laboratory results	- MSOT: Correlation of the signal for collagen determined with MSOT with laboratory chemical parameters	Day1
ULM quantification and sonography	Correlation of parameters of the quantified microvascular perfusion dynamics in the transplant kidney with sonography in transplanted kidney	Day1

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: Ferdinand Knieling, PD Dr. Dr., FAU Erlangen-Nuremberg

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): January 18, 2028
• Study Completion (Estimated): January 18, 2028

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: June 18, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: NTX_ULM_MSOT

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