Kids Kidney Research

Nephrotic syndrome is one of the most common kidney diseases in childhood. Originally, the majority of children died from complications of the disease, such as infections and thrombosis, but fortunately this has been greatly improved by antibiotics and especially the discovery of a clinical response to corticosteroid treatment. For this reason, nephrotic syndrome in children is typically classified into a steroid-sensitive and a steroid-resistant form and more than 80% of children presenting with nephrotic syndrome belong to the former group. Nephrotic syndrome in childhood is very different compared to that experienced in adults when steroid-resistance is much more common. The majority of affected children outgrow their disease before adulthood, although may run a chronic relapsing course, but in a small percentage it persists. Generally, adult nephrologists have less experience in managing steroid-sensitive nephrotic syndrome. Patients with persistent disease typically have a more severe form of nephrotic syndrome and require frequent and prolonged use of corticosteroids often in combination with other powerful drugs acting on the immune system. This has major implications for growth, body habitus and susceptibility to high blood pressure and infection as well as potential undesirable side effects on the eye, skeleton and reproductive system. We propose to create a specialised transition clinic for young people at the Royal Free Hospital, the adult nephrology centre closest to Great Ormond Street Hospital (GOSH). No such clinic exists in the UK and it would create a unique and fantastic opportunity not only to smooth the transition of affected patients into adult care, but also to facilitate the transfer of knowledge about the care of such difficult patients between paediatric and adult nephrologists.

In addition, we want to enhance our understanding of the molecular basis of nephrotic syndrome. We propose to develop comprehensive genetic screening for known genes associated with nephrotic syndrome, as identification of mutations in them directly informs clinical management, but is unavailable for the majority of them. Moreover, we have identified and recruited several families with one or more members affected by nephrotic syndrome, allowing identification of further disease genes. In many families both parents and siblings are affected and it is proposed that all patients would be seen in the specialised transition clinic for counselling and clinical management. In view of the high incidence of nephrotic syndrome in ethnic minority groups, special provision will be made for such families in this clinic.