Pediatric Nephrology – Radboudumc Amalia Childrens hospital
‘Research is fundamental to further improvement in child health’ (Brit Med J 2002:324: 1444).
The Pediatric Nephrology department at the Radboud university medical center (Radboudumc) is responsible for the clinical care of children with renal and electrolyte disorders. Furthermore, all children with chronic renal failure in the eastern half of the Netherlands (with a population of approximately 6 million) are treated here. In The Netherlands there are 3 centres for chronic dialysis and renal transplantation in children. This means that approximately one third of the Dutch patients with chronic renal failure are treated with dialysis or transplantation in the Pediatric Nephrology department in Nijmegen. It is a top reference center for this specific patient group and expert center in rare kidney disorders.
The Pediatric Nephrology center in Nijmegen has, as a result of the scientific research performed, specialised skills in the treatment of hereditary tubular disorders and typical (Shiga toxin producing E. coli) and atypical forms of hemolytic uremic syndrome (HUS). Each year we perform 1000-1500 hemodialyses and 3000-3500 peritoneal dialyses. Specialised techniques such as plasma filtration and continuous venovenous haemofiltration are performed by the team in Nijmegen when necessary. Each year approximately 10 children undergo renal transplantation either pre-emptively or after a phase of dialysis. These transplantations are made possible by both family and post mortem donations.
The Pediatric Nephrology department’s leading role became evident through the review of the Discipline Plan Medicine and the inventory made by the Nederlandse Vereniging voor Kindergeneeskunde (Dutch Pediatric Society). In both cases the Nijmegen Pediatric Nephrology department was appraised as the best in The Netherlands.
Besides practical clinical research , scientific research is performed in different areas, however, here we will focus on the complement mediated kidney diseases.
Research complement mediated kidney diseases
HUS is one of the most important causes of acute renal failure in childhood. The clinical picture of the typical form of HUS is caused by a shiga toxin producing Escherichia coli bacteria. At the moment we are one of the few groups in the world able to study the effect of shiga toxin on cultured human glomerular endothelial cells. The influence of the toxin is being studied in the glomerular endothelium, monocytes and granulocytes.
Besides this typical form of HUS a familial or atypical form exists. Considering the particularly poor prognosis attempts are being made to clarify the pathogenesis of atypical HUS. In the past two decades the team of Prof.Dr. L.P. van den Heuvel/Dr. N.C.A.J. van de Kar has focused on the pathophysiology and molecular genetics of HUS. Their national reference laboratory for all HUS and C3 glomerulopathy patients from the Netherlands and Belgium offers all the specific diagnostics for complement involvement in HUS and C3 glomerulopathy (genetic analysis of complement proteins, antibodies against factor H, antibodies against lipolysaccharide O157, sC5b-9 Elisa). With the new genetic techniques as microarray and whole exome sequencing, the search for the still undiscovered genes is performed at the moment in their HUS cohort. In the functional studies examining the new genetic variations, for example C3 and CFHR5, the laboratory works successfully together with the experienced laboratories of Prof.Dr.C. van Kooten, LUMC, Prof. Pickering, London, Prof. Dr. Mollness, Norway and Prof. Gros, University of Utrecht. From the purified human glomerular cell lines, isolated and characterized in the van den Heuvel/van de Kar laboratory, their glomerular microvascular endothelial cells (HGMVEC) formed the basis of the well-known and widely used conditional immortalized HGMVEC.
The clinical expertise in complemented related renal disease in children and adults is guaranteed by Dr.N.C.A.J. van de Kar, Pediatric Nephrology and Prof.Dr. J.W.F. Wetzels, Nephrology. Both are heavily involved in the new treatment options of complement inhibitors in aHUS and its legal and financial reimbursement status. Dr. van de Kar is a member of the International Pediatric Nephrology Working Group on HUS and contributed to the published classification and guidelines in diagnostics and treatment of HUS/TTP by this group.
For publications related to the CUREiHUS study, see page publications.