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.
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.
Known allergic disposition to SonoVue / other contrast agents
Tattoo in the area of the examination field
Pregnancy
Breastfeeding mothers
Parallel
Ultrasound Localization Microscopy (ULM)
Diagnostic testSingle Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).
Ultrasound Localization Microscopy (ULM)
Diagnostic testULM of the kidney after application of a contrast medium (SonoVue®, intravenous) at two different time points: Timepoint 1: Before initiation of therapy, latest day 50 before 1st high-dose methotrexate or cyclophosphamide. Timepoint 2: After termination of intensive treatment (after 6-9 months).
Blood sample
Diagnostic testBlood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access.
Blood sample
Diagnostic testBlood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access at Timepoint 1 and 2.
Urinanalysis
Diagnostic testExamination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.
Urinanalysis
Diagnostic testExamination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes at Timepoint 1 and Timepoint 2.
Renal sonography
Diagnostic testRenal sonography including resistance index (RI), Doppler signal, flow velocity, and others.
Renal sonography
Diagnostic testRenal sonography including resistance index (RI), Doppler signal, flow velocity, and others at time point 1 and time point 2.
CEUS Measurement 1
Peak enhancement (PE)
CEUS Measurement 2
Wash-in area under the curve (WIAUC)
CEUS Measurement 3
Wash-in perfusion index (WiPI)
CEUS Measurement 4
Wash-in rate (WIR)
Blood Count
Complete blood count with number of red and white blood cells and platelets per µl
Urine status
Measurement of proteinuria in mg/l with protein differentiation
RI
Resistance index (Sonography)
Flow velocity
Flow velocity in Doppler Signal (Sonography)
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