Characterization of Renal Microvascular Alterations in Patients With Active Urinary Sediment and/or Proteinuria Using Ultrasound Localization Microscopy (VARIOUS)

The goal of this study is the non-invasive visualization and quantification of renal microvascular dynamics in adult kidneys with proteinuria and/or active sediment.

Study Overview

• Status: Recruiting
• Conditions: Nephritis

Detailed Description

In this study, the microvascular architecture of the kidney in adults with active urinary sediment or proteinuria is to be examined non-invasively using Ultrasound Localization Microscopy (ULM).

Kidney diseases can broadly be classified according to the affected nephron compartment into glomerular, tubular, and tubulointerstitial diseases. Glomerular diseases include, among others, the nephrotic and nephritic syndromes, which differ in their clinical and laboratory characteristics: while the nephrotic syndrome is typically characterized by marked proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia, the nephritic syndrome is dominated by hematuria with acanthocytes, mild to moderate proteinuria, arterial hypertension, and impaired renal function. Tubular and tubulointerstitial diseases, on the other hand, often manifest as acute kidney injury (e.g., in ischemic or toxic injury), polyuria, salt wasting, or metabolic acidosis, often accompanied by nonspecific symptoms such as fatigue or dehydration.

In addition to these classical nephron compartments, renal vascular structures may also be primarily or secondarily affected, as in vasculitis, thrombotic microangiopathies, or hypertensive nephropathy. Although these vascular structures are not directly part of the nephron, they are functionally closely linked to it and have a significant impact on renal function.

To assess kidney status, pathophysiology, and the site of injury non-invasively, urinary sediment is analyzed. Urinary sediment represents a central diagnostic tool that provides information on the localization of kidney damage, thereby functioning as a type of "liquid biopsy."

If there is clinical suspicion of acute or rapidly progressive renal failure, nephrotic syndrome, significant non-nephrotic proteinuria, glomerular hematuria, or if a systemic disease with possible renal involvement is present, a kidney biopsy is usually indicated for further diagnostic clarification. Obtaining tissue samples for histological examination is an invasive procedure associated with inpatient hospitalization, considerable burden for patients, and potential complications. Currently, alternative imaging methods cannot replace kidney biopsy. Furthermore, CT, PET, or MR imaging is associated with radiation exposure or considerable additional effort (e.g., sedation).

Ultrasound Localization Microscopy (ULM) enables visualization of vascular architecture using contrast-enhanced ultrasound. Recently, glomeruli-the smallest functional units of the kidney-were visualized and even counted in both rats and humans. Thus, ULM enables an assessment of renal function potentially comparable to kidney biopsy, in which glomeruli are also counted and examined. Beyond the kidney, the microvascular architecture of the human brain has also been depicted at previously unknown resolution using ULM. ULM therefore offers both qualitative and quantitative visualization of vascular architecture and perfusion dynamics. In the latest studies, 3D ULM imaging has been achieved, allowing volumetric visualization of vascular architecture and thereby overcoming the limitations of 2D imaging. This three-dimensional depiction of vascular structures may potentially provide more realistic insights into disease-related changes that would otherwise not be possible.

In the following, the term 'ULM' is used inclusively for both 2D and 3D ULM. In this study, renal function and perfusion in patients with active urinary sediment and indication for kidney biopsy will be evaluated, compared, and correlated with results from histology (biopsy), laboratory tests, and ultrasound diagnostics. If possible, a follow up assessment via ULM/CEUS after treatment (for example pharmacological therapy) will be scheduled.

With ULM the investigators aim to visualize the microvascular architecture and glomeruli, and to investigate whether differences detectable by ULM can be identified for the various causes of active sediment. In addition, the investigators seek to establish alterations in perfusion dynamics as potential imaging markers of kidney function.

In the future, this could enable non-invasive differentiation of the underlying disease and assessment of renal function, potentially reducing the need for invasive, high-risk procedures and allowing faster diagnosis in patients with an indication for kidney biopsy due to active sediment or proteinuria.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Ferdinand Knieling, MD, PhD, MHBA; Phone Number: 091318533118; Email: ferdinand.knieling@uk-erlangen.de
• Study Contact Backup: Name: Henriette Mandelbaum, MD, PhD; Phone Number: 09131 85 33118; Email: henriette.mandelbaum@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • University Hospital Erlangen

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

One study population. Anticipated approx. n=30 adultswith above mentioned inclusion criteria with active sediment and/or proteinuria and indication for kidney biopsy

Description

Inclusion Criteria:

• Age ≥ 18 years
• Evidence of active urinary sediment and/or proteinuria >1 g/g creatinine
• Indication for kidney biopsy as part of study-independent diagnostics
• Written informed consent

