In search of biomarkers for the early detection of renal cystic diseases


Ann Van Schepdael, Pharmaceutical Analysis, KU Leuven, Leuven, Belgium (ann.vanschepdael@kuleuven.be)
Asmin Andries, Pharmaceutical Analysis, Ku Leuven, Leuven, Belgium
Charlotte Keulers, Pharmaceutical Analysis, Ku Leuven, Leuven, Belgium
Djalila Mekahli, Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium

This study is situated in the field of renal cystic diseases that may occur under the form of autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD) or tuberous sclerosis complex (TSC). More specifically, ADPKD will be investigated. It is the most common hereditary renal disease (incidence between 1:400 and 1:1000 live births) and is mainly related to mutations in the PKD1 or PKD2 gene. The cyst development starts early in childhood and a decline in kidney function occurs from the third decade, eventually leading to end-stage renal disease.

The overall objective of this study is to find early markers, specific of this disease. These are needed as a tool for early diagnosis and monitoring of disease progression. Various analytical techniques were used for urine samples, as urine is a convenient and easily accessible patient matrix.

The first aim was to measure oxidative stress in children with ADPKD and compare with healthy controls (by HPLC-UV). A bioanalytical method for the determination of allantoin and adenosine in urine was optimized and fully validated. Because of the rather long run time, efforts were done to shorten the method by applying core shell particles. A significant number of control and patient samples were analyzed, and the obtained data were statistically evaluated. A critical discussion of the results will show whether these compounds can act as early predictors of the ADPKD disease.

Future studies will tackle the next objective, namely to focus on the mTOR pathway by measuring the excreted urinary amino acids (by LC-MS/MS).

In a further step, it will also be important to find out the serum levels of the investigated compounds in order to support biological hypothesis testing.

If the investigated substances indeed appear to be of relevance, they might turn out to be suitable early predictors of ADPKD.


Abstract Reference & Short Personal Biography of Presenting Author

Ann Van Schepdael obtained a degree of Pharmacist in 1986, and a PhD in 1990 (KU Leuven, University of Leuven, Belgium, Medicinal chemistry). Following a post-doc at KU Leuven and the Barnett Institute (Northeastern University, Boston, 1993) she was appointed lecturer in Leuven in 1997. Since 2007 she is a full professor at the Pharmaceutical Analysis division, and heads the latter lab since 2010. Since 1990 her research focus is on analytical techniques, mainly capillary electrophoresis. Besides interest in electrophoretically mediated microanalysis (EMMA) and in immobilized enzymes, also liquid chromatography for bioanalysis is within her research focus. She teaches courses on instrumental analysis and analytical tools for drug development, as well as practical pharmaceutical analytical chemistry exercises in the bachelor and master programs at the school of pharmacy KU Leuven. She has published over 300 publications in international peer-reviewed journals, has been the (co)-promoter of 32 PhD theses and is currently promoter of 3 PhD students and co-promoter of 4 PhD students.

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