Galloway-Mowat syndrome is an autosomal recessive disorder characterized by early onset nephrotic syndrome and central nervous system anomalies. Mutations in podocyte proteins, such as nephrin, alpha-actinin 4, and podocin, are associated with proteinuria and nephrotic syndrome. The genetic defect in Galloway-Mowat syndrome is as yet unknown. We postulated that in Galloway-Mowat syndrome the mutation would be in a protein that is expressed both in podocytes and neurons, such as synaptopodin, GLEPP1, or nephrin. We therefore analyzed kidney tissue from normal children (n=3), children with congenital nephrotic syndrome of the Finnish type (CNF, n=3), minimal change disease (MCD, n=3), focal segmental glomerulosclerosis (FSGS, n=3), and Galloway-Mowat syndrome (n=4) by immunohistochemistry for expression of synaptopodin, GLEPP1, intracellular domain of nephrin (nephrin-I), and extracellular domain of nephrin (nephrin-E). Synaptopodin, GLEPP1, and nephrin were strongly expressed in normal kidney tissue. Nephrin was absent, and synaptopodin and GLEPP1 expression were decreased in CNF. The expression of all three proteins was reduced in MCD and FSGS; the decrease in expression being more marked in FSGS. Synaptopodin, GLEPP1, and nephrin expression was present, although reduced in Galloway-Mowat syndrome. We conclude that the reduced expression of synaptopodin, GLEPP1, and nephrin in Galloway- Mowat syndrome is a secondary phenomenon related to the proteinuria, and hence synaptopodin, GLEPP1, and nephrin are probably not the proteins mutated in Galloway-Mowat syndrome.

No abstract

No abstract

No abstract

We studied the plasma renin activity (PRA) and blood pressure (BP) responses to a single oral dose of captopril in children with renal scarring due to vesicoureteral reflux. The test was performed on 19 children, of whom 13 were normotensive and 6 hypertensive. Basal PRA was within the normal range for age for all except 1 patient. Mean basal PRA values for normotensive and hypertensive patients were not significantly different. At 90 min post captopril, the mean PRA increase was 3.61 ng/l per second (SD = 7.07) in the normotensive group but only 0.77 ng/l per second (SD = 0.83) in the hypertensive group. In 11 patients the average systolic BP 60-90 min post captopril was 0.9%-12.4% lower than the basal value. Diastolic BP decreased after captopril administration in 10 patients and increased in 9. The changes in mean arterial pressure and PRA between 0 and 90 min post captopril were inversely correlated (r = 0.605, P less than 0.01). Because of the PRA responsiveness in the normotensive patients with renal scarring, we suggest that there was activation of the renin-angiotensin axis in this group. However, it is not apparent whether such patients are more at risk of developing hypertension at a later time.