Exclusion Criteria:

• Known allergic disposition to SonoVue®
• Contraindication to the use of SonoVue®
• Pregnancy
• Breastfeeding mothers

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Study group; Patients with active sediment and/or proteinuria (>1g/g Krea) and indication for renal biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CEUS Time intensity curves	All CEUS outcomes will be generated in order to achieve time intensity curves in contrast enhanced ultrasound analysis	baseline and up to 10 weeks after baseline
CEUS Measurement1	PE (Peak-Enhancement) is an established measurement in CEUS analysis. It describes the highest signal intensity after administration of contrast agents and is measured in arbitrary units. All CEUS measurements are established measurements in Time intensity analysis (TIC) of contrast enhanced ultrasound data.	baseline and up to 10 weeks after baseline
CEUS Measurement2	Description: WiAUC (Wash-in Area Under the Curve (AUC(TI: TTP)))	Baseline and up to 10 weeks after baseline
CEUS Measurement 3	RT (Rise Time = arterial inflow until maximum signal intensity), measured in seconds, higer RT means faster arterial inflow	Baseline and up to 10 weeks after baseline
CEUS Measurement5	mTT (mean Transit Time local) (mTT-TI))	Baseline and up to 10 weeks after baseline
CEUS Measurement6	TTP (Time to Peak)	Baseline and up to 10 weeks after baseline
CEUS Measurement7	WiR (Wash-in-Rate )	Baseline and up to 10 weeks after baseline
CEUS Measurement8	WiPI (Wash-in Perfusion Index (WiAUC/RT))	Baseline and up to 10 weeks after baseline
CEUS Measurement9	WoAUC (Wash-out AUC (AUC(TTP:TO)))	Baseline and up to 10 weeks after baseline
CEUS Measurement10	WiWoAUC (Wash-in- und Wash-out-AUC (WiAUC+WoAUC))	Baseline and up to 10 weeks after baseline
CEUS Measurement11	FT (Fall Time - (TO-TTP))	Baseline and up to 10 weeks after baseline
CEUS Measurement12	WOR (Wash-out-Rate) QOF (Quality Of Fit between the echo-power signal and f(t)	Baseline and up to 10 weeks after baseline
CEUS Measurement13	QOF (Quality Of Fit between the echo-power signal and f(t)	Baseline and up to 10 weeks after baseline
Visualization and quantification of kidney perfusion with CEUS	CEUS imaging for kidney perfusion in kidney disease	Baseline and up to 10 weeks after baseline
Visualization and quantification of kidney mikrovaskularisation with ULM	ULM imaging for kidney perfusion and microvaskularisation in kidney disease	Baseline and up to 10 weeks after baseline
Visualization and quantification of glomeruli in the kidney with ULM	ULM imaging for glomeruli in the kidney	Baseline and up to 10 weeks after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ULM and Ultrasound	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with sonographic parameters (including resistance index a.o.)	Baseline and up to 10 weeks after baseline
ULM and CEUS	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with parameters of contrast-enhanced ultrasound (CEUS)	Baseline and up to 10 weeks after baseline
ULM and biopsy	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (including the number of segmented glomeruli) with histological parameters.	Baseline and up to 10 weeks after baseline
2D and 3D ULM	Comparison of visualized and quantified microvascular dynamics (including glomeruli) using 2D and 3D ULM	Baseline and up to 10 weeks after baseline
ULM and diagnosis	Comparison of the vascular architecture visualized by ULM (including the number of segmented glomeruli) with the underlying diagnosis in patients with active sediment and/or proteinuria >1 g/g creatinine and indication for kidney biopsy.	Baseline and up to 10 weeks after baseline
Comparison before and after treatment	Comparison of microvascular dynamics via ULM/CEUS in the kidney before and after treatment (e.g., pharmacological therapy)	Baseline and up to 10 weeks after baseline
Correlation between ULM and laboratory parameters	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with laboratory parameters (including kidney function parameters, inflammatory markers, immunological parameters.	Baseline and up to 10 weeks after baseline
ULM on different diagnoses	Comparison of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) between different diagnoses.	Baseline and up to 10 weeks after baseline
Assessment of renal function GFR	GFR (ml/min/1,73 m2)	Baseline and up to 10 weeks after baseline
Assessment of renal function urea	urea (mg/dl)	Baseline and up to 10 weeks after baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
urinary status	levels of erythrocytes and proteinuria in urine, microscopic examination of urine sediment	Baseline and up to 10 weeks after baseline

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: September 16, 2025
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: kidney; ultrasound localization microscopy (ULM)
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Nephritis
• Other Study ID Numbers: ULM_VARIOUS

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