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Published on: April 25, 2025
Early Detection of Tubulo-Interstitial Kidney Disease in Children Using Highly Discriminating SDS-Gel Electrophoresis
A Al-Bashir1, D Rohrmann, R Mertens
1Institute of Experimental Nephrology, Aachen, Saudi Arabia.
Insights
Optimized sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) detects kidney disease even with low proteinuria. This method aids in diagnosing and monitoring tubulo-interstitial kidney disease in children undergoing chemotherapy or with congenital obstructions.
Area of Science:
- Nephrology
- Biochemistry
- Pediatric Oncology
Background:
- Tubulo-interstitial kidney disease (TIKD) is often associated with proteinuria, but can exist even with physiological levels (<150 mg/day).
- Accurate detection of low molecular weight proteins is crucial for diagnosing TIKD.
- Optimized sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) offers sensitive detection of diagnostic urinary proteins.
Purpose of the Study:
- To evaluate the utility of SDS-PAGE for diagnosing TIKD in children treated with polychemotherapy for cancer.
- To assess TIKD in children with pyelo-ureteral junction obstruction.
- To correlate urinary protein patterns with disease progression and treatment outcomes.
Main Methods:
- Utilized optimized SDS-PAGE to analyze urine proteins in 115 children with cancer undergoing chemotherapy and 16 children with pyelo-ureteral junction obstruction.
- Monitored renal damage and tubular protein patterns during and up to three years after chemotherapy.
- Classified children with congenital pyelo-ureteral junction obstruction based on SDS-PAGE findings.
Main Results:
- Renal damage during chemotherapy varied by cancer type (leukemia 43%, nephroblastoma 56%, other tumors 79%).
- Abnormal tubular protein patterns persisted post-chemotherapy in a significant percentage of patients (25-62%).
- Persistent proteinuria indicated a high risk for irreversible renal failure; SDS-PAGE aided in surgical decision-making for congenital obstructions.
Conclusions:
- SDS-PAGE is a rapid, sensitive, and reliable method for diagnosing and monitoring TIKD in pediatric patients.
- Urinary protein analysis via SDS-PAGE can identify patients at risk for renal failure.
- SDS-PAGE assists in classifying congenital kidney issues and guiding surgical intervention.
Abstract:
Tubulo-interstitial kidney disease is characterized by moderate proteinuria < 1 g/day of low molecular weight proteins in range of MW 10.000-50.000. Even in the physiological proteinuria of < 150 mg/day, tubulo-interstitial kidney disease may exist. Using optimized sodium dodecyl sulfate polyacrylamid gel electrophoresis (SDS-PAGE) according to the method of Melzer, even in proteinuria of less than 150 mg/day all relevant proteins for diagnosis of glomerular or tubulo-interstitial kidney disease can be detected. This study evaluates the tubulo-interstitial kidney disease due to polychemotherapy for different types of cancer in 115 children and in 16 children with pyelo-ureteral junction obstruction. Fifty-two and 63 children were followed up during and after chemotherapy, respectively. During therapy, renal damage was recorded in 43% of patients with leukemia, 56% with nephroblastoma, and 79% with other tumors. Tubular protein patterns were seen up to three years after termination of chemotherapy (25% in acute lymphoplastic leukemia, 35% in nephroblastoma and 62% in other tumors). Patients with persistent complete tubular proteinuria or mixed glomerular/tubular proteinuria were found to have a high risk for irreversible renal failure. Children with congenital pyelo-ureteral junction obstruction could also be classified according to SDS-PAGE protein patterns. Patients without parenchymal lesions did not need surgery. Most of those with pathologic findings in SDS-PAGE exhibited partial or complete remission after surgery. The highly discriminating SDS-PAGE permits a rapid, sensitive, reproducible, and reliable analysis of urine proteins for diagnosis and follow-up of all kinds of congenital or acquired renal parenchymal kidney diseases.
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