MON-309 THE NEW ZEALAND PAEDIATRIC EXPERIENCE OF DIFFUSE MESANGIAL SCLEROSIS 1991-2018

Abstract

Diffuse mesangial sclerosis (DMS) is a rare cause of nephrotic syndrome in the infantile and childhood period. It is generally characterized by rapid progression to end-stage renal disease and can present in isolation or in association with Denys-Drash syndrome. The largest published series to date includes 14 children from a Spanish cohort 1973-2008. We describe the clinical presentation and outcome for our case series of children with DMS. We retrospectively reviewed all cases of DMS diagnosed via renal biopsy in our tertiary paediatric centre between 1991-2018. Starship Children’s hospital is the sole paediatric nephrology referral centre for New Zealand. A total of seven cases were identified consisting of four males and three females. Fiver patients were under 1 year of age at presentation. Two patients in the cohort were siblings. Three children had clinical evidence of Denys-Drash syndrome. The most recent five patients (presenting after year 2000) underwent genetic testing - three displayed WT1 mutations, including one patient who was found to have a novel mutation. This particular patient had a strong family history of focal segmental glomerulosclerosis. Unlike other published series, only four of the seven patients presented in end stage renal disease (ESRD). The remaining cohort displayed variable degrees of proteinuria only. Two patients with proteinuria underwent biopsy due to a significant family history of nephrotic syndrome. All four patients with ESRD on presentation required dialysis, and half of these patients subsequently had bilateral nephrectomies. Two patients proceeded to transplant with no relapse of the disease, though one transplant failed after fourteen years with the patient returning to haemodialysis. One patient died whilst on the deceased donor list due to cardiovascular complications. One patient is currently being worked up for living donor transplant. Two patients with proteinuria are currently being treated with ACE inhibitor therapy with improved proteinuria, normalisation of hypoalbuminaemia and maintainenance of a normal estimated GFR. One patient has moved overseas and is lost to follow up. There is a broad spectrum of DMS presentations ranging from mild proteinuria to ESRD. Karyotyping and genetic testing are important to establish the presence of syndromic associations and in particular WT1 mutations, as these patients require Wilm’s tumour surveillance if nephrectomies are not performed. Early detection of DMS and initiation of anti-proteinuric therapy is hoped to be beneficial to prolong native kidney function. Unfortunately, this may only be possible in patients for whom DMS is already suspected as a potential diagnosis due to a family history.