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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
30
Single Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).
ULM 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 draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access.
Blood 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.
Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.
Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes at Timepoint 1 and Timepoint 2.
Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others.
Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others at time point 1 and time point 2.
Department of Pediatrics and Adolescent Medicine
Erlangen, Baveria, Germany
RECRUITINGCEUS Measurement 1
Peak enhancement (PE)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 2
Wash-in area under the curve (WIAUC)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 3
Wash-in perfusion index (WiPI)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 4
Wash-in rate (WIR)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 5
Wash-out under the curve (WoAUC)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 6
Wash-in and wash-out under the curve (WiWoAUC)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 7
Wash-out rate (WoR)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 8
Time to peak (TTP)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 9
Rise time (RT)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 10
Mean transit time (local) (mTTI)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 11
Fall time (FT)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
CEUS Measurement 12
Peak enhancement (PE)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
Blood Count
Complete blood count with number of red and white blood cells and platelets per µl
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
Urine status
Measurement of proteinuria in mg/l with protein differentiation
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
RI
Resistance index (Sonography)
Time frame: Measurement of proteinuria with protein differentiation
Flow velocity
Flow velocity in Doppler Signal (Sonography)
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
Weigth
Weigth of the participant in kilograms
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
Height
Height of the participant in meters
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
BP
Measurement of systolic, diastolic and mean blood pressure in mmHg
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Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
Electrolytes
Concentration of serum electrolytes (Na, K, Cl, Mg, P) in mmol/L.
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care
Creatinin and urea level
Serum Creatinin and urea level in mg/dl
Time frame: Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care