National studies of kidney disease in childhood and adolescence

Kidney disease in children is rare, but highly demanding, both for the families and children, and for the medical services. The majority of the workload is managed in specialist children s hospitals, and requires facilities for dialysis and transplantation. If the diseases that lead to kidney failure could be studied more systematically, by collecting clinical information, blood and DNA samples from the whole UK population, then better strategies for preventing kidney failure could be devised.
This study will collect information from 2 such diseases, in an ongoing basis, and has the robust support of all the leading UK kidney organisations. This will be the first time such comprehensive disease information has been collated, and will set up an infrastructure for many more kidney diseases to be studied in the same comprehensive way.

The proposal is to develop a national cohort of two kidney diseases that present in childhood and adolescence, mesangiocapillary glomerulonephritis (MCGN) and focal segmental glomerulosclerosis (FSGS). These diseases are rare, progress to end-stage renal failure and are resistant to conventional immunosuppressive therapies. Health service costs attributable to these disorders in young subjects are disproportionately high. Both disorders lend themselves to modern investigation with new insights into abnormal complement regulation in MCGN and gene mutations that affect the glomerular epithelial cell (podocyte) in FSGS.

The proposal has the emphatic support of the relevant national organizations. To overcome the problem of disease rarity investigators will collaborate across all tertiary regional paediatric nephrology centers. A generic web-based data entry and management system will be developed: analysis will be centralized. The phenotype will be extensively defined by standardized investigations with expert peer review of the renal pathology to include stratification for chronic renal damage. There will be special investigations specific to each cohort. For MCGN this will include centralized investigation of complement activity and the role of antibodies that are thought to either induce complement dysregulation or participate in immune complex formation in the kidney. For FSGS it will include screening for known causative gene mutations. For both cohorts a biorepository will be established.

The cohorts will be large enough to permit prospective clinical trials, and for both disorders there are novel proposals for treatment. A steering committee to promote and regulate access will supervise each cohort. Consideration has been given to the long-term follow up of participants, particularly the transfer into adult medical supervision. The development of these cohorts is a test case for the renal community to develop similar studies of other rare kidney disease in association with the UK Renal Registry.