Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1).

Congenital nephrotic syndrome of the Finnish type (NPHS1) is a rare genetic disease caused by mutations in the NPHS1 gene encoding a major podocyte slit-diaphragm protein, nephrin. Patients with NPHS1 have severe nephrotic syndrome from birth and develop renal fibrosis in early childhood. In this work, we studied the development of glomerular sclerosis in kidneys removed from 4- to 44-month-old NPHS1 patients.

Clinical features and outcome of childhood minimal change nephrotic syndrome: is genetics involved?

The pathogenesis of minimal change nephrotic syndrome (MCNS) is still unknown. We performed a clinical and genetic evaluation of 104 adults (mean age 35 years) who presented with MCNS in childhood (mean follow-up 30 years). Clinical data and the present health status were evaluated.

Podocytes are firmly attached to glomerular basement membrane in kidneys with heavy proteinuria.

Glomerular epithelial cells (podocytes) play an important role in the pathogenesis of proteinuria. Podocyte foot process effacement is characteristic for proteinuric kidneys, and genetic defects in podocyte slit diaphragm proteins may cause nephrotic syndrome. In this work, a systematic electron microscopic analysis was performed of the structural changes of podocytes in two important nephrotic kidney diseases, congenital nephrotic syndrome of the Finnish type and minimal-change nephrotic syndrome (MCNS).

Nephrin gene (NPHS1) in patients with minimal change nephrotic syndrome (MCNS).

Background: Minimal change nephrotic syndrome (MCNS) is a major problem in pediatric nephrology. While the pathogenesis of MCNS is not known, the latest discoveries in the genetic diseases indicate that glomerular epithelial cells (podocytes) and the slit diaphragm play a primary role in development of proteinuria. Because nephrin is known to be a major component of the slit diaphragm, we analyzed the structure of nephrin gene (NPHS1) in patients with MCNS of different severity.

Tissue expression of nephrin in human and pig.

Nephrin is a major component of the glomerular filtration barrier. Mutations in the nephrin gene (NPHS1) are responsible for congenital nephrotic syndrome of the Finnish type (NPHS1). Nephrin was at first thought to be podocyte specific, but recent studies have suggested that nephrin is also expressed in nonrenal tissues such as pancreas and CNS.