Publikationsserver der RWTH Aachen University
Langfristige Entwicklung Zytostatika-induzierter Nierenfunktionsstörungen bei pädiatrisch-onkologischen Patienten
Abstract
dc:descriptionNephrotoxicity is a frequent complication of chemotherapeutic treatment. The aim of the investigation is to analyse the long-term nephrotoxic sequelar in patients with malignancies. Using optimized sodium dodecyl sulfate polyacrylamid gel electrophoresis (SDS-PAGE) even in proteinuria < 150 mg/day all relevant proteins for diagnosis of glomerular or tubulo-interstitial kidney disease can be detected. SDS-PAGE with silver staining is a method which is able to detect tubular or glomerular abnormalities in a more sensitive way than serum creatinin or creatinin clearance does. Laser densitometry of the protein patterns allows documentation and follow-up of urinary findings during and after treatment.79 patients (32 female) with a median age of 5.98 years (range 0.51 years - 15.60 years) at diagnosis are studied after a median time of 8.25 years (range 1.8 years – 21.6 years) after diagnosis of a malignant disease and beginning of chemotherapy. Following the chemotherapy the children received, patients were divided into four groups (acute lymphatic leukemia and NHL, Wilms tumor, ifosfamide / cisplatin, stem cell transplantation). Especially the nephrotoxic sequels due to ifosfamide, cisplatin, carboplatin, etoposide, and methotrexate are investigated.Altogether, 55.7% of the patients show a normal renal function. Slight damages seem to improve rather than serious damages that show a tendency to persistence. In the group of the children treated for leukemia persistent nephrotoxicity is rare, despite of the treatment with high-dose methotrexate. More than 70% of the patients show a physiological renal function. From the patients with renal sequelar, more than the half only have slight damage. From the patients treated for Wilms tumor a much bigger part shows chronic renal function reduction (77%). From the patients treated with ifosfamide, cisplatin and / or stem cell transplantation, 45% show normal patterns, 24% show mixed glomerular and tubular patterns, 24% show tubular patterns, and 3% show glomerular patterns.In literature, several risk factors for the development of chronic nephrotoxicity have been described, sometimes contradictorily. A reason for the different results may be the fact that in pediatric oncologic therapy protocols, cytostatics are combined as a matter of principle so that it is not always possible to discriminate between the nephrotoxicity caused by the different substances. Our study does not reveal a higher risk for younger children nor for a special sex. Children treated with a cumulative dose of ifosfamide of more than 12 g / m2 as well as children treated with a high dose of etoposide (possible threshold of 2000 mg / m2) seem to have a high risk for chronic nephrotoxicity. The combination of nephrotoxic cytostatics may cause increased renal damage. The synergistic toxicity of cisplatin or carboplatin and ifosfamide is well-known. Obvious improvements are seen in some aspects of toxicity in some patients while there is deterioration in others so it remains difficult to predict the occurrence of this toxicity with confidence. Highly discriminating SDS-PAGE permits a rapid, reproducible, and reliable analysis of urine proteins for diagnosis and follow-up of all kinds of reno-parenchymal kidney diseases and is suitable for follow-up tests of renal function during and after chemotherapy.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2006
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Probst, Kathrin
- Contributors dc:contributor
-
- Mertens, Rolf
Subjects
dc:subject × 14Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:61131