Responsible Center

	Hannover Medical School

Project Description

Currently no test is available to predict the development of renal function in ARPKD, Nephronophthisis, Barded-Biedl Syndrome or HNF1B Nephropathy. Therefore, no valid prognosis can be given for patients or their families, which leads to uncertainty.

The subproject 6 (ProtCyst) aims to establish a prognostic test using spot urine. This test will use capillary electrophoresis coupled to mass spectrometry (CE-MS) to analyze all peptides and proteins in the sample.

Inclusion criteria:

1. patient is included in the NEOCYST-register
2. GFR between 80 and 120 ml/min/1,73m² KOF
3. Age between 0-16 years at study entry (2-18 years at study end)
4. Patient’s guardians are capable to understand the purpose of the study.
5. Patient’s guardians have singed the informed consent. Patients older than 7 years of age have to consent participating in this study.

Exclusion criteria:

1. patient is on renal replacement therapy
2. patient receives immunosuppressant therapy
3. patient is pregnant
4. urinary tract infection within the last two weeks.
5. previous surgeries of the urinary tract
6. severe malformation of the urinary tract

The study is designed as a blinded, prospective, multicenter-Study.

All patients included in this study will be monitored for two years. During this time two study visits will be conducted. The first to include the patient in this study. The other will be done to estimate the GFR 24 months later.

When the databank of the clinical parameters is closed, all patients ate stratified by their GFR into two groups. The cases consisting of 30 patients with the sharpest drop in GFR and at least below 80 ml/min/1,73m² within the two years. The controls consist of 30 patients with the smallest drop of GFR and still between 80-120 ml/min/1,73m² within the same time frame.

Estimation of GFR to stratify patients will be done using Schwartz’s formula published 2009.

To establish the proteome pattern the individual proteome pattern of 15 randomly selected cases will be compared with randomly selected 15 controls. The person conducting the CE-MS will be fully aware of the patients’ condition. The results will be analyzed via software analysis in a p-dimensional space using support-vector-machine (SVM) learning. ROC-analysis will be used to determine the optimal cut-off point.

To validate this pattern the remaining 15 cases and controls will be analyzed. The person conducting this analysis will not be aware of the patients’ conditions.

Each patient will be stratified using the cut-off value previously determined. Thus, specificity and sensitivity can be determined after unblinding.

Leading Investigators

Prof. Dr. med. Lars Pape Deputy director of the Department of Paediatric Kidney, Liver and Metabolic Diseases and head of the KfH-Department of pediatric nephrology NEOCYST – Principal investigator P6 Prof. Pape is pediatric nephrologist with a full professorship for pediatric nephrology. His main research focus is the development and establishment of biomarkers in pediatric nephrology as well as health services research mainly in transitional medicine and improvement of care after kidney transplantation. He is council member of the International Pediatric Transplantation Society and Director of Studies of the German Pediatric Nephrology Association as well as deputy chairman of the task force kidney transplantation of the GPN and the national pediatric health system advisor for dialysis

Dr. med. Jens Drube NEOCYST – Deputy P6 Mr. Drube works at the outpatients’ department of paediatric nephrology since 2003. His primary research focus centers on urinary proteome analysis. Selected publication: Urinary proteome analysis to exclude severe vesicoureteral reflux. Drube J, et al., Pediatrics. 2012;129:e356-63 Urinary proteome pattern in children with renal Fanconi syndrome. Drube J, et al., Nephrol Dial Transplant. 2009;24:2161-9

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