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

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.

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