Steroid Resistant Nephrotic Syndrome

Background

People Panel A_2x4_Rare DiseasesSRNS is a rare disease of kidney filtration, with an incidence of approximately 2 to 3 per 100,000. It affects both children and adults and results from breakdown of the first filtering unit in the kidney, the renal glomerulus. This contains a highly sophisticated macromolecular sieve with size and charge restricting characteristics called the glomerular filtration barrier (GFB). Its malfunction results in excessive amounts of protein leaking into the urine. Normally only trace amounts are present, so this excess loss results in the other features of the syndrome such as low protein levels in the blood, consequent fluid retention and swelling, high blood lipid levels and eventual kidney failure. The extent of protein loss is a prognostic marker as well as independent risk factor for cardiovascular morbidity/mortality. SRNS may occur as an isolated kidney defect or be part of a syndrome involving other organ systems especially if onset is in early childhood. At present our understanding of how the filter becomes damaged is poor and as a result, only non-directed treatment strategies centred on immunosuppression with steroids and other toxic drugs is available. These alleviate symptoms, but rarely result in a cure, instead resulting in multiple side-effects from years of strong medication.

The most common type of kidney damage seen in SRNS is focal segmental glomerulosclerosis (FSGS); the pathological changes develop focally (not in all glomeruli) and segmentally (only in parts of a glomerulus). This pattern suggests that an initial localised insult caused by environmental stressors may lead to cell injury. It is also becoming increasingly clear that the response to injury is influenced strongly by the genetic background as some cases progress to renal scarring, whereas others manage the insult and are able to repair. Infections can trigger nephrotic syndrome and some damage may result from abnormal cell signals triggered by atypical immune activation. However the genetic errors and mechanisms underlying these responses remain unknown and their identification forms the focus of this project. Any genetic advances in SRNS would also provide insight into other glomerular diseases and in the longer term, the potential for individualised diagnosis and therapy.

Recruitment Criteria:

Inclusion Criteria
Massive protein urea
Elevated plasma creatinine

Centres at which SRNS is currently recruiting

Guy’s & St Thomas’ Hospital, London
University Hospitals Bristol NHS Foundation Trust

Leads
Dr Ania Koziell, Guy’s and St Thomas Hospital