With increasing survival rates in pediatric oncology, reports of long-term side effects persisting decades after treatment are also rising. Clinically evident nephropathies occur in about 5.5% of survivors more than five years after therapy. Chemotherapeutic agents such as ifosfamide, cisplatin, and carboplatin, as well as kidney-directed treatments like radiation, surgery, or stem cell transplantation, increase this risk. Acute kidney injury has also been described in association with cyclophosphamide and high-dose methotrexate, which are used in the treatment of acute lymphoblastic leukemia (ALL). Studies show a high prevalence of albuminuria (around 14.5% of childhood cancer survivors), an early marker of kidney damage, while standard parameters like creatinine often become abnormal only at later stages.

Leukemia survivors suffer from vascular late effects caused by persistent endothelial damage triggered by cancer therapies such as anthracyclines, cyclophosphamide, and asparaginase, which increase inflammation and thrombosis risk. These vascular changes may also contribute to kidney injury.

ULM is a high-resolution ultrasound technique that uses microbubbles to visualize the microvasculature and resolve dynamic blood flow changes with a resolution beyond the diffraction limit. ULM is independent of kidney or liver function, has been applied in various organs, and was recently used for the first time to visualize glomeruli-the smallest functional units of the kidney-in humans. This method enables early detection of glomerular injury as a consequence of vascular damage, even before albuminuria appears, potentially allowing earlier adaptation of follow-up and initiation of treatment.

This pilot project focuses on survivors of ALL, as they are the largest and best studied pediatric cancer patient group also regarding late effects and, therefore, a sufficient number of individuals can be expected for his monocentric approach. Vascular functional impairment of the kidney could be detected at an early stage and the follow-up structures and measures such as the early use of nephroprotective drugs could be adapted.

Inclusion Criteria:

• Diagnosed acute lymphatic leukemia
• From 3 years to < 18 years
• completed oncological treatment or treatment day < 50 according to therapy protocol and no administration of CPM before first examination.

Exclusion Criteria:

• Known allergic disposition to SonoVue / other contrast agents
• Tattoo in the area of the examination field
• Pregnancy
• Breastfeeding mothers
• Contraindication for the use of Sonovue
• Critical condition
• Known clinically evident renal impairment

The raw, individual and identifiable patient data are protected and are not available due to data privacy laws. Further data sets are planned to be shared.

Beginning 9 months and ending 36 months following article publication

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows:

Individual participant data will not be available Study Protocol and Statistical Analysis Plan will be available The data will be available beginning 9 months and ending 36 months following article publication.

The data will be available to researchers who provide a methodologically sound proposal.

The data will be available for individual participant data meta-analysis, only. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at https://www.uk-erlangen.de.

Restrictions may apply due to patient privacy and the General Data Protection Regulation.